ILSL - Internacional Journal of Leprosy and other Mycobacterial Diseases- ABSTRACTS OF CONGRESS- 15th International Leprosy Congress

ACTIVITY AGAINST LEPROSY BACILLUS OF A SINCLE DOSE COMBINATION OF OFLOXACIN PLUS MINOCYCLINE, WITH OR WITHOUT RIFAMPIN, IN MICE AND IN PATIENTS

Jacques Grosset,¹ Samba Sow,² Evelyne Perani,¹ Christian Lienhardt,² Vimala Diderot,¹ and Baohong Jr¹

Faculté do Médecine Pitié-Salpètrière. Paris, France,¹ and Institut Marchoux, Bamako, Mali²

As steps for developing a fully supervisable, monthly administered multidrug regimen for leprosy, bactericidal effect against M. leprae of a single dose combination ofloxacin-minocycline (OM), and rifampinofloxacin-minocycline (ROM) was evaluated in mouse footpads and in patients. In mouse experiments, results of proportional bactericidal metbod demonstrated that the activity ot a single dose OM was dosage-related; larger dosage, i.e, 300 mg; O plus 50 mg M per kg body weight, displayed bactericidal effect, whereas smaller dosage, i.e., 150 mg O plus 25 mg M per kg, was not bactericidal. The activity ot a Single dose of larger dosage OM was significantly inferior lo that of a single dose R, and the addition of either dosage of OM neither enhanced nor antagonized the activity of R. In terms of bactericidal effect, the consequence of excluding clarithromycin from dnig combinations is only marginal. In clinical trial, 20 previously untreated lepromatous patients were randomly allocated to 2 groups with 10 each, and treated, respectively, with a single dose of 600 mg R plus 400 mg O and 100 mg M (ROM), or a single dose of 400 mg O plus 100 mg M (OM). Adverse events, mainly gastrointestinal complaints, were mild and transitory, did not accompany by significant lindings on physical examination, indicating that both combinations were well tolerated. Seven days after the single dose, slight clinical improvement was observed in almost all patients in both groups; the mean values of bacterial index were virtually unchanged from prctreatmcnt values; the mean value of morphological index was significantly reduced in patients treated with ROM but not in those with OM. Bactericidal effect was monitored by titrating, through mouse footpad inoculation, the proportion of viable M.leprae hi skin biopsies taken before and 7 days after a single dose of treatment. A single dose of ROM displayed powerful bactericidal effect that the bacilli from 9 of 10 patients lost their infectivily for normal mice inoculated with 5000 organisms per footpad; a single dose OM also exhibited definite bactericidal activity in 7 of 10 patients, although it was significantly less bactericidal than that of ROM, as only in one patient whose organisms lost their infectivity for normal mice. Because of these promising results, a test of the efficacy of multiple doses of ROM in a larger clinical trial appears justified.

WHY MULTIDRUG THERAPY FOR MULTIBACILLARY LEPROSY CAN BE SHORTENED TO 12 MONTHS

The 24-month MDT for MB leprosy is still too long and becomes an obstacle in implementing MDT. It would facilitate implementation if duration could be shortened without significantly compromising efficacy. Following information may be useful to define the appropriate duration. First of all, due to a series modifications, definition of MB has become much broader, resulting in classifying many cases that would otherwise be PB leprosy as MB, and, unlike in early 1980s when all newly detected MB cases were skin smear positive, the proportion of positive cases in 1996 was less than half. Because bacterial loads of majority of MB cases currently classified are significantly smaller than in the past, overall requirements of chemotherapy for MB may also be less. Secondly, relapse rate after MDT is very low, about 0.2% annually among MB cases, indicating that there is enough room for further shortening the duration to less than 24 months. Despite the possibility that relapse rate could be significantly higher among MB cases with high initial BI, such cases become relatively few in the lields, hence, total number of relapses caused by them in a control program will be small. Thirdly, major role of dapsone (DDS) - clofazimine (CLO) component in MDT regimen in to ensure elimination of spontaneously occurring rifampin (RMP)-resistant mutants. estimated to be no greater than 10 in an untreated lepromatous case. Recent findings indicate that 3-month treatment with the component alone killed 299.999% of viable M.leprae, suggesting that all RMP-resistant mutants are likely to be eliminated by 3 months of treatment with DDS-CLO component in MDT. Fourthly, in a THEMYC multicentre trial, not a single relapse has been detected among groups of 500 MB cases (initial BI > 2) treated, respectively, with 24- or 12-month MDT, and followed-up for 3-5 years after stopping treatment, suggesting that 12-month MDT is as effective as 24-month. A clinical tnal in Malawi also concluded that IS-month MDT may be sufficient for MB leprosy. Finally, clinical and bacteriological progress of defaulted MB cases also suggest that treatment with less than 12 months MDT exhibited promising therapeutic effects among majority of cases. Based on these information, the WHO Expert Committee on Leprosy concluded, at its latest meeting of 1997, that it is possible that the duration of the MDT regimen for MB leprosy could be further shortened to 12 months.

Gertrude P. Chan. E.M.Gonzaga, M.F. De los Santos. L.M. Reyes and S.G, Franzblau

Research Institute for Tropical Medicine, Dept. of Health. Muntinlupa City, Philippines

Our short-term clinical trials on clarittromycin monotherapy and fusidic acid monotherapy showed that the former to be rapidly bactericidal and the latter to have activity roughly equivalent to that of dapsone or clofazimine, Other data suggest that fusidic acid may have reaction-suppressive activity and we took the position that the future of this drug in leprosy was dependent upon the cluneal demonstration of such activity. Two new multi-drug regimen were formulated consisting of (A) daily clarithromycin 500mg and minocycline 100 mg plus monthly rifampicin 600 mg and (B) daily clarithromycin 500 mg and fusidic acid 750 mg plus monthly rifampicin 600mg. Both regimens were taken for a total of six months These regimens were evaluated against the current recommended 2-year WHO MDT regimen (C) with regard to clinical and bacteriological improvement, leprae reaction, tolerance, adverse effects and patient acceptability and compliance. Fifty untreated multibacillary leprosy patients per regimen were recruited.

The clinical efficacy of regimens A and B as determined by rate of lesion resolution has been exceptional compared to C with a somewhat more rapid response observed with regimen A. The overall frequency of reaction among the three regimens is not significantly different It appears however, that regimen B may be superior to regimen A and C with respect to moderate to severe reversal reaction. All the regimens were tolerated. Trie acceptability and compliance is better among patients on regimen A and B. Significant number of patient with pretreatment bacillarv index of 3+ and above reactivated with clinical and baciilary index deterioration several months alter completion of treatment with regimen A and B With this findings, it can be suggested that regimen A and B is effective and sale but treatment should be extended to a minimum of 12 months among multibacillary patients

Chemotherapy (MDT) as a strategy is the only tool available to eliminate leprosy. However recent research on short course chemotherapy indicates possibilities of saving considerable manpower and resources. Single dose of rifampicin, ofloxacin and minocycline (ROM-1) is reported to be as effective as six months paucibacillary multidrug therapy for single skin lesion case of leprosy (WHO 1997). We present our observations on the use of single dose of ROM in 531 cases of 1-3 skin lesions in PB leprosy.

On confirmation of diagnosis, patients were given a single dose of rifampicin 600mg, ofloxacin 400mg and minocycline 100mg [half dose for children]. Patients under 5 years or over 65 years of age or those with pregnancy were excluded. Patients were assessed by scoring on the lines of WHO protocol initially and at 6 months and 1 year. Efficiency of treatment was evaluated on the rate of clinical regression and occurrence of reaction/relapses during follow up. The following table shows the occurrence of reactions over a period of 1 year.

No toxic or adverse effects of the drugs were noted. The main problem was type I reactions which were easily manageable. Treatment compliance was excellent Results demonstrate that a fully supervised regimen of single dose of ROM is efficacious, cost effective and well accepted by the patients.

Combination of Rifampicim, Ofloxacin & Minocycline is quite effective in Hansen's Monolesion cases. Adding Clarithromycin has additional advantage in terms of cure-rates & relapses.

476 cases, smear-negative, normal nerve monolesion (260 males 216 females), age-range 15-70 years (mean age 36.5 yrs) randomized in 2 groups.

Group A. 390 cases [ Rifampicin (600 mg) + Ofloxacin (400 mg) + Minocycline (100 mg)] single dose empty stomach.

Group B. 86 cases [(group A regime drugs + Clarithromycin (500 mg OD)], single dose empty stomach.

graded from 3 to 0 (score maximum 15, minimum 0). Follow-up-monthly for 6 months. 6 monthly lor 2 years.

Side effects in both groups comparable. Single day CROM is better than single day ROM in Monolesion PB cases.

Prof. Dr. A. K. Jha Amar. Dr. S. K. Tripathi; Dr. Devesh Sinha; Dr. R. N. Mishra

Quinolones have synergism with rifampicin and a combination has belter penetration and effective concentration rendering a leprosy patient mycobacterium free in shorter time. Oflaxacin / sparfoxacin in combination with Refampicin & Clarithromycin alone are being evaluated.

850 cases were divided in 3 groups: Group A (400) Rifampicin 600 mg OD (empty stomach) and ofloxacin 400 mg OD for 4 weeks Group B (400 cases) Rifampicin 600 mg OD (empty stomach) and Sparfloxacin 400 mg stat then 200 mg OD (for 4 weeks) and group C (50 cases) clarithromycin 500 mg OD for 8 weeks. Evaluation was done as per WHO guidelines.

Cure rate in 3 groups were 85%, 86% & 90%. Side effects of nausea, vomiting, arthritis were equal in 3 series. Relapse rate in 3 group were almost equal(about 10%). Sparfloxacin being most economical of these 3 and cure rate being comparable, combination of Rifampicin & Sparfloxacin is best among the newer drugs.

Monolesion is indicator of herd immunity. Effective MDT enhances monolesion cases. Rifampicin single dose kills about 99% M. Leprae, with Ofloxacin & Minocycline (ROM) synergism ensures 100% clearance.

750 fresh, smear negative, normal nerve, monolesion cases (male 390, female 360) Age (15-60 years) were randomized in 2 groups.

A : ROM (study group) 390 cases (Rifampicin 600 mg + Ofloxacin 400 mg + Minocycline 100 mg) empty stomach single dose.

were graded trom 3 to 0 (Maximum score 15, minimum 0). Monthly follow-up for 6 months then 6 monthly for 2 years.

Drop-out 93 cases (12.4%) [ROM 48 (6.4%), MDT 45 (6.00%)]. Of 657 cases completing evaluation 639 cases [ROM 303 (97.10%), MDT 336 (97.40%)] showed clinical improvement. Replase & side effects in both the groups were comparable.

Single dose of 600 mg Rifampicin, 400 mg Ofloxacin & 100 mg Minocycline (ROM) is as effective as 6 monthsWHO PB MDT in the treatment of negative skin smear, normal nerve, monolesion leprosy cases.

EFFICACY OF 7, 14 AND 30 DAYS DAILY DOSES OF COMBINED RIFAMPICIN AND MINOCYCLINE IN SINGLE LESION PAUCIBACILLARY LEPROSY

Department of Skin, STD & Leprosy. Dr R.M.L. Hospital. New Delhi-110 067, INDIA.

Aim: To evaluate the efficacy of 7, 14 and 30 days daily treatment of rifampicin 600 my plus minocycline 100 mg in single lesion paucibacillary leprosy.

Materials & Methods: A total 52 patients were included in this study All were bacteriologically negative and had histopathologically confirmed indeterminate, tuberculoid or borderline tuberculoid leprosy. They were randomly put into group A, B and C. Group A (17 patients) received 7 days. Group B (16 patients) received 14 days and Group C (19 patients) received 30 days treatment of rifampicin 600 mg daily plus minocycline 100 mg daily. All patients were followed monthly for 6 months and then 3 monthly for 24 months.

Results: In Group A, 2 of the 17 patients showed treatment failure in the form of increase in the size of lesion whereas in Group B and C no treatment failure was observed within 2 years of follow-up.

Conclusion: A minimum 14 days daily treatment of the above regimen is essential to treat a single lesion paucibacillary leprosy.

STUDY OF SINGLE DOSE CHEMOTHERAPY IN PAUCIBACILLARY LEPROSY PATIENTS WITH TWO TO THREE LESIONS

The comparative study on Single dose of Rifampicin, Ofloxacin and Minocycline (ROM), and the six-month WHO/MDT/PB regimen (Standard) in the treatment of single lesion paucibacillary (PB) leprosy, was extended to cover PB leprosy with 2 to 3 skin lesions. From five centres, 236 patients were allocated randomly to either of the two regimens. Information on clinical scores is recorded at admission and at 6, 12 and 18 months after admission. Follow-up at 6 and 12 months is completed and the 18-month follow-up will be completed shortly.

At admission, the mean clinical score was 19.86 and 19.78 (P > 0.6) for the ROM and Standard regimen groups, respectively. It was reduced to 7.15 and 7.06 (P > 0.8) at 6 months, and 5.10 and 4.90 (P > 0.6) at 12 months for ROM and Standard regimens, respectively. Clinical improvement was seen in most of the patients for both the regimens. Complete clinical cure (i.e., disappearance of all lesions) was observed in 13.0% and 13.9% (P = 1.0) at 6 months, and 31.8% and 33.7% (P > 0.8) at 12 months, with ROM and Standard regimens, respectively. Thus, in the study patients, over a period of 12 months, ROM administered as a single dose, compared well with the Standard regimen in the treatment of PB leprosy with 2 to 3 lesions. Final results upto 18 months, will be presented.

Rifampicin is the most bactericidal among all anti-leprotic drugs. Among newer drugs, clarithromycin, ofloxacin and minocycline are most promising and all bactericidal. Synergism of these drugs in MB leprosy cases renders them free from living bacilli in just 28 days and generates a new hope as an alternative treatment of leprosy.

9 smear-positive MB cases from both sexes (6 males 3 females), age range 20-50 years, were given (Rifampicin 600 mg OD, empty stomach + Clarithromycin 500 mg BD + Ofloxacin 400 mg OD + Minocycline 100 mg OD) for 28 days.

Efficacy monitored clinically alongwith BI & MI changes. Side effects noted with follow-up monthly for 6 months then 6 monthly for 2 years.

All cases showed significant clinical improvement with zero MI after 4 weeks. BI reduced gradually during follow-up. No case showed relapse.

CROM regimen for 28 days in frank MB cases is very effective and promising to become a rapid alternative of MDT in selected population. High cost of therapy limiting its universal acceptance.

RECOMBINANT INTERFERON ALPHA 2b IN THE TREATMENT OF MULTIBACILLARY LEPROSY - PRELIMINARY OBSERVATIONS

V V. Pai, U. Banerjee, J. Thomas, B. Saha, HO. Bulchand, RC. Chavan and R. Ganapati

The deficiency of the macrophage regulation system in lepromatous leprosy has been well documented. Role of cytokines like interferon in macrophage stimulation has not been evaluated though this has been described. We report our observations on the clinical efficacy of alpha interferon in multibacillary leprosy.

Forty multibacillary patients (BL,LL) were randomised into two groups. First group received standard WHO-MB-MDT (MDT) while group II received WHO-MB-MDT (MDT + I) with Inj. Alpha 2b Interferon given subcutaneously for 6 weeks, initially. Clinical features, nerve status, histopathology, lepromin reactivity and photographs were documented initially and after 3 months.

Out of 30 patients (10 in group I & 20 in group II) who were evaluated for histology, the fall in mean histopathological score was significantly higher (p = 0.029) in group II. In 37 patients evaluated for BI (13 in group I & 19 in group II), the mean fall in group II was also significant (p = 0.001). Clinical regression also showed significant difference in Group II. No difference was observed in lepromin reactivity and nerve function impairment.

From these preliminary observations, it appears that a short course of alpha 2b interferon in addition to conventional multidrug therapy will enhance fall of BI and result in improvement of histology favourably. Long term follow-up patients in of both these study groups may reveal a definite picture on the alterations of the natural history of the disease based on the above parameters.

K. Katoch. M.Natrajan, V.M.Katoch, V.D.Sharma, H.B.Singh, C.T.Shivannavar and U.D. Gupta

Multibacillary (MB) leprosy cases require a minimum of 2 years or more of conventional WHO MDT for the cure of disease. This study has been carried out to see if the addition of newer antimicrobial drugs could help in further reducing the duration of treatment. One hundred previously untreated smear positive (50 BB, 35 BL and 15 LL) patients were included in this study. A detailed history was taken, skin lesions and nerve thickening charted and amear examined and recorded. These patients were treated with a regimen comprising of rifampicin 600mg, minocycline 100mg and ofloxacin 400mg given as a monthly supervised dose combined with clofazimine 50mg and dapsone 100mg (unsupervised) dai1y. Treatment was stopped at one year and patients were followed-up on a placebo. Skin biopsies at the start and at the end of one year of treatment in each case were taken and viability was assessed by mouse foot pad, ATP and molecular methods. The patients tolerated the drugs well and there was no treatment failure. There was no increase in the incidence of reactions in the patients. Clinically the lesions regressed and there was complete loss of viability at the end of one year. Follow-up is continuing to monitor the progress of patients.

Reduction in registered prevalence rate (PR) in leprosy is directly related to the duration of treatment and the treatment completion rate. Currently practised MDT regimens have shown promising results in reducing the PR in all the endemic areas. Based on rifampicin (R), ofloxacin (O) and minocycline (M) combination, trials with monthly intermittent doses of ROM(24 and 12 for MB leprosy and 3 and 6 for PB leprosy) and RO-28 days for MB and PB leprosy are underway in different counties. ROM single dose for PB single lesion leprosy has been already recommended by WHO and Government of India.

Bombay Leprosy Project, covering a population of 1.8 million(50% slum population) started investigations in 1984 with the aim of rationalising the duration of treatment. MDT-12 months to MB leprosy patients was initiated in 1991. Subsequently short course chemotherapy(SCC) regimens based on newer drugs were introduced for both MB and PB leprosy and treatment completion rate was increased.

An analysis was made to calculate the PR with WHO-MDT and the figures compared with the PR following SCC regimens, strictly applying trial duration as recommended by WHO. In 1982 when MDT was introduced the PR was 18 per 10 000 population. After practising SCC, the PR declined rapidly to 0.01 per 10 000 population by the end of December 1997, thus achieving the prescribed levels of elimination of leprosy. Had we persisted with the standard WHO-MDT regimen for the prescribed duration in respect of all the patients, the PR would have been 1.4 per 10 000 population in December 1997.

CONTROLLED CLINICAL TRIAL COMPARING THE EFFECT OF WHO-MDT WITH INTERMITTENT DRUG REGIMEN IN THE TREATMENT OF LEPROMATOUS (BL-LL) LEPROSY

Villahermosa, LG, Fajardo, Jr. , TT, Cellona, RV, Balagon, MF, Abalos, RM, Dela Cruz, EC, Tan, EV, and Walsh, GP

The objective of this study is to compare the effect of intermittent treatment using Rifampicin 600 mg., Minocycline 100 mg. and Ofloxacin 400 mg. given once a month for 24 months with the standard WHO-MDT on bacterial clearance in treating lepromatous leprosy.

A total of 20 patients diagnosed with lepromatous leprosy were sequentially admitted and given either of the two regimens, namely:

Regimen A - Rifampicin 600 mg., Minocycline 100 mg., Ofloxacin 400 mg., given once a month for 24 months.

Regimen B - WHO-MDT: Rifampicin 600 mg., B663 300 mg-, DDS 100 mg. given monthly supervised, then B663 50 mg., DDS 100 mg. daily for 24 months.

Patients were evaluated as to clinica l response, changes in bocillary load, occurrence of drug-related side-effects and the occurrence of reactions while on treatment.

Sequential average B.I. taken from skin smears at specified intervals in both therapy groups showed constant reduction in bacillary load.

The clinical and bacteriologic response to treatment at the end of 24 months will be discussed. This study received financial support from the Leonard Wood Memorial Center for Leprosy Research.

A Thomas. S Chandra, M Nagarajan. Lalitha Hari and Sivagamasundan Tuberculosis Research Centre (Indian Council of Medical Research) Chennai - 600 031. INDIA

Advent of M D T has made it possible to shorten the duration of anti leprosy treatment. Though now it is the era of Fixed Duration Therapy. Initially the drugs were given till bactenal negativity and were followed up for a further period of 5 years. In a study conducted by us in 138 Multi Bacillary patients, 6 had relapsed after 6 years or more of follow up after remaining negative for varying periods Hence, we conducted a study in collaborauon with Tamil Nadu Health Services in Poonamalle Leprosy Control Unit to do one time assessment of all the patients put on MDT during 1986-87 and had completed 5 years of surveillance after being released from treatment. Of the 156 patients registered 129 patients were available for assessment. All of them were found to be clinically inactive and bactcnologically negative

RELAPSES DURING LONG TERM FOLLOW UP BY AMONG MULTI BACILLARY PATIENTS TREATED WITH MDT REGIMEN.

A.Thomas . M Nagarajan and Lalilha Han. Tuberculosis Research Centre (Indian Council of Medical Research) Chennai - 600 031 INDIA

210 patients classified as Lepromatous and Near Lepromatous with a BI of 2.5 or more were admitted to a controlled clinical trail initiated in 1977 The patients were randomly allocated to either a 4 drug regimen (Rif. INH Clof and Dapsone) or a 2 drug regimen (Clof and Dapsone) for 5 years followed by either Clof and Dapsone or Dapsone alone for a turther period of 2 years and subsequently continued with Dapsone or Placebo till 12 years It was proposed to follow them up till they complete 20 years from the start of treatment Till date 6 patients out of 138 have relapsed after remaining negative for varying periods. The month of relapse varied from 156 to 209 months after start of treatment. All of them were retreated with National Leprosy Eradication Programme regimen for Multi Bacillary Leprosy (2 discontinued) and they showed good response. The details will be presented.

Between 1986 and 1995, 8307 leprosy patients (MB 5981. PB 2326) from 7 prefectures in the three s-w provinces of China have completed FD-MDT and the relapse rate is 0.19/1000 py for MB and 0.55/1000 py for PB. Further surveillance till end of 1997 in 6 prefectures of 8790 patients (MB 6439, PB 2351). the relapse rate remains at 0.19/1000 py for MB within the limit of 10 years surveillance. In 2351 PB, 4 relapsed within the limit of 5 year surveillance, the relapse rale is reduced to 0.42/1000 py. In the 7 MB relapses, 3 relapsed beyond the WHO specified period of 5 years ( mean 5.71 yrs, range 4-8 yrs) and in die 15 PB relapses, all relapses occurred beyond 2 years ( mean 7.13 yrs, range 4-10 yrs). Additional data of 320 patients from kunming prefecture will be added and the significance of late relapses discussed.

Eight hundred forty-six leprosy patients were followed for varying periods (mean 34, range 1-168 months) after being cured with rifampin plus dapsone (R+D) , 43 relapses were noticed (MB 30/531, PB 13/315). Increasing significant difference in relapse rates were noticed in MB receiving <12 and >12 months R+D in the 4 different groups with increased duration of dapsone monotherapy prior to R+D. In PB, no such difference can be seen in groups receiving 60-120 and >120 months dapsone before R+D. All diagnosis of relapses were supplemented by laboratory tests and were successfully retreated with FD MDT. The relationship between dapsone and R+D therapy in curing leprosy will be discussed.

INTERVALS BETWEEN STOPPING RIFAMPICIN-CONTAINING REGIMENS AND OCCURRENCE OF RELAPSE IN MULTTBACILLARY LEPROSY

Institut Marchoux, Bamako, Mali, and Faculté de Médecine Pitié-Salpètrière, Paris, France

Between 1970 and 1992, 1421 multibacillary (MB) leprosy patients were treated with 20 different rifampicin (RMP) -containing regimens; 1325 (93.2%) of them completed the scheduled treatment and had been followed-up for relapse, i.e., seen at least once after stopping treatment. By the end of 1997, 195 relapses, or 14.7% of patients being followed-up, had been diagnosed. Relapse was defined as: i) occurrence of definite new skin lesion(s); and ii) an increase of BI >2+ over the previous value at any site. A significant proportion of these relapses were confirmed by mouse footpad inoculation through demonstration of viable M. leprae. Mean value of the initial BI, i.e., the BI before treatment with RMP-containing regimen, of the relapsed cases was 4.16±1.09, suggesting that relapse in MB leprosy may be associated with higher initial BI of the patient. Mean interval of relapse, i.e., period of time between stopping treatment and occurrence of relapse (the latter was defined as the mid point between date of last examination without relapse and first examination with evidence of relapse) was 70±31 months. The information is useful for design the duration of follow-up for relapse after stopping treatment in clinical trials.

RECIDIVAS EN ENFERMOS DE LEPRA QUE HAN COMPLETADO EL TRATAMIENTO CON MULTIDROGA

Programa Control de la Lepra. Instituto Dermatologico y Cirugia de Piel. República Dominicana

El estudio retrospectivo de las recidivas en pacientes tratados con multidroga esquema OMS, da lugar a cifras que concuerdan con los valores observados en otras publicaciones. Sobre un total de 6.614 pacientes en tratamiento a termino, se han presentado 11 recidivas por un 0,16% de estos, tres pertenecen a formas multibacilares y ocho a paucibacilares. Se señala el tiempo promedio que transcurrió desde la terminación del tratamiento hasta la aparición de la recidiva y áreas de piel donde se localizan las nuevas lesiones

RELAPSE IN MB LEPROSY AFTER RIFAMPICIN AND OFLOXACIN FOR 28 DAYS - A CASE REPORT

We report on what we believe to be the first case of relapse in multibacillary (MB) leprosy following short course chemotherapy for 28 days with daily doses of rifampicin (R) 600 mg and ofloxacin (O) 400 mg .

The following diagram summarises the events relating to a previously untreated 30 year old male BL-LL patient with initial bacteriological index (BI) of, 4.6 who received treatment with RO regimen from 27 December 1990 to 22 January 1991. BI showed gradual decline accompanied by clinical regression. The patient remained negative and sign free from 11 September 1995 (Ganapati 1996;Ganapati et al,1997). Relapse of BL/LL lesions were noticed on 21 February 1997 with a mean BI of 1.3. The case is under investigation for M.Leprae viability by mouse foot pad and drug sensitivity etc., the outcome of which is awaited. The patient was HIV negative.

The patient was treated with the same regimen of RO for 28 days under supervision and the relapsed clinical lesions are regressing. Currently the BI is 0.8. The satisfactory response to the same regimen so far indicates the possibility of "persisters" as the cause of relapse and not resistance to the drugs employed. The patient is under continuous observation.

All the remaining 55 MB patients with mean BI of > 3 included in the RO trial have reached a state of skin smear negativity over a period of 6 years. None of these have relapsed.

BACTERIOLOGICAL CHANCES AND RELAPSE IN 157 MULTIBACILLARY LEPROSY WITH HICK BI LOAD AFTER WHO/MDT.

In order to evaIuate the late relapse rate of multibacillary leprosy treated with WHO/MDT. the authors investigated the bacteriological changes and relapse rate in 157 MB cases with an average of BI 3.4 ~ 3.75 before MDT. Among 157 cases. 65(41.4%) cases have stopped treatment more than 7 years.The rate of smear negativity In 157 cases was 75.157 at the end of 4 years after starting MDT and 97.45% at the end of 5 years. The BI averagely decreased by 0.69 each year. The total of 948 patient/years have been followed up in 157 cases with an average of 6.02 patient/years.There were 2 relapsed cases with a relapse rata of 1.3% or 2.1 cases per 1000 patient/years. The 2 cases relapsed at the end of 3 and 4.5 years after stopping MDT, respectively. The data showed that the relapse rate of MB cases withigh BI load after completion of MDT was not a serious situation. But it is necessary to streng then the surveillance for MB cases after stopping MDT for collecting the valuable data on relapse.

Objective: To assess the viability and drug-sensitivity of M.leprae isolated from MB leprosy patients whose Bis had decreased slowly while on Multiple Drug Treatment (MDT).

Subjects: 41 patients who had completed WHO MDT and who had improved clinically, but whose bacteriological index (Bl) decreased by less than one log per year, were biopsied and assessed using the mouse-foot-pad assay system. Treatment was stopped and the patients were followed up.

Results: M.leprae was isolated from 11 patients. In 2 cases, drug sensitivity could be assessed and the organisms were found to be fully sensitive to all three drugs used in the MDT regimen.

After three years without treatment, 9 of the 11 patients were traced and examined. They were all clinically inactive and had negative skin smears. Of the other two patients, one had died and the other could not be found.

Conclusion: Viable bacilli can be isolated from some patients after completion of WHO MDT, but most patients can eliminate these bacilli without further chemotherapy and do not seem to be at great risk of relapse.

VIABILITY OF M.LEPRAE IN THE NASAL MUCOSA AND SKIN OF PERSISTENT SMEAR POSITIVE LEPROMATOUS PATIENTS AFTER 2 YEARS OF MDT.

Anand Job, Gigi Ebenezer , Sunita Abraham, Selvasekar Abraham and Arunthathi Siromani.

MDT has played a significant role in the treatment ot leprosy. Few studies have investigated the viability of persisting M.Leprae in the nasal mucosa ot MB patients who had completed 2 years of MDT, using the mouse foot pad. Il consecutive lepromatous patients who demonstrated positive skin smears with varying bacterial indices of 2+ to 4+ after completion of a regular course of 2 4 doses of MDT had their skin and nasal mucosa biopsied. Both biopsied tissues underwent mouse loot pad inoculation into T900r mice and wen; also studied histopathologically.

Foot pad harvests were done on 6th, 9th and 12th months. Except for one specimen from the skin of a lepromatous patient all inoculations showed no growth of bacteria in the mouse foot pad. Skin histopathology showed a BIG of 1+ to 4+ and a granuloma (raction which varied from 10% to 80%. The nasal mucosal tissue demonstrated atrophy, focal ulceration and stromal collogenization with a BIG of 1+ to 4+ . The extent of cellular infiltration varied.

The study strengthens the belief that persistent M.Leprae are not viable after 24 doses of MDT and demonstrates that the nasaI mucosa of these patients do not harbour viable bacteria.

Histoid leprosy, an unusual variant of lepromatous leprosy, has been known to occur in untreated patients and in patients relapsing after dapsone mono-therapy. The unique occurrence ot histoid leprosy in a leprosy patient who had completed treatment with anti-leprosy multidrug therapy is being reported.

A 9-year old boy diagnosed as having borderline tuberculoid leprosy had treatment with dapsone mono-therapy for 3 years followed by 51 pulses of multi drug therapy. After being skin smear negative for 7 years he presented with multiple discrote nodules in the upper and lower limbs and diffuse infiltration of the face. The nodules wore non-tender, shiny and firm. Histopathology of one of the skin nodules displayed dense compact granulomatous inflammation composed of spindle shaped macrophages arranged in a whorled pattern in the dermis with numerous clumps of acid fast bacilli that were long and solidly staining. The bacillary index was 5+. The clinicaI diagnosis of histoid leprosy was authenticrated histologically.

This is the first report of leprosy relapsing as a histoid varioty after being treated with multidrug therapy. Viability and drug resistance studies on the Mycobacterium Leprae obtained from this patient are being carried out using the mouse foot pad.

RELAPSE AND RECURRENCE OF LESIONS AFTER MDT IN LEPROSY: CLINICAL, BACTERIOLOGICAL AND HISTOPATHOLOGICAL INVESTIGATIONS OF 56 CASES.

Fifty six cases of leprosy treated with WHO recommended Multi Drug Therapy (MDT) were investigated for recurrence of skin lesions. The study included 36 multibacillary (MB) and 20 paucibacillary (PB) cases.

Twenty seven MB cases (73%) and 10 PB cases were confirmed as relapses. While in all MB cases except 3 the relapse manifested in the form of borderline lepromatous (BL) lesions. AII except 2 PB cases relapsed with appearance of borderline tuberculoid (BT) lesions. The precise cause of recurrence of lesions could not be determined in 9 MB and 10 PB cases. Three MB and 4 PB cases had received two full course of WHO-MDT.

The average incubation period for recurrence of lesions was significantly lower among patients who had received fixed duration treatment (6 months for PB and 24 months for MB) as compared to those who had received longer treatment. Forty four percent MB and 55% PB cases had received esteroid during and or after MDT. The MB cases who had received cortico steroid had shorter incubation period for relapse and among PB cases, there was a strong association between steroid intake and presence of viable bacteria. Other interesting observations will be presented and discussed

RELAPSES IN MULTIBACILLARY LEPROSY AFTER 2 YEARS TREATMENT WITH WHO-MDT REGIMEN.

Balagon. MF. Cellona. R.V., Fajardo. T.T.. Vtflahermosa, L.G.. Dela Cruz. B.C.. Tan. E.V.. Ahalos. R.M. and Walsh. CP.

The objectives of this study are to determine the frequency of relapses in MB leprosy patients completing the 2 years WHO-MDT regimen and to determine whether the relapses that occur are due to drug-resistant or to persisier organisms.

500 MB patients who completed 2 years WHO-MDT were recruited. They had no previous anu-lepriny treatment, finished the regimen wihin 24 to 30 months and no anti-leprosy treatment thereafter. Duration of surveillance now ranee 4 to 11 years which include yearly clinical exannnaions and skin smears.

Criteria for probable relapse are the appearance of new/active lesions and an increase in Bl at least 2 + at any site. Those found with probable relapse were biopsied and tested in mouse foot pads or armadillo io confirm relapse. Drug-resistant studies were also done. so far, 6 patients were found to have a probable relapse ranging from 6 1/2 to 10 years alter the end of their WHO-MDT treatment.

The cluneal and bacteriological characteristics of the patients in the study - their skin smears before and after treatment and during the surveillance period - the clinical, bacteriological, histopathological characteristics as well as the mouse footpad results and the response of the relapse patients to alternative anti-leprosy treatment - will be discussed

This study is funded by the Pacific Leprosy Foundation. New Zealand and the Sasakawa Memorial Health Foundation of Japan.

Sichian provincial Institute of dertmatology. Chengdu City, Sichuan Province. China

Liangshan Yi Autonomous Pretectural Epidemic Prevention Station. Xishang City, Sichuan Province. China

Three thousand seven hundred and thirty four leprosy patients (2 768 MB and 966) were treated with MDT. Two thousand four hundred fifty four PB had nine hundred fifty four PB had completed the presenbed course of the treatment. Six cured persons affected by leprosy previously diagnosed as LL were identied as relapses clinically, bactenologicaly and pathologically in the surveillance period. 2 of them were confirmed by mouse footpad inoculation. among 6 relapses 2 were early relapses and 4 were lale ones The overall relapse rate was 0,25% and the inculation period of the occurrence of relapse was 45, 48, 52, 60 and 80 months respectively Among 954 PB patients who completed FD WHO MDT. 1 previous PB case was diagnosed as relapse clinically, bactenologicaly and pathologically 107 months after completion of the treatment with an overall relapse rale of 0,1% and an incubation period of relapse of 107 months. The author suggested that FD WHO MDT has been proved effective with a low relapse rate, safe and feasible to use in the field

Green Pastures Hospital, P.O. Box 28, Pokhara, Nepal Agranulocytosis is a recognised side effect of dapsone. There are many reports of agranulocytosis due to dapsone when used for malaria prophylaxis or treatment of dermatitis herpetiformis. There are only few reports of agranulocytosis during treatment of leprosy.

In treatment of dermatitis herpetiformis agranulocytosis has been estimated to develop in 1 of 240 to 42S patients treated and in malaria profylaxis in 1 of 10 000 to 20 000 persons. In spite of the large number of people treated for leprosy with dapsone the number of reported cases of agranulocytosis is very small. The agranulocytosis develops usually during the first three months of treatment.

Three patients who developed dermatitis and agranulocytosis during treatment with MD T for leprosy are reported. They developed agranulocytosis between 3 and 8 weeks after starting the treatment. One of them had exfoliative dermatitis like dermatitis, but affecting mainly the sun exposed areas of face, arms and ankles. Second had itching rashes all over the body with some scaling. Third had a full-blown exfoliative dermatitis.

The first one had total white blood cell count of 3 000/mm3 of which 10% were neutrophils. His neutrophil percentage normalised in 6 days. The second one had WB C of 8 500Ymm3 of which 3% neutrophils. His blood count normalised in 6 weeks. The third one had WBC of only 1000/mm3 and no neutrophils were seen in peripheral blood. He fulfilled also the criteria for dapsone syndrome with enlarged liver, lympadenopathy and exfoliative dermatitis. He died two days later.

Dr. Sulekha Mishra. Dr. P. K. Roy, Prof, Dr. A. K. Jha Amar Patna Medical College, Patna.

Worsening ol the disease, intercurrent infections and increased incidence of lepra reactions are the main effects ol pregnancy on the women with leprosy Antileprotic drugs are not contraindicaled during pregnancy. Effect ol MDT during pregnancy is evaluated.

Total 37 cases ol MB leprosy associated with pregnancy were randomized in two groups.

Group A - 21 cases - MDT was given throughout the pregnancy. Group B. 16 cases - Placebo was given during pregnancy.

Incidence of lepra reaction, intercurrent infection were more in group B. Disease status and outcome ol pregnancy ol group B is less favourable than group A.So MDT should be continued in leprosy during pregnancy.

Gottfried Wozel, Katrin Gobel. Christian Blasum. Department of Dermatology. University Hospital Carl Gustav Carus. Technical University. Dresden. Germany

Dapsone (4.4' Diammodiphenylsuifone). commonly used for the treatment of leprosy and cerain chronic inflammatory dermatoses, is now applied extensively in HIV-patients suffering from opportunistic infections. In the literature the various adverse effects of dapsone are well documented A rather rare side effect of the sulfone is the hypersensitivy syndrome (so-called sulfone-syndrome (HS)) which is potentially lifethreatening. However, the real frequency of the HS has long been a subject of controversial speculations. Therefore, in order to ascertain exact data, published cases with HS in the world literature from 1949 the beginning of epoch-making sulfone treatment - to the end of 1995 were analyzed.

The results reveal a total number of 103 patients with HS. aged 7-76 years (44 female, 45 male, in 14 cases data are lacking). Concerning the global distribution of HS. Asia is most predominant (51 patients) whereas the occurence in the other continents is distinctly lower (Australia: 21. Afnca: 1, North-Amenca : 12. Europe: 5 patients) The most frequent indication for dapsone treatment was leprosy (80 patients) with chronic dermatoses, tuberculosis, other infections or prophylactic use in the remaining cases. Multiple statistical evidence argues against the possibility of a correlation between applied doses of dapsone and occurence or severity of HS The median of latency (time intervall from commencement of therapy to manifestation of the HS) was 4 to 7 weeks. Nearly all patients had exanthema, fever and/or lymphadenopathy. Most patients additionally showed hapatic disfunctions of varying seventy (from elevation of laboratory values and hepato(spleno)megaly to jaundice). In comparison to this, hematological changes were unexpectedly rare (leukocytoses 20,4%. eosinophilia 12.6%, atypical lymphocytes 9.7%). After withdrawl of dapsone and therapy with glucocorticosteroids 79 cases recovered, whereas 16 showed fatal outcome. It could be demonstrated that hepatic coma was (he most frequent cause of death. Considering the millionfold use of dapsone all over the world, the HS to dapsone has to be estimated as an extremely rare side effect with recovery in nearty 85% and a mortality of about 15%.

K.Venkatesan . A.Mathur, A,Ci rdhar and B. K .G i rd liar Central JALMA Institute for leprosy, Agra, India

SIow absorption, relatively much slower distribution and longer retention in selective tissues are peculiar features of clofazimine metabolism. CIinical and experimental studies conducted elsewhere have reported that the plasma l eve Is of the drufi are not correlated to t he dose and length of treatment. There have, however, been n o reports on plasma l eveIs of the drug in relation to the present dosage of 50mg daily. A study is therefore, being made at CJIL, Agra to evaluate plasma clofazimine levels in relation to cumulative intake of the drug mostly as 50mg daily by leprosy patients. With the cumulat ive drug intake ranging from 1.5 to 26.5g during the period of 1-18 months plasma levels ranged from 0.8-1.0 ug/ml. The mean plasma drug levels were 0.3 and 0.4 ug/ml after H and K daily doses of 50mg respectively. The plasma drug levels seem to be directly related to cumulative drug intake although the relationship Is not so linear. The steady state appears to be reached after about 30-60 daily doses of 50 mg as reflected by plasma drug levels. Our findings on clofazimine pharmacokinetics wil l be discussed in the light of the relevance of optimising drug admtnistration in the current scenario of chemotherepy.

Evolution of the leprosy problem in Anjouan (Comorcs) after 17 years of intensive treatment

S Grillone, S R Paityn. Leprosy Control Programme Comores Institute Tropical Medicine, Antwerpen, Belgium

From 1981 to I9S9 leprosy patients were treated with intensive treatment regimens Pll cases receiving 10 weekly doses of 600 mg RMP and MB cases 2 months daily RMP, ETH. DDS followed bv 10 months RMP 1/7 + ETH, DDS 7/7. Cure rate for PB was > 95% MB patients represent more than 4000 patients-years of FU. Ten relapses (0 25%) were observed after 71, 98, 120, 129, 132, 144, 153, 176 and 190 months respectively.

From 1989 on PB treatment was R600 C1200M 200 in a single dose. MB R600, Oilo 400. Clo 100 7/7 f Mino 1/7 for 6 weeks - cure rate of PB is over 85%. MB represents 535 PYrs of FU (mean duration 4 05 yrs). No relapses were observed.

remained remarkably stable, but the proportion of patients with < 3 lesions increased. PB patients also presented earlier after the first symptoms of disease, the detection of MB diminished slightly during the last 3 years.

Roshdy W. Monarch. Former Director, Lep^Cont. Dep. M.O.H of Egypt. Clinic , Ramsis Sq. Cairo.

Since the recommendation of the W.H.O. to use the M.D.T. for Leprosy control in 1982, it was applied to a group of Leprosy cases collected from a Skin & Leprosy clinic situated down-town Cairo.

Methods: All cases were examined clinically & bacteriologically, routine lab. Exams done. Colored slides were taken to all cases during the follow up.

The ages ranged between 5 & 75 years, with about 75% of the cases occurring in the age group between 5 & 40. The cases were classified according to the Riddly Jopling scale as follows: 'IT 12, BT 50, BL 29, LL 47. 76 cases (54.2 %) were mullibacillary.

E.N. I,.: was recurrent in all the cases inspite of regular M.D.T. 19 of the cases were followed for more than 2 years, while 9 cases were followed for more than 5 years. In 5 cases new crops of small red tender nodules continued to appear for more than 4 years after starting treatment.

Reversal Reactions: 9 out of the 19 cases were followed for more than 2 years. Recurrence of reaction occurred only in 2 cases.

In one case of L.L., the disease relapsed 2 times during the observation period of 15 years. The second relapse occurred shortly after sudden death of his wife.

W e have earlier observed bacteriological response In smear we M3 cases defaulted after 6-12 months of MDT, similar to that In the comparable pts having taken 2 years MDT.

In the present study, we tried to follow up 182 smear +ve leprosy patients who were registered from 1986 to 1990 and defaulted at variable period before completion of MDT for 24 months.

On repeated visiting in 1997, It was revealed that out of 182 cases, 15 were found ex pired, 17 had taken treatment elsewhere, ^6 left area permanently, 81 couId not be traced due to Incomplete address, while remaining 33 (18%) could be examined clinically and bacterlologically.

Out of these .33 cases, 12(37%) and 20(60%) had initial BI up to 2+ and 2.1 to 4+ respectively. 19(57%) took MDT up to 6 months, 8(24%) for 7-12 months and 6 for 13-23 months.Their Initial skin lesions varied from patchy infiltrations to disseminated nodular lesions.

Clinico-bacterlological check up carried out of all these cases revealed complete regression of all skin lesions and bacteriological negativity examined in three skin smears.

In San Francisco between 1979 and 1994, 125 new lepromatous leprosy patients (51 DL and 74 LL) were treated with a regimen of 100 mg dapsone and 600 rifampin daily. Patients ranged in age from 9 to 77 (mean 37) and included 44 Mexicans, 44 Filipinos, 23 Southeast Asians, 7 Pacific Islanders. 3 Indians, 2 Chinese, 1 Korean, and South American Rifampin was maintained for at least a year and often until skin smear negativity (average 5 years, range 1-15 years), while dapsone was continued indefinitely Prior to therapy patients were highly bacilliforms with a HI of generally 4+-6+. Significantly M. leprae from pretreatment skin biopsies were found uniformly fully sensitive to dapsone (0.0001% in mouse diet) and sensitive to nfampin (001%). Patients were seen initially six times annually and no less than twice annually with skin smears from the 6 disparate sites being performed generally every mo years On this regimen all patients improved clinically with rapid resolution of leprous infiltrates Skin smears also improved with most becoming negative in 2-5 years and all eventually attaining smear negativity. The total duration of follow-up of these patients ranged from 5-15 years (averaging 9 4 years) and patients were followed an average of 4.1 years (range 1-15 years) following smear negativity. Adverse events were not problematic and occurred at anticipated frequencies No patient during the course of follow-up was observed to develop new leprous infiltrates, a rising BI, or become skin smear positive alter once being rendered negative Thus this regimen was found to be reliably effective in treating BL and LL leprosy patients

The main question currently needing an answer is whether the frequency of relapses in mulhbacillary leprosy will be more after fixed duration multi-drug therapy for 24 months (FDT - 24). and after the currently recommended (WHO, 1997) duration of 12 months (FDT -12). This question assumes importance because of a few relapses reported amongst patients with an initial BI of >4.0 after FDT - 24 (Jamet et al, 1995).

We report our observations on 50 patients with BI > 3.0, 36 of whom had BI > 4.0 who were examined beyond a minimum period of 5 years after release from FDT - 24 and FDT -12. None of the patients were clinically active and their skin smears were negative. In other words nane of them relapsed.

If we include to this sample, the defaulter study sample of (1) 41 patients (Ganapati et al, 1992) and (2) 33 patients reported recently by Bhatki (1997) whose BI was ranging between 1+ and 5+, consolidated observations on relapse in Bombay sample alone extend up to a total of 124 patients, out of whom none has relapsed till today. All the patients have remained negative.

Recent questionnaire study (WHO,1997) of 761 patients also indicates that patients dropping out of treatment after 24 months of MDT behave in a manner comparable to those who have taken treatment for 12 months or less in respect of reaching skin smear negativity. Such observations do not however rule out the possibility of stray relapses.

Treatment schedule WHO MDT : PB 2 drugs (6 months) MB 3 drug (24 months) Follow - up : 6 monthly PB (2 years), MB (5 years).

COMPARISON OF 1 & 2 YEARS MULTIDRUG THERAPY (WHO) IN MB LEPROSY - A STUDY OF 3740 CASES.

Prof. Dr. Amar Kani Jha Amar. Dr. S. K. Tripathi, Dr. R. N. Mishra, Prof. Dr. Mathura Prasad

The morphological index becomes 0 within one year of MB MDT in majority ot leprosy cases. The Bacteriological index (accounting for all living, dying & dead bacilli) may remain positive evenafter2 years of continuous MDT, but becomes negative with oul any further treatment. Old approach of treatment till bacterial negativity was changed to a fixed duration chemotherapy of 2 years. It has been observed that if MDT is stopped at 1 year and cases kept in regular follow-up, the cure-rate is comparable with the series on 2 years treatment. A comparison between 1 year and 2 year MDT regimens in MB leprosy cases is being made.

3740 MB cases age range (15-70 years), 2700 males 1040 females) were randomized in 2 groups.

Cases were evaluated monthly for clinical activities and BI, Ml, SFG. Follow-up was done 6 monthly for 5 years in group A & 6 years in group B. At the end of 2 years and 5 years there was no significant difference between the 2 groups. Relapse rate was equal in 2 groups (2.5%) side effects (Ichthyosis, Lipofuscinosis) were less in group B. WHO MB MDT fixed duration Chemotherapy can be recommended for one year.

THE EFFECT OF MDF FOR 27 MONTHS AND POST TREATMENT SURVEILLANCE FOR 11 YEARS IN MB LEPROSY CASES

Since February of 1983, 47 active MB patients have been regulary treated with RFP. B663 and DDS for 27 months with satisfactory clinical, bacteriological and histopathological improvements and with mild side effects MDT was also effective in controlling type II leprosy reaction Alter stopping MDT, the clinical symptoms contineously subsided and BI steadily fell down In the sixth year after stopping MDT. all cases became skin smear negative, and the histopathological inflammatory infiltration also gradually subsided in the 11-year period of suveillance. Except 4 cases who diet of non-leprosy cause all the remaining 43 cases met the China's criteria of clinical cure and no relapse occurred. It indicated that MB leprosy patients could be definitely cured with short-term MDT regimen. Extensive implementation of FD WHO MDT has been proved very important in reaching the goal of basic eradication of leprosy in China by the end of year 2000.

A LONG-TERM OBSERVATION OF THE EFFECT OF MULTIDRUG THERAPY IN LEPROSY IN LIANGSHAN AND PANGZHIHUA

Da-ming Jian, Lu-fang Hu, Jiu-si Luo, Yong Ning, Yi-jing Zheng and Lang-chong Yu Sichuan Provincial Institute of Dermatology, Chengdu City. Sichuan Province, China

From 1984 to 1997, 1,229 MB and 775 leprosy patients were treated with FD WHO MDT in Liangshan Yi Autonomous Pretecture and Pan/hihua City. Sichuan province. China two hundard and twenty eight out of 775 PB patients, together with 1.229 MB were treated with FD WHO MDT - MB regimen and followed up for a mininum of 5 years PB patients wre treated with FD WHO MDT - PB regimen and followed up for 4 a mininum, it 2 years. Among 1 066 MB patients completed treatment with MDT, 1 053 (98 ... %) patients remarkedly improved and 13 (1 22%) improved clinically with an overall effeciwncy rate of 100%. In a period of 5 years after stopping MDT, the cumulative skin smear negativity rate of MB patients previously untreated with DDS monotherapy and those treated previously was 95 31% and respectively Ninety nine and point one per cent of those patients with a 131 of - 3.0 and 91.8% of those with a Bl of > 3.0 before MDT became skin smear negative. Among 758 PB patients with skin Iesions before MDT and completed MDT, skin lesions completely subsided in 69 52% of patients treated with MDT PB regimen and in 75 98% with MDT MB regimen. There was a close correlation between the number of skin lesions and the therapeutic effect of MDT (p<0,01). And among PB patients with Bl positive before MDT, the skin smear negativity rate after completion of treatment was 95% and 97 7% reflectively in patients completed treatment with MDT MB regimen and MDT PB regimen. Among 205 patients with reactions (Type I 135. Type II 70) during MDT and surveillance, reactions occurred in 112 patients (54.63) in the first year of MDT. Four patients ( borderline tuberculoid 1 and lepromatous 3) were diagnosed as relapses with a incubation period of relapse of 45, 48, 52 and 107 months. The relapse rates of MB and PB were 0 71/1000 py and 0.28/1000 py respectively. The results showed that FD WHO MDT regimens have been proved effective with a low relapse rate, sale and feasible to use in the field.

Evolutiun sous polychimiothérapie du statut neurologique des malades hanseniem nouvellement dépistes

lnstitut de Léprologie Appliquée de Dakar, BP 11023 CD annexe. Dakar. Sénégal

Les auteurs présentent les résultats, à 30 mois, d'un suivi longitudinal, par des bilans neurologiques standardises cl répétés, de cohortes de malades nouveaux cas de lèpre mis en traitement polychimioihérapie (l'CT). Les résultats concernent 87 de 121 malades dépistes et traités.

Le facteur déterminant djns l'évolution du statut neurologique des malades en traitement PCT est la survenue ou non d'une réaction lépreuse.

Chez 55 malades n'ayant jamais présenté une complication lépreuse (Réaction Reverse (RR) ou Krvihéme Noueux Lépreux (ENL)). l'évolution du statut neurologique est favorable dans 98% des cas : la polychimiotherapie stabilise et même améliore certaines lésions nerveuses (probablement les plus récentes). Celte constatation souligne l'intérêt d'un dépistage et d'un traitement précoces delà lèpre Cl dans ces conditions, le rôle certain de la PCT dans la prévention des invalidités.

Chez 32 malades ayant présenté une complication lépreuse ses ère. l'évolution du statut neurologique est surtout fonction du délai écoulé entre l'insialhiion des troubles - qu'elle soit biutale ou progressive - et l'institution d'un traitement par corticostèroides. Le délai « idéal » est inférieur ou égal à 90 jours. Dans cette condition, l'évolution du statut neurologique des malades est favorable dans 80% des cas. Par contre, pour un délai supérieur à 90 jours, l'évolution du statut neurologique n'est favorable que dans 42% des cas. Cette constatation pose le problème de la mise en epuvre d'une stratégie efficiente pour le dépistage précoce et la prise en charge adéquate des névrites lépreuses qu elles accompagnent ou non une réaction lépreuse cliniquement évidente. Dans cette optique, l'une des activités essentielles de cette stratégie serait la pratique systématique chez tous les malades dépistés d'un bilan neurologique trimestnel. notamment pendant la première année de suivi au cours de laquelle survient la majorité (74%) des épisodes réactionnels.

Sunil Anand. W. Kerketta. G. Rajan Babu. G S Waller The Leprosy Mission. CNI Bhawan. 16 Pandit Pant Marg. New Delhi-100001.INDIA

This paper presents evolution of single lesion PB leprosy without treatment from a retrospective study of 144 untreated single lesion PB cases detected during the AMPLE programme in Muzaffarpur district of Bihar between September 1992 and Jajiuan 1993 The studv was done as no treatment was Marled after detection for various reasons even after 18 months.

Self healing way seen in 63.8% of these cases. The age and sex correlation was not significant though lesions on the upper and lower limbs healed more than those on the trunk and face Of the remaining 36 2%, 22.4% remained stationary while 13.8% deteriorated 0,7% of the patients who did not self heal developed defornuty.

The large percentage of self healing raises the issue of the relevance of treatment but the studv highlights the significant percentage who did not self heal As there are no detinue indicators to which lesions self heal and which do not. the paper proposes that all single lesion PB leprosy patients be given treatment

Xinjiang Autonomous Regional Institute for Endemic Discases Control. Wulumuqi City. China

In Xiinjiang Autonomous Region, 994 cures by DDS monotherapy (MB 581, PB 413; male 596, fémale 398) have completed re-treatment by MDT for one year with a surveillance period of 5-11 years from 1986 to 1992 and no relapse occurred.

One hundred and ninety live relapsed cases detected from 1978 to 1986 among those cures who did not receive re-treatment with a relapse rate of 11 14%, but from 1987 to 1995 there were only 68 relapses with a relapse rate of 0,72%. There uaa a jigrufkant difference between relapse rates in two groups.

During the period of re-treatment with MDT, side effects octurred in varying degrees, but disappeared spontaneouly or only with general treatment not having influence to complete the course of MDT.

A mullieentne double-blind controlled clinical trail was earned out to compare the ellieaev of a combination of rifampiein 600jtttj plus ollovaem 400 mg plus minocycline 100 mg (ROM) administered as single dose with that of standard six-month WHO MDT PB regimen The duration of studv from the dax of intake was 18 month The trail has been earned out bv single lesion Multicentre Trail Group. Action Programme for the Elimination of leprosy. World Health Organisation

105 cases who have completed treatment under the above trail at leprosy control area of The Leprosy Mission. Champa. India, were further followed up lor another six month. The follow up assessment after 24 months from day intake has shown that ROM is almost as effective as the standard WHO/MDT/PB in treatment of single lesion PB cases

MINOCYCLINE USED IN LEPROSY CAUSES LO.NGTERM MARKED BLUE PIGMENTATION IN SKIN LESIONS

R. StC. Barnetson. Professor of Dermatology. University of Sydney, NSW 2006. Australia.

Two patients from S.E.Asia with borderline leprosy were treated with minocycline as multidrug therapy. Both quickly (within two months) developed marked blue pigmentation in their skin lesions which continued in both cases for over two years despite cessation of the drug.

The first patient wxs treated with minocycline in conjunction with rifampiein and clofazimine, because she had glucose 6 phosphate dehydrogenase deficiency precluding the use of dapsone.

When the minocycline was stopped, she was continued on dual therapy of rifampiein and clofazimine.

The second patient was treated with standard multidrug therapy (rifampiein. clofazimine, dapsone), and developed marked red pigmentation due to clofazimine, which worried him. He was therefore switched from clofazimine to minocycline whereupon his skin lesions became dark blue. This blue pigmentation had not completely faded even alter two years.

This marked pigmentation due to minocycline may preclude extensive use of this dmg in leprosy, particularly in fair-skinned races.

EIGHT-YEAR SURVEILLANCE OF 481 PB LEPROSY CASES WITH DDS AFTER COMPLETION OF WHO MDT REGIMEN

$ Jiangsu Provincial Institute of Dermatology, Nanjing City, Jiangsu Province China
• Xinyi City Station for Skin Diseases Control, Jiangsu Province
# Yanzhou City Station for Skin Diseases Control, Jiangsu Province
+ Suzhou City Station for Skin Diseases Control, Jiangsu Province

This article reported the effect of MDT in 481 paucibacillary leprosy cases. All cases have completed fixed duration of regimen of 6 months, 44 (9,15%) of them were released from treatment. 437 (90,85%) cases continued DDS monotherapy after MDT until all active skin lesions completely disappeared or skin smear became negative. Twenty eight cases of them even continuously treated with DDS monotherapy for as long as 36 months. The surveillance period ranged from 7 to 10 years with an average of 8 years, no relapse and reversal reaction occurred. The results showed thai it is necessary for PB leprosy cases to have a continuous treatment with DDS after completion of FD WHO MDT of 6 months.

FIELD TRIAL OF OFLOXACIN DRUG REGIMENS IN MULTIBACILLARY AND PAUCIBACILLARY LEPROSY. PRELIMINARY RESULTS.

Mª da Graça Souza Cunha, Antonio Pedro M. Schettini, Paula Bessa Rebello. Silmara Navarro Pennini.

From September 1992 to July 1994, 100 MB and 142 PB leprosy patients have bib included in the trial. A 1 month regimen of daily Rifampicina and Ofloxacin is compared with the standard WHO/MDT regimens in a multicenter double blind study. 98 MB and 136 PB patients have already completed the first 4 weeks of treatment. 94 MB and 133 PB patients have completed the prescribed course of treatment and are under surveillance. The clinical results are good and the incidence of side effects were low. 3 patients were decoded and dropped from the study because of severe side effects. Only one of these patients was receiving ofloxacin.

The PB cases will be follow for at least 5 years and the MB patients for at least 7 years. During surveillance period three patients, 1 MB and 2 PB. were clinically diagnosed as relapse cases. Mouse foot inoculation was performed with specimen from skin biopy of the MB patient. These 3 cases started adequate MDT and are progressing.

This investigation received financial support from UNDP / World Bank / WHO Special program for Research and training in Tropical Diseases (TDR)/DAHW.

LEPROSY REACTION IN MULTIBACILLARY LEPROSY PATIENTS AFTER 2- YEAR MULTIDRUG THERAPY.

Maria da Graça S. Cunha, Paula Bessa Rebello, Silmara Navarro Pennini, Megumi Sadahiro. Antonio Pedro M. Schettini.

In this prospective study 337 multibacillary (MB) leprosy patients treated with the standard 2- year multidrug therapy (MDT) had been followed for 7 years to establish the frequency, timing, and clinical features of leprosy reactions, mainly alter treatment.

Patients from 1987 to 1992 where included in the study, all of them without previous specific treatment. Clinical and skin smear examination were done once a year and histopalhological examination was performed in selected cases.

During surveillance peritnl 102 (33%) patients developed leprosy reactions of whom 68 (67%) have already had reaction episodes during treatment. All reactions cases were treated only with steroid or talidomide and had showed satisfactory clinical and laboratory results.

Relapse cases have not been detected among the group of patients who developed reactions but within the group without reaction, 1 patient had relapsed alter 6 years treatment. Mouse fool inoculation with specimen from skin biopsy of this patient was performed for evaluation of organisms viability and for drug sensitivity. Immediately alter that the patient were retreated with the standard MDT and is improving.

ANTI PGL-I LEVELS IN MULTIBACILLARY LEPROSY PATIENTS TREATED WITH OFLOXACIN COMBINED DRUG REGIMENS

Maria da Graça Souza Cunha*, Antonio Pedro M. Schettini*, Willian Antunes Ferreira*, Vânia L. D. Bonato**, Norma T. Foss** Faculdade de Medicina de Ribeirão Preto - USP**

In this double blind study IgM antibodies against phenolic glyeolipid-I (PGL-1) were measured in the serum of 100 multibacillary (MB) leprosy patients, receiving ofloxacin containing combined drug regimen or the standard multidrugtherapy (MDT). The patients were included in the trial from September 1992 10 July 1994 and all of whom had not previously been treated. IgM anti PGL-I antibodies were determined by ELISA method.

Before treatment, 100% of the patients were reactive lo antigen PGL-I. During treatment the IgM antibodies levels decreased significantly but slowly. There was a decline in IgM ami PGL-1 of about 37% from the starting level to the end of treatment. Alter 3 years follow up there were no significantly difference on antibodies titers detected in both groups .

During follow up period 1 patient were clinically diagnosed as relapsed case and the code was broke. Mouse foot inoculation with specimen from skin biopsy of this patient was performed for evaluation of organisms viability and for drug sensitivity. Immediately alter that, the patient started the standard MDT and is improving.

AN ANALYSIS OK 1 JIJ CURED LEPROSY CASES WITH MODIFIED WHO MDT REGIMEN IN JlANOSU PROVINCE

•• Jiangsu Provincial Institute of Dermatology. Nanjing City. Jiangsu Province

This article reported the results of 1 313 MB cases cured with MDT regimen (RFP 1200 mg, B663 300mg once monthly surpervised and B663 50mg, DDS 100mg daily self administered) until active skin lesions complelely disappeared and skin smear became negative two times with an interval of 3 months. Patches and plaques disappeared by 85,97% and 76,64% respectively after two year's tireatment nodules and difuse infiltration slower. There was a significant difference of BI values before and during MDT. BI during MDT gradually reduced and became skin sme ar negative alter 72 months treatment (Cot-Stuart test p<0,05). Reactions occurred in 18,82% and 5,60% (p<0,05) and desability rate was 57,88% and 4,70% before and during MDT respectively (p<0,05).

This MDT regimen has been proved effective for every case. The shortest Juration of treatment was 24 monthi and the longest was 74 months with an average of 41 months. The surveillance was conducted by leprosy staff. One hundred and seventy seven cases have been monitored for 8 years and 16 cases for 10 years with an average follow-up period of 65 months. No relapse case was detected during surveillance peried. This study revealed that it would be better to release MB cases from MDT treatment until the skin smear became negative and active skin lesions entirely disappeared

We report on what we believe to be the first documented case ot multiple drug resistance in a lepromatous leprosy patient treated with WHO-MB-MDT in combinabon with daily ofloxacin for 28 days. The following diagram summarises the events relating to a 45 year old male patient with initial BI of 6.00 who had received dapsone for many years and had florid lesions of LL on examination in January 1991. He was treated with WHO-MB-MDT from 17 January 1991 to 27 March 1993 along with ofloxacin 400 mg daily for 26 days during the initial period. BI showed gradual decline accompanied by clinical regression marked by a few episodes of Npe II reaction.

Studies revealed multiple drug resistance (MDR) to dapsone, rifampicin and ofloxacin by In vitro investigations using FDA, Fc receptor, EA resetting techniques as well as by mouse foot pad tests as reported by collaborating laboratory specialising in these tests. However continued administration of these drugs as per current recommendations resulted in bacterial decline and clinical regression. Patient continues to show smear negativity and has shown no signs of clinical relapse for the past 6 years, revealing lack of co-relation between viability, drug sensitivity and clinical behaviour. We believe that the laboratory evidence of MDR alone need not be considered as an indication for switching over to alternative drugs, unless there is definite clinical worsening of the disease and rise in BI.

REGRESSION OF CLINICALLY ACTIVE LESIONS AFTER SHORT COURSE CHEMOTHERAPY IN LEPROSY

With the advent of short course chemotherapy (SCC). clinical problems associated with residual skin lesions are assuming importance. The continuation of anti-bacterial chemotherapy beyond the recommended periods is often practised by physicians and leprosy programme managers. Though this may have only a placebo effect, patients are made to believe that therapy is needed for continued clinical regression. The ideal method of management of such patients ihrouqh counselling techniques is still a subject matter of research. This problsm is more keenly felt in the era of SCC with newer drugs, than with WHO-MDT. An attempt was made to assess the magnitude of the problem posed by patients left with symptoms after being released from treatment (RFT) in various research trials based on rifampicin (R), ofloxacin (O) and minocycline (M).

Clinical status at RFT and at sixth month follow up was assessed in 122 patients who received different regimens viz. ROM single dose(ROM-t) and RO-28 days treatment and ROM intermittent treatment (3,6 and12 months).

It is seen that clinical regression continues irrespective of regimens followed. This indicates the imperative need for devising suitable counselling techniques, to avoid currently practised advocacy of chemoiherapy beyond RKT on empirical lines.

Concepts of chemotherapy in leprosy have recently undergone a phenomenal change. Trials on intermittent therapy using rifampicin, ofloxacin, and minocycline (ROM) are underway in many parts of the world. Such drug regimens generally do not consider the clinical parameters for deciding the duration of chemotherapy. However many clinicians often resort to different regimens or re-introduce the same treatment for the following reasons:

We present, the details of an adult male patient who reported to us with S skin lesions. He was diagnosed as PB and was treated with ROM intermittent regimen for 3 months. Patient was released from treatment (RFT) after 3 months and kept under surveillance. On a visit to his native place in Uttar Pradesh 19 months after RFT, he was started on WHO-PB MDT by a private practitioner as he did not find any improvement in the skin lesions. Having taken three months MDT, he came to us with persisting skin lesions which were still there when last seen in February 1998. No new lesion or any significant clinical changes were detected when he reported.

We conclude that the continuation of treatment with other regimens had no effect on the clinical regression and it is necessary to counsel the patients and reassure them against over treatment.

The basic misconception about the Fixed Duration Therapy (FDT) in paucibacillary leprosy is that the persistence of granuloma, which takes its own time to regress indicates continuation of treatment. To allay the fears of those who are concerned about the withdrawal of chemotherapy after a fixed duration of 6 months in PB leprosy in the face of persisting granuloma, we summarise selected observations arising from two publications on histopathological (HP) studies in BT leprosy.

•These patients are showing continued regression ot the granuloma without further treatment. (Ebenezer, personal communication)

Except in a small proportion of cases , the granuloma continues to regress pointing out that beyond the optimum period for which chemotherapy is administered to achieve bacterial kill, the maintenance of granuloma is triggered mainly by the presence of antigens . How this stimulus can be overcome is a subject matter for basic research.

Department of Dermatology, Yokohama City University School of Medicine, Yokohama, Japan *Kusakabe Skin Clinic, Odawara, Japan

Seven male patients (age range 20-33 years) with leprosy took mainly 100 mg or 200 mg of sparfloxacin(SPFX) in the evening. Therapeutic effects were determined by clinical, bacterial, or histopathological findings. The study patients took SPFX from a few months to one year. 100 mg SPFX daily obtained excellent clinical, bactericidal and pathological improvement in a few weeks. We did experience reversal lepra reaction in one case. No other side effects of SPFX were observed. It seems that a few months of SPFX therapy is enough to treat leprosy, and combined therapy with clofazimine and DDS should be considered as lepra reaction and resistant bactcrias are indicated. We followed the patients for only a few years, and a long term follow-up study of the patients will be necessary for complete eradication of the disease.

New anti-leprosy drugs such as SPFX must be required in the treatment of MDT-resistant bacilli for the eradication of leprosy. Furthermore, SPFX should be examined for inclusion in a MDT regimen for the treatment of leprosy.

SPFX is a strong bactericidal agent against M, leprae, and a promising drug to treat leprosy. Skin involvement of all patients decreased or disappeared within a few months. The bacterial index of skin smears also decreased.

ACTIVITY OP MINOCYCLINE AGAINST M.LEPRAE EN MICE AND ITS EFFECTS ON LEPHOMATOUS PATIENTS

Sben Jiamping, Li Wensbong, Wang Heying, Wei Wanhui, Ye Ganyun, Xu Yuankun. Huang Wenbiao, Liu Fengwu, Ran Shunpeng and Yang Fugul

Institue of Dermatology, Peking Union Medical College, Chinee Academy of Medical Sciences , Nanjing, P. R. China 210042

The paper reported the activity of minocycline against M.leprae in mice and its effects on multibacillary leprosy cases in the abort-term clinical trial.The results showed that using the kinetic method,the growth delay of M.leprae in the foot-pads of Infected mice waj 144 days after treated with 25mg/kg minocycline daily by gavage 5 times weekly over a period of 60 days. Fourteen multibacillary leprosy patients were treated with 100mg/day minocycline for 3 months. The clinical Improvement such as softening and flattening of the nodules and plaques in the patients was found as early as 1 week after treatment. At the end of the trial, significantly clinical improvement was found in all patients. The average morphological index decreased from 8,29±3,29% before therapy to 0% at the end of the trial, and the average bacteriological Index, from 4,48 ±0,52 before therapy to 4,18±0,60 at the end of the trial. Of 8 cases detected by mouse foot-pads test, no -viable M. leprae were found in 4 cases after one month's treatment and In all cases after 2 months' treatment. Two cases developed mild ENL and one developed mild skin reversal reaction during the trial. All the patients had alight brownish pigmentation on the exposed akin lesions, but the patient* tolerated the drug well during the trial. The authors suggest that minocycline 1s effective and safe for treatment of leprosy and it can be used in leprosy chemotherapy.

While WiD MDT for paucibncillary (PB) leprosy has been generally effective, there have been problems of residual activity, late reactions and relapses. Clofazimine (CLF) is a proven anti-leprosy drug which is well accept ed in Indian population. This study is aimed at investigating the therapeutic efficacy of addition of clofazimine to current MDT In PB patients. In this study, 300 smear negative (99 TT, 173 BT and 28 Indeterminate) patients were randomely allocated to 2 regimens :(i) Regimen I was the WHO advocated therapy for PB patients (ii) Regimen II was the above regimen plus 50mgs of clofazimine daily. Treatment was stopped In both the regimens after 6 months. The CLF containing regimen (Regimen II) was well tolerated and there was no adverse reaction. There was lesser residual activity in the CLF containing regimen at the time of stopage of therapy which was more apparent after 2 years of post treatment follow-up. Two patients from the WHO regimen have relapsed whereas there have been no relapses in the CLF containing regimen in the follow-up period. Late reactions were observed In 8 cases in control group and in 1 case in CLF containing regimen.

From 1956 to 1995, in Chaozhou City with a population of 1.4 million (1995), a total of 2 728 leprosy patients (MB 558 and PB 2 170) has been found. Of whom 1 998 cases (MB 418. PB 1580) cured with DDS monotherapy and 119 relapses, including 51 MB (2.2%) and 68 PB (4.3%), occurred with an overall relapse rete of 6% Four cases relapsed twice and one case three times, actually there were 125 relapses with a relapse rate of 6.3% Among 11 MB and 246 PB with DDS monotherapy for 1 to 3 year. 2 (18%) and 30 (12%) relapses were diagnosed respectively, out of 92 MB and 219 PB with 3-5 year treatment 5 (5.4%) and 9 (4.1%), and of 315 MB and 1115 PB with 5-10 year treatment 44 (14%) and 29 (2.6%) relapses occurred respectively. Among the 119 relapsed cases. 20 (16.8%) occurred less than 2 years after cure, 24 (20%) in 2 to 5 years. 35 (29 4%) in 5 to 10 years and 40 (33.6%) more than 10 years. In other words, one third or more of relapses occurred 10 or more than 10 years after cure. Thirty eight MB (75%) and 56 PB (82%) relapses have been cured once again with DDS monotherapy. New disabilities or exacerbation of existing disabilities developed in 13 cases (10.9%). Four and 18 of original T relapsed cases became lepromatous type and borderline group respectively, and two of onginal lepromalous lype relapsed cases became borderline group. Since 1985, WHO MDT has been introduced and implemented. 108 cases have been cured with it and no relapse occurred up to now.

A double blind controlled clinical trial was done with the objective of determining efficacy of single dose (Rifampicin, Ofloxacin and Minocycline - ROM) regimen with standard regimen WHO-PB MDT Untreated PB leprosy patients with single skin lesion only were included They were followed up for 18 months after completion of prescribed MDT - including placebo 108 patients completed the treatment Clinical status was assessed with sconng system for individual clinical aspects like size, appearance, infiltration, sensory deficit, etc.

Lesion had completely disappeared in 38% of those who received WHO-PB MDT and it was 45% in those who received ROM regimen Overall improvement observed was 75% in WHO regimen whereas in ROM regimen it was 84%. None of the patients developed lepra reactions. Three patients developed drug related side effects in WHO regimen. None of the patients deteriorated in both the groups. Single dose regimen seems to be equally effective in comparison to standard WHO regimen of 6 months duration in single lesion PB leprosy.

EPIDEMIOLOGICAL SURVEY AND GENETIC IMPACT OF MULTIDRUG THERAPY IN LEPROSY PATIENTS AT COIMBATORE

Kaiaiselvi K¹, P Rajaguru¹, S. Muruqan², H Vinod kumar³, N. Elangeswaran³, Thomas Abraham², T. Jeyaraj devadoss², M llangovan², M.V. Usha Rani⁴

1. Dept. of Environmental Science, PSG College of Arts & Science, Coimbatore, India

The clostogenic effect of the antileprotic drug correlated with the physical condition and environmental factors. Epidemiological data was collected from 150 patients undergoing multidrug therapy, at CULES. MB cases are more than the PB cases. Thirty patients (22 MB & 8 PB) were selected for chromosomal study. The peripheral blood lymphocyte culture showed higher frequency of chromosomal aberration. The PB cases showed maximum chromosomal abnormalities. In both PB and MB cases the large chromosome was Involved in the chromosomal aberrations. Among the 30 patients. 24 of them are from consengunous family and 22 of them belong to MB cases and 2 belong to PB cases. They come under the age group of 10-60 years. 24 of them are male patients and most of them are chain smokers and alcoholics. The occupation of many of the patients were agriculture. The genetic disorder seen in the patients may also be influenced by environmental factors.

COMPARATIVE STUDY OF TWO DRUG REGIMEN AND THREE DRUG REGIMEN IN PAUCIBACILLARY LEPROSY.

Sixty two paucibacillary cases were randomly selected within the age group of 8-80 years, and put on two different multidrug regimen for 6 months. Regimen I was according to WHO (1982) recommendations consisting of Dapsone daily and six once a month rifampicin. In regimen II in addition to above two constituents, clofazamine was added 50mg per day in adults and doses according to body weight in children. The efficacy, acceptability and side effects of MOT were observed for a period of one year. Clinical and histopathological assessment was dene, on completion of MDT and there after every 3 months up to end of one year in all cases. A comparative evaluation of effects of two multidrug regimen in paucibaciUary leprosy patients is reported. Addition of clofazimine over WHO (1982) reccrnmended regimen appears to have marginal benefit with regard to period of inactivation, disease regression and incidence of reactions.

DR. S.B. MURUGESH. DR. Y.K. GURUPRASAD
PROP. & HEAD OF THE DEPT. OF
DERMATOLOGY & VENEREOLOGY
J.J.M. MEDICAL COLLEGE: DAVANGERE-577004
KARNATAKA STATE, INDIA.

A study performed on tuberculous patients prcv lously treated with several courses of chemotherapy but remain sputum positive, draw the attention of using other drugs.

In vitro susceptibility testing using ofloxacin (0 5 - 1 microg/ml) Norfloxacin (0.5 - 1 microg/ml) Kanamycin 2-4 microg/ml and Amikacin (0.5- 2 microg/ml) Mycobacterium tuberculosis shows marked sensitivity to these drugs. Marked improvement (in vivo) of mam of the chronic cases was noticed and sumo became sputum negative.

aminoglycosides after being mixed with Microbacter leprca and injecting in laboratory animals.

The significance of the results and effects of die aminoglycosides on Mycoba. Leprea will be reported and discussed.

COHORT RESULTS OF 383 RELEASED LEPROSY PATIENTS (MB). Oliveira MLW. Gomes HM. Gallo MEN. Nery JAC. Cunha MGS. Rebello PFB and Merçon M. Leprosy Unit. FIOCRUZ RJ. PHD Unit of Dermatology/UFRJ. IDTVAM- Brazil

In order lo evaluate the magnitude of relapses and their risk factors associated, a study both current and retrospective was undertaken. In a total of 383 MB patients with BI > 2+ and never treated before, released after 3 recent national treatment schemes (MDT/OMS 1, fixed duration MDT2 and previous national scheme-DNDS) were submitted to clinic mid laboratory exams.

The average of treatment term under DNDS scheme was 5 times higher than fixed duration MDT which was 26.43 month longer. Although the fall in BI average showed some differences according to high BI, clinic form, and treatment scheme, the follow-up evaluation (49,62 to 58,17 months) didn't show any significant differences. A group composed by the 3 schemes still presents positive smears (14%).

The relapse result was 0.33 in the MDT and 1.18/100 patients years observation in DNDS. The results of ELISA test applied to 155 patients and 182 health controls detected 12% of positivity in the control group and 52.25% inpatients groups (6.2% MDT1, 76.5% MDT2 17,3% DNDS)

Two risk group for surveillance were defined: one with positive smears and positive ELISA (32 patients)and another one composed by patients with ELISA levels (>0,800) and also positive smears (7 LL and 1 BL). Both groups present less reactions during and alter treatment A prospective study is need in order to confirm this association.

INTRODUCTION: Hydnocarpus has been replaced by other chemotherapeutic agents which have a better mycobactericidal effect However none of the currently used antileprosy drugs have been reported to have a positive effect in would healing Anecdotal reports claim that leprosy patients who have been given hydnocarpus capsules orally have shown more rapid wound healing.

In view of these reports a pilot experimental study has been undertaken to demonstrate the effect of hydnocarpus in experimentalis inflicted wounds on male Wistar rats. The wound healing effect of hydnocarpus is studied with reference to the collagenation. wound contraction and epithelialisation phases of healing The results of this pilot study will be elaborated and the possible mechanism/s of the action highlighted.

Detection of viable M.Leprae by sensitive laboratory techniques in patients who have completed MOT is generally interpreted as an indication for re-treatment with MDT or administration of even newer drugs. We present case reports of two multibacillary (smear + ve) patients under observation since 1990-91 as potential candidates for relapse.

Case I: Patient DS diagnosed as LL (Bl: 3.75) in 1979, remained absent from 1980 to June 1988. In 1988, (BI: 4.8) he received WHO - MB - MDT from July 1988 to June 1990. Biopsy of skin and nerve in April 1990 showed regressing LL. Bl of 4.3 at release from treatment (RFT) reached zero over 5 years. Skin and nerve biopsies ai RFT revealed growth of M.Leprae in the mouse foot pad. Patient has not relapsed so far.

Case 2:Patient CS diagnosed as LL with pulmonary tuberculosis (Hi : 5.2) in January 1980 was incompletely treated with antituberculosis treatment. In 1988 after 8 years absence 81 was 4.0 and patient received WHO -MB - MDT for 2 years from March 1988. At RFT BI was 3.0. Biopsy of skin and nerve at this stage showed regressing BL. Bl was negative in 1994 and growth of M.Leprae was reported in the mouse foot pad. Patient has not relapsed so far.

In both these cases, we are presumably dealing with dormant "persisters" which have not multiplied leading to clinical and bacteriological relapse. However, in view of stray reports of late relapses in patients with high Bl, we advocate observation of such patients for a longer period.

Leprosy like any other myco-bacterial disease cannot be devoid of relapses. We report our observations on a profile of leprosy relapses after WHO-MB-MDT encountered over a period of 15 years since MDT was introduced.

15 MB (+ve) cases treated with WHO • MB - MDT have so far relapsed (MB+ve → MB+ve). 11 cases had received extended MDT regimen i.e. beyond 24 months and 12 had also received dapsone monotherapy prior to receiving MDT. Initial BI of relapsed cases was 1 to 4.6 (>3.0 in 10). Skin smears were negative at RFT except one case. All the cases remained clinically inactive and bacteriologically negative during surveillance. Relapses were observed after a period of 4 to 13 years after RFT.

Relapses were confirmed by clinical, bacteriological and histopathological investigations. All were HIV negative. In 6 cases mouse foot pad studies showed growth of viable bacilli. On retreatment with WHO - MB - MDT, all the cases responded well. These relapses, we consider, are due to the 'persister' bacilli rather than to development of drug resistant strains to all the drugs employed, which is a very rare phenomenon.

Relapse in leprosy is generally considered to be due to multiple drug resistance and clinicians often resort to newer drugs or arbitrary regimens. We believe that the relapses after MDT should be managed with the same course of treatment.

AN ASSESSMENT OF EFFICACY ON MULTIDRUG THERAPY AMONG 795 MULTIBACILLARY LEPROSY PATIENTS IN SHANDON G PRVTNCE. CHINA

Multidrug therapy ( MDT) for leprosy was started in Shandong Province, in 1986 and the duration of treatment required before 1991 was long as until all active sin lesions completely disappeared and/or skin smear became negative. In this paper the authors analysed the efficacy of the regimen with which 795 MB caces were treated.

Out ol the 795 leprosy cases, 388 were newly diagnosed or relapsed cases without previous treatment or only treated less than 6 months before MDT(group A), and 407 cases were same cases mentioned but previously treated with DDS monotherapy for a certain period of time before MDT (group B). The average BI value in group A was 2.9 before MDT, among them, BI > 3.0 in 206 cases and BI<3.0 in 182 cases. The average BI value in group B was 2.2 before MDT, among them, BI > 3.0 in 88 cases and BI < 3.0 in 319 cases. The average time needed to reach the negativity of skin smear was 46.5 ± 20.8 months for newly diagnoied and 45.1 ± 26.2 months for relapsed cases in group A, while that needed for becoming negative of skin smear wai 44.7 ± 22.2 months for newly diagnosed and 43.9 ± 26.6 months for relapsed cases in group B. There was no statistical significance regardiing the time needed to reach skin smear negativity among mentioned 4 categories of patients.

A further analysis showed a close correlation between the time needed to reach skin smear negativity and BI before starting MDT, more than 50 months were needed for patients with BI > 3, while less than 48 months for the patients with BI < 3 before MDT. The higher the BI value before MDT, the more time needed to reach negativity of skin smear would be. When these patients were divided into groups by an increase of BI value in an order of 1+, the difference of time needed to reach skin smear negativity wai very significant among these groups. Relapses were also monitored annually after completion of MDT and no relapse was delected in a total of 5233 person years of follow up. The authors believed that the regimen were very effective in treatment of MD cases with a very low relapse rate, although they understand that not all MB cases should be treated until skin smear became negative.

DELAYED CLINICAL PROBLEMS IN SINGLE LESION PB LEPROSY AFTER SINGLE DOSE ROM TREATMENT

Single dose treatment of single lesion PB leprosy with a combination of nfampicin (R), ofloxacin (O) and minocycline (M) is being practised gradually by the leprosy programmes. Delayed occurrence of clinical problems like new lesions / relapse have not yet been documented.

We report here a patient who was treated with ROM single dose(ROM-1) for a single lesion PB leprosy in November 1994. The following table summarises the events relating to a 45 years old female patient with a raised single lesion PB leprosy on left forearm.

In December 1996, she reported with reaction of old lesion along with a erythematous and raised new lesion on dorsum of left foot She was treated with chloroquine. Skin biopsy of both lesions showed tuberculoid granuloma negative for AFB. In November 1997, 40 mg steroid was started to differentiate between type-1 reaction and relapse. The old lesion on forearm showed regression. However, the new lesion did not show any change except slight change in erythema. The patient is under steroid to decide about possible relapse.

OFLOXACIN CONTAINING COMBINED DRUG REGlMENS IN THE TREATMENT OF MULTIBACILLARY LEPROSY

Prasert Sampoonachot¹, Chaiwut Bundit¹, Somchai Peerapakon¹, Kowit Kampirapap¹, Sirisavapa Tiasiri¹, Somchai Surasondhi², Sakchai Supanwanit³, and Srisunthon Wiriyawipart⁴

¹Phrapradaeng Hospital, Samutprakarn 10130; ²Bangkaen skin clinic, Bangkok; ⁴Leprosy zonal center 6, Khon Kaen, Department of Communicable Disease Control, Ministry of Public Health, Thailand.

The results of Ofloxacin containing combined drug regimens in the treatment of 60 multibacillary leprosy cases from January 1989 to February 1998 are reported. The objective of the trial is to compare the antileprotic property of ofloxacin and ripampicin in multbacillary leprosy patients and to study the killing rate of M. leprae by ofloxacin and rifampicin before mass treatment can be recommanded.

The complications and side-effects of ofloxacin and rifampicin were of a mild nature and both drugs were well tolorated. Moderate to marked clinical improvement was noticed in a short period with Ofloxacin containing regimens in multibacillary Leprosy patients. No persisters were detected in any of the 33 specimens (of mouse footpads) that had been obtained after treatment for 6 months. Ofloxacin if added to the currently used WHO recommended MB-MDT regimen may shorten the duration of treatment. Ofloxacin, therefore, may be considered as a suitable alternative in suspected/proven Rifampicin resistant case and where Rifampicin is contraindicated.

The results were evaluated on the basis of the clinical conditions mycobactericidal effectiveness, sings of drug toxicity and side effects.

ACTIVITY OF MINOCYCLINE AGAINST M. LEPRAE IN MICE AND ITS EFFECTS ON LEPROMATOUS PATIENTS

The paper reported the activity of minocycline on agaisnt M. leprae in mice and the effects of minocycline on multibacillary leprosy cases in a short-term clinical trial. The results showed that using the kinetic method, the growth delay of M. leprae in the foot-pads of injected mice was 144 days afler a treatment with 25mg/kg minocycline daily by gavage 5 times weekly over a period of 60 days Fourteen multbacillary leprosy patierts were treated with 100mg/day minocycline for 3 months. The clilical improvements such as softening and flattening of the nodules and plaques in the patients were found as early as 1 week after starting treatment. At the end of trial, significant clinical improvement was found in all patients. The average MI decreased from 8.29 ± 3.29% before therapy to 0% at the end of trial, and the average BI from 4.48 ± 0.52 to 4.18 ± 0.60. Of 8 cases tested by mouse foot-pad one month after starting treatment, viable M. leprae was not detected in 4 cases, but after 2 months' treatment, viable M. leprae were not detected in all cases. Mild ENL and one mild skin reversal reaction developed in 2 and 1 cases respectively during the trial. All patients had slight brownish pigmentation on exposed skin lesions, but the patients tolerated the drug well during the trial. The results suggested that minocycline was proved effective and safe against leprosy and could be used in leprosy chemotherapy.

REACTION TO RIFAMPIN IN THE TREATMENT OF LEPROSY (MDT/WHO) RECORDED IN THE RIBEIRÃO PRETO REGION

Department of Internal Medicine. Faculty of Medicine of Ribeirão Preto. University of São Paulo. Brazil

The objective of the present report was to describe the adverse reactions attributed to the use of rifampin at the recommended monthly dose of 600 mg for the treatment of leprosy (MDT/WHO). recorded from 1992 to 1996 in the Ribeirão Preto region.

Fourteen cases, 7 men and 7 women aged 16 to 64 years, nine of them murtibacillary and five paucibaciliary, were observed. Fifty percent of these patients, all of them multibacillary, had been previously submitted to treatment (600 mg rifampin/day/3 months and 100 mg sulfone/day/5 years). Symptoms characteristically started 35 minutes to 3.5 hours after the ingestion of the supervised nfampin dose. We observed more than one organ or system were frequently involved. Among the adverse reactions, acute renal failure (ARF) and hepatitis predominated: 5 cases of ARF. 2 of them isolated and 3 associated with hepatitis; 5 confirmed and 3 suspected cases of hepatitis; one case of disseminated intravascular coagulation associated with hepatitis; one case of purpuric thrombocytopenia with possible hemolytic anemia; and 3 cases of flu-like syndrome. Eleven patients were cured, two developed mild to moderate chronic renal failure, and one patient died.

We emphasize the frequency of the combined involvement of various organs and the importance of the early recognition of adverse reactions to rifampin.

POTENTIAL APPLICATION OF MOLECULAR BIOLOGY IN FIELD TRIALS OF ANTI-LEPROSY VACCINES.

Dr. Ajeet Sodhi, Dr. M. M. Chaturvedi, Dr. A.K.Mishra, Miss, Anchal, Dr. K. D. Srivastava. Dr. T. Garg.

Dr. Hering Homoeopathic Hospital. Varanasi, Vidya Krishna Homoeo-pathic Anushandhan Akai, Varanasi.

Leprosy is a Chronic granulomatous disease caused by Mycobactrium leprae. "A unique relationship exists between immunology and central nervous system that governs the principle of clinical application in Homoeopathy. The immune system is not confined to single site in the body : rather governed by central motor nervous system, immunocytes and their secreted molecules traffic within and among lymphoid organs and various body compartments. Hence a highly complex system of communication has developed among the various cell types in the immune system. Homoeopathic medicines determine the pattern of chemical transformation in biological system, catalysed by specific proteinaceous macromolecules called 'enzymes'. The antigen combining regions of most of the high affinity anti bodies are encoded by immunoglobulin genes which acquire somatic mu tations. Serum levels of the immunoglobulins generally are normal in tuberculoid leprosy patient, whereas polyclonal hypergammaglobulinemia is a common feature Of lepramatous leprosy. The homeopathic medicines like Hura brazilienses and Hepersulf have been found to cause reduction in lymphoid swelling and levels of gamma globulins. These medicines irreversebly bind to collagens and are, therefore, are targeted to the infected cells.

Hura braziliensis and Hepersulf proposed to be new antileprae drugs, having recently met first phase of clinical trials. The initial results are promising, however, further studies are still awaited.

Of 2,743 Hansens patients being treated with MD T (Isoprodian-RMP) at Km 81 during Jan 1/87 through Dec 3 1/95, we have detected four relapses by MB patients and one by a PB patient. The control period, after the MB patient was released from treatment, was 5 years; and for the PB patient, 2-3 years. The observation is that the relapses by MB is presented between 7-10 years after release of MDT , and none during the conventional control period. The relapse rate in this period is, therefore, globally 1.8/1000.

RELATIONSHIP BETWEEN THE LEVEL OF PGL-IgM ANTIBODY AND RELAPSE IN CURED LEPROSY PATIENTS

In 1 515 cured leprosy paucnts (MB 917, PB 598) from 20 countis in Shandong Province, the level of PCL-IgM antibody was monitored for five yean. The patients with positive PGL-IgM antibody were randomly diveded into two groups. First group was purely followed (group A) and the second group (group II) was treated with MDT for one year. The patients with negative PGL-IgM antibody were followed as group C. All the patients were exam meted clinically and bacteriologically once a year for five years. At the end of the study, relapse rales in three groups were compared.

The results showed that in the first scar of monitoring, the positive rate of PGL-IgM antibody gradually increased in patients at the pole of tuberculoid leprosy towards the pole of lepromatous leprosy, and the shorter the time after cure, the higher the positive rate was. In the period of 5 years, 20 relapsed cases were detected 16(11.4%) in group A, 1 (0.71%) in group B and 3 (0.24%) in group C. The relapse me was higher in those with positive PCL-IgM antibody than those with negative, (p<0 001) Treatment with MDT had significant impact on the relapse in this study (p<0.001).

The authors concluded that: 1) there was a tendency in leprosy patients with positive PGL-IgM antibody to develop relapse after termination of DDS monotherapy; 2) blood spot method for monitoring of PGL-IgM antibody was feasible for use in the field; 3) treatment with MDT was very effective to prevent those with positive PGL-IgM antibody from relapse.

TWELVE-YEAR SURVEILLANCE OF 657 CURED PERSONS AFFECTED BY LEPROSY RE-TREATED WITH MDT

From 1983 through 1988, 657 MB patients clinically cured with DDS monotherapy together with BI of 2 or more at any site smeared previously were re-treated with RFP, B663 and DDS in combination. Four hundred and eighty seven of them were males and 170 were fermales Their age ranged from 17 to 70 years and disease duration ranged from 1 month to 39 years. Cured individuals not re-treated were used as control for this trail.

All patients were administered RFP and B663 1 200 mg each once monthly with supervision and DDS 100 mg daily self-administered. This treatment was continued for 12 months and was completed within a period of 15 months. Six hundred and twenty cases (94.37%) of them completed regularly the prescribed course but 37 did not due to the occurrence of side effects or side effects or complications. Exclusive of 2 who died and 1 migrated out of Shanghai after completion of re-treatment, the remaining 654 were followed uo for a period of 7-12 years (494 cases for more than 12 years) and the total follow up period was 8 926 person years, no relapses occurred. But there were 23 identified as relapses among the 137 control individuals, giving an overall relapse rate of 16.79% and an average annual relapse rate of 1.29%. The authors suggested that for a more reliable conclusion, these cases should and will be followed up until 20 years after completion of re-treatment.

Serum samples were taken before reaction, at reaction and during antireactional treatment in a prospective study.

The follow ing ma rkers were studied: TNFα. produced predom inantly by macrophages (normal value < 40 pg/ml); IFNγ, produced by activated T cells (normal value < 15 pg/ml); neopterin, produced by macrophages activated by IFNγ (normal value < 10 nmol/ml) and soluble TNFα receptor (= sTNFαr normal value <1.5 ng/ml).

Four patients with reversal reaction (RR) and one patient with several episodes of ENL and one episode of neuritis were studied.

TNFα, IFNγ and neopterin were simultaneously increased in two and TNFα , IFNγ in the other two RR. Levels decreased or normalized during antireactional treatment with prednisone.

Only TNFα was increased at ENL on two occasions; on the third occasion i.e. an exacerbation of ENL during prednisone treatment given for a neuritis TNFα level was normal.

sTNFαr levels varied but were increased in nearly all samples. In general, patients in reaction showed elevation of markers investigated. Laboratory markers may be helpful to support the diagnosis of reaction in leprosy patients.

NEUROLOGICAL ASSESSMENT OF A COHORT OF CHILDREN BORN TO MOTHERS WITH LEPROSY AND HEALTHY CONTROLS (A9 STUDY) - 1. CLINICAL AND CONVENTIONAL TESTS

M. E. Duncan (1, 2). M. Hungnaw (3). H. S. H/Mariam (3). L. Selassie (2). Z. Melaku (4). R. Kazen (3), A. Challis (5)

(1) Dept Medical Microbiology. University of Edinburgh; (2) Armauer Hansen Research Institute, Addis Ababa. Ethiopia; (3) All Africa Leprosy & Rehabilitation Training Centre. Addis Ababa; (4) Dept Neurology. Faculty of Medicine. Addis Ababa University; (5) Loch Fyne Services. Strachur, Argyll.

In a prospective (1975-1997) study (A9) of mouiers with leprosy and healthy controls, and their children, 15/99 of children were found to have very early leprosy at puberty (1990). Despite MDT 13/15 showed new nerve damage (1993). In 1993. 40% of the A9 cohon who had easily palpable/slightly enlarged nerves without suspicious skin lesion showed early ncurodysfunction. The aim of this study was to investigate if early nerve enlargement was a prodromal sign of leprosy.

Subjects: A9 cohort children: 85 (51 females and 34 males); distribution according to leprosy status of the mother mulubacillary leprosy (MBK:47), paucibacillary leprosy (PBK:22) and non-leprosy (NLK:16). [K=kidds!]. Control group: no lenown family or household leprosy contact (NKLCK:18).

Nerve enlargement: The A9 cohort had 45% with early/definite nerve enlargement (MBK 55%, PBK 36%. NLK 54%) compared with 25% NKLCK. Male:female ratio for nerve enlargement was 25:17, except in MBK (11:12). The ulnar nerve was the most frequently enlarged.

Sensory and motor nerve impairment (graded sensory testing (STG) and voluntary muscle testing (VMT)): A9 cohort had i) 32% sensory nerve impairment (MBK 40%, PBK 29%. NLK 14%) compared with NKLCK 13%. and ii) 12% motor nerve impairment (MBK 12%, PBK 14%. NLK 7%) compared with NKLCK 7%.

Nerve Conduction Velocity: measurements in 30 children who had evidence of neurodyjfunction were all within limits of normal for the reference laboratory.

NEUROLOGICAL ASSESSMENT OF A COHORT OF CHILDREN BORN TO MOTHERS WITH LEPROSY AND HEALTHY CONTROLS (A9 STUDY) - 2. TESTS OF SMALL NERVE DYSFUNCTION

M. E. Duncan (1, 2). M. Hungnaw (3). H. S. H/Mariam (3). L. Selassie (2). Z.Melaku (4). R. Kazen (3). S. Hansen (5). G. A. J am at (5). P. O. O. Julu (5). G.Ward (6). A. Challis (7)

(1) Dept Medical Microbiology. University of Edinburgh; (2) Armauer Hansen Research Institute, Addis Ababa. Ethiopia: (3) All Africa Leprosy & Rehabilitation Training Centre, Addis Ababa; (4) Dept Neurology, Faculty of Medicine. Addis Ababa University; (5) Peripheral Nerve and Autonomic Unit. Institute of Neurological Sciences. Southern General Hospital NHS Trust. Glasgow; (6) Oxford Optronix, Oxford; (7) Loch Fyne Services, Strachur, Argyll.

The aim of this study was to see whether neurodysfunction could be detected before ineversible nerve damage had occurred in the A9 cohort and healthy controls. The Thermal Threshold Tester (Triple-T: Medelec Ltd (see poster)) detects small nerve dysfunction in thinly myelinated A (cold) and unmyelinated C (heat) fibres. The Laser Doppler blood flow meter (Micro-Flo DSP: Oxford Optronix (see poster)) assesses function in autonomic (vasomotor) unmyelinated C fibres by recording skin blood How response to inspiratory gasp (LD-IG) and cold challenge (LD-CC) in tips of index and fifth fingers.

Triple-T: The A9 group had significantly increased hot and cold thermal thresholds (MBK 70%. PBK 70%. NLK 75%) indicating small fibre damage compared with NKLCK (18%).

LD-IG and LD-CC: LD-IG showed abnormal traces with established and subclinical nerve damage. The fall from resting blood flow (baseline) to the lowest point of the curve in response to LD-IG and LD-CC is expressed as % of the baseline. The mean LD-IG and LD-CC % fall in index and fifth fingers showed no differences between A9 and control groups. The percentage of children having i) abnormal LD-IG were MBK 22%, PBK 19%, NLK 17%. NKLCK 37%; ii) abnormal LD-CC were MBK 38%, PBK 33%, NLK 36%. NKLCK 33%.

ASSESSMENT OF THE A9 STUDY NERVE FUNCTION TESTS. HYPOTHESIS AND APPLICATIONS FOR LEPROSY ERADICATION

M. E. Duncan (1, 2). M. Hungnaw (3). H. S. H/Mariam (3). L. Selassie (2). Z. Melaku (4). R. Kazen (3). S. Hansen (5), G. A. Jamal (5), P. O. O. Julu (5), A. Challis (6)

(1) Dept Medical Microbiology. University of Edinburgh; (2) Armauer Hansen Research Institute. Addis Ababa. Ethiopia; (3) All Africa Leprosy & Rehabilitation Training Centre, Addis Ababa; (4) Dcpi Neurology, Faculty of Medicine, Addis Ababa Unjversity; (5) Peripheral Nerve and Autonomic Unit. Institute of Neurological Sciences. Southern Genera] Hospital NHS Trust, Glasgow; (6) Loch Fyne Services, Strachur, Argyll.

The prospective (1975-1997) study (A9) of mothers with leprosy and healthy controls, and their children, showed 15/99 of children with very early leprosy at puberty (1990). Despite MDT 13/15 showed new nerve damage (1993), while 40% of the A9 cohort with easily palpable/slighdy enlarged nerves without suspicious skin lesion showed early ncurodysfunction. In 1997 70% of the cohort had abnormal thermal thresholds, 32% had sensory impairment and 12% motor impairment. These findings from a well documented cohon are indicative of a significant level of as yet undiagnosed subclinical leprosy among teenagers and young adults in the "leprosy villages", potentially explosive and crippling in the event of widespread immunosuppression.

Hypothesis: Abnormal thermal thresholds, in effective measure of early small nerve fibre damage, arc the first evidence of subclinical leprosy (which at present is not treated).

Application: Thermal Threshold Tester ii simple to use. with high specificity and sensitivity. There is a strong case for using the A9 cohort with numbers augmented from surrounding villages, to carry out a controlled drug trial with appropriate MDT against placebos in both affected and unaffected populations to see whether treatment i) restores thermal thresholds to normal, and ii) prevents development of new cases and especially the nerve damage which causes disfiguration.

FACIAL 'BURNING SENSATION* IN MIDDLE-AGED FEMALE LEPROSY PATIENTS - A DIAGNOSTIC BLIND SPOT.

(1) Dept Medical Microbiology, University of Edinburgh; (2) Armauer Hansen Research Institute. Addis Ababa, Ethiopia; (3) All Africa Leprosy& Rehabilitation Training Centre. Addis Ababa.

Facial skin is so richly supplied with sensory nerves, chiefly Vth [Trigeminal] nerve, that even new active tuberculoid lesions may lack sensory loss. Three leprosy textbooks omit Vih nerve sensory loss, except conjunctival. For most leprologists this nerve escapes attention.

We repon six women (5BL, IBT/BL) from the A9 Study who presented with facial burning or pain, duration two weeks - two years. Three diagnosed "menopausal/ neurotic" received valium without relief. 'Burning sensation in the face" in middle-aged women falls on unsympathetic cars as 'menopausal'. Graded sensory testing (STG) revealed sensory loss of 300g in three and SOg in three. All six women had evidence of neuritis elsewhere and were treated as relapse / reaction with MDT and steroids: on follow-up. one had recovery to 50mg and a second lo 4g facial STG.

Nine other self-referring A9 women (7BL. IBT, ILL) were similarly assessed: 5 had faces fully sensitive to 50mg filament (IBT c/o "facial burriing" but had generalised post-part urn reaction); 3BL had 2 or 3 points sensitive to 200mg and felt 50mg elsewhere - two had new eye problems and one generalised neuritis; ILL, long-standing burned-out case felt 200mg all over her face.

Conclusion: Facial burning sensation requires urgent investigation with STG especially in "menopausal" women.

Forty forearm of human cadavers were dissected and studied. In 12,5% (5 cases) were found to have a MARTIN-GRUBER anastomosis (MG.A), two on the right side and three on the left side. From the total of five cases, two of this anastomosis occurred among the branches reserved to the flexor digitorum profundus muscle, one from the branch of the anterior interosseous nerve, and two directed from the median to the ulnar nerve.

Regarding to the electrophysiological study, 128 forearms of normal adults were studied and 20 (15,6%) showed evidences of MG.A. From this 20 forearms of 15 subjects, 5 (33.3%) presented bilateral MG.A and 10 (67,7%), unilateral.

In this study, the MG.A was found in agreement with the percentagens of the literature.

THE INFLUENCE OF HIV-1 INFECTION ON LEPROSY PATIENTS TREATED WITH MULTIDRUG THERAPY (MDT) IN WESTERN KENYA

An evaluation was acne among 10 HIV positive ana a similar number HIV negative leprosy patients who were put on MDT between 1989 - 1992, to determine the influence of HIV-1 infection on physical status, clinical status of the lesions, complications, occurrence /presence of reactions, occurrence of relapse and progression to ARC/AIDS and/or aeath. At the time of evaluation, it was found that 8/19 (42%) of HIV positive cases had died of AIDS relatea causes while one control 1/19 died of breast cancer. On the clinical status, 2/10 (10%) of the cases were reported to have reactivatea and 2/10 of the controls had signs of reactivation. The development of deformitie was not much different between cases 2/19 (10%) and controls 3/19 (15%). At least 2/19 (10%) of the cases were fauna to have developed ARC. It is therefore apparent from this study that 5 years after stepping MDT, most HIV positive cases ao succumb to death. However, the effect of treatment with MDT in terms of regression of the lesions appears to be similar for both HIV positive leprosy cases as well as HIV -ve leprosy cases.

Newly recorded patients with Positivity for AFB (Myco Leprae) at The Leprosy Mission Control area. Vizianagaram. Andhra Pradesh. South India are under study for 13 years of Mulh Drug Therapy (MDT) implementation from 1984-1996.

The present retrograde study deals with newly recorded 367 LL 5 BL patients wilh Positive Bacteriological Index for AFB among the total newly recorded patients of 4563 giving 8.04%.

The Bacteriological Positivity of patients is analysed year wise and also population wise at Risk. The study showed thai there is reduction of infective patients every year during Multi Drug Therapy implementation minimising the nsk to the Community under study.

The sensations and motor functions in hands of 52 MB pts. registered at the hosp. were examined with Nylon Monofilaments with gradod dlameters and by Standard motor powpr testing method respectively.The results of examination done initially and after every three months were ex pressed in numeric a1 scores. Out of 52 MB cases, 26(500 were +ve.

Pre-MDT analysis showed, normal sensory scores(scores=45) in 8(15%) pts, while 2-1 (46%) had bilateral and 20(39%) had unilateral sensory loss. Amongst those with sensory loss, 22(50%) had slight loss(scores > 35) while only 7(16%) had gross sensory loss (scores <10). The follow up showed higher %-age of improvement in sensory scores among the pts. treated with corticosteroides during 2 yrs period of MDT.

Pre-MDT motor function testing showed 37 (73%) pts with normal motor functions(scores=28). Out of 15 MB pts. with grade II deformity, 13(90%) were smear negative.Follow up of motor function scores did not show worsening in any of the patients.

The simple method of quantifying sensations using Nylon Monofilaments and motor functions by standard methods are useful even in the fieid conditions.

In Arabian Peninsula, leprosy is considered more as a social problem connected with strange imaginary stories. According to WHO reports. Yemen is considered as the mostly affected area in the Middle East.

To obtain a general idea about the social aspect and epidemiological and clinical pattern of the disease in the country, the files of 194 leprosy patients registered for MDT during 1993 will be analysed with a leprosy profile and community beliefs in Yemen

Leprosy patients in Bangladesh are not spared the usual dental problems in developing countries. This study is an attempt to further delineate the various dental problems and their prevalence among the leprosy patients in Gaibandha and Jaypurhat. These two districts, located in the Rajshahi division of the country, have a combined population of 3 million. The study consists of a survey of the patienls attending the leprosy clinics of the Gaibandha-Jaypurhat leprosy Control Project.

Patients are categorized with regards to their sex, marital status, PB-MB status, disability grade (and which particular organ is involved), and their particular dental problems: dental caries, periodontitis, pyorrhea, gingivitis, etc. Other oral problems like candidiasis, oral cancer, osteomyelitis, etc. are also noted.

Particular relationships to common habits like brushing teeth with neein twigs, chewing of betel nut and supari (local food items), oral hygiene, etc. are identified. Comparisons are made with a control group of general patients seeking treatment at the Dental Clinic in the Bogra Mission Hospital The incorporation of basic dental health education materials into the conventional messages of leprosy workers is explored.

INCIDENCE OF NEURITIS AMONG PAUCIBACILARY LEPROSY PATIENTS DURING TREATMENT AND SURVEILANCE

Dr. Annamma S. John, Dr. G. Rajan Babu, Dr. D. Vijaykumar, Dr. Helen G. Roberts, Dr. A. Dutt

Premananda Memorial Leprosy Hospital, The Leprosy Mission, 259/A, A. P. C. Road, Calcutta 700 006, India

180 Paucibacilary leprosy patients who did not have deformity or neuritis at the time of diagnosis were foil owed up during the treatment period and two years of sarveillance to detect neuritis. These patients were given PB/MDT for 6 months and some patients were continued upto 12 months on treatment if they had signs of activity. Neuritis is defined astrain and/or tenderness of a norve trunk and/or sensory impairment.

Out of 180 patients only 2 pattents (1.1%) developed neuritis. In both cases MDT has continued for 12 months. In the case of the female patient the neuritis developed after she became pregnant.

This study shows incidence of neuritis during and after PB/MDT treatment, irrespective of 6 months treatment, is low.

Departments of Dermatology and Urology, Christian Medical College and Hospital, Ludhiana-141008, Punjab, India.

A case of borderline tuberculoid leprosy of 2 years duration in a 22-year-old male Is reported. The patient developed exacerbation of the lesions and inability to retract the prepuce for one month. On examination,he had anaesthetic/hypoaes the tic erythematous plaques on different areas (about 10 lesions), and also one anaesthetic plaque on the penis, causing phimosis. Skin biopsies were performed from 3 different skin lesions,and circumcision was also carried out. The skin biopsies showed florid tuberculoid granulomas. The excision biopsy of the prepuce showed granulomatous and round cell infiltrate almost replacing the dermis. The nerves were infiltrated or surrounded by infiltrate. The patient received multidrug therapy, including daily rifampicin, and the plagues gradually flattened. Repeat biopsies done one year later from 2 subsided skin lesions showed only mild to moderate periappendageal round cell infiltrate. One large, unrecognisable nerve was seen infiltrated with epitheloid cells and round cells. Sequential clinical photographs during treatment will be shown, and also pre and post-treatment photomicrographs of this patient.

Introduction : La lèpre est une maladie infectieuse chronique a expression cutanée et neurologique. Elle peut aussi se reveler par des manifestations Ogénèrc* es et viscérales isolees . Le diagnostic de lèpre est rendu difficile par lu divers*té et parfois l'a*ypic des lésions cutanées ou par une présentation inaugurale extra-cutanée. Nous rapportons un cas de lèpre lepromateuse ayant donné lieu a un erreur de diagnostic.

Observation: Mme M.A. âgée de 29 ans. suivie dpuis 1994 pour une polyarthrite évoluant dans un contexte fe*rile, un nez tuméfié ***** ******ureux et une inflammation des pavillons des oreilles. Sur le plan biologique existait un syndrome inflammatoire. Le bilan immunologique était négatif. La biopsie de la cloison nasale montrait des signes de périchondrite. Le diagnostic de polychondrite chronique atrophiante (PCA) était retenu, Une corticotherapie a une dose d'attaque de 1 mg/k/j puis d'entretien de 10 mg/j avait entrainé la disparition des signes sans nouvelle poussée, deus ans après, elle a été rehospitalisee pour une fiévre avec epistaxis spontanés et polyarthrites. L'examen cutané montrait une rarefaction des sourcils, des lésions nodulaires érythemateuses et infiltrées siégeant au visage, aux lobules des oreilles et aux faces antérieures des jambes. Ces lésions étaient asymptomatiques. L'examen neurologique montrait une hypoesthésie dans le territoire du nerf sciatique poplité externe. La biopsie d'un nodule montrait de nombreuses cellules de Virchow avec des bacilles de Hansen (BH) en globi. Un traitement spécifique anti-lépreux a entrainé une régression des lésions.

Commentaires : Le diagnostic de la lèpre est difficile dans les pays à faible endèmicité lépreuse. Notre observation illustre la confusion d'une LLp avec la PCA. La PÇA associe une chondrite de l'oreille externe, du nez et laryngotrachéale et parfois des polyarthrites et des lésions cutanées à type d'érythème noueux et plus rarement a type d'aphtose buccale ou génitale, de phlébite superficielle, de pseudofolliculite. de livédo. de purpura, d'hyperpigmentation. etc. mais jamais de nodules cutanés ou sous cutanés (lépromes) comme la LLp, la chondrite dans ce cas correspondrait soit à une réaction inflammatoire de contiguité soit accompagne les manifestations inflammatoires articulaires. Les corticoides prescits avaient agir sur les phénomènes inflammatoire, auriculaire et articulaire expliquant les rémissions transitoires, et ce n'est qu'après 2 ans d'èvoluation avec l'apparition de signes plus spécifiques (chute des sourcils, lépromes de la ***** des lobules des oreilles et des extrémités) que le diagnostic de LLp était suspecté puis confirmé par l'examen histologique et bactériologique.

Pupil cycle time (PCT) was measured in 81 subjects (162 eyes), all under 45 years of age. to evaluate the autonomic innervation of the iris. This study included 9 tuberculoid (TT). 19 borderline tuberculoid (BT), 9 borderline bolderline (BB). 10 borderline lepromatous (BL) and 16 Iepromatous (LL) leprosy patients without any intraocular involvement undergoing multidrug therapy and 18 healthy volunteers. Mean PCT was prolonged in BB, BL and LL patients when compared with mean PCT of healthy volunteers and the difference was statistically significant (p<0.05). Some others functions of the autonomic nervous system were tested (blood pressure and pulse response to standing, body temperature, lacrimal and pupillary responses) and symptomatic involvement was also reported.

Bao-ren Wang, Shi-zen Wang, Zen-rong Zhu Instructor Zhi-gao Jiang Bine? Prefectural Station for Skin Diseases and SDT Control. Bine? City Guizhou Provine, China

In order to reduce ocular complications from leprosy, the authors suggested that the patients should be detected as early as possible, leprosy reactions should be timely managed, self care training should be given to patients and one of their family members at least and surgical corrections should be provided for those with paralytics lafophthalmos and ectropion if necessary

Regular eye examinations are conducted MDT was started in late 1982 5.513 patients were registered for MDT (MB 3.309 PB 2.204) and 3 041 completed treatment (MB 1.868 PB 1173) The rest were referred to various control units These records were verified and 1,457 patients were examined and 217 MB patients were followed up for 3 to 14 years. Routine screening was done once in 6 months with Slit Lamp. Observations were recorded and anlysed.

Eye complication did not occur in non Lepromatous patients except for lagophthalmos Eye complications in Lepromatous with short duration of diescase were fleeting in nature and minimal, subsided within six months of MDT and did not recur again.

Eye complications like ... in Lepromatous of long duration lasted for 6 Years and lead to blindness in a few with severe pre-existing lesions. Inspite of regular MDT eve complications appeared even after 1 to 2 years of MDT to persist for many years. During the past 7 years eye complications were not seen among new cases except for lagophthalmos and steroid induced ca ... leading to blindness in some. An occasional ... /Scle ... tis was seen in Mono Relased patient. Early detection of leprosy is very important in preventing eye complication Judicious use of steroid will minimice steroid induced eye complication like cataract. Treated patients will require surgers for cataract lagophthalmos care should be a part of the care-after- ... package.

AN EPIDEMIOLOGICAL SURVEY OF EYE BLINDNESS AND LOW VISION IN 1945 LEPROSY PATIENTS

National Center for STD and Leprosy Control. Institute of Dermatology. Chinese Academy of Medical Sciences and Peking Union Medical College. Nanjing. P. R. China 210012

In order to find out the prevalence, the causes as well as the distributions of blindness and low vision in leprosy, an epidemiological survey of blindness and low vision caused by leprosy among 1045 cases of leprosy was 7.76% unilateral blindness 4.4% bilateral low vision of various degrees 9.23%, unilateral low vision 5.34%. The prevalence of eye complications in different groups of patients was quite different, it was higher in fermales than in males, multibacillary patients higher than paucibacillary patients, in-patients higher than out-patients. Corneal disease was the commonest cause of blindnes in this group, to the second was iritie disease and cataract. The main cause of low vision was cataract. The main cause of low vision then normal and iritie diseases. Treatable blindness acconted for 62.7% and treatable low vision ... of the patients studied, 36,62% of cases with eye complications expressed their willingness to be treated there fore preven ... and treatment of ... ... ... blindness are very hard.

Ravanes, J.M. Cellona, R.V., Balagon, M.F., Abalos, R.M., Tan. E.V. and Walsh G.P.

The objective of this study is to determine the incidence of eye complications in MB patients during and after completion of WHO-MDT

300 newly diagnosed MB patients were recruited and followed up at the Cebu Skin Clinic. Cebu, Philippines. Regular clinical, bacteriological and eye examinations were done before, during and after treatment. The study is now in progress for 9 years.

One BL patient developed lagophthalmos before MDT and did not improve on treatment. Two BL patients developed lagophthalmos during treatment. 1 completely recovered but the other only partially 98% of the patients showed normal pupil evele time while 0,7% were lower and 1,3% in the higher ranges. Clofazimine deposits appeared about 6 months of treatment and disappeared aboul 12 months after treatment was stopped. Surprisingly, 61% of the patients showed no clofazimine deposits, 29% had depositis on the limbus only and 10% had deposits on the limbus and other areas of the eye. Corneal beading affected 5% of patients but disappeared 12 months on treatment. In addition, 2% of patients had hypovitaminosis A. Pterygium was found in 6% of patients. No increase in intra-ocular pressure was noted.

The clinical characteristics of the patients in the study, their demographic aspects and possible risk factors associated with the development of ocular complications will he discussed.

This investigation is funded by American Leprosy Missions (ALM) and Leonard Wood Memorial-American Leprosy Foundation (LWM-ALF).

In ten of Guangdong Province's leprosy villages, over an 18 months period, 845 cured cases of leprosy with, clinical symptoms of lacrimal deficiency were tested by using Schirmir test on all, while 80 were examined with slit-lamp. Forty percent had <10 mm tears and BVT<10'.

Findinqs suqgest that a high incidence of dry eye maybe caused by leprae drugs which restricts and damages lacrimal glands function, VII nerve damage affects secretion, damaged conjunctiva destroys conjunctival goblet cells, Vitamin A deficiency and presence of eye lid deformity effects tear film. Because of drying of the corneal epithelium, visual acuity is diminished and resistance of the cornea to withstand mild impact and infection occur.

Based on findings of dry eye in Guangdong, use of protective eye devices, tear substitutes, long term use of Vitamin A, and corrective surgery of eyelid deformity is recommended.

Although corneal ulcer continues to be a serious ocular problem occurring in leprosy patients, it has not been studied extensively in leprosy.

In a retrospective study of 58 leprosy patients admitted with corneal ulcers at our hospital from 1990 to 1996, 11 patients (19%) had a history of injury immediately preceding the ulcer. 3 of them gave a definite history of rubbing the eyes and 5 gave history of injury with a vegetable natter. 25 patients (43%) had lagophthalmos and in those patients in whom corneal sensation was estimated 72% had decreased corneal sensation. In 5 patients there was blockage of the naso - lacrimal duct. The most common organism cultured from the ulcers was pneumococcus. No anaerobic organisms were cultured. Mycotic filaments were found in 5 ulcers. The majority of ulcers were located in the central cornea and in the inferior temporal quadrants. Vis ion improved after treatment in 2 patients, remained static in 35 and deteriorated in 21 patients.

The importance of identifying risk factors that can give rise to corneal ulcers, early recognition of ulcers and appropriate treatment to be given are discussed.

Leprosy Mission Hospital & Control Unit, Nuzvid Krishna District, Andhra Pradesh, INDIA.

The changes in the manifestations of Lepromatous Leprosy over a period of 20 years, 1976 to 1996 is presented.

Leprosy has not only declined in numbers but also in the severity especially after the introduction of MDT.

Lepromatous Leprosy presented as Nodular, Jiff use infiltration (Polar varieties) and also as large symmetrical patches {suh-polarforms) during the monotherapy days. With the introduction of MDT in 1993, we have noted the changes from multiple nodules to few nodules and then to single nodule and no nodule. Diffuse infiltration all over the body to symmetrical patches then to localised infiltration.

The case histories of 4 of our patients manifesting with single lesion which proved positive for skin smear are presented.

This paper intends to alert field workers regarding mono lesion cases that may be "Localised Lepromatous Leprosy".

Kamal Abdel-Hafez, Sharaf El-Dine Ghoneimah, Mohamed Hany El-Tonsy, and Elhan Hamouda.

Department of Dermatology and Biochemiristry, Assiut Faculty of Medicine and Department of Dermatology. EI-Minia Faculty of Medicine. Egypt.

The present work was dsigned for screening the hormonal profile of the suprarenal gland in leprosy, namely, cortisol, dehidreniandrostcrone- sulfate (DHEA-S) delta-4-andros-tenedione and testosterone. In addition, the concomitant clinico-endocrinological manifestations, if any, associating those of the disease were also studied. This was carried out by the recruitment of 60 male leprotics (21, paucibacillary and 39 multibacillary) and 16 healthy males as control group.

The values of cortisol in both paucibacillaty and multibacillary groups were insignificantly higher than that of controls and the value of paucibacillary group was insignificantly higher than that of multibacillary group. The values of DHEA-S in both paucibacillary and multibacillary groups were higher than thai of the controls, with statistically significant difference with that of the paucibacillary grooup (P<0.05). No statistically significant difference between both paucibacillary and multibacillary groups. The values of androstenedione in both paucibacillary and multibacillary groups were significantly higher than that of controls (P<0,05 and P<0,01 respectively). On the other hand, the value of paucibacillary group was significantly lower than that of the multibacillary group (P<0,01) The values of testosterone in both paucibacillary and multibacillary groups were significantly lower than that of controls (P<0,001) for both). On the other hand, the value of paucibacillary group was insignificantly higher than that of the multibacillary group.

The results of this screening study have provided an argument for further studies to he held for thorough investigation and assessment of the adrenal function in leprotics.

Francisco Vega-López, Rosario Tapia, Gloria Serrano, Eduardo Castro*, Maria Eugenia Fonseca, and Amado Saúl**

Centro Médico Nacional, IMSS, *Centro Dermatológico Pascua, SSA, and **Hospital General de México, SSA. Mexico City.

This study was carried out in order to identify and define abnormalities in the testicular function of chronic leprosy patients Ten patients between 29 and 50 years of age with an established diagnosis of leprosy by the Ridley and Jopling criteria, and 20 male historical controls were included in the study Full clinical andrological assessment, hormone profile investigations, and testicular ultrasound were carried out in patients and controls Seven patients with leprosy presented with sexual dysfunction, abnormal testicular volume and/or gynecomastia. Baseline hormone levels of FSH and LH were significantly increased in all the leprosy patients. Moreover, 3 cases showed decreased testosterone levels, an abnormal E2/T relationship, and a low percentage in the testicular reserve test A positive correlation among erection dysfunction, hypospermia, hypergonadotropism, and abnormal sperm concentration was found in 5 leprosy cases One third of the cases with abnormal results presented with an established testicular damage, and one third with variable degrees of abnormalities undergoing progression. Mild incipient damage was found in the remaining leprosy patients. The testicular ultrasound and the testicular reserve tests reported high sensitivity to disclose progression of functional damage We suggest that hormone replacement therapy should be considered for selected cases with long term treated leprosy.

Suneel Qamra, Satish Ghei, Utpal Sengupta, *Pasumart Veeraraju, *Manyala Satyanarayanan & Anil Kumar.

Central JALMA Institute for Leprosy, Agra, India. *Human Genetics, Andhra Univ., Vishakhapatnam.

The association between different body builds and several diseases known to occur. However, no such study seems to exist to understand the morphological changes of leprosy patients despite having evident bony changes and deformities of body of leprosy patients. The present study is an attempt in this direction.

For this, 320 families(151 leprosy & 169 normal) belonging to poor SES have been studied from leprosy endemic area situated in south-east coastal part of India. The ages of leprosy in normal adults vary between 18-40 years. This age group has been selected purposely as changes due to senescence more or less static in this age group. The comparative morphological changes thus observed between leprosy afflicted and normal adults may probably be on account of leprosy only.

These morphological changes between these two groups wil l be measured through various body measurements such as, body weight, height,lengths, griths & breadths. These measurements are being taken using standard methodology and instruments. The various indices wil l be formulated to observe proportionate changes. The findings of this study will be discussed in detail.

EVALUATION OF FACIAL NERVE BY MAGNETIC RESONANCE IMAGING (MRI) IN LEPROSY PATIENTS.

Jane Tomimori-Yamashita¹, Marcos C. Floriano¹. Helio K. Yamashita². 1) Depart. Dermatol. 2)Depart. Radiology, UNIFESP-Escola Paulista de Medicina, São Paulo, Brazil

The facial or seventh cranial nerve is responsible for eye closure. In leprosy, the damage of facial nerve causes lagophthalmos, particularly affecting the lower lid. The MR1 is a technique, which is able to identify the affected segment of facial nerve, especially the infratemporal canal tract. It has been used for analysis of this nerve lesion in Bell's palsy. The diagnosis of facial nerve lesion could help the patients to prevent ocular sequelae. In the future, the MRJ could be an important method to detect an early lesion, indicating the segment lo be submitted to a surgical decompression. The authors studied 8 patients (1 LL, 5 BL, 2BT) with and without leprosy reaction, one patient presented clinical signs of facial nerve lesion. By the MRI, we could observe some irregular thickness of facial nerve in different segments, particularly in the mastoid bone intracanalicular tract The patient with lagophtalmos and reversal reaction presented a thick nerve and an enhancement of ganglionar segment after the paramagnetic contrast injection. The same aspect had been demonstrated in Bell's palsy. We conclude: 1) the etiopathogenesis of the contrast enhancement in the symptomatic acute facial palsy in leprosy could be due to a neuro-vascular mechanism as it had been described in Bell's palsy 2) the presence of the contrast enhancement is not a specific signal of acute lesion, but indicates the nerve lesion 3) MRI could detect early lesion in facial nerve in patients without clinical symptoms.

Blood levels of total lipids, cholesterol, triglycerides, and low density lipoprotein were studied in leprosy patients. The patient group for this study consisted of 40 treated leprosy patients classified as lepromatous (LL/BL) according lo Ridley-Jopling scale. 22 males and IS females between the ages of 55 and b5 years. The control group included healthy endemic controls of identical age who had no contact with leprosy patients. Blood samples from patients and controls were taken in spring-summer season at strictly determined time intervals: 8:00 - 10.00 am In lepromatous leprosy patients levels of total lipids, cholesterol and triglycerides were shown to approach those in healthy donors of identical ages, though to tend to decrease in active stages of the disease. At the same time in these patients low density lipoprotein level was significantly decreased as compared to controls. It was found out that patient's lymphocyte ability of spontaneous incorporation of ³H-thymidine in vitro was inversely related to ratio of total blood cholesterol to triglycerides. This finding supports the view of Memon el al. (Int. J. Leprosy 1997. 65: 1-11) thai certain factors of lipid metabolism may contribute much to leprosy pathogenesis. Besides, in patients with inactive lepromatous leprosy given DDS therapy blood levels of intermediate and final products of lipid peroxidation were estimated with using ultraviolet spectro photometry methods. The results obtained showed thai intensity of lipid peroxidation in the patients mentioned above was significantly decreased. This might be either ihe result of antioxidant effect of DDS or decreased contents of low density lipoproteins which are ihe most liable to oxidation among lipid-protein structures of blood. The possibility of interrelation between above factors cannot be ruled out.

INTRA-OPERATIVE ELECTRONEURODI AGNOSTICS TO DETECT TI IE MOST PROXIMAL LEPROUS NEUROPATHOLOGY IN SCIATIC NERVE

Using intra-operativc spinal root stimu lation, the most proximal site of a leprosy induced neuropathology of the tibial nerve was foun d. Patients with leprosy affecting the posterior tibial nerve behind the medial malleolus causing significant anaesthesia of the foot were investigated by spinal root stimu lation of mixed comp oun d nerve action potentials (MCNAP) which were then recorded from the exposed tibial nerve. In nearly all cases the MCNAP amp litudes were reduced or disappear at or before the bifurcation of the sciatic nerve in the mid thigh. This was always the case even though the nerve macroscopically looked normal. Epineurotomy within these app arently una tlected segm ents revealed mild fibrosis of the intra fascicular epineurium in 9 of the 10 cases. There was macroscopic and histological evidence ofdiscontinu ity from distal to proximal (skip lesion), in that there was less fibrosis deep in the proximal calf. Evidence for such a proximal leprosy nerve lesion w as corroborated by the finding of mild wasting of the proximal calf mu sculature, (Gastrocnemius an d soleous), mu scles not normally thought to be involved by leprosy nerve damage.

MANAGEMENT OF STEROID RESISTANT PATIENTS WITH SEVERE EPISODES OF PAINFUL ENL WITH REPEATED FRESH TRANSFUSION AND MINIMAL DOSE OF RIFAMYCIN AND CLOFAZIMINE.

G.B. Pant Hospital, Maulana Azad Medical College and University College of Medical Sciences. Delhi

Recently we reported successlul management of Mitsuda negative borderline and lepromatous leprosy patients with MDT plus active immunotherapy by low dose Convit vaccine. There was quick clinical cure, reversal reaction, early bactenal negativity and Mitsuda conversion. It is recognised that there are few leprosy patients with repeated episodes of ENL, who cannot be controlled by large doses of steroids. Here we report management of active BL/LL patients with steroid resistant severe repeated epidoses of ENL by rifamycin and clofazimine plus repealed transfusions ol tresh blood (containing lymphocytes) (3-10 units) donated by healthy Missuda positive donors over a period of 3-10 weeks. We observed that this method of chemoimmunolherapy could reverse the downhill course of the disease, reduce the bacterial load and interrupt the painful episodes of ENL. which cannot be controlled by steroids and MDT.

Rakesh Matumdhar. Joseph LeMaster and Paul Roche; Mycobacterial Research Laboratory. Anandaban Leprosy Hospital. PO Box 151. Kathmandu. NEPAL

A retrospective study of a large cohort of previously untreated bordeline lepromatous (BL) and lepromatous (LL) patients presenting at Anandaban Hospital between 1989 and 1996 was performed to measure the prevalence of erythema nodosum leprosum (ENL), the time of onset and the contribution of 9 clinical and laboratory factors to the risk of developing ENL. A preliminary analysis showed a prevalence of ENL of 57/326 (17.5%) in new patients. ENL reactions occurred an average of 7 months after the commencement of MDT (range 0-27 months). Patients had an average of two episodes (ranee 1 to 9) LL patients had a significantly higher prevalence of ENL (29%) than BL palients (9% p<0.001) Patients with diffuse skin infiltration (OR=5.0, p- 0.001) Bacterial Index greater than 4 + (unadjusted OR-3.2, p<0.01), skin nodules (OR=2.6, p< 0.01) or positive for IgM anti-PCL-1 antibodies (OR=2.0, p<0.05) were at increased risk of developing ENL. Age. sex. the number of body areas with disease, the morphological index and the number of patches were not significant risk factors. The identification of clinical features at presentation associated with high risks of developing ENL will be valuable in patient management and in minimising leprosy disability.

It is known that lesions in type I reaction may ulcer. However since times of Ryrie in Malasya, there are no studies about the occurence of this phenomenon in some leprosy cases. We will present 10 of such cases which were studied under clinical, bacteriological, histopathological and immunological aspects. Patients were submitted to a clinical I and of neurological examination and pictures were taken from iheir lesions. Smears for determination of BI and MI were taken from six sites and two biopsies were collected for histopathological studies. In all of them a Mitsuda test was performed.

The results obtained were variable probably because among these cases there is reactional bordehne cases and reactional tuberculoid cases, that is, cases with different grades of cellular immunity.

Theses results will be discussed as wel as the probable mechanisms involved in the occurance of the ulcerations

A. Wilder-Smith and E. Wilder-Smith Dept. of Neurology, University of Berne, Switzerland

Early detection of leprosy is the prerequisite not only to prevent lasting disability in leprosy patients, but also to reach the proposed WHO goal of world-wide elimination of leprosy. As there is both immunocytochemical and neurophisyological evidence that peripheral autonomic nerve fibers may be the focus of initial nerve damage in leprosy, neurophysiological methods testing for peripheral autonomic function may be useful in detecting evidence of early defects. Recent neurophysiologies methods have used vasomotor reflex doppler veloanielry which measures the degree of impairment of fingertip vasoconstriction in response to autonomic stimulus. Another method is the sympathetic skin response (SSR) which tests for sympathetic sudomotor function by measuring changes in voltage of the skin in response to exosomatic stimuli. Using these test methods, studies have shown that there is a high prevalence of abnormal vasomotor reflexes and absent sympathetic skin responses in leprosy patients.

In asymptomatic leprosy contacts, it is unclear to what extent exposure to the neurotropic M. leprae is associated withi the initiation of subclinical nerve damage. To investigate this, we performed vasomotor retlex testing (VMR) and the sympathetic skin response (SSR) in 36 asymptomatic leprosy contacts (25 household contacts, 12 hospital contacts) compared lo 47 age- and sex-matched controls in Pokhara, West-Nepal. As for VMR, the How reduction following an inspiratory gasp as recorded from finger and toe tips -.bowed a mean percent reduction of 57.8 (standard deviation 14.6) among household contacts, 61.9(17.5) among hospital contacts and 66.8 (7.8) among controls (p= 0.001 by analysis of variance). The prevalence of abnormal lest results was 54% among household, 42% among hospital contacts and 15% among controls (p=0.0005 by chi-square lest for trend). Further confirmation of autonomic nerve dysfunction in otherwise healthy Nepali leprosy contacts was shown by parallel testing with the sympathetic skin response. Contacts had a prevalence of 13.8% of absent SSR. controls 6.3%.

The implication of impairment in vasomotor and sudomotor function in leprosy contacts needs yet to be determined. However, we propose this to be a response to exposure to M. leprae which represents either ongoing nerve damage or nonprogressive residual autonomic nerve damage. The importance of abnormal autonomic testing as a predictor of progression to clinical disease can only be elucidated in prospective cohort studies, ideally complemented with immunological and histological studies.

Our results suggest that both VMR and SSR testing might be of potential value for detecting early leprosy before the occurrence of clinical motor or sensory nerve deficits.

We have observed 12 BL or LLs patients who presented with, or developed DTH reactions after the initiation of antibacterial therapy, but who subsequently developed erythema nodosum leprosum (ENL), the DTH to ENL group. During the same time, two LLs patients had ENL followed by relapseassociated DTH, a significant, p=0.02. difference in the sequence of ihe two conditions. The DTH to ENL group had statistically significantly higher Bis at the time of diagnosis of the DTH reaction compared with two DTH controls, seven multibacillary patients presenting with DTH reactions and 14 BL or LLs who developed DTH reactions after starting treatment but had no ENL. DTH-associated histological changes were less well developed in the DTH to ENL group than in either of the two controls, in the DTH to ENL group, 75% required prednisone in addition to thalidomide to achieve a complete remission, in contrast to only 10% of 21 ENL clinical controls. In the DTH to ENL group, the classical histological ENL pattern was present in only 36% of the DTH to ENL groups, in contrast to 88% of 33 ENL histological controls. In 8 of 8 of the DTH to ENL patients studied, after the ENL remitted, M. leprae -sonicate-stimulated lymphocyte transformation tests gave stimulation indicies within the range of our TT and BT patients.

The DTH to ENL group has a novel lability of host immunologic postures, sharing some features with, but differing in important aspects from . LLs patients who relapse as BT.

176 patients across the whole leprosy spectrum were investigated ¹³¹I accumulation in thyroid gland, level of organic ¹³¹I in body - by the whole body radtometry; Mood plasma levels of triiodothyronine (T3) and thyroxin (T4) - by radioimmunc tests Based on the data obtained all the patients under study were divided into tour groups: by % of ¹³¹I accumulated in thyroid gland (in per cents of count of the whole body): less than 45% - 1st, 45% and more - 2nd (average contents of organic¹³¹I in body of the patients of these groups were 1,53±0.13 and 2,42±0,30% of the total body count, respectively), by T3 level (in nmoles/l): less than 2 - 3rd group, 2 and more - 4th group. Prevalence of neuritis with marked painful syndrome developed before or after our investigation was significantly higher in the 1st group s compared with the 2nd and in the 3rd group as compared With the 4th (P < 0.05). Besides, severity of painful syndrome in patients of 1 st and 3rd groups exceeded that in the 2nd and 4th groups. At the some time in some patients of the above groups spontaneous and phytohemagglutinin-indueed activity of T-suppressers was studied Statistical analysis showed a significant direct correlation of Ts activity with endogenous thyroid hormone levels. Thyroid status-dependence of incidence of leprosy neuritis might suggest active influence of thyroid hormones on Ts functions by regulating autoimmune processes underlying the neuritic compIicalionJ of leprosy.

We studied retrospectively on the episodes and incidence of complications in B.1. positive leprosy patients who completed WHO MDT treatment and wore observed for two years after RFT, All 232 cases were skin smear positive at their first visit to the clinics. The symptoms and signs such as reaction, neuritis and deformity were observed both during the treatment and after RFT.

The classification of the cases was nine BT. 20 BB. 127 BL and 79 cases LL. The male and female ratio was 201 to 31. During treatment 47% of cases became B.I. negative. 24% remained positive and 29% uncertain.

Type-1 reaction during treatment occurred in 18.96% cases, and the reaction after RFT occurred in 2.58%. Type-2 reaction during treatment occurred in 27.58% cases, and the reaction after RFT occurred in 9.48%. During treatment. 25.43% cases developed neuritis, and after RFT period 3,44% developed it. Concerning deformity cases, at the onset of treatment. 105 cases indicated "No deformity". 65 cases Grade-1.34 cases Grade-2. and 26 cases uncertain. At RFT. 114 cases indicated "No deformity". 44 Grade-1, 42 Grade-2. and 12 cases uncertain.

Of each cases above, we want to trace how the deformity developed under, if any. particular circumstance, and also, we hope to point out if there is any measures we can take to prevent program of the deformity.

Dr D Porichha, Senior Pathologist, Medical Centre, Parliament House Annexe, New Delhi.

Dr H K Kar. H O D, Dermatology. STD and Leprosy. R M L Hospital and Dr M Bharadwaj, Senior Pathologist. R M L Hospital. New Delhi.

Presently single lesion leprosy is an important subject ot discussion due to its tendency ot sell healing in considerable number ot cases and the recent approach to treat these cases with a single dose ot multidrug regimen. This simplified approach raises a question on the morphological uniformity of single lesion leprosy. The present study attempts to analyse the range of histological variations in this entity and to find out if these cases are uniform enough to be clubbed together for a single regimen of drugs.

Skin biopsies from 152 patients, having a single skin lesion and registered in Urban Leprosy Centre. RML Hospital are included in this study. The skin tissues are processed, and stained as per standard techniques. Two sections one stained with H & E and the other with File Farraco stain are examined in each case. The main histological features recorded were : 1, Granuloma fraction, 2. Density and disposition of Lymphocytes and epithelioid cells. 3. Degree of focalisations, 4. Intensity of inflammation.

As per the histology there were 19 Indeterminate 44 TT and 89 BT cases. Fourteen BT cases showed some extent of type I reactioin. Granuloma fraction varied from 10 to 90%. The indeterminate cases showed varying degree of lymphocytes infiltration, and nerve involvements.

Single lesion cases are not uniform in their morphology. Since histology faithfully reflects the tissue response to M leprae or its antigen, ignoring this aspect completely in designing a drug schedule and going only by number may not be completely risk free.

The Present study deals with 1825 Mono Lesion Leprosy Patients out ot 4563 new patients recorded at The Leprosy Mission Control area in Vizianagaram. A.P.. South India during 13 years trom 1984- 1996.

The retrograde study is taken up to find out the changing profile of Mono Lesion patients over a penod. It is to record mat 39 99% of patients have single lesions. Ihe Men being 20.3% and Women 1968%. Mono Lesion patients belong to Tuberculoid 1657 (36 31%). Borderline Tuberculoid 156 (3.54%) and Indeterminale12 (0.65%).

The Data is analysed under Year wise, Age wise. Duration of disease. Multi-Drug Therapy. Surveillance. The study showed that Mono-Lesion patients are of same proportion over these years.

In several countries single lesion leprosy is being reported in large numbers The LCU Miraj has been involved for over 20 years in the National Leprosy Eradication Programmes and recently in a WHO supponed multicentric drug trial on monolesion leprosy including Rifampicin. Ofloxacin & Minocycline (ROM). We present case histones of two patients. An elderly male treated with ROM worsened at 9 months follow-up and then put on PB-MDT. While skin smears were reported negative, biopsies revealed a BI granuloma of 1+ and a solidly staining bacillus was seen In another case on PB-MDT from LCU Islampur, smears were not done as per guidelines for monolesion cases for that centre. He was about to be released from treatment when clinical suspicion made one of the authors suggest a skin smear on the patch. The bacteriological index observed on thai patch was 3+ on a single site. The patient was put on MB-MDT. Subsequent follow-up showed that the patient developed more lesions. The authors opine that examination of monolesion cases be done with utmost care. The significance of these findings, their relevance for leprosy control programmes and the role of skin smear examination are discussed.

R. Premkumar, E. Daniel, and P. S. S. Sundar Rao, Schieffelin Leprosy Research and Training Centre, Karigiri, India.

We studied the correlation of the 3 clinical classifications thai are in common usage in leprosy, namely, the 1995 WHO classification, the Ridley-Jopling classification, and the classification using a body area system, with the histopathological classification.

121 patients whose clinical and histopathological classifications were done independently while they were untreated as per Ridley-Jopling criteria were included in the study. Their slit-skin smear status were elicited and their body lesions were counted; major trunk nerve function losses were also scored in terms of the motor/sensory loss. Kappa coefficient were used to determine the chance-corrected agreement of the 3 clinical classifications.

The results showed that when histopathological classification was used as the "gold standard" of classifying leprosy, all 3 systems have fair to good agreement However, the Ridley-Jopling classification has the highest predictive value(0.69). The WHO-1995 clinical classification of counting skin lesions is second (0.63) and the classification using a body area system ranked third (0.43).

CORRELATION OF CLINICAL, HISTOLOGICAL AND IMMUNOLOGICAL FEATURES ACROSS THE LEPROSY SPECTRUM.

N.P.Shanker Narayan * G.Ramu **, K.V.Desikan ** and H.S.Vslliztuyco ***. *VH5 Leprosy Project, Zakthi Nagar 633 315, Tamil Nadu, India. ** Leprosy Histopathology Centre. Sevagram 442 102, *** CJIL Field Unit. Avadi. Chennai 600 054 India.

In this study. 89 patients clinically classified in the R-J scale showed an overall concordance of 89.9% in the histological Impression read blindly. The differences were between TT-BT and BL-LL and BB. The Mitsuda response mostly conformed to the clinical classification.

While the lymphostimulatory responses using BCG and its sonicate were high, responses to Dharmendra lepromin were poor despite good skin test responses in BT and TT patients. Leprosin. rML65 and delipidified components accounted for 46.9% in these patients. Humoral responses to 35Kda Protein. PGL-1 were within expected limits. IgG responses to rML65 denoted Mycobacterial presence.

CLINICAL. HISTOPATHOLOGICAL AND IMMUNOHISTOLOGICAL APPRAISAL OF REVERSAL REACTION.

V.D. Ramanathan** and *VHS leprosy Project. 638 315 Sakthi Nagar, TAMILNADU, INDIA. **Tuberculosis Research Centre,Chetpet, Chennai 600 031, India.

This study was undertaken to differentiate the vexing problem of reversal reaction from relapse.

Clinically the reversal reaction were characterised by increased erythema, swelling, tenderness of the skin lesion when pressed between the fingers and rubbery or Juicy consistency. Presence of oedema and Dil i reaction were observed in histological sections.

Monoclonal antibodies directed against T cell subsets in situ in paraffin section stained by immunoperoxidase has enabled differentiation of the reactional from the active stale. This is greatly aided by immunohistological staining for mycobacterial antigen.

The nature of early leprosy lesions, and the extent to which such lesions can self-heal, remain etusivo questions. The Lepra Evaluation Projoct (LEP) and Karonga Prevention Study provide a unique opportunity to study these issues. Two total population survoys were carried out during the 1980s, each covenng more than 110.000 persons, and thu population has been closely monitored since then, in conjunction with follow up for a vaccino trial. Dody charts have been completed for all individuals at every examination, including the drawing of all skjn blemishes, birthmarks, fungal lesions and scars, as well as lesions suggestive of leprosy. Lesions considered possibly attributable to leprosy are reviewed by a medical officer and biopsied rf he agrees that leprosy is a possible diagnosis. Whenever an individual is confirmed as a leprosy pationt. his/her earlier body charts are reviewed, for evidence of any signs which might have been present at earlier examinations. Approximately 15 % of apparently "new" cases are found, in retrospect, to have (had) evidence ol precursor lesions. This paper will desenbe these lesions, discuss the logic of infemng whether thoy do m fact represent early leprosy, and estimate (relative) risks that various lesions, in certain ago groups and sites, do in fact represent early manifestations ol clinical leprosy.

WHO has instituted fully supervised, intermittent regimen with rifampicin( R). ofloxacin (O) and minocycline (M) in certain countries (Pannikar.1997) and single dose of ROM (ROM-1) is already recommended for single lesion PB. Three groups of PB patients were treated as follows.(i) single lesion : ROM -1, (ii) 2 to 9 lesions : ROM - 3(monthly intermittent doses for 3 months) and (iii) 2 10 lesions : ROM-6 (monthly intermittent doses for 6 months). The patients under 5 years and over 65 years of age and those with pregnancy were excluded.

While our object is to make long term clinical and epidemiological observations, we report here preliminary observations on the occurrence of reactions during the first year of follow up after starting therapy.

There seems to be a gradation of the percentage of type 1 reactions in PB leprosy, as we progress from single lesion to more severe forms, the risk being determined by the extent of the disease before treatment with ROM.

A DOUBLE BLIND. CONTROLLED. DOSE COMPARISON STUDY OF THALIDOMIDE IN THE ACUTE TREATMENT OF ERYTHEMA NODOSUM LEPROSUM (ENL)

Karin Kook, Laarni Villahermosa. Matt Downs, Tranquilino Fajardo. Jr. Gerald Walsh, and Steve Thomas

Patients with acute, histologically continued ENL are randomized to thalidomide in a dose of either 100 or 300 mg day given once daily for 7 days; those who respond are tapered off over a period of 2 to 6 weeks. Patients are seen daily in the clinic for dosing and assessment of ENL and adverse events. Laboratory studies, and physical, ophthalmologic, and neurological examinations are performed at baseline and at the final study visit.

The study is presently ongoing. The blind will he broken in August when 25 to 30 patients will have participated. The efficacy and tolerability of the two treatment regimens will be compared. At the most recent interim review, IS patients had been entered. All were Filipino males with a mean age of 27 years. At entry, they had numerous inllamed lesions, ranging in number from 48 to > 500, and systemic signs and symptoms including fever, malaise, arthralgia, and anorexia. After 7 days of double blind treatment. 10 patients had no new cutaneous lesions; acutely inflamed lesions decreased by more than 80% in 6 patients, and 2 patients were treatment failures. Somnolence and rash were the most common adverse events, occurring in 50% and 28% of patients, respectively.

RESPONSE TO CORTICOSTEROIDS OK ACUTE NERVE FUNCTION IMPAIRMENT IN A PROSPECTIVE COHORT OF LEPROSY PATIENTS

Richard Croft¹, Peter Nicholls¹, Jan Hendrik Richardus², Alison Anderson³, Cairns Smith⁴

The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study aimed at investigating the epidemiology of acute nerve function impairment (NFI) in leprosy and its response to treatment 2.665 new leprosy patients have been recruited into the cohort and to date observed during 36 months.

Out of the 2,665 patients in the cohort, 409 (15.3%) presented with NFI at the time of registration, and 398 (14.9%) developed NFI during or after MDT Of these, 351 patients with acute NFI or other reactive events received a standardised course of prednisolone for 4 months. Nerve function was monitored by sensory and motor testing of the ulnar, median, radial, facial, lateral popliteal and postcnor tibial nerves. Nerve function scores taken at the start and completion of treatment with prednisolone and at I year's followup. are analysed.

The results of treatment are presented according to the nerves that were monitored in terms of full and partial recovery, no change, and deterioration. In approximately 60% of the cases there was partial or full recovery of nerve function In the remaining cases recurrent leprosy reactions and deterioration of nerve function necessitated further treatment of NFI, either by repeated treatment wtth steroids or by other interventions such as surgical nerve decompression.

THE EFFECTS OF PROPHYLACTIC CORTICOSTEROIDS ON THE INCIDENCE AND TIMING OF NERVE FUNCTION IMPAIRMENT IN NEWLY DIAGNOSED MULTIBACILLARY LEPROSY PATIENTS

Acute nerve function impairment (NFI) is known to occur frequently in multibacillaiy (MB) leprosy patients in the first few months after receiving multi-drug therapy (MDT) A pilot study was initiated to test the hvpothesis that corticosteroids given at the time of diagnosis can reduce the incidence and severity of NFI in newly diagnosed MB patients.

Newly diagnosed MB leprosy patients with no contraindications to MDT or corticosteroids were given prednisolone 20mg'day at time of diagnosis for 3 months tapering to zero in the fourth month, along with their MDT.

The incidence, timing and seventy of NFI events are compared with an untreated historical cohort taken from comparable leprosy patients included in the Bangladesh Acute Nerve Damage Study (BANDS) cohort Preliminary analysis of results after 12 weeks' followup indicates that the incidence of NFI/reactive events requiring higher doses of prednisolone for treatment are reduced by 50%.

PREVENTIONOF NEURlTlS AND DEFORMITIES IN TUBERCULOID LEPROSY PATIENTS BY PROPHY LACTIC THERAPY WITH CHOLORO QUINE AND LOW-DOSE PREDNISOLONE

CULES ALES - INDIA * 24-25 RAJALAXMI COLONY. TVS NAGAR. COIMBATORE - 641 025 INDIA

Tuberculoid Type leprosy patients during the MDT Therapy developing complications due to Neuritis irrespective of occurence of Type I Reaction was found in majority of PB TT patients

A study conducted on a population of 1.3 million of CULES Project. 351 TT Patients were selected. Out of them 72 patients were affected with Type 1 Reaction given Low Dose Prednisolone (10-mg OD) and chloroqume (150 mg BD) and observed for results during the followup period for six months. The other group of 279 patients were given only chloroqume in the same dose for six months period Among the reaction patients 65 cases were staved free from recurrencce of Type 1 Reaction Among the 279 patients 246 cases were reported. No Reactions or Neuritis during the sis months followup. Remaining 33 patients who presented with Tvpe 1 Reaction during the MDT Therapy early Neuritis with Dermal Nerve Thickening responded well after given tapering dose of Prednisolone for six weeks

We conclude that patients on risk of getting Neuritis and Type 1 Reaction if given Prophalactic Therapy with Chloroqume (150 mg -BD) for six months and Low-Dose Prednisolone (10 mg - OD) 3 days per week were greatly reduced the incidence of Neuntic complications in TT Patients and minimised the occurence ot deformity.

We conducted a comprehensive review of the published literature on the efficacy and safety of thalidomide therapy for ENL. Following the landmark observation of Sheskin. a computerised search utilizing MedLINE and seven other databases revealed relevant publications in six controlled clinical trials, twenty-six open label trials and fifteen cose reports involving a total of 1,848 patients. The six controlled tnals utilised 201 patients and 280 courses of thalidomide and were placebo (5) or aspirin (1) controlled. Each of these controlled clinical trials had clearly defined enrollment criteria, employed a scoring system for the seventy of the reactional state and the assessment of response, and found thalidomide superior to placebo or aspirin. In the total published literature thalidomide was found to be effective in over 90% of cases and in both sexes and a wide age range. Fever and skin lesions generally resolved in days, while other manifestations (neuritis, lymphadenitis, and orchitis) also responded, albeit more slowly (1-2 weeks) Also patients previously on corticosteroids responded, though again slowly In earlier studies daily doses of 300-400mgs were utilized, but lower doses of 100-200mgs are often effective. Maintenance thalidomide, often effective in even lower in dosage, prevented recurrent ENL.

Thalidomide treatment for ENL is generally extremely well tolerated. It's serious toxicities, birth defects and peripheral neuropathy, are almost never encountered in leprosy patients. Adverse events occurring in more that 1% of patients include: somnolence (6%), constipation (4%), and edema (2%). The only laboratory abnormality in treated leprosy patients which could be ascribed to thalidomide was mild Icucopenia/neutropenia (<1%). Because of thalidomide's reliable efficacy and safety it is the drug of choice in treating chronic recurrent ENL.

Leprosy patients are often treated with conicostenods as this is the drug of choice for severe Type-I and Type-ll Reaction. Neuritis, recent muscle weakness etc Traditionally all leprosy patients requiring steroids are being admitted m our hospital on the basis of the information that there is nsk of diabetes m such patients. This nsk has not been so far properly documented. The study was undertaken lo determine the risk of diabetes in these leprosy patients receiving steroidsand to know whether this risk was related to dose of steroid or number of courses of steroids or both. The study group consisted of 100 leprosy patients both male and female fulfilling the conclusion cntena. Their blood, unne and sugar was tested at the time of starting steroids, dunng the course of steroids and ideally within 3 months of stopping steroids. So far out of 87 patients, one patient developed diabetes towards the end of steroid Iherapy, 11 patients showed hyperglycaemia during the course of steroid but subsequently had normal blood sugar level. This shows that steroids can be used in leprosy patients whenever indicated and patients need not be hospitalised for steroid therapy.

Sample - The study was conducted on 160 adult women leprosy patients, attending leprosy clinics in Safdarjung Hospital, Dr Ram Manohar Lohia Hospital. Skin Institute and The Leprosy Mission Hospital of Delhi. Patients under treatment were interviewed using structured and pre-tested interview schedule.

Results - 121 (75.6%) of the women patients belong to low & lower-middle income group and live in either slums or single room accommodation. 111 (69.4%) are illiterate and 128 (80%) are economically dependent 128 (80%) are in their reproductive age group and are married. 121 of them co-operaied and expressed their experience. Of them, majority (101.83.47%) told that there has been no change in their sexual relationship. Only 9 (7.43%) reported infrequent sexual intercourse and 11 (9.09%) had no sex since their disease been diagnosed, of these 3 attributed this to the disease.

70 (54.68%) women became pregnant during their disease. Out of them 41 (58.57%) conceived before anti leprosy treatment was started 15 (21.42%) conceived during therapy and 14 (20%) both before and after the treatment was started. This shows that leprosy did not affect patient's option towards child bearing.

23 (79.3%) women continued their treatment during pregnancy while 6 (20.68%) stopped. Two of them stopped with the fear that medicines might be harmful for the baby, one did so under the family pressure.

Of the 70 women who conceived during the disease. 11 (15.7%) reported to have undergone abortion. Among them 7 (10%) had spontaneous abortion 4 (5.7%) did MTP. 61 women delivered during their disease of which 54 (88.52%) had normal babies. Out of the remaining 7(11.47%), there were two cases of still birth. 2 born normal but died within few days and 3 born with congenital anomalies and died subsequently. Whether it was due to the disease or its treatment, is not clear from the discharge slip. This coupled with 7 cases of spontaneous abortion is a considerable number and needs to be studied further.

Conclusion - Considering the higher percentage of fetal deaths and abortions in the women leprosy patiets during therapy despite its proven cause, it is advisable to postpone the pregnancy plans till the completion of anti-leprosy treatment.

Three pregnancies occurred within a cohort of 40 patients with leprosy over a six year period. There are few recent reports in the literature which deal with pregnancy in leprosy patients.

In Case 1, symptoms of the disease appeared during pregnancy. In Case 2, reactivation versus reaction occurred during pregnancy in a previously treated patient. In Case 3, the fetus was exposed to three antimicrobial drugs during the first trimester. These cases are placed within the context of the most recent published reports on the subject.

There are several conclusions to be drawn from the study of these cases and the literature review. The pregnant state causes a relative decrease in cellular immunity. This decrease allows M. leprae to proliferate which may precipitate or worsen disease leading to permanent nerve damage. Careful management of reactional states and maintenance of patients on monotherapy dapsone or a multidrug regimen may prevent this nerve damage. Infants are usually much less affeeted than the mothers; however, select ion of the mother's ant imicrobia1 reg imen must ensure adequate control of the bacteria while avoiding teratogenicity and in utero side effects.

J. Terencio de las Aquas and V. Gimero Ochoa. Sanatorio Fontiles. Alicante. España.

Charcot's Arthropathy is one of the most important complications of neurothrophic osteoarticular lesions in Leprosy with bone destruction. of the ankle and alterations of scaphoid, cuboid and calcaneum that originate important disabilitle of difficult treatment.

Eighteen cases of Charcot's Artropathy (frequency of 2,5%) 10 LL, 6 bordeline and 2 tuberculoides are presented.

The inicial and more advanced treatments in. which a Arthrodesis is necesary are reviewed.

In leprosy patients with neuropathic feet there is a high risk of new complications as ulcers or neuro-osteo-arthropathy (Charcot deformity) . Pain as an early sign for this is missing because of loss of sensory function. Local hyperaemia is also an early sign of ulceration and Charcot-deformity. This hyperaemia can be recognized as a local or diffuse warm foot. In investigations about this subject the temperatures were assessed using either Liquid-Crystal contact thermography or Infrared dermal thermography. In the normal clinical practice skin temperature is recorded by palpation. Therefore, we tested the interobserver reliability of measurement of skin temperature of neuropathic leprosy feet and normal feet by palpation, and the correlation between this and measurement by an infrared thermometer. There was a very high interobserver reliability between the two examinators in the leprosy group (kappa = 0.79) and a high correlation with infrared thermometry (Spearman's rank correlation coefficient 0.82 with p << 0.002). A field study will be undertaken in which the interobserver agreement and correlation with objective data will be determined between different field health workers, patient's family and the patient him/herself. The results of such an investigation can be a guideline for a therapeutic program for neuropathic feet in leprosy patients in order to prevent further complications.

DIAGNOSTIC PROCEDURES FOR SUSPECTED OSTEOMYELITIS IN NEUROPATHIC FEET OF LEPROSY PATIENTS

Increased temperature, swelling and erythema of neuropathic feel may indicate soft tissue infection, osteomyelitis, neuroosteoarthropathy (Charcot Foot) or autonomic disbalance. We investigated 21 neuropathic feet clinically suspected for osteomyelitis with a combination of imaging techniques ie: plain X ray.3 fase bone scintigraphy, leucocyte scintigraphy, magnetic resonance imaging (MRI ) with a recently developed fat suppression technique and i.v. Gadolineum. and more recently additionally bone biopsy under X ray guidance. Bone biopsies were processed tor bacterial culture and histopathological examination.

Gold standard for the diagnosis osteomyelitis were positive bone culture or clinical outcome, based on previously defined criteria, after a period of 6 months. Of the 10 bone cultures only one grew bacteria, whereas 5 of the 9 bone specimens showed signs of inflammation on histopathological examination. Only a few patients were diagnosed as having osteomyelitis based on the clinical outcome. In general the imaging techniques suggested the diagnosis osteomyelitis in higher numbers. MRI , executed with a fat supression technique and i.v. Gadolieum, seems to have high sensitiviry but low specificity.

The diagnosis osteomyelitis in neuropathic feet of leprosy patients is a problem for which no simple diagnostic tool is available. An important diferential diagnosis is the acute fase of neuroosteoarthropathy.

Detection of Peripheral Dysautonomia in Leprosy: Clinical versus Neurophysiological parameters

Histological and neurophysiological studies confirm that peripheral autonomic nerve fibres are the initial target of nerve damage in leprosy.

To determine frequency and type of peripheral dysautonomia in leprosy, we examined hands and feet for sudomotor and vasomotor functions of ibscnt sweating as determined clinically, subjective feeling of cold, skm temperature, skin vasomotor reflex (SVMR) and slun sympathetic reflex (SSR). Results were correlated to type of leprosy (pauobactllary, mulobaciilary), rime cbpsed since diagnosis and to indicators ot" sensory (touch sensitiviry testing (TST)) and motor nerve dp fun ebon (voluntary muscle testing (VMT)).

57% and 53% of leprosy cases had clinical and subjective loss of sweirmg respectively. 40% had subjective feeling of cold m hands/feet with median digit skm surface temperatures showing a trend to lower temperatures in those with subiecnve cold n a limb compared to controls. Objective temperature difference was only marginally statistic illy significant for the left hand (p=0.09). Overall comparison between leprosy and control group temperature showed no clear differences. Hut minimum temperature was always lowest for the leprosy group. 60.9% of measured extremities in leprosy sufferers had absent SSR compared to 6.3% in the control group, with all the latter neganve SSRoccuring in the feet. 61.2% of leprosy cases had abnormal SVMR and mean SVMR was statistically signiticandy reduced compared to controls. Absent SSR in an extremity was accompanied by significantly reduced SVMR in the same.

There was good coirelauon between present SSR and present subjective feeling of sweating and clinical detection rate of sweat (70-83.3% and 68.8-88.9% respectively). Sub|ectjve feeling of sweating correlates well with die clinical detection rate of sweating (64.9-72.3%). In contrast absent SSR correlates poorly with sub|ectivc feeling of absent sweating in the corresponding limb (5.3-28.7%) and sub|ectivc feeling of absent sweating correlates poorly with clinical dctecnon rate (11.3-15.6%).

MB type of leprosy lias more absent SSR than I'll, wnh no such correlation to SVMR. With increased time since diagnosis of" leprosy, prevalence ol" absent SSR (significant for hands) and SVMR (significant for feet) increases. In parallel to increasing seventy of sensory (TST)and motor (VMT) nerve dysfunction the rate of absent SSR and pathological SVMR significantly rises. Abnormal SSR and SVMR frequently occur in parallel but not seldom show separate dysfunction. The anatomical distribution of dysautonomy docs not run parallel to that of regional motor and sensory nerve dysfunction.

We conclude that vasomotor and sudomotor peripheral dysautonomy is common and patchy tn leprosy and best detected using SSR and SVMR which are better suited for picking up subtle focal dysfunction than clinical parameters.

Background: Several methods exist for sensory testing of hands and feet of leprosy patients. There may be various ways to test facial sensation, but these have neither been formalized in publication nor systematically applied to sensory testing of the face despite the fact that the tngeminal nerve and the great auricular nerve which supply sensation to the face are affected in leprosy.

Methods: In a sample of leprosy patients, face sensation threshold measurements were done using a set of three semmes Weinstein (S-W) monofilaments that gave a force of 0.05-0 07, 0.2 and 2 g. Sensation was tested by 3 examiners and intra and interobserver testing was used as a means of validation of the findings.

Conclusions: Within the limitations of this study, the results indicate that use of S-W monofilaments is a fairly reliable and repeatable method for sensory testing in the face, Dunng followup. a single filament with a force of 0.05-0.07g (2.83 marking number in S-W filament or any other filament with a corresponding gram force) could be used to assess sensation. A simple procedure of quantifying sensation in these nerves is suggested A method to incorporate trigeminal or great auricular nerves sensory testing into the existing sensory assessment charts is also discussed.

Selvasekar Abraham, Gigi Ebenezer and Vijayakumaran P SchiefTelin Leprosy Research & Training Centre, Karigiri, India. PIN 632 106.

Multi Drug Therapy (MDT) is believed to render leprosy cases non infectious. Pauci Bacillary (PB ) leprosy cases are usually skin smear negative. This group of patients are expected to possess varying degree of Cell Mediated Immunity (CM! ) against M.leprae when compared to MB leprosy patients. MD T is expected to kill all the bacilli and the CMI will clear these bacilli. We report on a PB leprosy patient who have received MDT-P B regimen (WHO) . Four years after completion of MDT , he developed fusiform swelling in peripheral nerves. Histo Pathological Examination (HPE) of this lesion revealed presence of M.leprae. Is this an event of relapse⁷He was treated with oral steroid therapy and the bacilli could not be demonstrated in subsequent HPE from the same site. The course of disease, details of investigations and management are discussed.

"Flu" syndrome is rarely reported on monthly rifampicin doses given to leprosy patients Although it is not uncommon with intermittent administration for tuberculosis it is resulted mainly due to the effect of the drug on the liver which is unlikely to occur when the drug is given only once monthly.

THE DIAGNOSIS OF PURE NEURAL LEPROSY AMONG PATIENTS WITH SYMPTOMS OF PERIPHERAL NEUROPATHY: A FOLLOWUP STUDY. Sckacel M.,^• Antunes SLG.,^•^•Jardim M., ^•Nery JAC., ** Sarno EN^•^•

This investigation was carried out on a group of 43 patients clinically followed in the Souza Araujo Outpatient Service. Institute Oswaldo Cruz, in the period from May. 1992 to August. 1996. fhe) presented exclusively neural symptoms at first reference, which raised the diagnostic suspeclion of pure neural leprosy. flic symptoms were distributed on the patients according to the following pattern: sensorial loss: 29; paresthesia: 20; nerve enlargement: 11; nerve pain: 11; Motor involvement: 12. Nine patients had the diagnosis of leprosy confirmed during the follow-up period by either the appearance of specific cutaneous lesions (2 borderline tuberculoid. 2 leproniaious leprosy. 3 reversal reactions), or by the turning up of neuritis (2). The average time elapsed between the beginning of follow-up and the diagnosis was 4.8 months, ranging from no time (diagnostic at first reference) to 12 months. These patients were submitted to MDT- WHO for paucibacillary or multibacillary patients. Among the leprosy-confirmed patients, seven had sensorial loss, six had paresthesia, four had nerve enlargement, two had nerve pain, and live showed motor involvement. These symptoms were never found isolated in these patients. One patient presented decrease of eletroneurographie sensitive response of the sural nerve. .Three patients went through nerve biopsies (previously to diagnosis) but no signs of leprosy neuropathy were detected. Clinical evaluation of neuropathic patients with close neurological and eletroneurographie followup was found to be the most effective method for detecting pure neural leprosy. The nerve biopsy did not contribute to the diagnosis of leprosy neuropathy in this investigation.

Se describen las características clínicas, parasitológicas, inmunologías, epidemiológicas y terapéuticas de una forma de leishmaniasis cutanea propia de la Republica Dominicana Todos los casos. 41 en total, presentaron prueba de leishmanina negativa, fueron descubiertos en el periodo 1974-1997 por el personal medico y paramédico del programa para el control de la lepra, especialmente en la region. Este del pais No se encontro otra forma clínica de leishmaniasis Una investigación en población sana de areas endémicas mostro 156 pruebas de leishmanma positivas entre 893 personas a tas cuales se les practico la prueba.

Pruebas de inmunolluorescencia indirecta practicadas en 510 personas de areas endémicas mostraron títulos positivos en 183. En muchos de estos casos se planteo el diagnostico diferencial con LT y LL.

Programa de Control de la Lepra. Instituto Dermatológico y Cirugía de Piel Rep Dominicana

Se estudian las características que le son particulares en termino de morfología de las lesiones, localizaciones anatómicas, evolución, formas clínicas y posibles fuentes de contagio. La cifra promedio en menores de 15 anos, en el periodo 1966-1997 es de un 22.3% sobre un total de 10.232 enfermos diagnosticados La forma LL presenta un porcentaje de 9.9, el grupo dimorfo representa un 20%, la indeterminada un 18.3% Lepra tuberculoide un 51.8% Lepra indeterminada al inicio del programa presento valores altos, para luego acusar un descenso importante y presentar cifras mínimas a partir del 1988

FIVE KINDS OF DISEASES WITH ENLARGED PERIPHERAL NERVES MISDIAGNOSED OR SUSPECTED AS PURE NEURITIC LEPROSY

M. lebrae prefers to invade peripheral nerves and skin. The enlarged nerve accompanying with loss of associated functions was the most important and common symptom and sign of leprosy, and even was considered as the feature only belonging to leprosy. Only nerve damage but skin lesions was diagnosed as pure neuritic leprosy. Making its diagnosis wis very difficult on a clinical basis. This paper reported patients with family hypertrophic neuritis, acute injure peroneal neuritis, intraneural ganglion of the lateral popliteal nerve, progressive spinal muscular atrophy and neurofibromatosis. All peripheral nerves of these patients were enlarged accompanying with loss of associated function and had been misdiagnosed as or suspected as pure neunlic leprosy clinically. We suggested that u was very important lor dilferential diagnosis to go into more detail about history and examination It' indeed, some features ol above mentioned diseases still could be found as indications to dillercntiate ihcm from pure neunlic leprosy, such as obvious family history and extensive, even enlarged nerves with abnormal root-type neural funcuon in family hypertrophic neuntis, acute and injury history in acuie injure peroneal neuntis, etc.. but predilection of given nerves and their sites, shuttle-like enlarged nerve with trunk-type or branch-type neural dysfunction are very charatenstic for pure neunlic leprosy As above whai to say, the enlarged nerve with neural dysfunction was nol features peculiar to leprosy, but diagnosis of leprosy should be considered first and further detailed examination should be made fur final diagnosis. Neural hist op alho logical examination could be helpful for diagnosis and differential diagnosis if necessary and possible.

DIFFERENTIAL DIAGNOSIS OF LEISHMANIASIS CUTIS AND LEPROMATOUS LEPROSY - ONE CASE REPORT

Yun-shan Deng, Han-qing Xu, You-fen Li, Jia-ju Zhang and Ji-de Xue Xi'an Medical University, Xi'an City, Shanxi Province, China

Mr. Xiong, male, 29 years of age, farmer, born in Huaying county, Shanxi province, China. Eight years ago, redness of skin appeared on foreneck and face, yellow and red small nodules developed gradnaJly on red patches, no abnormal sensation, nodules enlarged in size and increased in number in recent 2 tears Skin condiuon: red, infiltrated and thickened skin on face with nodules, (liontiasis) (Fig 1). Nodules of various size distributed on upper extremities, armpits, thorax, abdomen, buttocks, thigh, scrotum and penis; many smaller ones on tongue, upper palate and vesubulum nasi (Fig 2). Cubital, axillary and inguinal lymph nodes were sligluy enlarged. No enlargement of the trunk of peripheral nerves was observed. Normal skin sensation. Skin smear AFB negative but positive for L-D bodies (Fig.3). No API but a large number of L-D bodies were identified in biopsy sections, matched the appearance of leishmaniasis cutis (Fig.4), Typical L-D bodies could be found in macrophages in nodules electron-microscopic all y (Fig.5) and its line constructions were quite clear. The patient was cured by subiation. No relapse occurs alter 2 year follow up Key points in differentiating lepromatous leprosy from leishmaniasis cutis were discussed.

THERMAL THRESHOLD TESTER FOR DETECTION OF SMALL FIBRE NERVE DAMAGE BEFORE ONSET OF CLINICAL NEURITIS

S. Hansen (1), M.E. Duncan (2.3), G.A. Jamal (1), P.O.O. Julu (1), R. Kazen (4).

(1) Peripheral Nerve and Autonomic Unit. Institute of Neurological Sciences, Southern General Hospital NHS Trust, Glasgow; (2) Dcpt Medical Microbiology, University of Edinburgh; (3) Armauer Hansen Research Insiirute. Addis Ababa. Ethiopia; (4) All Africa Leprosy & Rehabilitation Training Centre, Addis Ababa.

First nerve damage in leprosy occurs in small unmyelinated nerve fibres, followed by small myelinated and lastly in large myelinated fibres only at a late stage of the disease.

Conventional electro-physiological examinations of motor, sensory and mixed nerve conduction velocity reflect activity in die fastest conducting, heavily myelinated nerve fibres, a small proportion of the total. A and C fibres, numerically the largest group of fibres in human cutaneous nerves, are not tested by these techniques.

The Thermal Threshold Tester (TRIPLE-T) measures thermal sensation thresholds to both cooling and warming of the skin by means of a computer controlled thermode applied to the volar surface of the wrist or dorsum of the foot. It thus provides an index of function in the small diameter thinly myelinated A (cold) fibres and unmyelinated C (heat) fibres. TRIPLE-T has been validated in diabetic and small fibre neuropathy. It has a particularly important role in the sequential and quantitative monitoring of small nerve fibre function.

TRIPLE-T detected small fibre damage in 70% children from families affected by leprosy compared with 18% children from non-leprous families living nearby. Its method of detecting nerve damage before clinical neuritis has occurred will be demonstrated

USE OF LASER DOPPLER FLOWMETRY IN THE DETECTION OF AUTONOMIC NERVE DEFICIT IN LEPROSY.

(1) Oxford Optronix. Oxford; (2) Dept Medical Microbiology. University of Edinburgh; (3) Armauer Hansen Research Institute. Addis Ababa. Ethiopia; (4) Loch Fyne Services, Slrachur. Argyll; (5) All Africa Leprosy & Rehabilitation Training Centre, Addis Ababa, Ethiopia.

Autonomic small diameter unmyelinated C nerves are destroyed early in leprosy. 56% of patients in Ethiopia present with established (autonomic and/or somatic] nerve damage. Present tests of sensory nerve function do not show abnormality until 30% of nerve axons are destroyed, nor can they predict which new patients will develop neuropathy leading to disability.

Skin Blood Row (S8F) is regulated by autonomic (vasomotor) nerves. Under controlled conditions, specific autonomic provocations are used to stimulate SBF changes. Alteration in SBF is thereby used as a measure of autonomic nerve function.

Laser Doppler Flowmciry (LDF), a non-invasive technique for measuring changes in SBF. samples a nominal hemisphere 1 mm in radius. The system is small, lightweight and adaptable to field conditions. Multiple channel systems allow simultaneous assessments of multiple sites, thus reducing assessment time.

LDF has shown in leprosy patients and contacts significantly impaired vasomotor reflexes of fingers, compared to non-exposed persons (1,2); and abnormal responses following inspiratory gasp where nerve damage is present (3).

1) Can impairment of small nerve function be graded and docs this recover with treatment?

2) How does small nerve function loss relate to development of neuritis and disabilities?

3) How does LDF compare with traditional tests in diagnosing and monitoring leprosy neuropathy?

VALORACIÓN DE LESIONES TRÓFICAS EN ENFERMOS DE LEPRA INACTIVOS CLINICA Y BACTERIOLÓGICAMENTE HACE MAS DE 10 ANOS.

¹José Ramon Gómez Ecnevarria, Vicente Gimeno, Ochoa, José Terercio de las Aguas, ²María Olarizu Diaz de Otazu.

¹Sanatorio San Francisco da Borja, Fontilles, Alicante, Espana. ²Hospital Santiago Apóstol (Servicio Radiología), Vitoria, Alava, Espana.

Se realiza una valoración de las lesiones tróficas residuales (especial atención a las lesiones óseas) en 60 enfermos de lepra controlados en el Sanatorio de Fontilles (Espana), inactivos clínica y bacteriológicamente hace más de 10 anos.

Se valora la evolución de dichas lesiones tróticas desde el momento de la inactividad hasta nuestros días.

AF Hoeksma, AJ v.d.Kleij, WR Faber, R Dahmen, HW de Valk. Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Neuropathy of a foot can cause changes in the form and function of the fooc. This may lead to ulceration and/or neuro-osteo-arthropathy (Charcot foot) . A neuropathic foot commonly occurs in Diabetes Mellitus - often associated with angiopathy - and in leprosy patients.

We designed a diagram in which the neuropathic foot and its complications can be described in a simple and unequivocal way: foot: form (F), ischemic factors (I) , neuropathic factors (N) and ulceration (U): the so-called FINU-diagram. Regarding foot form, a differentiation ir made into no deformities, reversible deformities, irreversible deformities, skeletal deformities and various amputación levels in the foot. Ischemia is evaluated by assessment of the pulsations of the arteries at different levels. Neuropathy is an obligatory condition in order to speak of a neuropathic foot. In the FINU-diagram, there is a differentiation according to the cause of the neuropathic foot between diabetes mellitus and leprosy. The ulcers were at first classified according to Wagner's classification. Since we do not find this classification to be sufficient practical, this part of the diagram was adapted, using the latest version of the "Dutch consensus statement on the diabetic foot" (1997) . This classification contains assessment of the depth of the ulcer, microbiological components and the cause of the ulcer.

On the reverse side of the chart, the site and magnitude of an ulcer can be depicted in a standard drawing of a foot.

LOW FREQUENCY OF TESTICULAR DYSFUNCTION IN 125 PATIENTS WITH LEPROMATOUS LEPROSY - A RETROSPECTIVE STUDY.

Divisions of Endocrinology and Dermatology. Faculty of Medicine of Ribeirão Preto. São Paulo. Brazil.

The association of lepromatous leprosy (LL) with abnormalities of testicular function has been well recognized. In order to assess the occunency of involvement of the testis in male patients with LL in lhe last 15 years in the University Hospital of the Faculty of Medicine of Ribeirão Preto, São Paulo, we reviewed the data of 125 male patients with LL. The diagnosis of LL was made on clinical, bacteriological and histopatological grounds. Complaints related to testicular dysfunction were found in only 7 cases (5,6 ") . The age of these patients ranged from 20 to 50 years. Impotence was the most frequent symptom (5 cases). Two patients had a history of orchitis. Leprosy was of more than 4 years in duration in 5 cases. Hypergonadoihrofic hypogonadism was confirmed by laboratory tests in 6 patients. The frequency of complaints related to testicular dysfunction in our patients is well below of that described in literature (up to 50 %) . This finding might be explained by a lack of a systematic search. Thus, we conclude that this frequency is underestimated, considering the high prevalence of leprosy in our population and the importance of gonadal impairment associated to LL.

Gomes, MK, Igreja, R.P; Pinto. GA. Castro. MGC. Trope. BM; Femandes. NC. Maya. TC

Dermatology Unit and Infectious Diseases Unit/HUCFF/UFRJ. Rio de Janeiro. Brazil

Paterson (1964) describes three kinds of bone lesions which may occur in leprosy: I- specific ones, directly caused by Mycobacterium leprae; 2- inllammatory or degenerative ones, as a final result of sensibility loss; 3- osteoporotic ones, mainly due to disuse. The specific ones are seldom observed, and represent 3 to 5 percent of all bone lesions in leprosy. According to Opromolla (Hansen. Int. 21(1 ):fi7-74, 1996), they may be related to immune changes, which are characteristic of reaction episodes.

The authors present the case of a Lepromalous leprosy / Multi-drug therapy / WHO patient. In the eighth month of treatment, this patient developed a clinical picture of high fever, malaise, big joints edema with (logo sis, painful eritematous nodules disseminated with severe ostealgia. A clinical diagnosis of eritemta nodosum leprosum was made and anti-reaction treatment was started beside the specific therapy. General examinations were done, as well as X-ray studies which showed extensive bone lesion. Bone biopsy and bacteriological study of surgical piece proved the presence of acid-fast bacilli.

Reason for presentation: discussion of immunopathology of type II reaction (ENL) and its relationship to specific bone lesions.

The poster presentation depicts photos of this disease (which can easily be mistaken for Leprosy): it can co-exist with Leprosy: is of unknown origin, and for which there is no known treatment. Where the lesions co-exist with Leprosy lesions, they cause the patient little inconvenience; after the initial irritation period is over, which may be only a few months,but in some patients longer. On presentation, lesions tend to resemble the Tuberculoid type, wich raised edges; but plaque like lesions of the Major Tuberculoid,and Borderline types of Leprosy may be seen. Lesions come and go at will:with or without Leprosy chemotherapy. An interesting feature of G.M., is that new lesions can appear on the identical sites of resolved G.M., lesions. There is no loss of sensation in lesions, and no nerve involvement. No M. leprae found in smears. Diagnosis confirmed only by biopsy. It is important that Field Workers and others, ace aware of G.M., to avoid a Leprosy patient's treatment being unnecessarily continued after their Leprosy lesions are resolved: also to avoid G.M., being treated, erroneously, as Leprosy. In both instances thereby questioning the credibility of the Field Worker of examiner. G.M., appears to be Worldwide, but regionalised in a Country, where observed.

Pathological mechanisms ol nerve damage in leprosy are still not enough studied, in particular, a role of antibodies towards peripheral nerve antigens is not clear. In this connection we developed EL1SAbascd test-system for detection of anti-peripheral nerve antibodies (AbPN) in blooJ serum and assessed i:s prognostic value in leprosy. As antigen for sensibilization of microtias plates a sonicate of ischiatic nerves ol" normal rabbits at concentration ol" 6 mkg ml was used. Screening tine of the sera tested was 1:100, antibodies against human total immunoglobulins labelled with peroxidase was used as ontispecies conjugate. Blood sera from 40 leprosy patients (LL-33, BL-4, BT-3) and 14 patients with non-leprosy neuropaties were investigated. Preliminary results demonstrated high levels of AbPN in multibacillary patients (LL, BL). mainly in those having high levels of anti-M.leprae antibodies. There was no correlation between clinically proved neuntis and AbPN levels. In case of nou- leprosy neuropaties increased levels of AbPN were observed only in patients with proved autoimmune nature of their disease, Our data agreed with the opinion of existence of anttgetiS in M. leprae and peripheral nerves, but pathological mechanisms of neuritis in paucibacillary leprosy forms still remain to be solved.

A METHOD OF ASSESSMENf OF FUNCTIONAL STAIE OF PERIPHERAL NERVE SYSTEM IN LEPROSY PATIENTS WITH USING ELECTROACLTUNCTURE DIAGNOSIS

Peripheral nci-e damages in leprosy patients remain a pressing problem of leprology. Monitoring of functional state of peripheral nerves is of peculiar significance. A method of assessment of functional state of peripheral nerves by means of eleetroptincture diagnosis is presented. This method is based on diagnostic system ryodoraku (Nacaiani, T, Yamashita, K. Ryodoraku acupuncture. Tokyo, 1957). Conduction velocity of 24 bioactive points in upper and lower extremities located on 12 main paired acupuncture meridians is estimated. Testing direct current is 200 mcA, voltage - 12 V. Functional state of ulnar nerve is judged by conduction velocity in points IG 4, C 7, TR 4; of radial nerve - Gl 5, P 9; of median nerve - MC 7; of fibular nerve - E 42, VB 40; of tibial nerve - R 3, RP 3 After the conduction velocities have been measured the data are statistically processed. With normal values of velocity in bioactive point the results fit in the "physiological corridor". When values of registered cnnent go significantly beyond the physiological limits, disturbances in velocity conduction in a given zone of skin innerxation might be suggested. In acute neuritis conduction m corresponding representative points is increased, while in the development of degenerative changes it is decreased. Analysis of the results of eleciropuncture testing against the data of clinical observations in 4S leprosy patients suffering with specific neuritis showed 92,7% coincidence of diagnosis, suggesting a high significance of the method proposed.

AN EXPERIENCE OF USING PHARMACOPUNCTURE IN TREATMENT OF CHRONIC NEURITIS IN LEPROSY PATIENTS

Treatment of peripheral nerve damages in patients with leprosy, especially of long-standing duration, remains to be an important problem of leprology. Therapeutic methods available are not enough effective. Results of plunnacopuncture (acquapuncture) treatment of 46 leprosy patients aged 2S-62 years suffering from chronic peripheral neuritis ore presented. The method involved introduction into certain bioactive points of upper and lower extremities of commercial aloe extract for injections. A dose of injectionable aloe extract per one point was 0,1 - 0,5 ml, maximally dose of 2,0 ml for all points. For ulnar neuritis phormacopuncturc was done into points IG 8, C 7; for fibular neuritis - into VB 34, VB 40; for median - MC 7; radial - GI 5, tibial - R 3, RP 3. In case of polyneuritis of upper extremities pharmacopuncture was prescribed as follows: points TR S, MC 5 and in polyneuritis of lower extremities - points VB 39, RP 6. Usual course of treatment included 10-15 procedures each other day. Courses of treatment were repeated, if necessary, in 3 - 4 weeks. Clinical observations showed subsidence of painful sv ndromc. increase in muscle strength and mobility of damaged joints against the background of pharmacopuncturc given. The patients observed general improvement and amelioration of sleep and appetite. Eleciropuncture testing of bioactive points before and during treatment according to the principles proposed showed increase in their nerve conduction suggesting functional improvement of peripheral nerves.

AVERAGE AGE OF DEATH AND FREQUENCY OF CANCERS
- COMPARISON BETWEEN LEPROMATOUS AND TUBERCUOL1D PATIENTS

Shin-ichi Kitajima. Masamichi Goto, Masaomi Imaizumi National Hansen's Disease Sanatorium Hoshizuka-Keiaicn. Kanoya. Kagoshima 893-8502. JAPAN

In 1983 ihe re were 773 patients in our leprosy sanatorium. According to the Japanese criteria for activity of leprosy, more than 80% patients were clinically cured, hut many of leprotnaious patients still take dapsonc due to prevention or fear about relapse for a long time. Average age of death and frequency of cancers were investigated to clarify the elfect of long duration dapsonc intake. The patients were classified as lepromatous type (L. including LL and UL), tuberculoid type (T, including TT and BT), and others (BB and unknwon) based on die medical records.

In the beginning of "83, there were 531 (Male 347. Female 184) L type patients and 232 (M 97, F 135) T type paiients. From 1983 to 1997. 157 L type patients and 95 T type patients were died. The average ages of death were L type Male 74.1 ±10.0. T type male 77.0±10.0, L type female 77.1 ±9.8. T type female S3.0±ILL But the average age of death were not significanUy different in the age-matched groups. Relative risk of cancer in L type patient was 1.40 (95% C.I. 0.75-2.53. Con hazard model), but it is not statically significant. Numbers of female liver cancers and male gallbladder/bile duct cancers were higher than expected number of the whole Japanese cancer frequency. Average age of death of L type patients with cancer was 10.1 years lower than that of T type patients. Further investigation is needed to clarify the relation between the dapsone metabolism and liver, gallbladder cancers.

This study analyzed 25 leprosy patients with histoid leproma (HL) in Shanghai from 1970 to 1997, and related relerences were reviewed IE. were more found in men and were seen m all age. One of 4 pnmajs HI. was proved to be resistant to DOS. and 7 HB in secondary were resistant to DDS and TBI both. showing that incurrence of HL. was related with resistant-bacilli.

Skin lesions HL were polymorphous, nodules and plagues were commonly seen, and always occurred after diffuse infiltration lesions. The most common sites involved were face, neck, estremities or buttocks, but hand, foot, genitalia and mucus mem brace were locations seldom invaded. HL in nerve was rarely seen.

BI and Ml values of HL, patients were more higher than those of non-HL patients. Ratio of solid bacilli between HL. and non-HL patients was 49.14 to 1, and their difference was significant statisically.

HL was not easy to be differentiated from other dermatoses and related disorders due to not specific clinically and histopathologically. Final diagnosis could be made by routine skin smear examination with acid-fast staining.

Maria de Fatima Maroja. Maria Sigride T. de Souza. Alessandra B. Ferreira and Julia I. Salem.

Leprosy in the State of Amazonas, Brazil, still represents an important health problem. In 1995, 1.464 new cases were registered, 36.5% were female of which 60.9% were of child-bearing age.

The objective was to study the clinical comportment of leprosy during pregnancy, taking into consideration Out during this penod hormonal and metabolic alterations occur and a reduction in resistance could lead to the appearance of reactional states. The study included 38 pregnant patients with leprosy and a control of group oh 50 patients with leprosy who were not pregnant or had no recent history of pregnancy.

In the group of pregnant patients. 50% had multibacillary forms and in the control group 44% had multibacillary forms.

In relation to the presence of reactional outbreaks in the group of pregnant patients there was a frequency of 53.3% cases and in the control group 54%. As to the type of reaction, in the study group isolated neuntis affected 28.7% of the cases and neuntis associated with type 1 lepra reaction in 23.8% with isolated neuntis.

Of the pregnant patients in reaction, 34.2% had reaction during their pregnancy and were already developing reaction in the period before their pregnancy and in 1 patient duruig puerperium.

In our study did not lead to an increase in outbreaks of reaction, but. reactions in this period are difficult to control and can cause an "at risk" pregnancy.

NASAL LESIONS ON HANSEN'S DISEASE: THERAPEUTIC AND PROFILATIC PROCEDURES. Moreira JS. Nery JAC. Aprigliano Filho F. Fabri L. Pantoja A. Diniz F and Ribeiro FC. Evandro Chagas Hospital. Leprosy Laboratory. Oswaldo Cruz Foundation. Av. Brasil. 4365 - Manguinhos, RJ - Brazil.

This study reports the follow up of 181 Hansen's patients from eprosy unit who were examined at Otorrinolaringology clinic FIOCRUZ. The most frequent manifestations where nasal obstruction (40%). epistaxis (37%). sinusitis (26,5%) infiltration (100%) and ulceration (23%) of the mucous membrane. Due one of the main manifestations of Hansen's Disease be vasculitis on the mucous membrane, the treatment should he topic anti-inflammatory drugs as corticosteroids or similar. In order to clarify which drug: would be more indicated for treatment and protllaxis we have used Diproprionate of the BecIometasona (spray).

The results showed dial deproprionato de beclometasona aquoso solution was the only drug that induces total regression of the lesions. Therefore this is a drug of choice for treatment of nasal pathologies associated to Hansen's Disease, but meticulous evaluation of the all nasal pathologies is hand, and the use of vasoconstrictor drugs must be avoided due their side effects.

(1)Rio de Janeiro State Health Secretary, (2)Ministry of Health -Secretary of Health Care/SAS/MoH

A retrospective study has been carried out in order to determine if the number of lesion could be used as a criteria for classifying leprosy patients before starting MDT treatment. 769 patient forms have been analyzed. (389 MB and 380 PB). 19 38% showing no lesion and 28 61% a single lesion. Validity was assessed by compu ting the relationship (A%) between the num ber of lesions (less or mo re than 5) and the skin smear examination (Bl positive MB, Bl negative PB), sensitivity (SE) an d specificity (SP) of the num ber of lesions as comp ared to the patient classification. Agreement percentages was 75% Sensitivities ranged from 6273%. and specificities ranged from 75-84%. Patients with positive sk:n smear had a great number of skin lesion (more than 5 'esions) as compared to those being smear negative These results sug gest that, the num ber of lesion could be an useful tool in simp lifying classification for prescribing leprosy treatment.

DESCRIPITIVE ANALYSIS OF A SERIES OF CASES WITH HIV M LEPRAE CO-INFECTION TREATED IN THE LEPROSY OUT-PATIENT CLINIC. LABORATORY OF LEPROSY. Nery JAC Galhardo MCG. Périsse ARS. Valentim A. Vieina LMM. Sampaio EP. Leprosy Laboratory and Evandro Chagas Hospital, Oswaldo Cruz Foundation. Av Brasil, 4365 - Manguinhos. Rio de Janeiro - RJ. Brazil

As the disease evolves in HIV-positive individuals, a variety of opportunistic infections may develop, some of which are directly related to deficiencies in the cellular immune response. The potential effects of HIV infection on leprosy has been discussed by many authors, although the association between the two diseases remains uncertain.

In this study 19 co-infected leprosy x HIV positive patients are reported. 84.6% of whom showed AIDS. Some of these patients had first been diagnosed with leprosy and others became HIV-positive after contracting leprosy. Thirteen patients [9(69.2%) PB and 4 (30.8%) MB] were treated and followed up after discharge the analysis of the immunospecific response to M. leprae (lymphoproliferation test and interferon-gamma production) as well as analysis of mononuclear cells in peripheral blood were evaluated in this study. All patients received the WHO-recommended multidrug therapy regimen. Of the 13 cases under treatment. 7 (53.8%) were men and 6 (46.2%) were women avenaging 41.4 and 36.8 years of age, respectively. Nine (69.2%) patients were classified as paucibacillary (7BT. 2 pure neural leprosy) and 4 (30.8%) as multibacillary (3 BL: I LL). Five (38.5%) of the patients presented a lepromin-positive test (> 5 mm). Eight (61.5%) presented reactional episodes (6 reversal reaction, I erythema nodosum leprosum and 1 neuritis). These patiets were treated with thalidomide for ENL and corticosteroid for RR and neuntis). The multidrug therapy was equally effective in all 13 patients with clinical and bacteriological regression in all cases including the reactional episodes. Only one patient did not make use of the antiretroviral drugs. Ten patients were discharged from MDT. Twenty-three percent of the patients eventually died due to HIV-related complications, and 3 remain in treatment.

The analyses of the in vitro response of PBMC (lymphoproliferation and gamma-interferon production) at diagnosis for both PB and MB patients was negative for M. leprae. Even so, among the five patients with reversal reaction, four presented a positive lymphoproliferalion response (S>2.0: Δcpm > 2000) during their reactional episodes. The analysis (by cell sorting) of the frequency of mononuclear cells in peripheral blood showed an inversion of the CD4/CD8 relationship in all cases.

MULTIBACILLARY LEPROSY AMONG THE 0 TO 14 YEARS OF AGE GROUP DATA GATHERED AT THE LEPROSY OUTPATIENT CLINIC OF THE OSWALDO CRUZ FOUNDATION (FIOCRUZ) RIO DE JANEIRO, RJ - BRAZIL Nery JAC. Garcia CC. Sales AM. Gallo MEN. Vieira LMM.

Leprosy Laboratory, Oswaldo Cruz Foundation, As Brasil, 4365 - Manguinhos Rio de Janeiro - RJ. Brazil.

Pathology Departiment - UERJ. Rua São Francisco Xavier. 524. Maracanã, RJ - Brazil.

Clinical and epidemiological studies carried out in patients dignosed with MB leprosy up to the age of 14 could be used as indicators of trends in the evolution of the disease in endemic countries like Brazil.

According to official data, 10% of the total number of cases detected in 1996 were in this same age group. In the hopes of contributing to a belter understanding of the clinical and epidemiological characteristics of the disease in this particular age group, the results of 19 patients classified as BB, BL and LL (Ridley- Jopling are presented. The patients were treated in the Leprosy Outipatient Clinic with the MDT WHO regimen. At diagnosis, the forms, Bl and grade of disability.

The frequency of occurrence and type of reactional manifestation were evaluated during the 24 doses of MDT.

The results of the sample studied suggested that no differences existed in the parameters evaluated among the patients of this age group when compared to the adult MB patients.

Departament de Sanitad i Seguretat Social. Generalitad d Catalunya.Hospital de Sant Pau.Barcelona.

A 44 year old male with L.L.diagnoses in 1994 was admited to hospital beacause of lepra reactivation. He had been previously treated with MB for 2 years. FoIlowing reinitiation of triple therapy, he developed severe necrotic erythema nodosum leprosum, polyarthritis, renal in volvement and a leukewoidrreacction, which eventually resolved following treatment with thalidomide and prednisone. Leukemoid reacction is an extremely intrecuent complication of type II lepra reacctions. The transiet nature of reaction, absence of hepatoesplenomegaly and high leucocyte alkaline phosphatase score allow differentiation of leukemoid reaction from leukemia. Increased serum levels of tumor necrosis factor alpha and other myeloid-stimulating cytokines might be involved in the pathophysiology of this reaction.

Leprosy Is a chronic disease where systemic Involvement la reported during the course of disease. Throughout the spectrum some studies reported rare occurrence of cardiac problems In leprosy patients owing to the lowering of lipid profile. These people reported lowering cholesterol, lnsmunoglobullns and total-lipid level and attributed this to the host dependence of the M.leprae. On the other hand reporti were available showing Increased levels of various enzymes like CPK, LDH and others.

In order to understand the actual conditions of heart of leprosy patients we Initiated a project for studying lipid profile, llpoprotelni various enzymes like CPK,CK-MB and LDH iaecitrate dehydrogenase. These enzymes and their isoenzymes were analysed using various standard methods and elactrophoretlc techniques through the spectrum In comparison with the healthy controls. Interesting results were obtained indicating involvement of bone,apart from organs like liver, kidney and heart.. Results will be presented and discussed.

* Dhoolpet Leprosy Research Centre, Hyderabad, Andhra Pradesh. India, PIN: 500 006.

A cohort of 125 patients treated with Prednisolone for neuritis in an out-patient setting during 1990-93 were followed up for five years.

The aim of the study was to determine whether those patients who initially responded to steroids maintained this response over 5 years. Initial neurological response was monitored using Voluntary Muscle Testing (VMT). Long term outcomes were assessed by the VMT, numbers of further episodes of neuritis, development of motor deformities and ulceration. Preliminary data suggests that those patients who make a good initial response to steroids maintain this response.

Minan Lane O. Rodrigues: Vani Aparecida M. Moscardíni; Darlene Arruda; Norma T. Foss

Division of Dermatology, Faculty of Medicine of Ribeirio Preto, University of Sao Paulo, Brazil

A 17-year old white female patient born in Itumbiara, GO . and living in Ribeirio Ptcio. SI*. Brazil, a student, repotted die onset of fever 4 months before, hemopioid sputum and loss of approximately 5 kg. Pulmonary tuberculosis was diagnosed and treatment wiih isoniazidc + rifanipicin (200 mg 4> 300 mg, 2 tablets/day) was started. Seven days later she started to present erythematous-infiltrated, papulous to nummular lesions located in the LL and UL. trunk, and face. Examination showed [hernial, tactile and painful hypoesthesia in the skin lesions and diennal anesthesia in some. Based on a diagnostic hypothesis of reactional tuberculoid leprosy, a biopsy, the Mitsuda test and bacilloscopy were performed. The Mitsuda test was positive (20 nun), bacilloscopy was negative and histopalhological examination showed tuberculoid granulomas preferentially located close to nerve fillets. Faraco staining did not reveal BAAR.

An MD T treatment schedule for paucibaciltary disease was started and the skin lesions improved. The patient was transferred to her town of origin and was lost to follow-up. Reason for the presentation: Demonstrative. To report the association of two diseases whose course involves deficient cell immunity.

Mirian Lane O. Rodrigues; Maria H. Takada; Ana Maria F. Roselino, Norma T. Foss.

Division of Dermatology. Department of Medicine, Faculty of Medicine of Ribeirão Preto. University of São Paulo.

A 25-year old black female patient born and living in Ribeirão Preto, SP, Brazil. with a diagnosis of Virchow leprosy was on specific multidrug therapy for multibacillary disease since February 1994, After the 3ª dose, she started to prevent frequent episodes of erythema nodosum which were treated with prednisone (0.5 mg/kg/day) because the patient had not been submitted to tubal ligation. On the occasion of the administration of the 12ª dose she presented anemia, jaundice and necrotizing erythema nodosum. Physical examination revealed a febrile. pale (++/4), jaundiced (++/4) patients with subcutaneous erythematous nodules most of which progressed to ulcers with purulent secretion, some of them being covered with necrotic scabs, located on the buttocks. LL and UL. Folic acid and ferrous sulfate were introduced and tests of hepatic and renal function, G6PD, Coombs: test and others were requested. The patient, who had 2 healthy children, was submitted to tubal ligation at the beginning of April 1995. At the end of April 1995. thalidomide was introduced (100 mg at 12 hour intervals). The necrotizing erythema nodosum reaction was controlled with thalidomide, with marked regression of ulcers. The MDT treatment schedule was maintained. The patient presented further episodes of non-necrotizing erythema nodosum which responded well to the use of thalidomide. Reason for the presentation: To emphasize the good therapeutic response to thalidomide in cases of necrotizing erithema nodosum.

Mirian Lane O. Rodrigues; Maria Paula V. Chiossi; Cristiana A. Sassamoto; Cacilda S. Souza; Renata Nahas; Darlene Arruda; Norma T. Foss

Division of Dermatology, Faculty of Medicine of Ribeirão Preto. University of São Paulo, Brazil

Leprosy often presents clinical manifestations and reactional states differing from the usual pattern. We present here a case with extensive ganglion involvement as the major manifestation of the reactional state.

A 26-year old white male patient born and living in São Sebastião do Paraiso, MG, with a diagnosis of Virchow leprosy was on specific multidrug therapy for multibacillary disease. After the 3^rd dose he started to present erythema nodosum and diffuse adenomegaly as well as neuritis and was treated with prednisone and thalidomide. At the line of the 16ª dose he presented fever an exacerbation of the inguino-crural adenomegaly on the right and the onset of an erythematous plastron, local pain and an area of inflammation measuring about 7 cm in diameter. A diagnostic hypothesis of a reactional and differential state with avenereal lymphogranuloma was raised and a ganglion aspirate was obtained, which showed ihe presence of BAAR (3+); hisiopathological examination of the ganglion revealed necrotizing granulomatous lymphadenitis. The reaction was controlled with prednisone, 1 mg/kg,day, with a marked regression of adenitis.

The MDT schedule was maintained and no recurrence of acute adenitis has been observed thus far (21ª dose) at any ganglion site.

Reason for the presentation: to emphasize the importance of leprosy as the differential diagnosis of acute adenitis in endemic regions.

LATE IMPROVEMENT IN CHRONIC CUTANEOUS LEISHMANIASIS CAN MIMIC LEPROMATOUS LESION OF LEPROSY IN PROVINCE OF KERMAN

This study has been done on 796 patients affected by cutaneous Leishmaniasis, who have been found among 20695 new dcrmatologic outpatients from endemic zones of Merman, from the year 1988 until 1996. Among them only 173 cases have shown more than 2 years delay in improvement of have lupuid recidivency after improvement. The skin lesions of this type of cutaneous Leishmaniasis mimic lepromatous leprosy. Typical findings of pathological cut section and or positive direct smears for Leishman bodies are known to be valuable especially in cases with non healed chronic cases of cutaneous Leishmaniasis.

Departments of Internal Medicine and *Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil

A necrotizing skin lesion associated with diffuse non-nodular leprosy was desenced by Lucio and Alvarado m 1842. After the histopathological alterations were recognized, this reaction was called Lucio's phenomenon by Latapi and Zamora. in 1948. This is considered to be a type of leprosy reaction associated with necrosis of artenoles, whose endothelium is massively invaded by M. leprae Lucio-Latapi Leprosy and Lueo's phenomenon, which correspond to the level of high susceptibility to the bacillus, are common in Mexico and Central Amenca but infrequent in oiher parts of the world. In Brazil, despite the prevalence of the disease, few reports of Lucio's phenomenon are available.

We report here a clinical descnption and the evolution of four cases of Lucio's phenomenon observed in our service: four patients (three males and one female) with lepromatous leprosy charactenzed by a discrete erythematous-infiltrative process diffusely involving the face and extensive areas of the tegument, with absence of nodules, associated with coalescent purpuric lesions forming plaques and ulcers covered with necrotic tissue, which ascendmgiy and progressively spread from the distal to the proximal end of the upoer 3ND lower limbs. Histopathology revealed focal necrosis of the epidermis, in the superficial and deep dermis, a morphonuclear inflammatory infiltrate rich in foamy histiocytes grouped around skin adnexa. nerve fillets and blood vessels. There was necrosis of sweat glands as well as thrombosis of small arteries with a focal deposit of fibnnoid material on the wall. Large numbers of BAAR bacilli were present, forming globies m the histiocytes and endothelial cells. This set of histopathological alterations is comparable to vasculitis of the Lucio's phenomen on type in the diffuse nonnodular clinical picture of leprosy.

Rifampin is a semisynthetic broad spectrum antibiotic widely uded in the treatment of leprosy and tuberculosis. A number of side elfects have been repented with Rifampin. However, cutaneous side effects due to Rifampin are rare Though an urticarial form of fixed drug eruption has been described earlier, the classical form of fixed, drug eruption due to Rifampin with residual hyperpigmentation has not been reported as yet. This is a report of a case of classical fixed drug eruption due to Rifampin occuring in a leprosy patient.

We are presenling a patient with unusual presentation of recurrent blistering eruption and ulcers on the acral region for a duration of 2 years before the diagnosis of leprosy was made.

A 63 year old-female presented to us with a 1 year history of recurrent blisters and ulcers affecting the hands and feeh which were slow healing There was no history of trauma or injury There was no documented neurological deficit No other family members were affected. Skin biopsy revealed subepidermal bulla (may be secondary to porphyria cutanea tarda, epidermolysis bullosa or burn) Direct immunoflorescence and antoimmune markers were negative. Full blood count, urinalysis, ESR and porphyria screen were normal One year after the initial presentat.on, she developed new erythematous plaques o;i the 'ace.arm and upper back and careful neurologica! examination revealed predominant sensory perphcrial neuropathy There was no nerve thickening. Skin-slit smear were reported as acid fast bacilli -the bacterial index (BI) being 4+ and morphologic index (MI) < 1 %. The patient was treated with multidrug therapy consisting of dapsone, nfampicm and clofazimine as recommended by WHO for multibacilkjry cases The patient responded clinically on subsequent follow up with no recurrence of the blisters.

Marcia C. N. Yoshioka, Marcos C. Floriano, Cristiane R. Alonso, Claudia G. S. Uehara, Solange M. Maeda, Adriana M. Porro. Jane Tomimori - Yamashita.

Leprosy is a chronic and insidious disease, which clinical presentation is well described. When the first cases of AIDS (Acquired Immunodeficiency Syndrome) were described, it was supposed that the leprosy incidence would increase with serious forms in these patients, as it has been reported in tuberculosis and other mycobacteriosis. We describe two cases of leprosy in H1V+ (Human immunodeficiency virus) patients.

Case 1: An 27-year-old white woman, CDC IVC group, had erythematous, annular, anaesthetic plaque, with a central superficial erosion. Biopsy of the border revealed tuberculous granuloma with edema. The Mitsuda's reaction was 11 mm and the slit-skin smear was negative for acid-fast bacilli (AFB). CD4+- = 174 cell/mm³.

Case 2: An 27-year-old white man, CDC II group, presented multiple erythematous-violaceous plaques on the thighs, legs and arms. Histological study revealed an infiltrate of foamy macrophages with the presence of AFB. The Mitsuda's reaction was 3mm. CD4+= 207 cell/mm³.

In the first case, we could observe that even in a cellular immunocompromised AIDS patient a specific cellular immunity against M. leprae could be preserved This patient developed a typical tuberculous leprosy. The second case was characterized by a polymorphous clinical presentation, which has challenged the leprosy classification.

CHARACTERlSTICS OF PATIENTIS IN TREATMENT IN THE LEPROSY OUTPATIENT CLINIC OF THE OSWALDO CRUZ FOUNDATION (FIOCRUZ) RIO DE JANEIRO. RJ - BRAZIL. Vieira LMM. Nery JAC. Ferreira MLC. Matos HJ Gallo MEN Leprosy Laboratory. Osvvaldo Cruz foundation. Av. Brasil, 4365 Manguinhos. Rio de Janeiro - RJ. Brazil

The National Leprosy Reference Centers in Brazil continually carry out clinical and laboratory studies whose results has been of great benefit for the control of leprozy in Brasil. With the purpose of providing detailed clinical, epidemiological, and laboratory data on the patients treated in the Leprosy Outpatient Clinic of the Oswaldo Cruz Foundation in Rio de Janeiro, the results obtained from 1.392 patients who were treated between Septembeer 1986 and December 1997 are presented. The data were evaluated as follows:

50.9% of the patients had been referred to the Clinic after being diagnosed in the public health care system. In 17.5% of the cases, diagnosis was achieved by way of household contacts. And 59.2% of the total number of patients vvere men. The age group comprising those between 20 and 39 years of age was predominant (42.1%). Classification according to clinical form was as follows: 1(12.2%); TT(0.7%); BT(30.4%); BB(110.4%); BL(21.2%); and LL(27.2%) - 3.2% were not classified.

Among the MB cases, 20.9% presented BI > 4 at diagnosis: and 23.4% presenied Bl > 3 at the end of treatment. The degree of incapacity was > 1 in 38.1% of the cases at diagnosis and in 32.2% at discharge. The MDT/WHO regimen was administered in 87% of the cases, of which 81% completed the regular treatment. The default rate was 9.4%. The results observed coincide with those found in National Program, except for the high detection rate among household contacts in this study as well as the default rate, which was significantly lower among the patients in our Clinic.

Loss of sensation is a very destructive complication of leprosy frequently resulting in deformities and disabilities, 152 ramdomly selected cases with disabled hands and feet were analyzed. The results showed that the frequency of sensory loss in MB cases was 45.59% in hand and 78.43% in foot respectively which was more severe than that of 15.80% and 42.6% respectively in PB patients. On the other hand, the frequency of sensory loss in different nerves was 81.25% (tibial nerve), 56.24% (ulnar nerve) and 44.08% (median nerve). The results also revealed that the presence of 40.90% of sensation loss in the palm of hand was higher than that of 30.66% in finger cushion. Similarly, the presence of 71.07% of sensation loss in the site of head of metatarsal bone was higher than thai of 59.21% in the heel. Moreover, the sensory loss in hands and feet were bilateral symmetrical. The authors emphasized the importance of regular sensation test in leprosy patients, espacially in MB cases.

OBSERVATION OF THE EFFECTS IN 24 CASES OF SILENT NEURITS TREATED WITH PREDNISONE

Twenty four cases of silent neuritis were diagnosed from 1990 through 1993. Totally 66 peripheral nerves involved. Prednisone tablets were self administered at home for six months after diagnosis. In all 24 cases of patients with damaged naves, functions recovered completely in 19 cases (79.1%) and 54 nerves (81.8%), and partly recovered in 4 cases (16.6%) and 16(16.6%) nerves. Only one case with one damaged nerve remained unchanged. No noticeable side effects took place. The shorter the time of nerve damaged, the better the effects of treatment were. For the leprosy control programme to be more fruitful, to improve the diagnosis and treatment level of leprosy workers and basic health workers in preventing early nerve damage, making its diagnosis in time and treating such patients with prednisone at patients' home are very important measures to be carried out.

Taking into account the remarkable efficacy of the Elimination strategy as well as the present or possible difficulties, il appears that action should be taken urgently in three main directions.

1-In view of its tremendous achievements so far and the hopes it raises, the programme should go on. However, an indepth evaluation of the epidemiological and operational status should be conducted at all levels. The main objective should be to identify the areas (especially those with high leprosy incidence) which will require strengthened programm e activities beyond the year 2000.

2-It is not certain that the presently available technology (i.e. MDT) alone will allow leprosy to be « eliminated » in particular in areas with high incidence. Thus, it appears necessary to reactivate research activities, in order to develop new diagnostic, prophylactic and even therapeutic tools.

3-It is obvious that it will be possible to carry out the two above kinds of activities only if the programm e receives during all the required time, i.e well beyond the year 2000, all the required support, especially from political and financial nature.

TREND OP LEPROSY IN THE LEPROSY MISSION ASSISTED PROJECTS EN BANGLADESH, ETHIOPIA, INDIA, INDONESIA, NEPAL AND TCHAD

Nathaniel M. Casabianca and Maureen Ong.
Evaluation Unit, The Leprosy Mission
International, Singapore..

A study was conducted lo determine the trend of leprosy in 22 of The Leprosy Mission assisted projects from 6 countries. Data for 10 years i.e. from 1986 to 1995 was obtained from 19 of these projects while the other 3 provided data for the recent 5-7 years.

MDT coverage, mode ofcase detection, prevalence, annual case detection rate, child rate, multi-bacillary rate, gender ratio and disability rates were analysed. The study revealed thai in several of these projects Leprosy Elimination levels will be reached by the year 2000 A.D.. However signs of interruption in the chain of transmission are not yet clearly evident. The scenario from most of these projects in this context suggests that there is no appreciable change while in a few projects a declining trend is just emerging.

Thus it is concluded that it may take a minimum of 10 years of 100% MDT imp lementation in an area to observe the desired declining trend. The study recommends that we need to continue our efforts with increased grit and determination and monitor the occurrence of new cases with uniform operational methods of case detection as monitoring incidence is more appropriate and relevant.

CASE DETECTION THROUGH LEPROSY ELIMINATION CAMPAIGNS IN 21 DISTRICTS OF BANGLADESH

Ahsan Ali, Derek Lobo, L.R.Talukdar, Jalal Uddin Ahmed, Nepisha Begum, Nooruddin Ahmad

BANGLADESH is one among ten countries that contribute 90% of the global leprosy case-load. The current estimate of the number of cases in Bangladesh is 40,000, giving a prevalence of 3.3 per 10,000 population. With the aim of detecting the remaining cases and to achieve the leprosy elimination goal. Leprosy Elimination Campaigns(LECs) were planned for 21 of the 64 districts of the country in 1997/98. LECs were conducted through mobilisation of village volunteers and existing general health and NCO workers, after appropriate training and orientation.

The campaign duration was twenty-two(22) days with the following main activities:

The details of case detection through LECs will be presented and discussed including the impact, usefulness and cost-effectiveness of LECs.

PROSPECTS OF ELIMINATING LEPROZY: QUO VADIS? 40 YEARS EXPERIENCE IN A HYPERENDEMIC AREA

Gudiyatham Taluk (Vellore District) of Tamil Nadu State in India was one of the hyperendemic areas for leprosy. Since 1962. the NLEP was carried out with great vigour, supervised by Medical Officers and Epidemiologists. This area also served as one of WHO field centres for testing MDT and continues so. Over the past 3b years, nearly 25,000 pat ient3 have registered and were treated initially with DDS and from 1982 with MDT. The trends in new case detection rates over time, across villages and in relation to age. sex. type and mode of detection are summarized in thi3 paper.

While there have been appreciable declines the slowing down and current stagnation in incidence rates causes concern, requiring strategic planning and implementation of specific activities. The integration of vertical control programme with general public health system in Tamil Nadu State needs to be capitalized to ensure elimination of leprosy.

Serious community involvement, not just lip service. true collaboration between government and non-governmental agencies better MIS and IEC, discarding ineffective and outdated methods are urgently needed. Strong recommendations are made in this direction as we move towards a world without leprosy.

CAN INDIA REACH LEPROSY ERADICATION TARGET BY 2000?. AN EPIDEMIOLOGICAL AND STATISTICAL ASSESSMENT.

Problem: The objective set by World Health Assembly in 1901 to eliminate Leprosy as a public health problem (< 1/10000) by 2000 and voice concerning it at Governrnenta 1/NGO levels has been at the centre stage. However, efforts have not been directed with required intensity to detect and treat cases. Activities largely centers on reported cases at health centres/Institution. Hardly any sincere attempt has been made to detect cases at population level where large reservior is expected to exist. Besides, there are problems related to incomplete treatment,cases (RFT,re1 eased from treatment)but still infectious and relapses. These together silently helping transmission to continue at community level. As a result, India still reports 400,000 cases in 1996 (Leprosy Review,68(3)1997). In reality, this may be manifolds higher. The paper would examine in detail several such issues to help to understand as where we stand and what needs to be done.

Methodology: Data from several stud ies would be examined and reported trend of leprosy cases in last 30 years at the centre would be presented. Infectiousness has been estimated using Catalytic models.

Corine van Marrewijk¹, Abraham Meima¹, Sumanta Chowdhury², Richard Croft², Jan Hendrik Richardus¹, Dik Habbema¹

Objective: To study the importance of (household) contacts in leprosy control.

Material and methods: This retrospective study reports on the contact status of 1199 new leprosy patients detected in 1987-1996 in a selected area in the leprosy control programme of the Danish-Bangladesh Leprosy Mission in Northwest Bangladesh. The programme employs several methods of active case finding, including contact survey.

Results: Cumulative percentages of having a known contact for widening circles of closeness of contact for newly detected cases:

Conclusion: Cases who are contacts of known leprosy patients are an important part of the total new case load. The importance increases with younger age. Prospective studies are required to describe in detail the role of contact in leprosy transmission according to degree of closeness (e.g. including neighbours), and to determine to what extent interventions should be directed at contacts of known leprosy cases.

LEPROSY ELIMINATION MONITORING - ACTION PLAN FOR THE NEXT FIVE YEARS - STATE OF SÃO PAULO. BRAZIL

Mitie Tada L.R.F. Brasil (1), Mary Lise C. Marzliak (1). Wagner Nogueira (1), Tanya E. Lafratta (1). Norma Foss(2), Rosa M. Soubhia(3).

The State of São Paulo. Brazil, had 33 585 961 inhabitants in 1996 (estimated), living m 626 counties. The Leprosy control activities are normalized by the central State coordination but the service is totally decentralized and under direct responsibility ol the county authonties. There are 5 Reference Units each of them providing technical and laboratory support for difficult cases to a group of counties Several of these Relercnce Unrt are related to Medical Schools. The Leprosy services are fully integrated into general health services and lhe state surveillance system meets some difficulties to obiam fast data according central standardized criteria . There are a standardized group of epidemiological and operational indicators recommended to evaluate and monitor elimination of leprosy at the county level. In order to monitor the leprosy elimination at the local level , the central state surveillance team and reference Units proposed and developed a special surveillance plan for the next five years. Initially, the two selected health regions are Ribeirão Preto and São José do Rio Preto. These two regions have some similar desirable charactenstics such as: counties in different endemic level; good reference services related to Medical Softools; good local health services in most of the counties; important urban centers and well-defined rural areas . The region of Ribeirão Preto has 1,028.713 inhabitants and 24 counlies. 5 of them with no detection of new cases and one with no prevalence. The region of São Jose do Rio Preto has 1.214.397 inhabitants and 92 counties. 34 of them with prevalence rate under 1/10,000 and 41 others have not detected a single new case in 1996. Counties with zero or under 1/10,000 prevalence are now developing a special educational project called 'Alert Sign Project* (an educational project integrated to the local community). They also will develop a special surveillance project which will last 5 years, starling 1998. The project will use PGL-1 tests in samples of adult population and intensify the BCG vaccination to the household contacts and. if possible, extend the vaccination to all community Data will be evaluated on a yearly basis utilizing standardized epidemiological and operational indicators to monitory leprosy elimination. The geographical information will also be analyzed together with other health and social economics indicators like migration.

The world wide use of Multi Drug Therapy (MDT) in leprosy control programme, as per the recommendation of WHO has drastically changed the global leprosy scenano. In order to bring out a leprosy free world the WHO has put forth an Action Plan for elimination. This elimination strategy in Leprosy as per WHO definition is to bring down the level of leprosy prevalence below 1 per 10,000 population by the year 2000 A.D.

Keeping this in view a 10 years retrospective study was conducted involving 87 leprosy control programs supported by German Leprosy Relief Association and Swiss Emma us Leprosy Relief in INDIA.

This study revealed that though there is a decline in the leprosy prevalence, the incidence of leprosy is remaining almost static, which indicates that the transmission of the disease is soil continuing. This study also revealed that many projects especially in the states of Uttar Pradesh, Bihar and West bengal are soil getting new untreated leprosy patients from out side the Project area, where MDT has not reached so far. Hence it indicates that there are soil uncovered pockets for MDT implementation. The premature integration of leprosy control work with general health services may result in poor active case finding in the field which may also slow down the elimination process.

A STUDY ON THE IMMEDIATE AFTER EFFECTS OF LEPROSY INTEGRATION IN RURAL TAMIL NADU

Dr. Thomas Abraham, T. Jayaraj Devadas. C.S Cheriyan. Venkata Ramana. GLRA/ALES-INDIA, #4, Gajapathy Street, Shenoy Nagar, Chennai 600030

Leprosy integration in Tamil Nadu was started during the last quarter of 1997. With the drastic reduction in the number of leprosy cases registered for treatment aner the advent of MDT, vertical programme designed for leprosy programe have been less cost effective. Equality of opportunity to all members of a communiry including leprosy patients to revive optimal health care u a basic right of every human being, Integration in leprosy wort means provisions of medical care to a leprosy patient as close lo a community as possible.

A study was conducted among 350 patients ui rural Tamil Nadu where leprosy vvork has been integrated.

Adequate preparation in terms of general health service delivery should have been made before launching the tntearanon process Intensive awareness campaign and adequate framing of the general health staff could help to bring down the deficiencies surfaced through this study.

*Assistant Director of Health Services (Leprosy), Mumbai- 400 080, Maharashtra, INDIA.

** Joint Director of Health Services (Leprosy), Pune - 411 001, Maharashtra, INDIA.

The Modified Leprosy Elimination Campaign involving 4986 Searchers to achieve a total population coverage by rapid survey. All 12 Leprosy organisations participated and covered 23 wards of Mumbai. Each organisation selected and trained teams of volunteers with Suspect cards. 2493 teams of volunteers suspected leprosy cases, which were later screened and confirmed by leprosy workers.

A population of 76,87,824 was examined out of 1,05,90,104 enumerated (72.5%). 22,286 individuals suspected to be having leprosy were identified by these searchers. Of these 1275 turned to be leprosy cases. The new case detection rate was 0.1/ 100,000. 180 (14%) were of MB type, 47 (5.9%) were skin smear positive MB type. 670 (52.5%) were single lesion PB leprosy. The MLEC experiment in Mumbai helped to detect 1275 new cases in addition to 3170 new cases detected as routine activity in 1997-98. This gives a NCDR of which is significantly higher than NCDR of 3.8 in Mumbai.

Similar MLEC should be conducted in other Mega cities in the country to make Leprosy elimination by 2000 AD a reality tn India.

LEPROSY IN LOW-ENDEMIC HILLY AREAS OF U.P., INDIA: PROBLEMS AND STRATEGIES TO ACHIEVE THE ELIMINATION GOAL.

V.P. Bharadwaj , A.R. Hatwal and 1.5. Samant. Consultant LeproiogistfGovt. of India), P.O. Box 1158 AGJÎA -282 001. INDIA

MDT has been in use for nearly 3 years in hilly districts of Chamoli and Tehri Garhwal, U.P., INDIA.

The prevalence of Leprosy in these districts has significantly come down but NCDR is nearly the same.

This indicates that hidden sources of infection stiil remain within the districts. Understanding and jdopting proper methods to identify jnd manage these uncovered areas will certainly help early achicvement of elimination of leprosy. Most of the villages in these districts being in hilly terrains have remained inaccessible. Thus systematic surveys in the past faced lot of difficulties. Health education and mass awareness is poor. Stigma against leprosy exists in these difficult to approach villages. To overcome these difflculties and hurdles. Govt, of India has launched SAPEL programme and MLEC is shortly going to be carried out. The overall scenario of leprosy and out come of these novel approaches will be presented and discussed.

SITUACIÓN EPIDEMIOLÓGICA DE LA LEPRA EN BRASIL: PERSPECTIVAS DE LA ELIMINACIÓN DE LA MISMA COMO META.

Fundação Nacional de Saúde
Centro Nacional de Epidemiología
Coordenacao Nacional de Dermatologia Sanitaria Brasil

Brasil es una República federativa con veintesicte estados aproximadamente 6.000 municipios por lo tanto tiene tres esferas de gobierno autónomos.

Siguiendo la trajcióna de todos los países em desarollo, Brasil vive en una franca transisión epidemiológica com Índices altos de accidentes de tránsito, enfermedades cardio-vasculares, enfermedades degenerativas, registrando al mismo tiempo altas tasas de enfermedades infecciosas, como la malaria, tuberculosis, lepra e otras.

En este contexto apesar de todos los esfuerzos gubernamentales y no gubernamentales, la lepra sigue siendo un grave problema en la salud pública.

En este trabajo los autores discuten tas perspectivas de eliminar la lepra como meta en el país, analizando cada estado por separado.

Se discute también las estrategias adoptadas para buscar dicha meta, a partir del análisis de los indicadores epidemiológicos y operacionales de los últimos diez anos.

Authors: CASTRO.C.R.. VENTURA.D.V.R.. PATROCLO, M.A. A., OLIVEIRA, M.LW. , BARRETO. S.M.

This paper presents the results of the research "Influence of Social Communication on the Brazilian Leprosy Elimination Strategies", which aimed m understanding the role of social communication in the elimination project, as an agent of change of the diseases social representation and as fundamental element for ihe early search of treatment, greater treatment adherence and broader coverage of the exam of contacts It identifies how the messages disseminated in educational campaigns through the dilTerent media, organized by the National Coordination for Sanitary Dermatology (NCSD) of the Brazilian Ministry of Health, have influenced the perception, attitude and bchav tor of individuals suspected or diagnosed as having Hansscn's Disease in different pans of the country.

In the first stage, on October 25th 1997, we interviewed customers who went to those health units olTcnng dennalologic examination together with the multivaccination campaign, in 4 out of 20 states carrying out this activity. These interviews allowed measuring the impact of the disseminated messages, building qualitative indicators and describing live profile of the population who searched the health units in response to (he media. Results showed (hat ihe largest number of people who had a dcnnalologic exam corresponded to individuals who were screened in the multivacctnation waiting lines, but that detection was more effective among the group of people who spontaneously searched this service, motivated by the messages. The second stage of the survey m seven states which had and had not adhered to the campaign aims to known in the sample of newly diagnosed cases in the post-campaign period the impact of the media on message retention, incorporating the dynamics of the recipients social plurality and applying statistical models to explain the results.

P Vijayakumaran, T Prabhakar Rao, P Krishnamurthy, Damien Foundation India Trust, Manda Colony, Harihar Singh Road, Morabadi, Ranchi - 834 008 Bihar, India

India is the major contributor to global load of leprosy Multi Drug Therapy (MDT) programme has been implemented since 1984 in majority of leprosy endemic regions. The cases on record has declined from 3 m (1984) to 12m (1996). There are few regions where it was difficult to implement MDT in an intensive manner. Bihar stale was one such region where MDT programme was introduced in 1993 in a low key. Bihar contributes 21% of case load in India and 12% of global case load.

Damien Foundation India Trust was allotted 16 districts (43% of population in Bihar state) for assisting in implementation of MDT. Support teams provided by DFTT, one for each district, assisted in screening of existing cases, planning case finding, treatment debvery in line Kith national guidelines Intensive training programmes were done for various categories of faff Action Plan was implemented in all the 16 districts New case detection improved by 228% and case discharge after completion of MDT improved by 135% when compared to the previous year's performance.

The support teams consisting of expenenced personnel can hasten the implemaitaticn of MDT programme in regions what it is delayed or being done in slow pace.

Leprosy control programme in Nepal was implemented as a vertical programme Since 1996 In line with the goverrment's policy of integrating all vertical prolamines into the basic health services, since 1987 leprosy control programmes was assimilated into basic health services. With integration leprosy services benefited as larger population was covered. MDT was extended to all the districts as well as to all registered leprosy patilients, regular services were provided, coordination among INGOs and HMG staff was improved and proved to he cost effective in terms ol manpower, transport and finance However, leprosy control activities suffered because of unforeseen technical and operational constraints Leprosy was found to be accorded low priority and because of wider coverage adequate supervision could not he provided In addition low motivation and morale of health workers as well as poof health facilities has caused obstacles in providing effective leprosy services The government is taking necessary steps to reddress these issues by conducting regular training programmes, meetings ol prevjamme managers and FNGOs at different levels .ind increasing the frequency and quality of supervision in order to achieve the goal of elimination by the year 2000.

Damien Foundation India Trust, Manda Colony, Hariharsingh Road, Morabadi, Ranchi, Bihar, India.

Bihar Stale in India contnbutes 12 % to global leprosy case load DFIT is involved m leprosy elimination through theff support teams since May 199o Smghbhum is an endemic district with 3 5 million population. Support team organised a campaign for case detection tn the 3rd quarter of 1996. All the available field workers were involved in the campaign with the assistance of expenenced leprosy workers from olhci States. Teams of doctors. NMS and PMW were formed Each team was provided with a vehicle. The teams visited several villages dairy. Propaganda was done by audio system and with the help of Qaah cards rapid enquiry survey was done They also visited "Haal" in the afternoon where large number of people gather from neighbouring villages. Suspected cases were scieened and active leprosy cases were started on MDT.

New case detection was (4953) equivalent lo Ihe total new cases detected in the district during the pievious one year The whole exercise was completed in 45 woikmgdays covering 55% of Ihe population of the district The campaign helped m improvement of the skills of the local stalf and there was positive change in motivation and work culture.

NATIONAL LEPROSY ELIMINATION CAMPAIGN - BRAZIL (LEC). Valladares D: Ledra VJ. Glath R. Pereira GF and Oliveira ML W

The proposal of national LEC draws on two previous experiences on mass media campaign and additionally incorporates the strategy, of WHO LEC proposal including nol only information but also diagnose and treatment. It was held in 20 of the 27 stales of Brazil and reached only 14% of the total of existing municipalities with leprosy programs, in those states involved (305 2.255) in spite of being the most populous ones. The Brazil LEC inovation was to add the examination of individuals with skin symptoms simultaneously with multivaccination campaign (10 25 98) This strategy presents some advantages and disadvantages such as opportunities foe mothers and children examination, logistics facilities at health network, mobilization of communities as well as promotion of integration.. On the other hand such strategy may jeopardize the health workers' tasks mostly where there are scarcity of them Thus leading to overwork. It decreases the cost benefit of new cases finding is harmed (too many exams of mothers and children for few cases found). Some municipalities choose a dilferent day for ihe campaing eigther before or after.

The conclusion was: I) around 2.400 new leprosy cases were diagnosed in single day and 63% started MDT (practically the same number was considered suspected of leprosy) which means 5.3% of yearly estimated detection Mans others cases are still being found as a result of the campaing. 2) in a huge country like Brazil, the national LEC is very useful to reach large number of people specially if including the "big media" as TV. And also to sensitize the many local authorities and thechnicians as to existing hidden prevalence of leprosy. It has to continue be repeated on the next immunization day but local LEC proved to be more effective and must be kept in high endemic municipalities.

a) spreading of leprosy awareness in the community; b) Proving the low coverage of diagnosis and treatment, c) certifying the hidden prevalence Therefore, ihe LLC results are being used lo increase Ihe coinmitiemeiit of both local and central level authorities of SUS to deccntrili/e the attendance.

This proposal received funds of WHO and logistic support of PAHO/Brazil Unifyed Health System of Brazil

German Leprosy Relief Association, 35, Hill View, Independence Layout, PO Box 18158, Ogbete Enugu, Nigeria.

This paper is not about whether TB and Leprosy control programmes should be combined or not. Indeed the author acknowledges the substantia 1 benefits potentially accruing from combination. In order to reap these benefits however, certain operational issues have to be recognised and carefully thought through by policy makers and programme managers contemplating combination. Based on his experiences as a state TB/Leprosy Control Officer and Medical Adviser to a leadinj NGO supporting the Nigerian national programme, the author highlights some important areas of concern. These include issues related to miera scopy network for TB control in areas where diagnosis and monitoring of treatment ofleprosy have been based on clinical parameters alone, balancing 'cure' in TB with 'care' in leprosy, the implications of using many general and tertiary hospitals as intake centres for direct observation of TB treatment, recognising and addressing apparent and inapparent conflict s between erstwhile leprosy and TB control staff as we11 as between supporting NGOs with differ ing policies regarding the combined programme. Options for solutions are suggested.

The paper concludes on an advisory note: transitions from sinyle-disease leprosy and TD programmes to combined control programmes must be planned and not brought about by mere executive fiat.

Françoise Portaels, Julia Aguiar, Marc-Christian Domingo, Augustin Guedenon, Christian Steunou and Wayne Meyers

During recent years the prevalence of leprosy decreased significantly in West Africa, as a result of efficient programmes and help from NGO.

At present, another mycobacterial disease, Buruli ulcer (BU) , is increasing. BU is a cutaneous infection caused by Mycobacterium ulcerans, the third most common mycobacterial disease in immunocompetent humans, and was recently recognized by the World Health Organization as an important reemerging disease. Prevalence has increased in recent years, especially in West Africa and in Australia. New foci were discovered recently in Toyo, Angola, Guinea and Peru.

To delineate the extent ot the disease in Benin, we conducted an epidemiological study, the first of its kind, based on data from the records of 867 patients treated at Zangnanado Hospital between 1989 and 1996. BU had spread contiguously and widely in southern Benin. All afTected areas are in the valleys of the Ouéme, Zou, Mono and Couffo rivers The total number of BU patients detected between 1989 and 1996 increased exponentially, and now exceed those of leprosy and tuberculosis in many endemic sub-prefectures.

Implementation of a Benin National Anti-Buruli Ulcer Programme proved essential for the development of a BU central reporting system that would increase the knowledge of the epidemiology of BU, assure earlier diagnosis, improve patient care in the endemic areas and diminish the financial burden of the disease, for the health care delivery system, the patients and their families.

In West African Countries with a BU problem, the excellent leprosy control programmes could take part in the responsibility for this new burden, since there are parallelisms between leprosy and BU e.g. in PIRP and rehabilitation. One strategy would be to have National BU control programmes associated with leprosy control programmes.

Damien Foundation India Trust, 27 Venugopal Avenue, Spurtank Road, Chetput, Chennai: 600 031. India

Damien Foundation India Trust, an ILEP agency working for leprosy control in India, supports 34 leprosy eradication projects in India. Trend of the disease in the past ten years in 13 of the DFTT- supported projects (3 in the north and 9 . the south) has been analysed for New Case Detection Rate, deformty proportion, positives, single lesions and relapses. Only those projects which had a well-established programme by 1987 have been included for analysis. These projects have well established programme of case detection and case holding, a good laboratory facility, and the criteria they follow for selection of cases for smear examination lias not changed.

The total population oi these projects in 1987 was 3 029 838 and the projected population in 1997 was 3 502 206. The 13 projects had detected 62586 cases since: 1987 (10036 in 1987 and 3713 tn 1997). Number of positive cases detected from 1987 was 3062 (356 in 1987 and 138 in 1997), and the number of relapses 718 (55 in 1987 and 35 in 97).

The trend of the disease in terms of NCDR, new positives, proportion of BI 3+ and above among he positive cases, proportion of deformity and single lesion cases among the new and relapses and the prospects for ekmination in these projects would be discussed.

Emilia Pereira dos Santos; Cleonice Oliveira Souza; Mª de Fatima Maroja; Mª da Graça Souza Cunha

Two urban and one niral areas of the Ama/onas Stale with highest prevalence of leprosy, and highest proportion of defaulting eases received an intervention to reduce these rales. The intervention consisted to retrieve defaulter patients by home visits and their evaluation, leased on detected reasons lor defaulting and clmical status, aeiums were taken, including restart MDT tn a flexible way. whenever it was necessary.

In the urban area, from 110 defaulter patients. 5X (53%) have moved out and wen removed from the prevalence area. From 52 (47%) patients retrieved, 14 (27 %) were released from treatment as cured . 19 (36 %) have not attended to the clinic alter home visit. 10(19 %) restarted MDT 4 (8 %) patients were receiving or completed treatment in another health unit, 2 (4 %) refined to treat and 3 (6 %) patients expecting result of biopsy to subside procedure. The main reason for default in urban areas was that most of them fell cured. In the rural area from 79 defaulters identified. 23 were retneved of whom: 17 (75%) staned MDT (previous dapsonc monotherapy), 4 (17 %) re staned MDT due to presence of active lesions, 1 (4%) was released as misdiagnose and 1 (4) was released from treatment as cured. The main reasons for defaulter in rural area were long distances between small communities and health unit and also lack of transponadon. Due to these problems we decided to make elTorts to establish MDT, in the area, by training health agents.

This investigation received financial support from UNDP / World Dank / WHO Special pmgram for Research and training in Tropical Diseases (TDR)/DAHW.

LEPROSY ELIMINATION CAMPAIGN COMBINED WITH THE ANTI-POLIO VACCINATION - MUNICIPALITY OF RIO DE JANEIRO - BRAZIL

Vera Andrade (1),Tadiana Mana Alves Moreira (2). Rachel Tebaldi Tardm (3).Antonio Joaquim Wemeck de Castro (4), Artur Custodio Moreira de Sousa (5)

(1) Ministry of Health-Secretariat of Health Care/ SAS / MoH, (2) Rio de Janeiro State Health Secretary.(3)Rio de Janeiro Municipality Health Secretary. (4)Ministry of Health-Secretanat of Health Care/SAS/MoH. (5) Movement of Reintegration of People Afected by Leprosy

The objectives of the campaign were to raise awareness about leprosy amongst the people of Rio and to encourage people with signs of the disease to report to their local health centres, particularly in those areas not covered by normal leprosy control services. The model of polio mass vaccination was used in developing plans for LEC in Rio. This mass campaign was combined with the anti-polio campaign (july 1996) when the second shot of the oral Sabin vaccine was administrated. Screening of suspects was done in 70 health units during a single day. More than 10 000 persons (volunteers from MORHAN and civil club) were envolved in public information on leprosy. In relation to the objective of the campaign to diagnose cases in areas not covered by the Programme, it was observed that 57.18% of the examined population was examined in health units where leprosy control was net previously implemented.

THE PROFILE OF THE UTILIZATION OF HEALTH CARE AMBULATORIAL SERVICES BY LEPROSY PATIENTS IN BRAZIL

The Secretanat of Health Care/SAS/MoH has established a cost-effective national momtonng system, Monitonng of service utilization and cost can not be done through the existing epidemiological information system. The number of cases of leprosy can be determined from multiple national databases such as Out-Patients system (SIA/SUS) and inpatients Information system (SIH/SUS). These databases allowed to analyse data at national, states and municipal levels and/or health units involved in leprosy care. Data from the National Out Patients System were analyzed for better understanding the profile of utilization of health care services by leprosy patients. Notification sources (105 520 registered cases in 1996) were used for calculating the cost per patient. From January to November 1997, the cost for care leprosy patients in Brazil was 0.06% of the total care amabulatorial cost, In average 2.24 medical consultations and 8 procedures were offered for each patients on registers. The cost per patient was USS 19.55 for utilizing health pnmary services (excluding drug cost). Large variations were observed between states and regions. This type of analysis from multiple sources can assist in assessing leprosy programme performance in various levels.

LUCHA ANTILEPROSA EN LA CIUDAD DE SANTO DOMINGO. LOGROS Y PROBLEMAS PERIODO 1973-1997

Programa Control de la Lepra. Instituto Dermatologico y cirurgia de piel. Rep Dominica

Santo Domingo, capital Je la Republica Dominicana, con una población de 2.389.937 habitantes, la mayor parte de ellos por migración interna ha sido un foco muy activo relacionado con lepra con un diagnostico de casos que representa alrededor del 50% del problema del país Los logros alcanzados, con las medidas del programa, se evidencian por medio de las tasas de incidencia y Je prevalência que de 17.4 y 14.8 respectivamente en 1973, se han reducido a 2.9 y a 0.63 en 1997. Una de las estrategias empleadas para conocer a fondo el problema y lograr una prevención secundaria ericaz fue la atención medica gratuita a partir del ano 1995 para la población de los barrios marginales con donación de medicamentos en las manifestaciones dermatológicas mas frecuentes de poca complejidad. Se discuten los problemas que acarrea la lucha antileprosa en las grandes ciudades.

The Leprosy Mission International, National Coordinator's Office, PO Box 3318 Minna, Nigeria.

How much do statistical reports of registered prevalence reflect the actual number of patients in the clinics? A review of clinic records was done in 7 States of Nigeria to compare the reported with the actual point registered prevalence of loprosy at the end of the 3rd quarter of 1996. Instead of the 3,586 patients (2.0 per 10,000) reported, 2,276 (1.3 per 10,000) were found. The total discrepancy of 1 ,310 cases represented 1,411 nonexistent and 101 unreported cases. It was significant that 2 in every 5 reported patients from the 7 States were 'ghost' or fictitious cases. The proportion of ghost ca-.es in the individual affected States ranged from 20.6% to 67.0%. This significant reporting of fictitious cases in soae States suggests that the actual national registered prevalence of loprosy could be lower than is reported. Apart from the economic importance of statistical over-reporting, the elimination of leprosy as a public health problem may be even sooner than the national or global figures would declare. Quarterly, structured and fiel d supervision of information system activities by programme co-ordinators is recommended to eliminate the prevalence of ghost patients.

The author proposes (and suggests a sample) of a checklist as a useful supervisory tool.

DEVELOPMENT OF SUSTAINABLE LEPROSY CONTROL SERVICES BY ADJUSTING LEPROSY ORGANIZATIONS IN SHANGHAI

Guo-wei Liu, Jia-kun Chenh, Jia-yu Yue, Fu-tian Ii, Zai-ming Wang,
Ren-bao Zhang and Jia-lin Zhang
Shangai Zunyi Hospital, Shangai China

Shangai Municipality had met China's criteria of basic eradication of leprosy in 1990. Since then, a sustainable leprosy control service has been developed gradually and successtully.

In 1994, the Shangai Municipal Health Service decided to combine Municipal Station for STD control with Shangai Municipal Zunyi Hospital to make their resources yield well Clinics for skin diseases and STD and special wards for care of aged patients with non-leprosy disases have been established resulting in significant social and economic benefits.

In recent years, health education about leprosy has continuously been carried out through mass media. A report on "Seeking the Way of Returning Back to the Society" informing that there is still the last generation of unfortunates in Shangai has evoked strong repercussions in the community. A number of social societies, welfare agencies, industries and resident population have actively provided assistance. The living conditions of cures contineously stayed in the hospital have been markedly improved with a monthly living expense of 300 yuan each. A new well-equipped ward building has alredy been put in use as a home from home for cures to make their remaining years peaceful and carefree.

Los datos estadisticos, demuestran un aumento anual de la tasa de deteccion por 100.000 habitantes que alcanzo un 10 2 en 1975. Posteriormente se aprecia una disminución continua de la misma hasta llegar a 3 8 en 1989. Desde este año, los índices proyectan un estancamiento franco que se atribuye a que los factores de nesgo (del Individuo y socio-economicos) se han mantenido sin modificación. Por otro lado, la tasa de prevalencia presenta una caida continua a panir del ano 1980 (8 33) hasta llegar a 0 48 por 10,000 enfermos en tratamieno en 1997, situando a R. D entre los países en donde la lepra no presenta problemas de salud publica.

International trends government pohey similar disease control atrategies and improved service capabilities are all cited as reasons for merging leprosy and tuberculosis programmes. We describe the experiences of an INGO programe with 200 staff serving a population of 2 5 million in the Mid Westem Region of Nepal, which was created by the merger of two separate programmes in 1995. After describing some of the advantages of the disadvantages of joint operations and ... the management process involved we present data en leprosy case finding and treatment outcomes. These indicate that far from distracting programmes away from good leprosy control carrefully managed combinations can enhance our effectiveness. However ... must be matched with integration at government and donor levels. They in turn must listen to field managers and be prepared to be flexible for successful implementation.

Now that leprosy has reached a level where it may not be justifiable to continue as a special vertical programme, the problem of its integration into the general health programmes of the country will have to receive attention.

A major difficulty in such integration is that the primary health centre (PHC) which was devised to preside an integrated preventive, promotive and basic curative services in a decentralized manner has itself reached a low ebb due to the 'target' pressures of a variety or vertical programmes under the influence of a hierarchial bureaucratic approach. To try and integrate the leprosy programme into the general functioning of a PHC, which has been reduced to a target oriented institution to serve the needs of National Disease and Family Planning Programmes, may result in loss of the achievements to dates.

The answer to this, as for many other diseases, is to involve the community and their health functionaries for early detection and also for ensuring regularity of treatment, with the PHC providing the supportive service for confirming diagnosis and providing the recinie and the drugs for treatment which can then be undertaken most effectively and at low cost by the community's own functionary.

Harnessing of the "Student Power" for the elimination of leprosy in Indu is a new concept which a nut at all in vogue in any other part of the World This concept was first tossed by the German Leprosv Relief Association with the objective lo educate, trace and treat the hidden cases of leprosy which had hitherto eluded detection by conventional modes of ease detection.

Through VMC all forms of student groups were brought under one common banner of "Student Volunteers" irrespective of their affiliation to groups and schemes of actions to realise the following objectives:

♦ To mobilise a mass of student volunteers lavuiirabiv disposed towards eradication of leprosy

♦ To enable die community to identify the ludden ca-ses among themselves through voluntary reporting.

♦ To tram student volunteers to identify the early signs and symptoms of leprosy and to mould them as a "Task Force" to be deployed in the community.

During the initial campaign and immediately after that 34 MB cases and 103 PB cases were registered from the operational areas through the efforts of the student volunteers. These initial results would speak of the greater role VMC could play in the detection of new cases and the mass education they impart to the public.

In the modern days running a Leprosy Control Programmes have become very expensive in all aspects viz.. Investments, Personnel Management, Maintenance of equipment! and utilities and Administrative overheads. This is mainly due to the inflationary trend prevailing in the country.

A study was conducted involving 5 leprosy programmes covering a population of 4,129,593 having a total budget Rs. 7.133,897/- and the findings revealed that by adopting the following measures the expenditures could be reduced by 30%

a) Investments in Buildings as well as Vehicles and equipments for the project can be made after assessing the real need and full use.

b) Unproductive staff can be offered voluntary retirement and responsible positions can be provided to efficient and qualified persons. Only qualified staff for the appropriate positions to be appointed .

c) Expenses under maintenance of buildings, utilities and equipments can be minimised by using austenty measures without bringing down the quality. Similarly preventive maintenance can save unnecessary expenditure.

d) Administrative expenses like printing of stationery and records, communication expense and such other expenses can be curtailed to the minimum.

It is suggested for future that the Project Holders can be explained to strictly follow the policies of the Donors and the cost effectiveness ui respect of managing the projects when the goal of elimination is not very far.

Crash Population Surveys (CPS) have been experimented by German Leprosy Relief Association (GLRA) and Leprosy Relief Work Ernmaus Switzerland (LRWES) since 1993 with the objective to demonstrate the skill ot" sytematic and rapid case finding in a short span of time.

During the 5 year period 23 crash population surveys have been conducted in II states. The teams consists of 20 Para Medical Workers,2 Non Medical Supervisors and One Doctor This involves efficient and well trained workers who will act as trainers to the concerned project field staff.

It was observed that the average case detection rale per 10.000 population examined was 16.3 prior to the demonstrative survey During the Survey the team could detect an average case detection rate of 84.3 per 10,000 population In a follow up review after one year it was noted that the case detection rate in the participant projects have gone up by 33 V This excerciac can be used to orient the stafT to detect the hidden cases in the community in the fag end of the elimination phase.

THE SINGLE HEALTH SYSTEM AND THE NEED FOR REMODELING THE PROPOSAL FOR UPGRADING OF HUMAN RESOURCES FOR HANSEN'S DISEASE CONTROL

This paper presents a model for upgrading of human resources for Hansen's disease, planned with basis on the need of corrections posed by the implanting of the Single Health System and, especially, in the process of transferring actions for local levels.

The proposal developed by the Hansen's Disease Control Program in Sã o Paulo includes the local realization of actions and the upgrading of services, preferrably regional.

The phases of previous planning are presented, as well as the phases employed for implanting the proposal, strategies employed the results reached.

Specificity of roles and attributions of central levels are also detailed, in regional and local levels of the cities involved.

IMPLEMENTATION OF TUBERCULOSIS PROGRAMME IN AN ONGOING TRIBAL LEPROSY CONTROL PROJECT STRATEGY AND RESULTS

Bhuskade R.A. . Prabhakara Rao V, Sudhakar K.S, Ranganadha Rao P.V. and Desikan K.V.

In a hilly tribal district in India, Leprosy Control Project was started in 1991 covering a population of 1.5 million in 6500 villages.

Taking advantage of the close liaison with community under the project, a DOTS programme for TB sputum-positive cases was implemented in a pilot project covering a population of 261000.

Active case finding by house-to-house enquiry survey was carried out and 9508 samples of sputum were collected, 3 samples from each symptomatic. Finding of bacill i in at least 2 of the 3 samples from a symptoma Lie was the criterion to confirm diagnosis.

263 patients were thus detected. Excluding those who left area and died, treatment was initiated for 216 patients.

Treatment results are satisfactory. Patients' compliance, sputum conversion rate, strategy of case detection, drug delivery by DOTS, problems of work in difficult terrain and other details are presented.

A HSR project carried out in a mountainous county in Wenshan (1994.08-1996.07), alter a short period of training of primary health worker (PHW) and intensive health education to the public, the detection of leprosy by the PHW has increased from the previous two year period (1992.08-1994.07) 5/36 (detection by PHW/total detection) to 26/45 (1.32 X), at the same time there was an increase of detection among non-contacts from 13 to 31, increase of PB from 13 to 26, decrease of grade II deformity from 12 to 6. Thus signifying the advantage of relieving the workload of case finding and drug delivery from the wide area and high population coverage for the individual leprosy worker in the vertical leprosy administration system.

Cost factors implied in leprosy control at the mass level are neglected areas of leprosy research. We present the data on field experiments carried out by Bombay Leprosy Project functioning with minimum establishment and infrastmctural budgets.

Health systems research in leprosy assumes greater importance in the current low endemic scenario than at any time in the past.

HOW TO DETECT LEPROSY PATIENTS IN AN INTEGRATED HEALTH SYSTEM WHIN REACHING THE GOAL OF ELIMINATION' EXPERIENCE F ROM MARCHOUX INSTITUTE

Marchoux Institute, a research and training center for leprosy, is charged to coordinate lepras) control in eight Francophone Countries of West Africa. The implementation of leprosy programs with WHO/ MDT. through integrated health system approach, allowed those Countries to reduce live burden of leprosy. The prevalence rate of leprasy fell from 2 1 6 to nearly one case per 10.000 inhabitants between 1987 and 1997. During the same period, the detection rate remained stable (between 15.8 and 10.4 per 100.000 inhabitants). Those findings conducted us to assess the quality of the diagnosis of leprosy done by general health workers at peripheral level. We also evaluated strategies of case-finding used in the region covered by Marchoux Institute. The results of these studies conducted from 1995 to 1997 showed the following main conclusions:

-Quality of the diagnosis of leprosy done by trained general health workers at peripheral level is sufficient for a leprosy control purpose (one false negative among 529 patients and four false positives among 41 suspected cases)

-Active case-finding methods are more efficient than passive ones when conducted from time to time rather than yearly

-The number of patients actively found gets greater with the distance between health centers and villages.

These results suggest that detection of cases of leprosv should be conducted combining passive and active approaches. Active case-finding would be applied on remote areas or villages far of more than 30 kilometers from common health centers, involved in leprosy case-finding.

MEDIA (RADIO/TELEVISION) CAM PLAY A MAJOR ROLE IN DEFUSING STIGMA, INCREASE IN VOLUNTARY REPORTING AND ULTIMATELY ASSIST IN THE ELIMINATION OF LEPROSY

The challenge of eliminating loprosy by the year 2000 has motivated people to envisage and adopt new methods besides TRADITIONAL*TO detect new cases, in early stages to bring maximum number of patients under the Mu1ti Drug Therapy.

With the above objective a study was conducted to measure the effect of media in creating awareness.

In 1995, a message of 45-80 seconds in National Network of Doordarshan brought, 5568 letters , in 1996, a 3 minutes song, 10752 letters and a 45 seconds message in 1997, 3451 letters, seeking information on treatment etc . and thus follow-ing observations were made.

Television/Radio,a relatively cheep and effective method of case detection will increase voluntary reporting. As in 1995 -0.25%; 1996 - 2.5% and in 1997-0.25% written requests came seeking help. (This percentage is based on the fact that 5 lakhs newpatients are found every year in India). The expenses incurred in 1995 were-Rs.5,000; 1996-Rs.25,000 and 1997- Nil due to repeat programme.

Hence media(Readio/Television) plays a manor role in increasing voluntary reporting ann ultimately assists in eliminating leprosy Regional language programmes can give more information incl nd inct pi aces, of . ava i 1 abi 1ity of treatment.With this 96% polulation can be roache.

EMPOWERING THE COMMUNITY TO DO CASK DEFECTION AND DISSEMINATION OF SCIENTIFIC FACTS OF LEPROSY -A PRELIMINARY REPORT

N. K. NANDA, K. R. RATRE, B. C. SEN, K. DAS, THE LEPROSY MISSION, B. L. HOSPITAL, PO-CHAMPA DISTT- BILASPUR, (MP), INDIA

The objective of the study is to assess how far the commuity in able to detect cases on its own and try to spread the scientific facts of leprosy.

It is by two tier system of education. In the first place 300 leaders of the community,elected village Presidents and community health workers who til l now do not take part in leprosy care, are given orientation on leprosy. The questionnaire is given to them at the time of orientation to assess their knowledge. Those trained community leaders in turn train 10-15 village councilors, women care takers of pre school children and other interested women in the village. The trained village men and women volunteers each visited 30 families (100-150 persons approximately) and Iook for signs and symptoms of leprosy and oducato families regard ing leprosy.

This research study was done in an endemic a rea having a population of 325634. The results of the answers to the quostionnairs are compared. The number of social prohlems before and after are compared. Analysis is done of the comparis on of before and after results of the study.

Rajan Babu. G., Palla.J.P., Robins Theodore, Nanda. N.K., Baskaran.T.J.. Kerketta.W.J., Margery Emmanuel and Paul Jeyaraj.

A multicentric study has been carried out in five Leprosy Control Areas with an aim to provide leprosy workers a tool to identify whether case detection of leprosy is a gender problem and if so. to enable them to make case detection methods more gender sensitive.

The case detection activities by rapid survey in these areas are earned out by paramedical workers who are men. For the purpose ot the study, seven women at each centre who had onentation in leprosy for two weeks were involved in house to house survey along with male paramedical workers. A female volunteer from each village has been identified to help in survey in that village. The village presidents were involved in planning and implementing the study.

The population examined was 1257659 and 5425 new cases were detected which is three times more than cases detected every year. The cases detected among adult female is 4 times more than adult female cases detected every year.

The study has shown that many cases still exist in community which needs to be detected. Involvement of female workers, female volunteers and community leaders is proved to be effective in case detection.

SUPERVISION: NA EFFECTIVE ALTERNATIVE FOR MONITORING AND MANAGING LEPROSY CONTROL ACTIVIES

This paper presents the results ol the methodology shared by a group of the National Coordination for Sanitary Dermatology's technical staff and by health professionals from the 27 Brazilian states, performing different functions in the leprosy control activities at the different levels of the Brazilian Unified Hearth System.

It led to the creation of the supervision instrument for monitoring leprosy control activities by area: diagnosis, treatment and disability prevention, critical inputs - drugs, laboratory, information system and management.

Result of a collective creation involving 105 local professionals in 4 workshops and applied in the services, this instrument uses task analysis and professsional performance analysis, taking into account the type of professional who carries them out. the local context, the evaluation, the assessment from both customer and health professionals, in concrete interventions. The decoded tasks and subtasks are broken down into knowledge, attitude and skills required, defining the minimum level acceptable for considering a task completed.

The methodology used allowed each actor, supervisor and supervised satff, to lead a critical reflection about the task, reviewing its practice, taking joint decisions towards changing the reality, improving the resolution of I he correction of identified deviations and discussing the local and regional management's structural framework.

Doctors of 10 townships in Wenshan county were, trained on basic knowledge, of leprosy. Popular population took, health education frequently through banc medical units in townships. The way of leprosy control turned into a "network-type" service of combining vertical service with basic health care. This reform has much improved case detection of leprosy with an increase of 25% of newly detected patients comparing with that before reformation. The proportion of new patients detected through basic medical units and passive modes went up from 13.9% and 55.6% to 57.8% and 80% respectively, detected non-familial new patients increased from 36.1% to 68.9% and WHO II and III disability rate among new cases reduced from 33.3% to 13.3%.

Disability rale also dropped from 40% and 53.8% to 13.9% and 16.1% respectively among new cases detected by passive modes and non-leprosy household contacts. The cost for detecting one new case decreased from 330 to 140 Chinese yuan. The above results strongly suggested that programme of vertical service in combination with basic health care should be expanded in the field of leprosy control.

PAST AND PPESENT STATUS OF HANSEN'S DISEASE (LEPROSY) IN TAIWAN -SUCCESSFUL LEPROSY CONTROL IN TAIWAN

Taiwan Leprosy Relief Association and Dept. of Dermalology. Taipei Medical College Hospital

Background: Leprosy control and its problem was traced to historic events of the islands' ruler from 13th century on Taiwan by original Hills' Tribes, then in successively by an occupation of the Mongol fleet, Portuguese who named it as "Ilha Formosa" in 1590. Holland, Spain in 1624-1661. Koxinga a champion of Ming dynasty in 1661-1681, and Ching dynasty till the mid-18th century when First literature on leprosy described.

Aim: To report Taiwan achievement on leprosy work during past 262 years included the recent 50-year experiences, by dividing into three stages.

Materials and Methods: The first stage of Leprosy Problem was recorded as institutional care of leprosy, simply for socio-relief purpose in the Yongche-ln(insitution) in the Country Annals and accepted by the rest of several Socio-Relief Institution over the whole Taiwan for about 160 years.

Second stage, modem medical care in Christian hospital & . clinic from 1900 after the western medicine was brought in Taiwan in 1865. Leprosy Control Program was employed from 1925 to 1945 with the strict isolation law, such as segregation in two leprosaria with social relief program, which was published in Japan in 1901 because Taiwan was under Japanese rule.

Results: It showed a decreasing in prevalence rate, 1,60 in 1945 but in the third stage, sudden increaing due to influx of a great number of refugees and soldiers after World War II from China. Later, however, chemotherapeutic regimens was successfully employed included WHO-MDT. The accomplishment was due to cooperation with Taiwan Leprosy Relief Association Clinics, local and central health organizations of the government, which also enforced BCG vaccination for anti-TB program for more than 40 years till now.

Conclusions It showed that the maximal registered case of 4,942 with 117 new cases for treatment ever since 1977 when population was 16.783.000, decreased to the rate of 2.1 per 10.000 in 1984 with 29 new cases In 1997 record, 7 new cases included 3 imported in the total case of less than 99 for MDT when population was 21.3 million.

Multidrug therapy (MDT), a new technological intervention recommended by WHO in 1982, was implemented in Betim in 1987 Its implementation and course was influenced by the historical past of the population and went through different political moments. Although there has been great improvement in the health system organization, now considered a model for all the country, leprosy control is still a challenge for the municipality.

MDT was, however, a revolutionary intervention which marked a new era in leprosy control in this municipality despite the conflicts between agents and clients. The new proposal has brought reflections about the approach to the patient and control of this disease clearly showing that leprosy control is complex and demands not only diagnosis and specific treatment but a new ample intervention to cure the organic, psychic and social lesions caused by leprosy.

The greatest challenge for the third millennium is not only to eliminate leprosy as a public health problem but to eliminate leprosy as a human problem. Thus, we arc working towards a world without people suffering from problems related to leprosy.

For Karakalpakstan leprosy is an ancient heritage, but regular efforts towards leprosy control were initiated since 1933 after national health protection and leprosy service had been organized. To intensify antileprosy activity in 1962 Karakalpak Leprosy Control Branch of Uzbek Institute for Study of Dermatovenerology was opened and two outpatient clinics and six leprosy units were organized. Since 1957 active case-finding through regular sample and mass surveys with annual coverage of up to 100 000 inhabitants were carried out, identified foci of leprosy were put under surveillance with chemotherapy of both leprosy cases and their contacts, and just in 1960-1964 these efforts resulted in finding 490 new leprosy cases. Rates of leprosy incidence sharply contrasted between north and south parts of the country. Thus, in I960 when the highest rate of total incidence for the country was observed (30,4 per 100 000) it was 43,7 in the north districts, approaching 185,6 in Muinak while in the southern parts it reached only 2,8 per 100 000. This difference is due to various factors, including genetic, besides living and economical conditions (Abdirov Ch.A. et al., 1973, 1977). Successful combined chemotherapy resulted in gradual decrease in leprosy incidence. By 1980 a tendency towards sporadic incidence began to be observed, ranging from 0,83 to 0,7 per 100 000 in 1987. In recent years only single cases of leprosy have annually been registered in the north territories, and Karakalpak focus acquired features of disappearing endemicity. Meanwhile, difficult ecological and economical situation, long incubation period, absence of antileprosy vaccine and high susceptibility of a part of the population to leprosy could induce burst of leprosy incidence on Karakalpak territory.

Leprosy is an endemic disease in IRAN. The number of registered cases has progressively declined since 1984.

The cumulative number of cases reported over the past years stands at 10310. In the computerized data collection system established tu 1992, the total number of cases after deleting the repetitions were reduced to 9669. Out of this figure, 1608 cases had already died. From the remaining 8063 patients, 7355 cases have completed their treatment and 708 cases are under MDT.

Considering all those who are under-treatment at the end of 1997, the prevalence rate of the disease is 0.11 per 10.000.

It is clear that leprosy is in the elimination phase in the Islamic Republic of IRAN.

REFLEXIONS SUS LA PRISE EN CHARGE THERAPEUTIQUE ET LA REHABILITATION SOCIALE D'UN GROUPE DE MALADES KMJSENIENS APRES UN SUIVI DE LONGUE DUREE (1963-1998)

APRES AVOIR SITUE LE CADRE DE CES REFLEXIONS ET LE NOMBRE DE MALADES ACCOMPAGNES DURANT CETTE LONGUE PERIODE, 1 'AUTEUR FAIT PART DE SES OBSERVATIONS SUR:

1 - L'EVOLUTION DE LA MALADIE CHEZ SES AMIS ET SUR LES CONSEQUENCES DES AFFECTIONS INTERCURRENTES OUI LES ONT FRAPPES.

CETTE REFLEXION GLOBALE MURIE PAR UNE OBSERVATION ATTENTIVE ET DE LONGUE DUREE VOUDRAIT ETRE UTILE AUX DIFFERENTES CATEGORIES DE PERSONNEL SOIGNANT EN VUE DU "MIEUX-ETRE" DES PERSONNES SOIGNEES PAR ELLES.

Leprosy control in sudan is under severe constraints due to the civil war, which has been going on for 15 years. This has caused more than four million people to be displaced inside and outside the country, in some areas travelling has become dangerous. Resources tor health care have reduced over the years, and man y patients therefore encounter problems in getting treatment.

Even under these dificult circumstances leprosy control activities have increased over the past 5 years. Under the guidance of the late Dr. Khallafalla M. Ahmed, the number of health centres providing leprosy treatment has increased from 25 in 1991, to 401 in 1996. Continued effort is needed to improve the qualify of care.

GOVEHNMENT/NGO COLLABORATION IN LEPROSY ELIMINATION ACTIVITIES - THE BANGLADESH EXPERIENCE and MODEL

In Bangladesh, NGO work is fully integrated into the National Leprosy Programme through a Govt/NGO Memorandum of Understanding(MoU) by which 23 districts and 7 urban areas, representing a population of 47 million or 40% of the country is allocated to NGOs for MDT implementation.

*NGOs run leprosy services within Govt health centres with Govt and NGO staff jointly involved in case-finding diagnosis, treatment, case-holding and care.

*Govt and NGOs assist each other and pool their resource for activities like training, IEC etc.

*NGOs submit periodic reports to the Govt and attend the review meetings at various administrative levels.

The Govt/NGO partnership in Bangladesh is a MODEL that other countries should consider because it has ensured optimum utilisation of resources, avoids duplication of work, complements the strengths of each and has achieved remarkable results, which will be presented and discussed.

En 1985 une association de lutte contre la lepre (ALL) s'est créée à Sfax arec l'aide du comité internationale de l'ordre de Malte d'aide aux lépreux (C10MAL) pour entreprendre une action efficace et adaptée aux conditions pidémtologiques de la lèpre en Tunisie.

1) Moyens de contrôle : un fichier •lèpre• a clé établi est se compose de: une fiche individuelle de dépistage,un registre sommier-matricule.un carnet de traitement.un cahier de traitement

2) Activités de l'Association : l'activité de l'Association est basée sur les enquêtes menétS sur le terrain autour des contacts des malades, voisins et collectivizes dans les tones considérées a forte endOémicité lépreuse (écoles, marchés, casernes...).

3) Création d'un centre dermatologique d'hospitalisation : les malades sont hospitalisés pour un bilan biologique et anatomo-pathologique avant de démarrer la thérapeutique spécifique basée sur la polychimiothérapie ou pour recevoir des soins complémentaires.

4) Bilan d'activité 1985 - 1997 : 210 cas sont fichés et répertoriés selon les normes internationales. Les régions les plus consernées sont: Mahdia 32 % . Medenine 25 %. Sfax 23 %. Ces statistiques révèlent

l'existence de 2 (ayers a endémicite lépreuse relativement importante : Maltouleche, Béni Khadcche. l'exode rural est a l'origine du troisième foyer Sfar. L'incidence reste autour de 0.01 pour dix: milles habitants et la prévalence de 0.03 pour dix milles habitants ce qui place la Tunisie parmi les pays â faible endémicite lépreuse. 60% des malades sont des lépromatcux. Le pic d'âge est situé entre 60 et 64 ans. On note cependant quelques cas entre 10 et 19 ans. La contamination reste essentiellement familiale. 20 % ont une invalidité de degré 3. 150 malades sont mis sous polychimiothêrapic ; rifampicine (dose unique ou mensuelle) selon l'éloignement du malade, disulone ou fanasil, iamprène. 110 malades sont en état d'observation sans traitement. Au cours de cette période, l'équipe mobile a parcouru 549 897 km, a réalise 7665 examens bactériologiques et a examiné 17 712 sujets soit des contacts des malades, soit des citoyens de la collectivité.

5) Instauration d'un cours de léprologie : En vue de sensibiliser le personnel médical et paramédical, chaque année un cours de formation nationale léprologie est tenu dans différentes régions de la Tunisie.

INCREASING THE MDT COVERAGE IN ISOLATED AREA OF NOMADIC PEOPLE BY USING COMMUNITY LEADER APPROACH

Indonesia is a country of islands with a population of about 200 million (1997) and leprosy has been a public health problem in a number of island. Health Services specific to leprosy were not that well organized in some of the islands due to poor accessibility, some cultural and other factors. Waropen atas with a population of 5,373 is one sub-district our of 9 in Yapen Waropen district located on a small island.

Only leprosy cases were on record with poor regularity of treatment in Waropen Atas in 1995. It was suspected that a large number of leprosy cases might have got accumulated and remained undetected in the area, due to poor accessibility and other reasons. A Special Action Project for Elimination of Leprosy (SAPEL) was planned and implemented in Waropen Atas in 1996 from January to December with funding from WHO. Emphasis was put on training and utilizing the services of community leaders in detection of all hidden cases of leprosy and their treatment Project implementation resulted in detection of new cases of leprosy and putting them on MDT treatment. Activities were followcd-up and the treatment regularity was found increased markedly, beside detecting 15 new cases.

This project might not have contributed significantly to the national leprosy elimination goal, but stands as an example of making available leprosy control services to under served and difficult to access population through their community leaders.

A COMPARISON OF EXPERIENCES WITH DIFFERENT METHODS OF INTENSIFIED CASE DETECTION APPLIED IN SOME STATES OF EASTERN NIGERIA

German Leprosy Relief Association, 35 Hill View, Independence Layout, Enugu, Nigeria

In the face of decreasing (registered) prevalence and shorter treatment duration, many leprosy control programmes are embarking on intensified case detection strategies. Given the dearth of resources in many of these countries, it is important that the relativ e merits of varions options are considered before settling for a particular approach.

This paper presents experiences made in some States in eastern Nigeria with methods of intensified case finding for leprosy at local government level (equivalent to districts). The methods compared comprise a Leprosy Elimination Campaign conducted with technical and financial assistance of WHO and locally developed "mini-LECs" using mainly locally available human resources. The paper will describe the main characteristics of the applied methods and the environment. The various approaches will be compared and critically discussed regarding case holding, cost effectiveness and sustainability.

GEO-MEDICAL ANALYSIS AND THEIR IMPACT ON A HUMAN DISEASE: A CASE STUDY OF LEPROSY IN TAMILNADU, INDIA.

Dr.V.Saranavabavan, Resource person, Department of Geography, Madural Kamaraj University, Palkalainagar, Madural - 625021, Tamilnadu, India.

Dr.S.Shanmuganandan, Professor of Medical Geography, Madural Kamaraj University, Palkalainagar, Madural - 625021, Tamilnadu, India.

Leprosy has emerged as a major public health problem in india especially in tamilnadu. There were 15 leprosy affected parsons for every 1000 as agaist the national average of 5 per 1000. A deterioration in the ecosystem of live elements such as personal hygiene, poor tana sanation, overcrowding, housing density, illiteracy are responsible for an increase in the case detection rate of leprosy. Since there is an association between the live elements in geoecosysten with reference to the origin of leprosy, the present study attempts to analyse the following major objectives:

1) To analyse the leprosy situation in tamilnadu with reference to regional variation among the districts; 2) To analyse the living environment and ecological perspectives of leprosy and the leprosy patients; 3) To identify the live elements that largely contribute for the origin of leprosy with reference to spatial distribution of leprosy patients; 4) To identify the major dimensions which determine the patient attitudes towards treatment and follow-up of drug schedule.

The study was based on a questionnaire survey by direct observation method conducted among 300 respondents chosen in all the districts of Tamilnadu. The data ware analysed with the help of multivariate statistical technique known as factor analysis. The dimensions extracted from the analysis indicate that the life elements of leprosy patients are related to the qeoecosystem of tamilnadu. Fourteen major dimensions were emerged with an eiqen value of ranging from 1.00 to 3.45 and with a total variance of 42,33%. The dimensions worth mentioning are; 1) leprosy and Socioeconomic status 2) Physical deformity and permanent disability 3) attitudes of leprosy patients on MDT programme .... The study thus identified the major life elements of leprosy patients and their significance in geomedicalsystem, and their effects on Health cara system in Tamilnadu.

AD, has positioned leprosy on the verge of integration into general Health System (GHS). All Cogitations in this regard, are in the view of dwindling prevalence rate and economic motives.

The paper intends to examine the prospects of leprosy integration programme in the context of knowledge and perception about leprosy in the society. The study was conducted in the metrocity of Bombay and other places with varying endemicity of leprosy.

The study reveals that the tlae is not yet congruous for integrated programme. In view of diagnosis and treatment of leprosy society has shown least faith in GHS.Shockingly, the attitude of the youth seems to thwart the prospects of integrated programme, as one third still favour concept of isolation and 60% opposed to establish marrital relationships with leprosy patients. More than one third (36%) do not seem to accept Germ Theory. Authors strongly believe that dependency on leprosy institutes for service and expertise is an obstacle in post elimination scenario. The authors, reproach authorities for having ingnored the faculty of health education, in the wake of advances in the chemotherapy of leprosy.

The failure in bringing about attitudinal changes in the society may be attributed to the traditional health educational policies. The paper concludes with a word of caution that if health educational activities are not rejuvenated, the integrated scheme will revert leprosy situation to pre-leprosy control era.

Due to the fetters of the tradicional concepts and people's fear, leprosy was a "forbidden zone" for publicity for several decades after the founding of New China. However, after the reform and China opening to the world, Dr. Ma Haide pointed out that technical policies and measures of leprosy control, particularly its publicity work in China shoud be reformed. In 1988, the Ministry of Public Health reissued "The Administrative Regulations for National Leprosy Control Programme", whith freed the publicity work as one of the important measures and since then has been carried out throughout the process of leprosy control with fruitful results. This essay showed that, during "China Leprosy Day", i.e World Leprosy Day in China, how the workers in the field of leprosy practised what they advocate, how the patients made demonstrations with their own experiences, how the government officials, workers of mass media and people from all walks of life involved in and gave support to leprosy control. Also the social and economic results achieved through publicity work were analysed proving that it is really correct and necessary to make the publicity as one of the leprosy control tactics in out country. It also demonstrated that the commitment of governments at various levels and involvement of people from all circles are major factors for a success. The author stressed that only by making people believe and respect science and by usyng scientific thinking and methods to observe, analyse and deal with the issue, could we get rid of man-made obstacles in leprosy control and consequently achieve the goal of early casefinding, prompt treatment, reducing infection, preventing disability and helping persons affected by leprosy return back to the society. Meanwhile, by analysing the exising problems, the author emphasized that efforts must be made continously in popularization of science and scientific knowledge about leprozy.

APLICATION OF RANK SUM RATIO IN EVALUATING THE OUTCOME OF LEPROSY CONTROL PROGRAMME

•Southwest Prefectural Health Service, Xingyi, 562400, Ghizhou Province, China

••Southwest Prefectural Health and Epidemic Prevention Station, Xing-yi, 562400, Ghizhou Province, China

The authors evaluated the outcome of leprosy control programme using rank sum ratio (RSR) in Southwest Prefecture (administratively divided info 8 conties) of Guizhow province. Early detection rate (EDR), disability rate and prevalence were selected and conversed to EDR ring comparison (defined as the change range between EDR among newly detected cases of reporting year and that of previous year), EDR comparison(defined as the comparison value of EDR of the designate county and that of the whole prefecture), disability rate, prevalence ring comparison (defined as the change range between prevalence rate of reporting year and that of previous year) and prevalence cross comparison (defined as the comparison value between prevalence of the designated county and the average prevalence rate of the whole prefecture)as 5 essential indicators for evaluation (EIE). Based on experiences reported and author's own understandind of the importance of these 5 EIEs, their experience weight coefficients, right weight coefficients and RSRw were defined and calculated. These values and their grades directly reflect the outcome of leprosy control programmes in the whole prefecture more scientifically and objectively.

CR.Revanhar. R.Thiruvengadam, D.Girija, MS.Antony Samy, V. V Pai and R. Ganapati

The urban slums are considered to be a difficult population group for achieving the elimination of leprosy with MDT. Dharavi, the largest slum in Asia located in Bombay and reported to have an approximate population of 600 000. was taken up for intensive leprosy control activities by.Bombay Leprosy Project in 1979. WHO-MDT was introduced in 1982 and later short course chemotherapy(SCC) based on rifampicin, ofloxacin and minocycline combination was introduced. Along with regular active case detection methods, intensive case detection activities including special campaigns were undertaken to identify hidden cases at regular intervals using medical students, nurses, community volunteers as well as para-medical personnel. A massive "leprosy elimination campaign" (LEC) using essentially volunteers from the community as well as primary health care workers ("searchers") was undertaken recently to assess the current leprosy situation in trie slum.

A total of 2849 new cases were identified since 1982 out of whom 635 were MB leprosy (skin smear +ve). The registered prevalence rate was 14.4 per 10 000 population in 1982. This declined to 0.1 per 10 000 population by the end of December 1997, thus reaching the level of leprosy elimination in the slum. Though the annual smear positive case detection showed a significant declining trend, it remained more or less unchanged alter 1990 which is considered to be a feature of the elimination phase.

These recent observations indicate that leprosy can be eliminated even in vast slums characterised by several operational difficulties by employing 'searchers' described above to identify backlog cases followed by intensive MDT.

Monhai county of Yunnan borders on Burma with more than 20 minorities (mainly Daizu), a high illiteracy rate (37.7% in children) and an area of 5.511 square kilometers. The highest prevalence of Ieprosy was 1.25‰ in 1978. The average annual detection rate was 6.9/100 000 of last 5 years. Because of shortage of specialized workers, 77.3% of newly detected patients were identified by passive case finding and 84% of them were diagnosed at leprosy clinics. Of 14 townships of this county, leprosy in Monza and Monhai townships were more endemic and the average annual detection rate of last 5 years was 45/100 000 arnd 12.7/100 000 respectively. In the recent 5 years, the total number of newly detected cases in both two townships occupied 77.3% of that of the whole county. Based on the Statement by Member-Associations of the ILEP (July 1994, Hanoi), a SAPEL project was implemented in Monhai and Monza townships by a team of specialized doctors from provincial, prefectural and county levels from 13 to 27 of January 1996. Through deep-going health education to the community and training of health workers at basic level of the whole county with simple language and object teaching method for only two days, then, main attention was paid on household (especially MB households) survey and examination of suspected of clues. Eventually, 22 patients with leprosy were detected among 496 suspected clues and 15 among 431 households of known patients (13 cases from 314 MB households 2 from 117 PB households) with a detection rate of 56/100 000 (Monhai 133.3/100 000, Monza 20.0/100 000) which was 8.1 times as many as of average annual detection rate of last 5 years. The sex ratio of these 37 cases was 0.95 and its type ratio was 0.40, much lower than 3.9 and 1.7 of last 5 years respectively. Afterwards, the project was carried out in another 5 of the rest 14 townships. Up to the end of June of 1996, 22 additional new patients were identified with a detection rate of 10.3/100 000, which was 2.9 times average annual detection rate of last 5 years (3.6/100 000). It indicated that the implementation of active casefinding activities and health education in Monhai county were not efficient and inadequate inthe past, and it also indicated that the SAPEL project was proved effective and feasible for promoting, and speeding up the process of elimination of leprosy in high endemic areas.

CR Revankar. HO Bulchand, Kalpana Chavan, SS Salunkhe, MS Antony Samy, Rashmi Pai, SS Deshpande and R Ganapati

To reach MDT to all undetected leprosy patients in endemic areas the National Leprosy Eradication Programme(NLEP) India initiated a county wide modified Leprosy Elimination Campaign(LEC). Bombay Leprosy Project undertook LEC in its project area covering a population of 1.8 million as a part of statewide campaign in Maharashtra between 30 January and 5 February 1998.

A total of 748 volunteers ("searchers") both from primary health care and community were offered one day training to screen and suspect leprosy in their area of allotment using colour diagnostic cards while going from house to house.

A total of 923,004 residents of the project area, mainly slum dwellers, were screened in seven days. 2190 individuals suspected to be having leprosy were enlisted by the searchers. The field staff of the project confirmed cases and identified 70 new patients. The new case detection rate was 7.6 per 100 000 population. The new case detection rate during 1997 was 13 perl00 000 population.

This campaign showed that a simple task oriented training to community volunteers is adequate to suspect leprosy though it is possible that some leprosy cases especially of the early lepromatous variety might have been missed. This cheaper work force can be used to strengthen the existing manpower involved in leprosy control to refer the suspects to treatment centres for confirmation. The deployment of such searchers will enable us to reach realistic levels of leprosy elimination in metropolitan cities.

A STUDY OF COMPREHENSIVE MEASURES USED IN LEPROSY CONTROL FOR PROMOTING BEASIC ELIMINATION OF LEPROSY

Shandong Provincial Institute of Dermatology, Jinan City, Shandong Province, China

Shandong Province is situated in the east part of China with a population of 87 milhon and 135 counties/cities. About 2500 yeaes ago, the first leprosy case, namely Ran Boniu, was recorded in "Lun Yu" The prevalence of leprosy was high in the past and no leprosy control measures were carried out. After the founding of New China, the government has paid more attention to leprosy control. Since 1955, the comprehensive measures for leprosy control have been implemented in Shandong as following: early case finding, case holding, chemotherapy, management of leprosy control programme, research and health education. Through 38 years of active leprosy control, a prominent achievement was obtained. By the end of year 1992, the cumulative number of leprosy patients was 53.274 and that of cured cases was 39.578, only 321 active cases remained with a decrease of prevalence from 0,45‰ (1960) to 0.0037‰ in 1992. The incidence and detection rates reduceed from 0.05‰ and 0.1‰ during 1955-1959 period to 0.0003‰ and 0.0006‰ during 1988-1992 respectively. After the evaluation of the Leprosy Expert Group of the Ministry of Public.

Health in 1994. Shandong, at the first province in China, was proved to met the China's criteria of basic eradication of leprosy.

In the years of 1994, 1995 and 1996, the total number of registered active cases was 272.231 and 254 (225 in 1993) and the incidence and prevalence rales were 0.00043 ‰, 0.0005 ‰, 0.0006 ‰ and 0.0031 ‰, 0.0027 ‰ and 0.0029 ‰ respectively in this province. It is considered that the achievments of leprosy control have been consolidated in Shandong.

S.S. Naik, R. Ganapati, U.H. Thakar and A.Pharande Acworth Leprosy Hospital for Research, Rehabilitation and Education in Leprosy, Wadala, Mumbai - 400 031, India.s

There is no doubt that due to the impleaentatlon of multidrug therapy the prevalence rate (PR) of leprosy has declined drastically. New case detection rate, however, has reduced only marginally or has remained static in certain areas, this may be due to the foci of infections in the society lurking in unapproachable areas or due to mobility of the community members and spreading the disease.

a) The examition 3030 labourers of five different construction work places revealed six leprosy cases giving a PR of 20/10000.

b) The group of male fishermen (304 persons at Panvel) who remained 8 months on sea were examined in rainy season revealed four new cases (PR 131/1000) of which one was smear positive MB case.

c) The examination of 3457 tribal population on hilly area of Pen yielded 11 leprosy cases (PR 32/10000) of which five were MB.

Such pilot studies suggest that special surveys of selected population groups may have to, undertaken systematically, if the leprosy elimination target by the year 2000 AD is to be reached.

Chittoor is One of the endemic districts in Andhra Pradesh India. It is having a population of 3.26 Millions (1991 Census). National Leprosy Eradication Programme is being implemented in this district both Government and Non Government Orginsation as a vertical Programme. Multi Drug Therapy is started in 1987 and now on way towards the goal of elimination by 2000 A.D.

Impact of M.D.T. on Leprosy Profile in the District is substantial on Prevalance, incidence and other indicator as given below.

Conclusion: These achievements give us the hope to reach the goal of elimination of leprosy in this endemic district by 2000 A.D.

The introdution of MDT in treatment of Leprosy has resulted in substantial in case reduction. Though global elimination Leprosy as Public Health problem (<1/10,000) has been targeted by 2000 A.D. the trend of new case detection (20/10,000) indicates that the problem will continue even after specified period. It therefore, calls for a modified strategy to combat the situation.

The suggested strategy is the reorganisation of the existing infrastructure and a coordinated effort to detect early cases through intensive health communication supported by regular clinic services .

In Balarampur Control Unit of Gandhi Memorial Leprosy Foundation, an experiment was conducted to assess the efficacy of Health Education. The unit with a population of around 2,20,000 was divided into 4 zones. In zone D, mass surveys were conducted in routine SET pattern while In zone C, only Intensive Health Education programmes were undertaken with total population survey every 5 years.

Comparative analysis of 15 Year's (1980-1994) achievement of the zones show that total cases detected in zone D were 1904 (MB-247, PB-1657), self reported cases were 682 (MB-131, PB-551) while in zone C, total cases detected were 2159 (MB-262, PB-1897), self reporting was 1640 (MB-226, PB-1414). Besides, involvement of community leaders were nore viable in zone C.

LEPROSY AFTER THE YEAR 2000: SCENARIOS ON THE BASIS OF THE LEPROSY SIMULATION MODEL SIMLEP

Caims Smith², Abraham Meima¹, Jan Hendrik Richardus¹, Gerrit van Oortmarssen¹, Dik Habbema¹

Although the last decade has seen a dramatic fall in numbers of cases registered for leprosy treatment because of shorter treatment duration, the number of newly detected cases worldwide has remained more or less stable. The case detection trend is decreasing in some areas, but stagnant or even increasing in others. It is therefore unclear what will happen to the leprosy problem after the year 2000. This is of particular concern because WHO has previously set its elimination target for the year 2000.

The following questions can be raised. Which factors determine trends in leprosy? Will disease trends proceed to eradication, or will the pattern of disease become static? Can leprosy control efforts be relaxed? Can leprosy resurge after having reached the elimination target? What is the role of large scale BCG vaccination? This paper opens the discussion on these very important questions on the basis of exploratory scenarios for the future of leprosy that have been derived by bringing together relevant assumptions on transmission and control in the leprosy simulation model SIMLEP.

Preliminary simulations indicate the possibility of persistence of the leprosy problem in the first decades of the new millenium, and of failure to eliminate leprosy if control activities are interrupted too soon.

PROGRESS OF LEPROSY ELIMINATION ACTIVITIES AND TRENDS/ PROFILE OF LEPROSY CASES OVER A FIVE-YEAR PERIOD F ROM 1993-1997 IN BANGLADESH

BANGLADESH National Leprosy Programme was re-organised, integrated into the general health services and accelerated by the Government of Bangladesh through support from the World Bank and World Health Organisation. The accelerated programme has many achievements to its credit within a short time-frame:

*Country-wide establishment of MDT facilities-a total of 600 facilities established " Over 31,000 general health staff trained in leprosy

*Formal collaboration with NGOs by which 23 of the 64 districts are allocated to NGOs for MDT implementation

*Country-wide information and data collection including Geographical Information System. The trends and status of leprosy in terms of prevalence new case detection, MDT coverage, PB/MB ratios, cure rates and deformity rates for the 5-year period will be presented, data analysed and discussed.

Comprehensive Leprosy Care Project & Medical Aid Association, Ciba Compound, Diana Cinema Lane, Tardeo, Mumbai - 400 034.

Leprosy elimination from India by 2000 AD is the stated goal of NLEP. The constituent states follow the guidelines of NLEP. However, there are various constraints and NGO's can help in achieving the goal by removing or reducing these constraints. At Goa, CLCP is providing support for leprosy elimination since 1991. The prevalence is on decrease but currently new case detection and prevalence are almost the same. We were able to identify the areas of support including MDT and disability care and rehabilitation services. Considerably good results have been achieved and disability primary and secondary have decreased appreciably. The cumulative load of leprosy disabled have almost become half of what was at 1990 level. We will present the constraints and help rendered as an example of true bond of partnership for elimination drive in the state of Goa.

THE DRIVE TO ELIMINATE LEPROSY IN BANGLADESH: RESULTS OF SURVEYS IN GAIBANDHA AND JAYPURHAT

Guizhou Provincial Institute of Dermatology, Guiyang City, Guizhou Province China

During the period of 1994-1995, 538 leprosy patients were detected in Guizhou province through a routine modes with a case detection rate of ******* per 100 000 population, an average age at onset of disease of 34.9 years and an average disease duration of 3.3 years. The highest grade II Disabylity rates were 39.3% and 33.5% amongst new patients detected by reporting of suspected cases and trace-survey respectively. With regards the age distribution, no children case ws detected by trace servey but with a peak at age 45-55 group, and no patients with an age of 55 or above was detected by contact examination 45-55 and 35-45 were the peak age groups of leprosy patients detected by trace survey and through passive case finding (self-reporting ang examination at outpatient department of dermatology) respectively. The proportion of patients with a disease duration less than 2 years was 79.2% and 44.4% in new patients detected by contact examination and self reporting. The number of patients newly detected by trace survey, self reporting and skin disease clinic acconts for 82.5% of the total number of newly registered cases. Its is considered that these three case finding methods shoud be implemented as main modes continucously particularly in low endemic situation from the cost-effectiveness point of view. Training of general health workers should be strengthened to improve the quality of early diagnosis and health education should be intensifield to reduce disability rates amongst new patients as well.

Guangdong Provincial Institute of Dermatology, Guangzhou City, Guangdong Province, China

Dongguan Hospital for Chronic Diseases Control, Dongguan City, Guangdong Province, China

Dongguan city lies in the south of Guangdong province with a population of 1.450,000. The total registered leprosy patients were 3.990 during 1950-1995. The prevalence and incidence rates were 1.71‰ and 4.88/100 000 in 1959 and 0.05‰ and 0.76/100 000 in 1990 respectively. To detect leprosy cases timely in such a low endemic area, the authors combined the case detection with the primary health case network during 1991-1995. The measures used were training paramedical workers of primary health care network with leprosy knowledge, developing suspected cases reportring system, widely conducting propaganda about knowledge of leprosy and health education to the community and rewarding the health workers or doctors who detect new cases. The results showed that 35 new cases were detected during observation period. The early detection rate was 85.7% significantly higher than that of 64.1% in 1986-1990 (p<0.01). The disability rate of grade II among new cases decreased remarkably from 35.9% in 1980-1990 to 20% (p<0.01). The authors conclude the adventages of case detection throng this way: 1)through the involvement of general health staff of primary health care netrwork, leprosy control service could be permanently acessible for the patients and common people. 2) a large auxiliary team of leprosy control was developed through implementation of leprosy training programme. 3) the awareness of self health protection of the masses increased, once suspecious symptoms appear they will seek medical advice actively. 4) because of setting up a clue-card reporting system, doctor's attention and responsibility in detecting suspected cases have been improved. 5) a lot of manpower as well financial resources could be saved. The authors suggested to expand this king of way for case detection.

Poladpur Leprosy Control Programme is covenng a population of 2.37,600 and is mostly hilly area and trie villages are scattered into man y small wadies.

Twelve free skin diagnostic camp s were conducted in 12 villages with an ai m to detect new leprosy cases along with the persons who have skin diseases in three months penod and 1430 people were examined. 933 with other medical problems and 497 skin patients were diagnosed and treated and amon g them 6 leprosy PB cases were detected and all 6 patients do not have any deformities. Out of these were 2 Female. 2 Male, 1 Female child. 1 Male child. Even though only 6 cases were detected in these skin camps, il has shown that organising the camp s on a larger scale frequently will help in detecting leprosy cases.

Thus skin diagnostic camps are useful in the leprosy case detection and also to increase the community awareness of leprosy and will help in the inlegrated approach of leprosy services.

El programa de atención primaria en Dermatología se inicio a mediados del ano 1973. Lentamente se ha extendido por todo el territorio Nacional Laboran en el programa los Directores de las diferentes Unidades Dermatologicas Médicos Dermatólogos, residentes en Dermaiologia y los auxiliares de campo del programa de Lucha Antileprosa que reciben un entrenamiento adecuado a ese respecto el proposito básico del programa es el diagnostico y tratamiento de las dermatosis de poca complejidad, descubrimiento de nuesos casos de lepra y control de la endemia en la zona rural. Parte importante de su labor es la educación sanitaria de la Población rural en materia de dermatología y lepra. Recientemente se comenzo un proyecto piloto en la región Suroeste para el manejo igualmente de las ETS en la zona rural.

The Network of Leprosy Non-Governmental Organizations in Nepal was founded in 1995, in response to a need felt by various project leaders to have a forum available to discuss matters of mutual interest. The past 3 years have seen The Network grow in membership numbers and in influence. lts achievements include better understanding of each other's work, and practical contributions to the Nacional Leprosy Elimination Progamme. Athough The Network has no funds of its own, no oflice and no staff, it has become a well established and valued forum, with a distinctive role to play in relation to The N.L.E.P..

The style of interaction represented by the Network could usefully be copied in other countries or regions.

EVALUATION ON KEY COUNTY ACTIVITY FOR LEPROSY CONTROL F ROM 1990 TO 1996 IN GUANGDONG

In 1990, there were a population of 62 millioms and 1.675 active leprosy patients in Guangdong Province. Out of its 99 counties (cities), 23 have already reached the China's criteria of basic eradication of leprosy, but the prevalence was still as high as more than 0.1‰ in 10 and more than 0.05‰ in 5 counties. So the 15 counties (cities) were regarded as key inits where emphasis should be put on for being able to reach the of basic eradication of leprosy in the whole province by the year 2000. Special measures were adopted includind refreshed training of professional staffs and doing individual guidance by provincial leprosy experts under the leadership of the Provincial Health Service.

After 6 years, i.e. by the year 1996, the leprosy control service has been greatly improved. Following were basic epidemiological and operational indicators avaliable in key counties in comparison with those in average of the whole province marked in parentheses: a reduction of active cases by 78.4% (71.8%) a decrease of prevalence by 79,7%(74,1%) increasing coverage of MDT to 99.2% (97.3%) and increasing regularity of MDT to 99,5% (96,3%). The authors realized that the leadership of government and support from concerned departments at all levels, scientific management and individual guidance according to local situations were key points for the success of this project.

The project started on January, 1994 and the rural villages located along Purus and Jurua rivers in Amazonas State were the pilot areas. These areas wore chosen for its high leprosy prevalence, restricted access to health services, high rales of leprosy defaulter patients and low MDT coverage. The main objectives of the study was to implement MDT and reduce the leprosy defaulter patient rates. The strategy was to identity and to train rural health agents and other community leaders, to supervise MDT regimens, and to detect and refer new leprosy cases.

During the project implementation, 94 rural communities were visited, 106 rural health agents and other leaders were trained, 11,462 skin exams were done and 55 new leprosy cases were diagnosed and put on MDT promptly. Besides that, the leprosy prevalence of the project areas was reduced and the main reasons for this results were: patients have moved out, have been released from treatment as cured or informed as died for other causes.

After 2 years, of the project implementation, at Carauan Municipality (Jurua river) the prevalence rate decreased from 87.2/10.000 (1993) to 34,2/10.000 (1996) and the NDT coverage increased from 66.43% (1993) to 93.69% (1996); at Boca do Acre Municipality (Purus river), the prevalence rate decreased from 43.9/10.000 (1994) to 28.9/10.000 (1996) and the MDT coverage increased from 63% (1994) to 93% (1996).

This investigation received financial support from UNDR/World Bank/Who Special program for Research and training in Tropical Disease (TDR)/DAHW.

THE DECREASE OF HANSEN'S DISEASE PREVALENCE IN THE STATE OF MINAS GERAIS - BRAZIL F ROM 1986 TO 1997

Maria Aparecida de Faria Grossi, Maria Ana Araujo Leboeuf, Eni da Silveira Batalha de Magalhães , Maria Aparecida Alves Ferreira.

State Coordination ol Hansen's Disease Control - State Secretary of Health- Minas Gerais / Brazil

The State of Minas Gerais is located in the southeast region of Brazil and has had the largest number of Hansen's Disease cases for some years. This study shows the main strategies used to get the decrease of the prevalence from 39.862 cases, on the active register in 1986, down to 7,640 cases in December 1997.

The main indicators of Hansen's Disease Control were studied from 1986 to 1997 and compared with the number of trained people during this period. Obstacles and facilitating factors were analysed.

The principal facilitating factors for the prevalence decrease were the annual planning and evaluation of actions ; multiprofessional training courses in order to decentralize the Hansen's Disease Control to the municipalities; involvement of different institutions such as Health Regional Directories, Universities, Health National Foundation, Non Governmental Organizations, Health Municipal Secretaries and the Local Health Services.

Great obstacles, due to the lack of human and financial resources faced by the State, were overcome.

The Hansen's Disease prevalence rate in Minas Gerais State was decreased from 27,0 to 4,5 /10,000 in this period of time.

PRIORITIZING MUNICIPALITIES - STRATEGY FOR HANSEN'S DISEASE CONTROL IN A BRAZILIAN STATE WITH 853 MUNICIPALITIES

Maria Aparecida de Faria Grossi, Maria Ana Araújo Leboeuf, Eni da Silveira Batalha de Magalhães.

State Coordination of Hansen's Disease Control - State Secretary of Hearth - Minas Gerais / Brazil

The State of Minas Gerais is located in the southeast region of Brazil It has an area of 587.172 Km² and a population of 16.904,977 inhabitants. This State has the largest number of municipalities (853), and of Hansen's Disease cases in our country, which makes it difficult to control the endemy.

In order to face the difficulty of working with all the municipalities, the State Coordination has adopted since 1995 the strategy of prioritizing some municipalities for more intensive actions with the goal of decreasing (he prevalence of the disease.

This strategy has increased the involvement and commitment of municipal authorities and has made the organization of training courses, supervisions and the assesmcnt of the progress of Hansen's Disease control easier.

This study shows the evolution of the indicators of Hansen's Disease control by comparing data from December 1994 with 1997 in prioritized municipalities and the State where there was a decrease of 21,546 cases ( 13.29 / 10.000 ) to 7,640 cases (4.5/ 10.000).

After 40 years of leprosy contorl with comprehensive measures in Hainan Province, the prevalence of leprosy has decreased to 0,008‰. The average incidence rate in recent 5 years was 0.07/100 000. Seven thousand and forty five cases were detected in totol and 5.654 of them were cured. There are only 60 active cases at present. Fifteen counties have basically reached the goal of basic eradication of leprosy with a marked decrease of endemicity.

But the counties where leprosy were basically eradicated are facing following problems: 1) The attitude of leaders and ataff of specialized institutions turned into passive; 2) The funds for leprosy control from the government decreased; 3) The propaganda and education of leprosy Knowledge were loosened; 4) In order to keep the "achivements" some counties consealed their actual number of cases. Under this condition, the authors recommended that: 1) To strenghen the propaganda and education about leprosy making people fully aware of its importance; 2) To maintain and eahence the leaderchip on leprosy control and keep the organization, funds, ataff-team and task unchanged; 3) To detect new as early as possible and promptly treat them with MDT and put them under surveillance after treatment; 4) To teach new cases and cures to promove their own rehabilitation and self-care; 5) To tighten up the management, report epidemic situation actually and conduct regular evaluation; 6) To hold training courses on early case finding, MDT and POD continuously for helth workers at grassroots; 7) To improve and expand servies of specialized (skin) clinics to further promote leprosy control.

LEPROSY ELIMINATION PLAN - BAIXADA FLUMINENSE/RJ: AN EXPERIMENT ON UNIVERSITY - HEALTH SERVICES INTEGRATION.

Regarding number of leprosy cases Brazil ranks second in the world. Epidemiological indicators, as of 1995 (Brazilian Ministry of Health), are: prevalence rate: 8.82/10.000 population; detetion rate: 2.30/10.000 population: detection rate before age fifteen: 0.63/10.000 population. Around 74.07 percent of its population live in high prevalence areas, such as the towns of Queimados and Belford Roxo (Baixada Fluminense, metropolitan area of Rio de Janeiro) - prevalence rates: 7.9/10,000 reputation and 7.0/10.000 population; detection rates: 2.9/10,000 population and 2.3/10,000 population: abandon rates higher than 40 percent, what is probably related to the centralising model of endemy control adopted by the city health departments (only one health care center with leprosy control program).

Aiming the reduction of the cases to levels lower than 1/10.000 population by precociously detecting all expected new cases and beginning and concluding treatment MDT/WHO of 90 percent of active cases, the School of Medicine of UFRJ (Federal University of Rio de Janeiro) engaged in elaboration and execulion of the leprosy elimination plan in those towns as defined in the Leprosy Elimination Plan/WHO.

The chief charactensuc of this research is its being interventive. The action plan consisted in the integration of the institutions involved, evaluation of human and material resources of city health network, capacitation of 90 percent of health personnel in diagnosis suspicion, capacitation of seven health units previously selected for discentralisation process, participation in open-air health fairs, home visits (active search of missing patients), educational action in schools and community associations so as to publicize signs and symptoms

The authors present their results alter two years of work and its interference in the epidemiological indicators of those municipalities. The work had financial support from WHO in its first year.

Irma E Guerra, BSN, MPH, Ambulatory Care, National
Hansen's Disease Program, Carville, Louisiana. USA

An estimated 200 - 250 persons are diagnosed with Hansen's disease (HD) annually in the U.S.A., which has a population of 269,765,000 (1997). The number of persons currently under treatment for HD is estimated at 600, with 4,200 receiving outpatient care as needed for the residuals of HD.

Challenges to HD care delivery in the U.S.A. include decreased level of interest for education on HD diagnosis/treatment, low index of suspicion for HD by medical community, decreasing levels of funding by government entities for HD services, and, consequently, lack of competition for supplemental grants among providers. The large geographic area of this country and misinformation about HD in the general population also impact HD programs.

A variety of approaches being used to meet these various challenges to HD care delivery will be discussed in this poster presentation.

Before 1958,Guangzhou had one of the highest cases of leprosy among, cities in China. Due to lack of statistics in the past, the figure of leprosy in Guangzhou is oncenain.

The first leprosy control project, including case-finding, treatment, surveillance, education and research, was started in 1958.

From 1958 to 1996 there were seven general surveys, seven expertise examinations and two clue survevs were carried out in Guangzhou Eleven million people(person-time)were examined. People with HD traced to clinic of general hospital and other health system added together came lo a figure of 7419 cases. Fexcept the death from old age and from other diseases, active cases of leprosy in Guangzhou by the end of 1996 was 30 only.

Dapsone monotherapy was implimented from 1958 to 1985 in Guangzhou and after 1986, MDT for leprosy was implimented.

The prevalence rate decreased to <1/10.000, detection rate to <1/100,000 and incidence rate to <1/100.000 in 1985 and met the criteria of WHO's goal. The Prevalence rate decreased from 12.8/10.000 (1965) to 0.08/10.000 (1996), detection rate from 20.31/100,000 (1961-1965) to 0.23/100.000 (1992-1996) and incidence rate from 12.59/100.000 (1961-1965) to 0.06/100.000 (1992-1996), and met the goal of basic eradication of leprosy in China.

Except for prevalence rate, detection rate and incidence rate, the incidence rate of the age from 0-14 years from contacts with HD patients, and the relapse rate of the disease have reach the goal of leprosy control. The facts implied that leprosy can be completely controlled by comprehensive measures including full case-finding and regular trratment.

LOT QUALITY ASSURANCE SAMPLING (LQAS) TECHNIQUE FOR MONITORING LEPROSY CONTROL PROGRAMMES

Conventional survey methods to monitor leprosy control are expensive, time consuming and impratical. Funher, with the attainment of the desired target level of leprosy, the programme administrators" concern should be shifted lo smaller areas (e.g., districts, regions) for assessment and. if needed, for necessary intervention. In this context. Lot Quality Assurance Sampling (LQAS) technique, tried successfully for monitoring and evaluating immunization programmes, was explored. For simulating various situations and strategies, a hypothetical population of 10 million people mimicing Tarnilnadu, India, was generated. Each individual in the population was marked to have the disease or not. by examining the probability (prevalence) of having leprosy. This procedure was done for prevalence rates ranging from I per 10.000 to 10 per 10.000. Assuming Type-I error of 5% and Power of 90S, sample sizes and the corresponding critical values were computed using Poisson approximation. Households, instead of individuals were used as sampling units. Initially villages/towns were selected from the population with probability proportional to size (PPS) linear systematic sampling and from each selected village/town, households were selected using systematic sampling. Puis sampling procedure was simulated 1.000 times in the computer from the base population. Sample size varied from about 3,000 households to 8,000 households.

The results in three different situations were on expected lines in correctly picking up smaller areas with prevalence upto the target level and also simultaneously in classifying areas with prevalence below the acceptance zone. Certain critical factors such as diagnostic efficiency in terms of sensitivity and specificity, non-response, possible heterogeneity, need consideration. LQAS methodology can be considered for rapid assessment of leprosy situation for monitoring purposes after validation under field situation.

The objective of this double blind, controlled field trial is to study protective efficacy of three candidate vaccines, ICRC, M.w, and a combination vaccine of BCG and armadillo derived killed M.leprae , against development of leprosy in healthy population with special reference to progressive and serious forms of the disease.

At Intake, 256,000 persons were examined in Chingleaul District, Tamilnadu. South India. Intake for the (rial wis completed between June 1991 and July 1993, "vaccinating" 170,000 persons. The prevalence of gross and active leprosy at Intake was 25.4 and 9.4 per thousand, respectively. First Resurvey was completed between August 1993 and February 1995. About 265,UK) persons were clinically examined for leprosy, and the prevalence of gross and active leprosy were 17.8 and 4.0 per thousand, respectively. The incidence was 2.3 per thousand per year. 622 new cases were detected from the "vaccinated" cohort. First Resurvey helped in weeding out cases possibly missed at Intake. No decoding was done after First Resurvey.

As per the protocol, a gap of 2 years was allowed following First Resurvey, and Second Resurvey was started in January 1997, Till the end of January 1998, about 165,000 persons were clinically examined for leprosy. Second Resurvey is expected to be completed by August 1998, and it would provide adequate number of cases to judge the protective efficacy of the candidate vaccines. Decoding will be done at the conclusion of Second Resurvey and results are expected by the end of 1998.

1) Data analysis of 10.017 patients with leprosy from 24 provinces and autonomous regions of the country hospitalized and treated in Hanzhong Sanatoriun was provided as follows

*male 7917, fermale 2.100, MF=3.77 *** age: <15 yrs 1.240 (12,38%), >60 yrs 279 (2.79%), 20-40 yrs 7 144(71.32%); MB 7.299, PB 2.718, MB/PB=2.69 1,

*duration of the disease(>5 yrs/2 yrs) at diagnosis: 71.92%/14.04% in 1937 and 2.67%/80% in 1997;

*cumulative relapse rate after monotherapy 4.16% no relapse after MDT, active case 3.526% in 1959 and 29 in 1997.

2) The results showed that isolated treatment of the patients played an important role in reducing transmission of the disease before the introduction of MDT.

3) With the implementation of community control, health education, professional personnel refreshed training, scientific research, physical and socio-economic rehabilitation, the goal of basic eradication of leprosy has been reached in this province.

THE RESULTS OF LEPROSY CONTROL IN YANGZHOU PREFECTURE OF JIANGSU PROVINCE, P R OF CHINA, F ROM 1949- 1996

Institute of Dermatology and Venereology, Yangzhou Prefecture, Jiangsu Province, P R of China

Accumulated cases of leprosy detected in Yangzhou Prefecture from 1949-1996 numbered 19,585 14,701 were male, and 4,884 female. Clinically 2,560 were classified as lepromatous cases, 205 as borderline, 16,797 as tuberculoide and 23 as indeterminate. A total of 14.496 cases were cured through DDS monotherapy from 1949-1983 and a further 1,191 cases by WHO MDT regime from 1983- 1996. There were still 76 Active cases on MDT at the end of 1996. A total of 335 cases relapsed after DDS monotherapy, giving a relapse rate of 2.13%. 3 cases relapsed after WHO MDT, giving a relapse rate to date of 0.26%. The highest prevalence rate was 18.9 per 100,000 population, found at the end of 1973. This decreased to 0.8 per 100,000 at the end of 1996. The highest detection rate was 25.8 per 100,000 population at the end of 1964 followed by a decrease to a rate of 0.096 per 100,000 at the end of 1996.

The authors consider that the success of leprosy control in Yangzhou Prefecture can be mainly attributed to DDS monotherapy but that improvements in socio-economic and living conditions are also playing a role.

The WHO disability grade II rate it over 60% in accumulated, living cases. Thus much work has still to be carried out to minimise secondary impairments in patients with nerve lesions and to improve socio -economic conditions and community acceptance of the disabled where indicated.

STATISTICAL DISCHARGE - COHORT STUDY OF HANSEN'S DISEASE PATIENTS WHO BECAME PREVALENCE CASES AGAIN AFTER HAVING BEEN ADMINISTRATIVELY DISCHARGED DUE TO DEFAULT

State Coordination of Hansen's Disease Control - State Secretary of Health- Minas Gerais / Brazil

A Statistical discharge from prevalence is done following specific administrative cnteria In Brazil these criteria have been changed in past years, in order to decrease the time that defaulting patients continue on the active register

This study demonstrates the patients needing to be treated again arter having had a statistical discharge from 1990 to 1996 in the State of Minas Gerais Analysis was done on length of default time, disability grade, and clinical classification.

Out of 15,727 patients that were statistically discharged, 219 patients (1.4%) returned to prevalence by December 1997 Of these, 36 8% came back within 2 years Deformities were present in 47.2%. The disability grade decreased in 35.2% of the patients 91 8% of these patients were classified as MB when returning, of these 68 % had been previously classified as PB 42.5 % of these patients returned by themselves.

The authors intend to continue this study Currently it shows that there is a small percentage of returns after statistical discharge. This is an administrative procedure under the influence of service and information system organization. Most of the patients wrongly discharged from the active register returned within 2 years.

Lipu and Pingle counties, bordering on one another and with similar natural environment, health status, culture and education backgrounds, economic condition and endemic situation of leprosy, were selected as projected areas. For de purpose of prophylaxis of occurrence of leprosy, DADDS injections were utilized for 3 years in household contacts of known leprosy patients in Lipu county, not injected household contacts in Pingue as controls. The results of 18 - year surveillance showed that no new case detected in 788 injected subjects, but 6 new patients (LL 4, BB 1, TT 1) were diagnosed in controls with a significant difference one another (p<0.001) suggesting satistactory long term effects of leprosy prophylaxis by DADDS injection.

Zhu-min Mao, Zheng-tian Xu, Wei-zhao Zhang, Feng-cun Wang, Jia Zhou and Wen Hong Weifang City Station for Skin Diseases Control, Shangdong Province, China

A general survey of 4.390 cured persons affected by leprosy has been carried out to investigate thier disability status and other diseases they suffered from in recent 2 weeks. The authors also estimated the cost for their non-leprosy disorders. The results showed that the visible disability rate of 4.390 cures 71.95‰ and the prevalence rate of various non-Ieprosy diceaces in two weeks was 94.31‰ about 4.26 times that of general popalation. The average income per member of cures families was 885.3 Chinese yuan only half that of their country residents.

It was stimated that approximately 850 000 & 683 879 Chinese yuan will be needed annually for general rehabilitation and managment of common diseases needed by 4 390 cured people affected by leprosy investigcted. The authors considered that there is a great need of developing suitable models for leprosy control and its financial management.

2) CJIL Field Unit, and Institute for Research in Medical Statistics. Indian Council of Medical Research. Chennai. India

Partial knowledge of leprosy epidemiology and uncertainty about the effects of interventions make it difficult to explain observed trends in leprosy incidence and to predict the future of leprosy. Knowledge of the short and long term public health effects of leprosy control strategies is required for decision making in leprosy control.

SIMLEP is a computer model for transmission and control of leprosy that can be used to simulate region-specific epidemiologic trends over time, producing output on indicators such as prevalence, true incidence and case detection rates of leprosy. In SIMLEP. compartments have been defined that represent immunologic and health conditions with respect to leprosy. Two interventions are incorporated: vaccination and case detection plus chemotherapy. Assumptions can be varied, including those on natural immunity, incubation period, asymptomatic infection, delay between onset of disease and start of chemotherapy treatment, and the dynamics of leprosy transmission.

SIMLEP will be used to improve the understanding of observed leprosy trends by determining the combinations of assumptions that explain these trends. In addition. SIMLEP allows for scenario analyses, in which the effects of control strategies combining different interventions can be simulated and investigated in relation to each other and the range of plausible scenarios for the future of leprosy can be examined. The eventual aim of the development of SIMLEP ts to conduct policy research and support actual decision making by assessing the cost-effectiveness of control strategies.

1945- Estimated 40,000 Leprosy persons in old Ogoja Diocese, South Eastern Nigeria
1946 1,073 patients receiving Chaulmoogra oil
1949 3,000 patients in Ogoja (Obudu-Abakaliki) 3000
19521578 patients receiving Dapsone + 700 children
1953 1,000 patients discharged- cured from 1945
1959 7,482 patients Ogoja, 4994 Ikon Abakaliki estimated 20,000 in area incidence 10%
1960 7019 patients Ogoja + 8190 (Ikom Abakaliki)
1973 5321 patients Ogoja.
1988 Review - 1586 patients on M.D.T.
1995 572 patients- incidence 1.7% children 20%
1997 420 patients children 20%

Masako Namisato¹⁾²⁾, Faouzia Smahi³⁾, Abdelhak Sekkat⁴⁾, Shinzo Izumi⁵⁾, Kunio Murakami¹⁾, Hideoki Ogawa²⁾

1) National Hospital Tama-Zenchoen, 4-1-1 Aobacho Higashimurayama-shi Tokio 189 Japan 2) Juntendo University School of Medicine, 2-1-1 Hongo Bunkio-ku Tokyo 113 Japan 3) C N L Ain-Chok Casablanca Morocco, 4) H.M.I MohammedV. Rabat Morocco, 5) National Hospital Oshima-Seichoen. 6034-1 Ajicho Kida-gun Kagawa-ken 761 Japan

At the Leprosy congress of west-African countries in 1981, the prevalence of leprosy in Morocco was reported to be around 0.75-1.5‰. During 1980 to 1986, the trial of unique poly-chemotherapy (PCT) was carried on to MB patients, replacing for the DDS monotherapy. The PCT regimen (for adult) includes 900 mg of RFP weekly, 100 mg of DDS, 6 days / week and 100 mg of Clofazimine daily Based on the encouraging result of this trial, in 1992, a new system was formally adopted as the national program of leprosy control in this country. It is composed of 1) perfectly supervised PCT-regimen of 3 months duration for both of MB and PB patients, followed with DDS monotherapy for 5 (MB) or 2 (PB) years with regular survey of twice a year. 2) follow-up for another 5 years of MB patients, 3) regular contacts survey for 10 (MB) or 2 (PB) years and 4) socioeconomic and educational support to all the patients and their family members.

The PCT is more intensified regimen than WHO/MDT of greatly shorter duration and common for MB and PB patients.

The prevalence rate of leprosy in 1996 was 0.42/10,000 and no relapsed case has been found until the end of 1997 among more than 13 hundreds cases who had completed PCT. One of the factors for this successful result is the dedication of AMAAF (Association Marocaine d'Application Agricole et de Formation; NGO) which has been supporting leprosy program in Morocco since the year of 1950

The transitions of Bl of skin and nasal smears and the serum levels of anti-PGL-l and LAM-B antibodies of MB cases aged from 17 to 60 years old are now on the vvay of monitoring from the beginning of PCT.

Brazilian social and economical situation in the past decades significantly contributes for Ihe payment of low wages to Halth Professionals and, also for the high level of shifts among personnel. Therefore, this is a very important problem for the State Hansens Disease Control Program since actions in the training of such professionals are often required The lack of a system for the control of Human Resources resulted m the fact that Human Resources upgrading activities were designed according to the demands from the Control Program. A system for Control of Human Resources was designed in 1995 and has been working ever since, withe the use of computers, registering data from Hansen's disease control actions per service, local health branch, professional category courses performed and times when such courses were offered, with the following advantages for the Control Progam

Perfecting the assessment of human resources training for control actions This paper presents the results of this system wich was fed with the data form the registers of the State Coordination collecteds in regional health branches up form 1988, showing that, in this period, more than 10.000 professionals were trained for control actions in Hansen's disease, assessing the shifts of personnel and pointing out the advantages mentioned before.

IMPLANTING SPECIAL PROCEDURES FOR EPIDEMIOLOGICAL SURVEILLANCE OF HANSEN'S DISEASE IN THE MUNICIPALITIES OF THE STATE OF SAO PAULO (BRAZIL WITH ELIMINATION PREVALENCE

Wagner Noqueira. Otilia Simoes J Goncalves, Heleida N Metello, Maria Ap. P. Sanches, Zenaide L.Lessa, Maria de Lourdes B. Diniz

The State of Sao Paulo (Brazil) with over 35 milion inhabitants (over 20% of the country population), for a long time has registered the largest absolute number of sick people in the country," reaching the mark of over 40.000 cases registered for 1988, distributed over the total area of the State, with more than646 cities. After mass implanting of the polichemoterapic schemes/WHO and subsequent recuction of the prevalence coefficien, in 1994 the state registered over 200 cities with no Hansen's disease cases registered.

In the end of 1994, the Elimination Plan was designed, including among the strategies, the starting of special epidemiological surveillance procedures in the cities with no case diagnosed in the previous year.

During the years of 1995, 96 and 97, meetings with the responsible for Hansen's disease control of 18 of the 24 health regional branches were scheduled, involving every city no cases detected. There were also undertaken actions for upgrading of personnel in the health services, as well as health education actions were performed with the population of these cities. This paper presents the results of this intervention, wich has included over 400 cities and circa 1800 health professionals of local levels, showing that despite investments made, there were no changes in the detection cases of the State, allowing us to believe that the absence of cases in many cities is the result of a new epidemiological reality.

The State Hansen's disease control program has developed and implanted a program for monitoring the use of Thalidomide in the State of São Paulo, with the use of computers, designed up from the compulsory notification of the prescription of such medicine by the state health services network of the State, with control actions implanted.

Results are presented according to year, sex, age bracket and reason for prescription, pointing out that use of this medicine in Hansen's disease shows a discreet decrease tendency. The use of thalidomide in women in fertile age has also decreased. In the same period the use has been increased for other pathologies, pointing out its use in AIDS, Lupus. Plane Liquen and Behcet Syndrome.

INFORMATION NATIONALE SUR LA LEPRE A TRAVERS DES APPELS GRATUITS AU MINISTERE DE LA SANTE -BRESIL

Auteurs: Magalhâes. C.;Ayer, E.Z.; Oliveira. M L.W.: Torres W.; Ledra. V.J.; Penna.G.; Coordination Nationale do la Dermatologie Sanitaire Ministère de la Santé du Brésil SOS SANTE (DS-Disque Saùde) est un service téléphonique grauit qui met à disposition de la société un canal d'accès à l'information de plus, avec une amplitude d'action aussi étendue que la compagnie des communications téléphoniques du pays en soi. Elle débuta avec MST (Maladies Sexuellement Transmissibles) et dispose aujourd'hui d'informations comme: donation d'Organes: Conseil National, par Étal et Municipal de Santé; Maladies du Coeur; Cancer de Poitrine: Maladies Transmissibles comme cholera, dengue, varicelle, tuberculosa et Ilèpre. Le service fonctionne du lundi au vendredi, entre 8:00 h et 20:00 h avec réception "on line* iinteractif, au número de téléphone 0800-61-1997. Durant la nuit, les samedis, les dirmanches et Iles fériés, une unité de réponse automatique (URA - Unidade de Resposta Automática) en fonctionnement 24 heures par jour, renseignent automatiquement sur les maladies et actions relationées à la santé.

En octobre 1997. en guise de stratégie adoptées en vue d'augmenter l'adhésion â la diffusion du combat à la lèpre, on intégra au Plan d'Actions du Ministère de la Santé le thème de cette maladi-la qui sont diffusés par le service SOS SANTE. A chaque appel reçu par le service SOS SANTE, et même si il ne s'agit pas d'une question sur la lèpre, les technicies et/ou un enregistrement informent sur la maladie. De plus, le numéro du service SOS SANTE a été divulgué a travers 9 millions de pamphlets distnbués á la population. Le nombre d'appels lors des semaines antérieures et postérieures à cette activité (25/10) a augmenté de 38 fois en relation au début du mots. L'analyse des principales questions, provenance et caractérisques de ses acteurs fournirent d'importantes recours qui permettent proposer cette stratégie pour adapter et étendre Ha communications, et de plus obtenir des informations sur la qualité de l'assistance.

Leprosy control started in 1958 with the National Service Fighting against Leprosy which established mobile brigades (204) all over the country to identify new leprosy patients and fixed facilities for their treatment and care, these included 18, leprosana run by the government or by Chnstian medical services. 549 treatment centres owned by government. Private Enterpnses or Mission Health Centres In 1974 were registered 15280 patients and 791 new cases detected.

After independence m 1975. the country entered a long period of civil war (1975-1992) which resulted m the massive migration of the population towards the cities (urban population passing from 15 % to over 60 %) , the destruction of 60 lo 80 % of infrastructures, a severe shortage of competent trained staff, medication and equipment As the whole Health system collapsed, the Leprosy Program was totally paralysed and survived through a few institutions caring for leprosy, patients.

In 1994 a revised Leprosy Control Program was initiated with ALM's input and in 1996 the first results became tangible: Patients are treated in 32 fixed structures, (60 % are situated in altes and provincial capitals); mobile structures are limited to 4. 1 governmental and 3 Church related . There are. 3301 registered patients and 390 new cases detected. The migration of people has created in the cities communities with a high prevalence of leprosy, reflecting the situation of the area they came from , (slum of Malange people in Luanda aty).

Where are the 120O0 other registered cases ? Most of them have been lost from the registers, they have not received MOT, and have not been cured The dramatic fall of PR from 25.3 in 1974 to 2,8 in 1996 is not a success story, but reflects the total disruption of services.

The future perspectives include: the training of nurses to recognise and treat leprosy using MDT as the only leprosy treatment in the country; integrated care in Municipality Health Centres and other Health facilities to increase MDT coverage ; prevention and management of deformity , and develop public awareness. The increase of new cases means that we can overcome the negative impact of war on leprosy control, as we work < towards the elimination of Leprosy in Angola ».

Emilia dos Santos Pereira, Maria da Graça Souza Cunha, Maria de Fátima Maroja, Tomazia Tavares, Lúcia Saenz Ibanzez, Maria del Pilar R.Berbegal.

Leprosy is endemic in the Amazonas status, Brazil and according to the World Health Organization, about ¼ of leprosy cases in endemic regions, have not access to diagnosis and treatment. The lack of information about the first signs and sympioms of this disease in some groups of the population and health workers, is in greater part what stilt makes difficult the early diagnosis therefore delays its control process.

With the objective to increase awareness and mobilize the general population to early diagnosis of leprosy one of strategies for the year 1997 was the leprosy campaign carried out integrated to mass multivaccination campaign. At the period before the campaign all means of communication available (TV, newspaper, outdoors, radio, posters at supcrinarkets and collective meaas of transportations etc) were used.

In this campaign were involved 921 people amongst health workers and community volunteers. At the day of the campaign, a number of 688 units for basic educational activities and referring suspected cases besides 53 reference health centers were available. 29 leprosy cases were diagnosed and 22 suspected with more details at the present work.

IMPLEMENTATION OF JOINT TB PROGRAMME IN A LEPROSY PROJECT - PARTICIPATION OF ANGANWADI WORKERS (GRASS-ROOT LEVEL) IN ADMINISTRATION OF DOTS.

A join t TB/AIDS programme is undertaken in part of a leprosy project in a tribal district of India with a population of 260 thousands.

The strategy for TB control is to detect sputum positive cases by rapid survey and treatment with DOTS. Anganwadi workers were utilised to monitor the daily treatment as the terrain of the project is difficult and the accessibility to general health services are poor. They were also responsible for DOTS in their respective villages.

210 anganwadi workers were imparted training in TB. A rapid survey was conducted. 271 TB cases were confirmed and 216 cases were put under DOTS. These patients were distributed in 174 villages.

The treatment compliance and the results of treatment are very satisfactory. The Anganwadi workers are identifying and referring new symptomatics.

IMPACT OF IEC COMPONENT ON KNOWLEDGE, ATTITUDES AND PRACTICES OF COMMUNITY ABOUT HIV/AIDS IN A JOINT LEP/TB/AIDS PROGRAMME

Jaydev Sahu PrabhakaraRao V, Tilak S Chauhan. BhuskadeRA, SudhakarKS. Ranganadha Rao

TB/AIDS awareness programme was incorporated into an ongoing leprosy programme experimentally in a tribal district in India. The project covers a population of 2.6 lakhs. DOTS was implemented for TB control. HIV awareness was considered as a very important component of the programme as the TB problem gets compounded in association with HIV.

The major educational inputs were group talks by PMWs at clusters of house-ho Ids during rapid survey, public meetings in different villages and group meetings for service and youth organisations. Before launching the IEC campaign, a pre-test was conducted to have base-line information about the knowledge, attitudes and practices of the people. 1614 group talks attended by 15339 people and 31 public/group meetings attended by 3176 people were conducted.

To assess the changes in the levels of KAP after the educational interventions, a questionnaire was administered to 50 persons selected from among those who attended the educational programmes. Interesting data about changes in knowledge, attitudes and practices of the people about HIV/AIDS has been recorded. The details are presented.

Leprosy elimination is the goal of WHO and National government. There is a need lo understand the perspectives of the field workers in elimination of leprosy. This study was done to measure perspectives of field workers regarding their perception of level of prevalence for elimination of leprosy, maximising and early case detection, improving compliance rate, effective methods of creating community awareness and their suggestions for elimination of leprosy.

1) 52% of the field workers are aware of the prevalence rate at which elimination of leprosy will be reached

2) 60% of the workers felt that they need to do intensive/census survey to detect early cases.

4) 66% of workers feit film shows on leprosy to be ara effective melhod of creating mass awareness.

5) 50% of the workers relt that health information and follow-up within 15 days will enhance the compliancerale.

6) 42% of the workers felt that modilied leprosy elimination campaign using entire health infrastructure in the districtwould a go a long way in elimination of leprosy.

It is estimated that up to 80% of rural populations depend on Traditional Health systems for the management of their ailments. Traditional systems are mosily locally available, sustainable and at low cost. They have often Seen undervalued by those trained in scientific method in the principle 'western' schools of medicine.

One field in which Traditional Medicine is most easily examined is wound healing. Chronic suppurative wounds are common and costly to health services, communities and individuals. The new plague of antibiotic resistant organisms is often generated and spread by such wounds. This is only one of many reasons for examining other systems of medicine as a panacea.

Tissue repair is now well understood and the properties of 'dressings' likely to assist healing can be tested in the laboratory and on the patient.

This poster on Traditional Medicine illustrates 1) cheap locally available systems of debridement, 2) agents that are antibacterial, 3) agents that are antioxidant.

It examines the management of the dying epidemic of the 'leprosy ulcer' against the background of a rising epidemic of traumatic, diabetic, vascular degenerative and decubitus ulcers.

By the end of year 1996, the cumulative number of registered leprosy patients was 55.342. The prevalence dropped from the highest of 62.96/100 000 in 1973 to 0.535/100 000. The dectetion and incidence rates also decreased from 5.69/100 000 and 5.49/100000 in the period of 1956-1960 to 0.16/100 000 and 0.14/100 000 in the period ol 1991-1995 respectively. The proportion of children cases of 0-14 year reduced from 19.82% in the period of 1951-1955 to 1.78% in the period of 1991-1995. On the other hand, the ratio of MB to PB increased gradually from 16.24% in 1966 - 1970 to 115.87% in 1991-1995. The MDT coverage rate was 99.17% in the whole province and the compliance rate was 99.13%. The relapse rate decreassd gradually from the highest of 0.531% from 1961 to 1965 to 0.72% from 1991 to 1995. By the end of Angust 1997, all the counties in Jiangsu province have reached the China's criteria of basic eradication of leprosy.

Department of Dermatology and Venereology. Institute of Medical Sciences, Banaras Hindu University, Varanasi. Inida

In Varanasi a cosmopolitan city situated midway between Delhi and Calcutta, the holy river Ganges washes away all sins for which Leprosy was said to be a punishment. Sushrata giving good clinical account and treatment of Leprosy with hydnocarpus oil in Sushrat Samhita (600 BC) lived in Varanasi Social factors like over crowding along trade and pilgrim routs were considered important by Hansen alter discovery ol*Leprosy bacillus Several leprasona and temples arranged for food to thrown out sufferers of this contagious and communicable disease Varanasi is the holiest of the holv pilgrimage for Hindus. Buddhists, and Jains for yetting cosmic knowledge and salvation. It is a tourist centre of international importance and no foreign tourist goesback to his country without witnessing the rising sun on the Ganges and an evening at Sarnath Banaras I lindu University unique in imparting knowledge in all known disciplines in a single campus and Institute of Medical Sciences the only one of its kind having both Modern Medicine and Indian Medicine as its faculties are engaged in integrating health services with Urban. Rural and Training Centres for Leprosy under National Leprosy Eradication Programme Thus. Varanasi the oldest living city of our planet is working toward a world without Leprosy a disease of antiquity.

Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto. University of São Paulo, Brazil

The late diagnosis of leprosy is usually accompanied by a higher frequency and greater seventy of the involvement of penpheral nerves, with a consequent increase m physical disabilities at the time of detection.

Objectives: To charactenze some possible obstacles in the way ot an early diagnosis of leprosy, such as looking for health services late, difficulty in perceiving tho eaify signs and symptoms of the disease, ihe involvement of prejudice, operational difficulties for medical care, and incorrect diagnoses.

Patients, matinais and, methods: The medical records of 40 patients seen at the Teaching Health Center of the Faculty of Medicine of Ribeirão Preto, USP, were examined and the patients were evaluated during an interview

Results: The 40 patients evaluated (75% males and 25% females) were 13 to 76 years old, 85% of them with incomplete primary schooling. With respect to the clinical form of the disease, 85% of the patients were multibacillary and 15% paucibacillary (7.5% of those with the indeterminate leprosy). Evaluation of disability peiformed on 87.5% of the patients showed that 52.5% were Grade I, 10% Grade II and 35% had no hand or foot disabilities. Skin lesions associated with sensory alterations were reported by 53% of the patients, only skin lesions by 27% and predominantly sensory disorders by 20%. Among the patients interviewed, 32.2% had been inadequately treated for other diseases. Some knowledge about the disease before diagnosis was detected in 45% of the patients. The diagnosis was mad e 1 to 3 years after the perception of symptoms in 27.5% of the patients, < 12 months in 45% of them, and more than 10 years elapsed before diagnosis in 2.5% of the patients.

Conclusions: The results suggest that the slow and insidious nature of the disease possibly impairs the perception of early signs and symptoms, which were observed in 53% of the patients. In 55% of the patients, a period of more than 12 months elapsed between the perception and diagnosis of the disease An incorrect diagnosis had been mad e in 32.2% of the patients, and 55% of the patients ignored the signs of the disease. These results suggest that continuous investments in education of the population are of fundamental importance, together with the training of health personnel for the early diagnosis of leprosy.

- Leprosy stigma was a serums Health problem in Vietnam.
- Health Education has been conducted intensively for many years (posters, radio-TV broad casting, pamphlets, ... even so the passive detection rate and disability rale among new cases were very high.
- New approach/method of Health Education was carried out in some regions.
- Statistic: comparison has been made

- To get data and analyse statistics.
- To evaluate efficacy of the new approach/method

- Selection of areas wuh average prevalence in the delta and remote areas
- Implementation of the new approach:

+ Teachers and school children in primary and secondary school (every families have children at school, many people confidence in teacher's statement)
+ Head/active members of families/Red Cross association members
- Using loudspeaker network plus Radio-TV broad casting, posters, pamphlets... with very impressing picture, timetable for school children with new concept and early signs of leprosy.
- Distribution of questionnaires to every families for knowledge evaluation and detection of suspected cases;

- Number of notification and voluntary cases has been increased.
- The proportion of disability among new cases has been decreased

This approach/method is practical, effective, not expensive, can be applied everywhere.

Chirtagong Leprosy Conttrol Project GPO Box No. 964, Kulshi, Chittagong-4000, Bangladesh.

Leprosy Control Assistant is a peripheral field worker in a project (Paramedical WonXer) and he is responsible for a thana (District Subdivision), with 300 000/400 000 (3-4 lakhs) population Therefore, it is not possible to cover all population by one worker due to inaccessibility and large distance one person has to travel Therefore, photo exhibition is a new method used in reaching out large number of populalion. who are often illiterate, scattered throughout a parts of thana Eacn thana has an average 300 to 3S0 sq km area for coverage Through the newly introduced photo exhibition and voluntary reporting we registered 610 cases from '.he community, during the last one year Another 459 cases were detected by various surveys during the year Nearly 57% cf total 1070 cases were voluntarily reported in 1997.

We are reporting an analysis of various modes of new leprosy case detection with photo exhibitions in this presentations Photo exhibitions combined with Rapid galloping survey phenomenally improved our new case deioction rates In tho last one year Therefore, we are recommending it as a new innovative method of case detection to be incorporated in all Leprosy Control Programmes globally This method is highly cost effoctivo also.

LEPRE ET LUTTE ANTILEPREUSE DANS LES HUIT PAYS MEMBRES DE L'OCCGE DE 1935 A 1997

Alexandre Tiendrebeogo et les Coordonnateurs Nationaux de Programme Lepre des huit Pays OCCGE

L'Institut MARCHOUX. centre de recherche sur la lèpre de l'Organisation de Coordination et Coopération pour la lutte comte les Grandes Endémies (OCCGE). a été cree en 1935 II est charge de la coordination de la lutte ontileprcuse dans les X Liais membres de cette Organisation Les informations sur la lèpre sont disponibles dans les archives de eei Institut à travers les rapports fournis par les Responsables nationaux de la lutte aiUilcprcuse des Pays Membres Liles pcrmeiteni de tracer les courbes d'évolution de la prevaicnee et de la détection des cas dé lèpre de 1935 a 1997 et de comparer l'importance de l'endémie lépreuse dans les Pa>s à l'aide de cartes epidemiologiques

Les deux indicateurs (prévaienec et détection) montrent une évolution en trois phases:

- augmentation de I'endemie au cours des premieres années (1935-1955).
- stabilisation de l'endémie au cours de la décennie 1956-1965.
- diminution de l'endémie a partir de 1965.

Cette évolution est a meure en rapport avec les activités de lutte coordonnées par l'institui Marchoux:

- debut du recensement des cas de lèpre en 1935.
- lancement de la campagne de masse de lutté avec la monothcrapie a la dapsone en 1957.
- introduction de la PCT dans des zones pilotes a partir de 1983
- extension de la couverture PCT depuis 1987.

A la fin de l'année 1997. cinq des huit Pays ont atteint le seuil d'élimination de la lèpre.

Mohan D Gupte¹, Ramakrishna S Vallishayee¹, J Arokiasamy¹, Bathyala Nagaraju¹, B Kishore Kumar¹, Abraham Meima², Dik Habbema²

(1) CJIL Field Unit, and Institute for Research in Medical Statistics. Indian Council of Medical Research, Chennai, India

SIMLEP, a deterministic simulation model for leprosy, has been developed as a collaborative effort between CJIL Field Unit, and Department of Public Health. Erasmus University, supported by LEP. WHO. and NSL. respectively. Validation of this model is presently in progress using the following data.

(3) Data from few NGO centres where details on case detection and intervention are available.

Exercises involving sensitivity analysis are completed. Model based predictions and actual observations are now being compared.

A COMPARATIVE ANALYSIS OF NEWLY DETECTED LEPROSY CASES IN PERIODS OF 1985-1989 AND 1990-1994

Fujian province, where a cumulative number of 28.837 leprasy patients deteced by the end of 1995, was one of leprosy high endemic areas in China. By analysing comparatively the characteristics of cases newly detected in the period, or 1990-1994 with those of 1985-1989, the authors described the results of leprosy control in this province and preferable means to detect leprosy case in different periods. The total number of leprosy cases newly registened in the above ten years was 1.746 including 1.069 cases of 1985 to 1989 and only 177 of 1990 to 1994 with a reduction of 36.7%. In adition, the three rates (prevalence, case detectiom rate and incidence rate) as well at the number of children leprosy patients in the latter 5 year-period were much less than those in the period of 1985-1989. On the contrary, the number of early cases detected in the latter 5-year period increased greatly. All of these indicated that leprosy has been well controlled in Fujian. However, case detection work has become more and more difficult. In order to consolidate the achievements in the field of leprosy control, the authors suggested that it should be necessary and important to detect new leprosy control, the authors suggested that is showed be necessary and important to detect new leprosy patients through various modes of case finding according to different situations in different counties with an emphasis of diagnosis at the departments of skin diseases, which should be an integral part of organizations for leprosy control.

Dalian Municipal Institute for Prevention and Treatment of Skin Diseases, Dalian City, 116021

The Dalian Municipal Institute for Prevention and Treatment of Skin Diseases was previously Liaoning Provincial Leprosy Hospital, which was responsible for isolated treatment of leprosy patients for Liaoning, Jilin and Heilonguang three provinces. With a marked reduction of the number of active patients through leprosy control activities efectivelly implemented in past decades, the leprosy hospital experienced many difficulties in exerting its function of controlling leprosy because of various reasons, mainly of heavily overstaffed vertical leprosy control programme and financial constraint. In October of 1984, with the approval of both provincial and municipal health services, the leprosy hospital was reorganized as the present institute expanding its function from single leprosy control to prevention and treatment of skin diseases including leprosy and STD. This has been a historical "turning point" of the leprosy hospital. Since then a big change has taken place. Compared with 1984, the number of outpatients to the clinic and annual income have been increased by 19 times and 64 times respectively in 1997. Reform policy has brought about an increase of vigor and vitality in the institute whith will definitely promote organization of sustainable leprosy control service.

Leprosy control programme has been carried on for more 40 years, most of registered leprosy patients have been cured, the incidence has been decreased to a low level, and there were only 432 active cases at the end of 1997. After 1987, MDT was introduced for the treatment of leprosy, and treatmemt of leprosy patients and rehabilitation for the patients with disability have been implemented in conbination. As those changes have taken place, the leprosy control programme in conbination. As those changes have taken place, the leprosy control programme in Guangdong province has reached a big achivement.

The mode of case detection was quite different now. Between 1970-1987 years, most of new cases were detected by mass survey and notification, only a few cases were delected through skin diseases clinics and by self reporting In the last 15 yean, 62.07% of new leprosy cases were detected through clinics. 23.5% by self reporting, and only 2.1% by household contacts survey. Most of new cases were detected in time and treated at early stage. In the period of 1985-1987, 3 009 new leprosy cases were diagnosed, the number of new cases detected in the second 5 years of 1988-1992 was only hall of the first 5 years. The total number of newly detected cases in the last 15 yean obviously decreased than before. At present, most of cities in Guangdong province have reached the China's criteria of basic erdication of leprosy. Incidence of children with leprosy was also significantly lower than before, only 145 cases were detected in the last 15 years. The average annual children incidence was less than 0.001%. showing that the infection of the disease has been basically controlled.

Relapse has been lhe main trouble lor DDS monotherapy. The number of relapses after cure has increased gradually from 1983 to 1996 with a proportion as high as 21.27% among the newly registered cases in 1989 and an avenge proportion of 15.91% in the last 15 years. Majority of relapsed cases were cures with DDS monotherapy. Since 1988, thousands of leprosy patients have been cured by MDT. Up to now, only 3 relapses were detected. The authors recognized that MDT has been proved effective in reducing the number of relapses and consequently very helpful for eradication of leprosy in China.

EPIDEMIOLOGY AND CONTROL OF LEFROSY IN FUJlAN PROVINCE CURRENT STATUS AND FUTURE PROSPECTS

Dai-nan Zheng, Zhi-lin Jiang, Bi-ying Yu, Wen-bin Wu, Jian-feng Zhang Fujian Provincial Hospital for Skin Diseases and STD Control, Fuzhou City, Fujian Province Shou-ji Yuan snf Guang-ming Zhang
Fujian Provincial Health Service, Fuzhou City, Fujian Province, China

On the basis of every known patient's history record, space-time -population clustering data and epidemic characteristics of the disease in Fujian province of the past forty years (1954-1996) were analysed. At the same time, the number of counties in Fujian likely reaching the goal of basic eradication of leprosy by the end of 1998 was predicted.

By the end of 1996, 28 951 leprosy cases (MB: 9 365; PB 586 ) were diagnosed with a sex ratio of 2.72 and an avenge age at onset of 32.74 ± 15.49. Prevalence, incidence and case detection rates decreased as time goes on, but the speed of the decline of the above three rates increased gradually.

With a comparison of the data of the periods of 1975-1984 and 1985-1994. the proportion of newly detected patients with an average disease duration of less than 2 years increased from 44.75% to 57 8%. disability rate of the new cases dropped from 22.77% to 13.33 % and average age at onset increased. More and more high or medium endemic counties have become low endemic areas. All of these demonstrated that leprosy has been effectively controlled in Fujian. However, there are still many patients cured with DDS monotherapy, possible relapses among them should be given more attention. Furthermore, the proportion of MB patients amongst active cases went up as high as to 97% in the period of 1990-1995, which was only 65% in the period of 1985-1989, indicating that source of injection still remain in the society.

The authors suggested that: 1) health education should be carried out conlineously. 2) early detection and prompt and regular treatment should be intensified and reached to every patient in need of chemotherapy; 3) In order to timely detect relapsed cases, follow-up of cured persons affected by leprosy also should be carried out regularly.

It was estimated that the China's criteria of basic eradication of leprosy could be reached in 97.5% of all counties in Fujian province by the end of 1998.

The intrinsic minus deformity following ulnar nerve involvement in leprosy is commonly known as claw hand deformity. With passage of time, uncorrected & jnattended claw fingers develop soft tissue contractures and stiffness at the proximal interphalangeal joints. Reconstructive surgery almost ceases to play a role in such hands. The new dimensions of 'Law of tension stress' principle was originally developed by Ilizarov for limb lengthening. The tissue distraction by gradual tension stress was developed later by Joshi's external stabilisation system. This apparatus for distraction was applied to leprous claw hand. The technique involves insertion of K wires, fixing distraction rod and gradually increasing the tension in required direction. Results in soft tissue release and improvement in range of motion in a study of 15 cases will be presented along with funcional benefits. The use of this technique has widened the horizon of reconstructive surgery in leprosy.

The social dimension of leprosy often surpasses the public health dimension. Therefore, it is necessary to consider an integrated action plan consisting of strategy for elimination, disability prevention, care and rehabilitation. Elimination should be achieved not only at the macro level but also at the micro level. The capacity building of leprosy staff in delivering the qualitative care for their disability and their social integration has been carried out to make reaching out possible. Reaching out to disabled PAL's is not an 'outreach* service but the total involvement in understanding leprosy disability care activity from the perspective of the afflicted and establishment of a 'care' system. The model development by CLCP has a decades experience behind it.

The 'handicap' so far referred to has only been as perceived by the opposite party and not as persons 'participation' in activity of daily living or occupation. Long standing & chronic physical abnormalities seen in leprosy make adoptative changes in PAL's behaviour and social outlook Th effort t improvement i aidin th PAL's to enhance their standing ira their own eyes, in family and society require provision of learning, aids and appliances and rehabilitative services. The evolution over a decade demonstrate the feasibility of the integrated services and rehabilitation activities by which more than 8000 PAL's have benefited thereby enhancing the value of the health care delivery.

RETROSPECTIVE STUDY COMPARING RECOVERY OF MOTOR NERVE FUNCTION DEFICIT WITH AN ALTERNATE DAY REGIMEN OF STEROIDS AND A ONCE DAILY REGIMEN.

This study involved use of the data available from in-patient records, consisting of patients who were treated with 60 milligrams of prednisolone on alternate days for 6 months with those patients and patients who had received the daily regimen.

48 nerves were studied under the OD regimen, and 39 under the AD regimen. The power of muscles as graded according to the BMRC score (Grades 0 to 5) was used, and the lowest scoring muscle for each nerve was recorded as the power for that nerve. All patients were either on treatment, or had been treated with MDT and the episode being investigated had not been treated with any other drugs.

The variables studied were: type of disease, duration of disease, duration of neuntis. nerve involved, power at diagnosis and after treatment, maximum power regained, duration of steroid therapy and time taken to attain maximum power.

IMPACT OF COMMUNITY BASED DISABILITY SERVICES IN AN URBAN SLUM - A QUESTIONNAIRE STUDY

Bombay Leprosy Project has implemented a Low Cost Disability Management (LCDM) programme in an urban slum in Bombay, where significant reduction in prevalence of leprosy was achieved after successful MDT programme. 25,000 population was covered and disability care was offered at the doorstep of 35 disabled leprosy patients through community volunteers living in the same slum. In order to evaluate the impact of the programme a questionnaire study was initiated focusing on three groups.

The first group consists of deformed leprosy patients who were assessed for their level of disability care measures which they were practising. The second group consisting of family members and neighbours was evaluated for their attitude and involvement in the care of disabled leprosy patients and distant community members formed the third group whose knowledge regarding leprosy related disabilities was also subjected to assessment Similar questionnaire study for purposes of control was conducted in another area where institutional based disability care was offered by trained professionals.

The study indicates that 65% of the disabled leprosy patients do not regularly practise disability care in spite of receiving constant instructions about self care measures in both these areas. 82% of the family members and neighbours acquired more knowledge about leprosy and actively assisted in disability care of the patients in study area as compared to 66% in control area. The study also revealed that the acceptance and participation by the family members was 78% in study area and 54% in control area. It was anticipated that practising disability care in the community will indirectly contribute to an increased awareness in the slum under study. However the intensive health education campaign practised in control area has resulted in increased knowledge about leprosy among the distant community members.

Early identification of nerve function impairment (NFI) which is insidious in onset and prompt treatment are crucial to prevent disabilities in leprosy. Though it may be possible to detect NFI by using sensitive tools, it may be difficult to adopt these in a field situation.

A retrospective analysis of 980 leprosy cases registered in the field clinics of Bombay Leprosy Project revealed that the proportion of nerve trunk involvement increases with an increase in number of skin lesions. Patients with more than 5 skin lesions had more nerve trunk involvement

We have developed a simple flow chart for the use of field level leprosy staff to identify risk prone cases among patients with more than five skin lesions and also have suggested the method to manage these cases more effectively.

The Danish-Bangladesh Leprosy Mission. Nilphamari. Bangladesh and The Department of Public Heaiih. University of Aberdeen. Aberdeen AB25 2ZD.

There is much interest in methods which reduce impairment and deformity amongst leprosy patients. While definitions and methods of detecting change in nerve function may be well established, methods of analysing and summarising outcomes remain complex. The multiplicity of disease types, of nerves, of nerve functions and of outcome measures makes this a particularly difficult area in which to produce a meaningful yet accessible statistical analysis and summary.

Based on the data collected in the Bangladesh Acute Nerve Damage Study the present paper is concerned with identifying appropriate methodologies to address hypotheses concerning the effectiveness of steroid treatment in reducing the seventy of nerve function events during followup. For 2664 patients studied during a two year follow up period some 2.000 nerve function events were identified. A convenient way to summarise these events is in the form of transition matrices, tables summarising the probabilities of cases moving from one level of impairment to another in successive assessments.

The Table presents the data for right ulnar impairment based on ball pen sensory testing of five points on the right hand. The row labels represent the number of points down at assessment one. the columns at assessment 2. Thus aggregated over the period of the study the probability of a patient rated at 2 points down by ball pen test at assessment 1 moving to 0 or 1 points down at assessment 2 is found to be 57.1%. The methodology used here is described in detail and in extended form allows comparisons between patient groups of interest, for example, to illustrate differences between steroid and non steroid groups, the latter summarising spontaneous recovery in the cohort. Related methods are used to explore the importance of other patient and disease characteristics assessed at diagnosis.

DETERMINATION OF RELIABILITY AND ACCURACY OF COMMERCIALLY AVAILABLE MONOFILAMENTS FOR THE MEASURE OF SENSIBILITY

David Giurintano, John Figarola. Larry Pfeifer, Denise Brasscaux, and Alicia Hoard

Monofilament devices arc widely used for the monitoring of neuropathy of the hands and feet. Variance in the production of the nylon filaments used in the monofilament devices can result in a difference in the production of force between each manufacturer's device. Currently, there are seven manufacturers of monofilament devices. Each manufacturer was requested to send ten monofilament kits for testing. The manufacturer's ten kits were placed in a random order and each monofilament was tested by five testers for eighteen trials.

A commercially available force transducer was used to measure the forces of the lighter filaments and a spatula strain gauge was used to measure the heavier monofilaments. The accuracy of force calibration and the reliability of force production was determined. The results will be reported and discussed.

THE SIGNIFICANCE OF NERVE FUNCTION ALTERATION IN PATIENTS DURING THE SURVEILLANCE OR POSTSURVEILLANCE PERIODS IN LEPROSY

In leprosy patients released from treatment (RFT), nerve function alteration appearing during the surveillance or postsurveiUance periods is generally considered as a sign of relapse or late reaction. Our study, based on histopathological examination of nerve biopsies, is intended to evaluate the significance of this complication of leprosy.

Our retrospective study includes the period from 1^st January. 1090 CO 31 ^stDecember. 1997. We examined the clinical data from 110 patients referred for nerve biopsy evaluation in whom a clinical diagnosis of relapse was made, based on recent motor and/or sensory nerve function deterioration.

The histopathological examination has confirmed in only 19% cases the clinical diagnosis of relapse (12%) or reaction (7%). In the remaining 81%, the finding was that of a healing and scarring phenomenon. We assume that the latter phenomenon plays an important role in this complication in bacteriologically cured patients.

The use of steroid therapy in the management of reactions and neuritis in leprosy is now gaining more importance in view of the possible nerve function impairment if not managed properly at the appropriate time. Steriod treatment js generally arbitrary and symptom - based. It would be easier for the leprosy workers to manage reactions and neuritis at the field level, if the schedule of steroid therapy is standardised.

We present our observations with the standard steroid regimen schedule devised by us for the management of reaction and neuritis,the maximum initial dose being 60 mgms of prednisolone and maximum duration of 28 weeks for acute neuritis, 40 mgms for cutaneous lesions (24 weeks), 30 mgms for ENL(16 weeks) and 20 rngrns for recurrent ENL(8 weeks ) with clofazimine (6 months ).

Since May 1994, 426 leprosy patients who had reaction were included in the trial and were treated using this standard steroid regimen. All the patients were screened by leprosy workers at the field clinics and given treatment after ruling out the contraindications with the help of a simple guideline. This group was compared with 350 patients treated with arbitrary regimens. On follow up 109 (26%) patients in standard regimen and 138 (40%) in arbitrary regimen developed recurrence of reaction. They were treated with an alternative schedule of steroid regimen. The commonest side effect seen was 'moon face' in a considerable proportion of patients. None of the patients developed any serious complications and in none the nerve function deteriorated.

We conclude that the use of standard steroid regimen will facilitate the leprosy workers to manage the reaction and neuritis more effectively at the field level.

REGISTRATION DELAY AND OLD AGE: PRIMARY RISK FACTORS FOR IMPAIRMENTS IN NEW LEPROSY PATIENTS

Abraham Meima¹, Paul Saundersom², Shibru Gebre², Ketsela Desta², Dik Habbema¹

2) All Africa Leprosy. Tuberculosis and Rehabilitation Centre (ALERT). Addis Ababa. Ethiopia

Material and methods: This study reports on 592 new leprosy patients enrolled in 1988-1992 in the prospective ALERT MOT Field Evaluation Study in central Ethiopia (AMFES). The main outcome measures are odds ratios on impairment for the risk factors sex. age. registration delay, classification in combination with Bl. contact status, and distance to clinic which were calculated using multivanate logistic regression.

Results: 32% of new patients presented with WHO impairment grade 1 and 23% with grade 2. Old age. registration delay and MB classification with Bl value 0 were significant risk factors for impairments. With as baseline age group 15-29. odds ratios ranged from 0.46 for the youngest (0-14) to 5.0 for the oldest age group (60*). 35% of new patients had a registration delay of 2 to 3 years. 21 % of 4 years and over. Their odds ratios for having any impairment were 4.1 and 8.5 respectively. Compared to PB. the odds ratio for MB with Bl value 0 was 2.85.

Conclusion: Registration delay and old age are the main risk factors. The registration delay in central Ethiopia should be reduced. This calls for improvement of accessibility to leprosy treatment, reduction of the stigma of leprosy, promotion of appropriate health seeking behavior and contact tracing.

Prevention of disabilities is the most important and cost effective approach to disability care. Primary prevention is achieved by early case detection and regular treatment with MDT. MD T has reduced the occurrence of disability as compared to DDS monotherapy. Nevertheless, new cases arc still detected with disabilities and this has added a substantial number of patients to the overall disability load in the community. If disability care services are provided in time, they not only prevent the deformities but can also limit the worsening of disabilities. The sensory motor recovery by corticosteroid therapy or neurolysis in an early recognised reaction is possible and avoids the development of deformities.

The other key modalities include : patient education on self care, physiotherapy exercises, domicilliary delivered prefabricated standardised splints designed by us for claw hand, ready to strap on foot drop splint, Modulan grip-aids, ulcer care delivered by 'Ulcer Care Kit', combined approach of referrals and camps for reconstructive surgery and economic rehabilitation. CLCP has pioneered the approach and by and large succeeded in standardising the field level disability care delivery system. Our experience and results will be presented.

PLANNING & ORGANISING DISABILITY PREVENTION, CARE & REHABILITATION SERVICES AS INTEGRATED LEPROSY CONTROL ACTIVITIES.

With the decreasing load of patients for providing treatment the existing leprosy infrastructure can be oriented to disability prevention and care services. Disability management is now considered under disease control. Envisaged to achieve this situation almost a decade back, CLCP has pioneered the integration of disability management since 1989. The stepwise approach comprises the data collection, computerisation of data & analysis in the manner which help field based, low cost disability care services. Task oriented training in defined modality of services viz. Self care. Prefabricated splints, Modulan Grip-Aids, Early identification of nerve damage, MCR footwear etc. form the integral part of field based services. The study involves more than 5000 patients cared for and their assessment. The cumulative disability load in community per 10,000 population needs to be taken as the basic indicator for estimation and resource planning. The gradual decrease in this indicator points to prevention of disability. Reporting format and monitoring has demonstrated that high quality of results can be achieved even at the field level. The experiences at various levels in different geographical region, their similarities and feasibility of replication will be presented.

Recent advances in computerised management information system have been applied extensively to the disability management in our projects. The baseline requirements have been standardised. Reporting format for updating the records for service delivery has been designed for field level application. The follow-up of patients, improvement or deficiency in coverage & quality of care can be analysed quickly and appropriate corrective actions can be taken. Midcourse corrections are easy to derive and the ultimate care of the disabled improved. The report generation requires some additional skill in use of computers but can be simplified if proper software is developed. Geographical information right-up to village level can be obtained to the advantage for strategy planning & resource allocation. Graphics and making of presentations is simplified. Our methodology and experience in disability management information system will be demonstrated.

Comprehensive Leprosy Care Project & Medical Aid Association, Ciba Compound, Diana Cinema Lane, Tardeo, Mumbai - 400 034.

The most difficult problem in qualitative care of leprosy affected persons is the management of foot care. We have devised the systematic approach to reach majority of required services like self care education, ulcer prevention and promotion of healing by two way interaction of domicilliary care by affected person and supply of required services like contact cast or walking P.O.P. by trained personnel using 'Ulcer Care Kit'. The approach to foot drop was reorganised with early identification, steroid therapy and prefabricated foot drop splint. The decompression of nerves if required or the surgical correction were the referral services provided. However, the maximum benefit is obtained by providing regular supply of different design of footwear standardised at Leprosy Management Training Centre. Our experiences and results by the systematic approach will be presented.

Los Angeles County USC and Cedars-Sinai Medical Centers, Los Angeles, California, U.S.A.

Loss of fibro-fatty tissue is associated with calluses and painless pressure ulceration. During a 34-year period (1964-1998), silicone fluid (dimethylpolysiloxane) was studied as an injectable soft tissue substitute for pressure keratoses and insensitive ulcers. Among 1420 cases were 30 with diabetes and 3 with leprosy, median age 59.9 years (range 38-36) with loss of sensory response plantarly. Each in this subgroup had one or multiple episodes of skin breakdown with healing at 36 plantar sites (11 hallux, 22 metatarsal heads, and 3 metatarsal bases). Upon healing, serial 0.10 - 0.20 ml amounts, mean 1.65 ml (range 0.60 - 5.0 ml) were sub-dermal ly injected beneath points of maximum pressure. Externally placed pressure-reducing devices were not used. In 1-20 year follow-up, mean 6.9, 28 of 36 (77%) did not recur. No serious complications were observed.

Skin specimens gathered from 34 patients postmortem, mean 13.2 years postinjection (range 2-29^1/2) were analysed by light and electron microscopy. Silicone consistently induced a relatively bland fibrosis and histiocytosis without untoward reaction. These favorable clinical and histological findings conclude fluid silicone is a safe and effective biomaterial for the treatment and prevention of some common pressure-related foot disorders, including insensitive pressure ulcers.

Jessica Kiewied, Tezazu Alemu, Heather Currie, Roland Kazen, Paul Saunderson, Guido Groenen

Objective: To assess frit cut-outs as a method of improving the healing of plantar ulcers in leprosy patients.

Subjects: 32 leprosy patients with small to medium size uncomplicated ulcers of the forefoot or midfoot were randomly assigned to one of three groups:

The patients were seen every 2 weeks for 8 weeks, and the evolution of the ulcer size was monitored.

Results: For the care + felt group, the mean ulcer size reduction was 87% and 1 had healed completely. Continuing felt therapy resulted in complete healing in 4 more patients.

In the POP group, 5 refused the treatment, and 2 abandoned within 2 weeks. 3 out of the remaining 4 patients were completely healed at 4 weeks, the fourth one had an ulcer reduction of 89% at 4 weeks but refused further POP treatment.

Conclusion: Although POP clearly works well, it has a very low acceptability. Felt therapy is a useful alternative. It is a very effective addition to standard ulcer care, significantly improving ulcer healing at 8 weeks. It is also very well accepted by the patients. The cost of 4 weeks of felt therapy is, at US$ 7, comparable to one POP application.

Samples of felt cut-outs and diagrams showing their application will be presented. A list of suppliers will be provided.

Dr. K. UDAYA KIRAN, Dr. August Beine, Sr. Elsamma, V Sivananda Rehabilitation Home Hyderabad. In Leprosy patients with sensory loss in the feet there is a increased risk ot injury. In this paper we wish to present our experience with regard to the usage of a standard foot wear 'ASRASS' for this problem when the patient has a forefoot problem/ulcer. ASRASS is a standard design advised and found useful in a majority of patients to manage forefoot ulcer & to prevent. During the last three years about 2000 pairs of ASRASS foot wear were supplied for the needy leprosy patients. ASRASS - design incorporates the usual rigid shank and anterior roller and support which help to reduce and shift the damaging forces from the ball of the toot (metatarso phalangeal joints). Scooping is done where required.

The cost of the foot wear is $ 4 each (Rs.160/-) Materials used, weight will be mentioned and discussed with regard to other foot wear and patient acceptance. Colour slides wil l be presented. We found that like standard MDT for Leprosy, standard steroid regimen for Type I reaction - standard foot wear "ASRASS" Will go a long way in encouraging its wider usage usage for the benefits of needy leprosy patients.

Objective: To compare the distribution of pressure on the sole of the foot while walking in plastazote shoes made from moulds taken with the patient sitting (as advised in currently available shoe-making manuals) or standing (as may be deemed more physiological).

Subjects: Two people with feet deformed by leprosy were examined. Subject 2 had a right-sided drop-foot. Design: Pressure measurements at three points were made on each foot during periods of walking in a figure-of-eight pattern. Pressure transducers were calibrated and connected to a computer for recording purposes. Each foot and each shoe yielded 120 measurements at all three sites, giving a total of 2880 individual readings.

Main outcome measures: The mean peak pressure at each point for both feet using both shoes was calculated. Units are Newtons/ sq.cm.

Results: Change in pressure associated with changing from the sitting mould to the standing mould:

Conclusions: The pressure on the back of the foot is increased by a small amount when the mould is made in the standing position. The pressure over the head of the first metatarsal, on the other hand, is decreased by a large amount, except in the case of the drop-foot. As over 70% of leprosy-related ulcers occur in the forefoot, reducing the peak pressures in the forefoot is a major objective. Moulds made in the standing position are therefore more likely to reduce the risk of plantar ulceration.

The Foundation for Research in Community Health. 84-A, R.G. Thadani Marg. Worli. Mumbai 400 018. India.

The most intractable problem in the rehabilitation of leprosy patients is the anesthetic foot and subsequent ulceration.

Contrary to common belief it is rigidity of the sole, and not a paded paded insole, which redistributes pressures. The Foundation for Research in Community Health has developed in conjunction with the Indian Institute of Technology. Bombay a controlled rigidity fibre glass shank to fit into any off the shelf normal footwear. This is superior to the traditional leprosy footwear without the associated stigma.

Plantar foot ulcers arc an important continuing problem in leprosy care after MDT. accounting for more than half of all admissions to Anandaban Hospital. We have investigated the bacteria infecting simple and complicated ulcers at the surface, inunderlying tissues, joints and bones. We have speciated and tested for antibiotic sensitivity. The relationship between tissue type, ulcer type and past history of ulcers and the species isolated will be presented. We have also investigated the involvement of joints underlying deep ulcers on the first metatarsal head to quantitate the proportion of deep ulcers which result in septic arthritis. The efficacy of current practices in the management of ulcers will also be discussed.

Jacob Mathew. Antony P. Ethiraj T. Krishnamurthy P Damien Foundation India Trust (DFTT), 27, Venugopal Avenue, Spot Tank Road, Chetput, Chennai - 600031, India.

The objective of the study was to make patients self reliant in the care of their plantar ulcers in their own homes.

Paramedical workers of 8 DFIT projects were trained (3 days), in imparting training to patients on self-care and also in monitoring progress. About 588 patients in these projects were trained in self-care of their ulcers, using took found in their homes and own surrounding and teaching them to become responsible for themselves for the care of their limbs. The follow-up period was about 1 year

At the end of the study period, there was a reduction in ulcer prevalence by about 60%. Various factors related to personal and family characteristics of patient and provider characteristics bearing an influenceon self-care practice and outcome will be discussed.

This study of Prevention and Treatment of Plantar Ulcers took place at Out-Patients Service of the Health Department of Piraquara PR - Brazil. This area is a satellite village settled by patients who left the colony, after the compulsory isolation, whem the treatment at public health centers had its start in the late forties. All patients of this study are cured and we have followed them up during two years and a half, in order to observe the effect of Prevention and Treatment of Disabilities by Application of Simple Techniques.

UTILIZATION OF SEMMES-WIENSTEIN MONOFILAMENTES FOR CONTROL OF THE POTENTIAL IMPAIRMENT IN HANSEN'S DISEASE

The Monofilaments of Semmes-Weinstein are useful for Disabilities Prevention and Treatment by Simple Tecniques of Hansen's Disease at Out-Patients level, beside specific treatment. This sensory testing requires the use of Semmes-Weinstein style nylon filaments which produce the range of forces: 0,05 g, 0,200 g, 2,0 g and 4,0 g. This valuation of sensibility shows different levels of impairments and points out potential injuries (plantar ulcers, traumatic lesions, burns). The use of Semmes-Weinstein filaments tests may be used to follow the development and treatment of neuritis.

Dept. of Neuromuscular Diseases, Imperial College School of Medicine. London. UK.

licensed thalidomide tor the management of erythema nodosum leprosum (ENL). No evidence was produced both at the FDA hearings, and the subsequent workshop, that ENL leads to renal amyloidosis, or is associated with nerve damage, uveitis, orchitis or arthritis. Thalidomide has thus been used in leprosy patients for 30 years to manage a complication which is not serious or life threatening. Thalidomide neuropathy is a very serious complication and sensory loss is permanent in half the patients even years after stopping the drug. A symmetrical loss of sensation only occurs in the late stage of lepromatous leprosy.and in a personal series was present in 4 out of 14 patients with ENL. Thus the use of thalidomide may inflict intractable sensory loss on a leprosy patient which would not have developed as a result of the disease. Yet thalidomide neuropathy has not been recorded in any leprosy patient, although when the drug is used in non-leprosy disorders, 21 % of patients have developed a neuropathy.

Because other drugs such as pentoxifylline are available, and because of the recent teratogenic disaster in Brazil reported by the media, thalidomide should no longer be used to manage ENL.

A REVIEW OF THE ASSOCIATED OCULAR LESIONS AMONGST THE LEPROSY SUFFERERS WITH LAGOPH THALMOS.

300 leprosy sufferers with lagopthalmos in Eastern India are reviewed on a retrospective way. 1/4th of them were on active treatment and the rest completed MDT/sulphone monotherapy. There were sponteneous on set of lagopthalmos in 80% of the study groups without any specificity of affection of either side. 80% had corneal hyposthesia with corneal opacity amongst half of them. 39% were blind in one eye (corrected vision less than 3/60) and 20% were socially blind (corrected vision less than 3/60 in the better eye). Cataract, corneal scar & chronic iridocyclitis were the causes of blindness. Chronic Dacryocystitis, Ulcerated extremeties, Osteomyelitis etc. were associated with 75% of the cases to make the eye under 'High risk group'. Only 3% of the study group had tarsorraphy and the rest were totally neglected without any surgical or regular medical supervision. No such intregrated arrangement was observed in most of the centres to render proper eye health care to this community. An urgent measure is suggested to deploy a mobile eye care unit to look after these leprosy sufferers with lagophthalmos.

Leprosy patients with visual impairment are in double jeopardy: while a quarter million leprosy patients are estimated to be blind. the extent of ocular morbidity is unknown. since data available are often inaccurate and based on hospital patients. The pathways to blindness could be several, both due to leprosy as well as associated physical and socioeconomic problems. These aspects are best studied through population- based cohort studies. Such a study on Ocular leprosy (LOSOL) was initiated by WHO among newly diagnosed MB patients registered at Addis Ababa. Cebu and Karigiri (India) in 1989, using standardized methods.

The findings from Karigiri centre (supported by LEPRA) are presented based on 280 MB patients enrolled so far. At registration, one-fifth of eyes already had cataract: and another significant number have corneal or other morbidity.

Incidence of ocular morbidity during multidrug therapy, revealed that nearly half the patients had various eye complications. Such high ocular morbidity needs careful study to identify, possible risk factors to such problems.

PREVALENCE OF DISABILITY IN AN URBAN SLUM - AN ASSESSMENT WITH REFERENCE TO REHABILITATION

Assessment of the real magnitude of the problem' of rehabilitation of those handicapped due to a variety of disabling illnesses including leprosy needs an epidemiological approach. It is estimated that 7 -10% of the population in developing countries are physically disabled.

We have earlier demonstrated that the involvement of community volunteers to offer disability care to the leprosy disabled at the door step in an urban slum in Bombay was successful and cost effective. We initiated a comprehensive disability survey of 4937 residents of a small part of a large slum through the community volunteers covering a part of the slum, as a first stage before launching a community based rehabilitation programme. The outcome of this population based survey indicates the prevalence and distribution of different categories of disabled persons in an urban slum are as follows.

It is seen that those disabled due to leprosy form only about 17% of the total. 90% of these disabled persons were able to secure rehabilitation services from the institutions in Bombay. It is interesting to note that the disability rate is maximum in the adult age group and most of them required vocational and economic rehabilitation. We conclude that the resources and manpower used for offering community based disability care to the leprosy disabled can be integrated with the rehabilitation services for the general handicapped. We believe that such activity carried out in the community can replace the present patchy institution - based approach for the rehabilitation of the disabled in urban areas.

Objective: To compare the impairment status of leprosy patients. 5 years after RFT, in those with and without active surveillance.

Subjects: All patients released from treatment in an area of central Ethiopia (where no active surveillance was being done) during the period 1990-1992 were eligible for inclusion. 116 of 184 eligible patients were traced and their impairment status was ascertained. A similar group of patients has been actively followed up as part of the ALERT MDT Field Evaluation Study (AMFES). Of these, 144 have complete information available and were included in the study.

Main outcome measures: Patients were assessed by means of the EHF Score; deterioration or improvement was noted by comparison with the same indicator measured at RFT.

Results: There was no difference between the groups in their impairment status at the start of treatment nor in the change in status before RFT. Outcome after RFT:

Odds ratio (adjusted for age, sex and classification, by multiple logistic reression analysis): 2.1 (95% CI: 1.2 - 3.8)

Conclusion: Active surveillance could make a contribution to the prevention of further disability, but as a relatively expensive activity, may justifiably be replaced by more cost- effective measures.

We know that most of the suffering of Hansens Disease patients is a result of the stigma that this disease carries. This stigma is directly related to physical and social impairments, disabilities and handicaps. We can not ignore the physical disabilities because they are part of the disease called Leprosy or Hansens Disease. We would like to show, based on several models functioning in South America, that we can offer Rehabilitation at a low cost and with a great impact on destigmatizing the disease. A course on Rehabilitation for Leprosy is offered at the Instituto Lauro de Souza Lima in Bauru, Sao Paulo, Brazil, four times a year. All aspects of clinical, physical, psychological and social disabilities is taught and possible solutions for these problems. The course is open to all possible members of the Rehabilitation. Team and not only for surgeons. The course is mostly to motivate people. When somebody really wants to start a Rehabilitation Program at home, we assist with local in-training and local courses to implement this program. Periodic visits follow this initial in-training to encourage and supplement the teaching of the surgeon and the team. As a result of this program we have independently working Rehabilitation Programs in Paraguay, Venezuela and in 14 different cities in Brazil. Most programs are integrated in the control program in a Teaching Hospital or in a major Health Centre.

Zhang Guocheng. J Watson, A Piefer, R Winslow, WCS Smith. P D Samson. Ministry of Health. Peoples Republic of China. The Leprosy Mission International. 08-06 Golden Mile Tower. 6001 Beach Road. Singapore 199589

The People's Republic of China has long since reached the WHO leprosy elimination goal. However, disabilities have been the major cause of social stigma in leprosy patients in China and present major hurdles in their rehabilitation.

We have implemented the Prevention of Disability (POD) programme of leprosy patients in 15 provinces in China. Our objectives were: 1) to prevent or control the occurrence of new deformity. 2) to prevent further loss of sensation or strength diagnosed by early detection and treatment of neuritis. 3) to reduce the prevalence of wound* and open cracks by 20%-30%. 4) to prevent any increase in vision loss, joint stiffness and bone loss following nerve dysfunction. 5) distribution of footwear for insensitive feet up to 50% in the first year. 6) 50% of disabled cases should be trained in self-care and the slate of amputees improved by supplying artificial limbs. Training to the health staff i.e doctors, supervisors and basic health workers was the key to the programme's success. A total of 325 training courses were conducted and a total of 11.891 participants were present. 2.078 supervisors were also trained in this programme. This training took place at the central, provincial, prefecture and county levels. The programme involved the process of transferring POD technology from experts to basic health workers to leprosy patients. A total of 381 neuritis cases were detected and treated with prednisolone. Self-care training of eyes, hands and feet were conducted for 11.215 people and 70% were able to practive self-care on their own. A total of 25.880 pairs of protective footwear were distributed to 14.378 people having insensitive feet. Surgical treatment was given to 1.917 and 726 have shown good progress. Out of 706 prostheses. 612 were given to patients with satisfactory results.

We have implemented POD programme using the existing health system and grassroots level workers who are the backbone of the programme. Basic health workers have successfully transferred the POD technology to needy leprosy affected people. Community participation helped patients to care for their disability.

Irma E. Guerra, BSN. MPH. Ambulatory Care. National Hansen's Disease Program, Carville, Louisiana, USA

As the year 2000 approaches, and the global MDT treatment objective is perceived as a goal soon to be accomplished it is time to focus on the next challenge in Hansen's disease care: the chronicity of its disability, including the effects of aging; to make the transition from curing to caring This is vitally important for facilitating a person's social and economic reintegration into the culture/society, since the stigma of HD is associated with its physical effects.

A person diagnosed with HD, who may have only minimal loss of sensation or peripheral nerve damage, and has managed well without further decompensation, is at risk for significant disability due to aging factors alone or because of other chrome diseases.

In the United States (U.S.). the majority of persons diagnosed with HD ranges from 24-80 years of age at time of diagnosis, with the largest number of persons between 24-60 years of age. Disability problems account for at least 50% of the readmissions at the Gillis W. Long Hansen's Disease Center in Carville, Louisiana. The two largest outpatient HD climes in the U.S. referred 25-50% of their patients for specialty consults such as occupational or physical therapy, orthotics, orthopedics, or podiatry in 1997.

In the U.S. the cost of chronic care is twice that for an acute condition. This fact, along with an increased life expectancy, and the chronicity of HD disability, underscore the need for a change ion the focus now for program planning the field of HD care.

Programs will need incrementally more, not less, funding to assist those with the disabilities of HD to achieve independence and an optimum level of functioning.

The leprosy Control Program of Santa Fe Province has, for 30 years, carring out different activities tryng to reduce the prevalence rate reaching the present: 1.2 per 10.000 inhabitants.

Till now the basic activities have been MTD impementation, training of personnel, detecting new cases, retrieval defaulters.

different kinds of disabilities, our Program has been working for 3 year on a specific plan for Prevention of Disabilities and Rehabilitation under what is called "Integral Attention of leprosy Patient", forgotten by health staff and the sanitary policy.

A certain number of patients have been taken as samples in order to have a clear idea of the existing situation.

Degree 2: 81% passed from degree 2 to degree 1 It is considered that the results obtained are good enough to justify the implementation of this plan as a specific strategy for Leprosy Control Program in our Province, taking into account that at this moment we had not this kind of plan before.

EXPERIENCE OF POD PROGRAMME IN AN URBAN LEPROSY PROJECT INVOLVING PARAMEDICAL WORKERS.

Prevention of disabilities programme was incorporated in an urban leprosy project. 5 years of experience in preventing disabilities by involving PMWs and NMSs is presented.

Assigning risk grades of developing disability to all registered patients and follow-up of high risk patients by regular monitoring of nerve function at DDPs was the methodology of POD activity. Patients with signs of nerve impairment were treated with prednisolone and physiotherapy.

1729 patients (63Z) of new patients were found to be at high risk, of them 280 developed nerve impairment. The effects of nerve impairment were regularly followed-up by recording improvement or deterioration of sensory perception and muscle power/ movement. 168 hands (69.4%) and 291 feet (56.1%) have shown improvement in sensory perception. With regard to muscle paralysis/weakness, 196 (48%) have shown improvement in muscle power/movement.

Regular assessment of nerve function and providing proper treatment prevents disabilities. Stratifying patients according to their risk - improves attention to high risk groups.

RESULTS OF THE NEUROLOGICAL STATUS AND THE DISABILITY GRADE OF 358 HD PATIENTS FOLLOWED IN 6 BRAZILIAN OUTPATIENT FACILITIES FOR 1 ½ YEARS

Dermatologia. Hospital das Clinicas. Universidade Federal de Minas Gerais. Belo Horizonte. M.G.. Brazil

Dermatologia. Fudação Oswaldo Cruz (FlOCRUZ). Ministério de Saúde. Rio de Janeiro. R.J.. Brazil

Gillis W. Long National Hansen's Disease Center (GWLHDC). Carville, Louisiana. USA

Damage to peripheral nerves is the primary cause of deformity and disability in Hansen's disease (HD). The WHO disability grade is helpful tor determining early diagnosis of disease and quality of treatment. One of the purposes of this study was to demonstrate nerve function and impairments. Hand and loot data were included in all centers, whereas ocular impairments were included in fewer centers.

Six centers were selected because of their greater than 2 years of experiece of quality work in nerve function testing, disability grading, and interest in neuritis and reaction. A minimum of 2 persons from each center were trained in the study protocol, in standardized evaluation technique, and in documentation of results. Testing was repeated a minimum of every 6 months for 1 1/2 years from 1992 to 1995 Documentation and testing was periodically supervised in all centers.

This presentation will focus on the following results: The nerve function assessment including sensory, motor and nerve palpation results; the WHO Disability Grades of 0,I, II, and III; and the most frequent ocular impairments observed over 1½ years. In addition, the results of what study participants learned from participating in this study, their observations and recommendations will be presented.

Self-care for eyes, hands and feet in leprosy patients is one part of the collaboration project between MOH, China and TLMI. The aim of self-care is to prevent and control International Journal of Leprosy 1998 disabilities and deformities. In this activity, regular follow-up was taken in every six months. The PALs selected for self-care were taught in skin care, exercise, prevention of injuries/uclers, wound care and the use of protective devices for eyes, hands and feet. Necessary materials, e.g. eye drops, glasses, eye covers, gloves, foot-drop suspensions and arch support are given out to PALs.

9995 self-care cases who were available for follow-up between May 1995 and May 1997 were analysed. The mean follow-up period was 23 months. Out of 9995 cases, 77.5% were males, 22.5% were females; 86.2% were WHO disablity grade II, 13.8% were WHO disability grade I.

After two years practice of self-care in 9995 cases, the number of red eyes, hand cracks, hand wounds, foot cracks and foot wounds were decreased by 56.6%, 85.9%, 81.3%, 76.7% and 30.8%, respectively.

A study was carried to find the leprosy patients with disabilities in the leprosy control area of The Leprosy Mission Shantipur. Out of 4839 patients registered in the control area 2518 were still found to be living in the control area which included those under treatment and completed treatment. It is found that 606 patients have WHO G-I and G-ll disabilities.

Further analysis of their Socio Economic status revealed that 170 patients required community based rehabilitation.

Verification of known cases in a given area will be helpful in carrying out disability care activities and rehabilitation requirements.

TREATMENT OF NERVE FUNCTION DEFICIT USING AN AMBULATORY ALTERNATE - DAY REGIMEN OF PREDNISOLONE - A RETROSPECTIVE STUDY

Recovery of nerve function deficits in 24 nerves of leprosy patients suffering from neuntis and the occurrence of side effects of steroids was studied. The patients received a constant dose of 40-60 milligrams of predisolone on alternate days for 6 months, while MDT was continued. The drug was not tapered before it was discontinued. Hospital records were used for collection of data.

The average BMRC grade for muscles supplied by the effected nerve was used to assess motor power, and 10 points on each palm or sole were tested for sensation, and the number of anaesthetic points were noted.

Only one patient reported a possible side effect of steroids, and 14 nerves showed recovery of motor function to more than grade 4 on the BMRC scale 39% of nerves with motor deficits recovered full (grade 5) function.

Due to ethical constraints, it was not possible to conduct one. but the authors recommend a prospective case - control study on the efficacy of this regimen.given the optimistic findings from this study.

TEACHING PATIENTS ABOUT SELF CARE: AN EVALUATION OF A HEALTH EDUCATION PROGRAM FOR LEPROSY PATIENTS WITH ESTABLISHED NERVE FUNCTION LOSS

Patient education in self care is a key strategy for the prevention of further disability in leprosy patients with established nerve function loss.

A health education (HE) program for patients with sensory loss was designed and tested on a cohort of 209 patients from 4 rural leprosy clinics of the Guera Leprosy and Disability Control Project. Chad. A set of standardised messages and instructions was formulated covering the topics of skin care, regular inspection, rest for ulcers, self care for small wounds and danger signs. For each topic an indicator was defined to monitor whether the methods were actually being put into practice. Health educators were specifically trained for the task, emphasis was put on communication skills and on making the messages culturally appropriate. Patients were followed up both at the MDT-clinics and through home visits using a checklist. The patients progress was recorded. Patients were graded A once education had been gtcn. B when they could repeat the instructions given and demonstrate the procedures taught arid C when there was evidence that the knowledge was actually applied.

Of the 209 patients, only 107 (51%) had 3 or more health education sessions. Of these, less than one third progressed to C. Depending on the topic. 30-50% of the patients never progressed beyond the level of having received education. The concept of danger signs was poorly understood both by the health educators and the patients, and many patients felt that rest for small wounds was not a realistic proposition. The best results were obtained in those patients that had 9 to 12 HE sessions, in this group approx. 2/3 of the patients progressed to level C in skin care. Increasing the number of HE sessions beyond 12 gave no appreciable advantage.

We conclude that the quality of patient education in self care needs to be improved. Some possible reasons for the poor results arc: finding a teaching style appropriate to the patients background, the fact that HE topics did not correspond to the patients perceived needs, and the difficulties in the follow-up of patients living in remote areas.

Introduction: For many years, patients with disability have had to rely on leprosy clinics for wound care and prevention of further disability. This home-based self-care group programme, in which we are trying to decrease dependency and promote self-reliance, started very recently in the ALERT leprosy control programme.

Objective: To find out how far the disabled ex-leprosy patients help each other in a group without external help. The level of improvement in physical condition was also assessed.

Method: Groups of people involved in the home-based self-care were interviewed about the programme; the physical condition of individuals was assessed at entry, and then every month for 6 months.

Results: 54 people were assessed on their physical and attitudinal status. 19 people who had cracks initially and 14 people out of 16 who had ulcers, had healed these wounds within the 6 month period.

As regards physical status, 26 had improved, 26 stayed the same and 2 had slight deterioration. 41 (76%) showed improvement in attitudinal status, while 13 (24%) stayed the same.

Conclusion: A lot of money and effort has been spent on patient care at leprosy clinics and patients have to walk for hours to reach them. Although the prevalence of leprosy has drastically reduced, we are left with many patients with irreversible disability who need sustainable solutions, with the involvement of the patients themselves, and the use of locally available resources. This study shows that the current programme is a worthwhile start and needs expansion.

The Present study deals with 2950 Disability Patients at Visakhapatnam District of Andhra Pradesh, South India.

The study showed that the Disability rate is 11.4% and the Disability Prevalence is 7.96/10.000 population. Grade-I (WHO) Disability is 26.30% and Grade-ll (WHO) Disability is 73.70%.

The Disability in individual organs of Hand. Foot. Eye and combined organs involved is presented. The aim is to plan the model care of Disabled patients in field for better compliance of the patients without dislocating the patients as 60%- 75% of the care procedures can be taught to patients (transfer knowledge) in field reducing the dependence on workers for life long.

Paul Saunderson. Heather Currie, Peter Byass. Abraham Meima P.O.Box 165, Addis Ababa. Ethiopia

Objective: To investigate the correlation between the EHF Score and more detailed assessments of impairment; and to assess its ability to measure change in impairment over time.

Subjects: 842 patients from central Ethiopia, starting treatment between 1993 and 1995. Changes in impairment status could be assessed for 511 of the 842 patients.

Main outcome measures: The EHF Score was compared with scores for primary impairments (measured by standard sensory tests and voluntary muscle tests) and secondary impairments (ulcers and bone loss) and the sum of those scores. Changes in the scores over time were also compared. As the data are non-parametric, the Spearman Rank Correlation Coefficient (r_s) was used.

Results: Correlating EHF Score versus the sum of primary and secondary impairments gave r_s - 0.91 (95% cl 0.90 - 0.92). Similarly, the change in EHF score versus the change in the sum of impairments gave r_s - 0.60 (0.54 - 0.66).

Conclusions: The EHF Score is a sensitive indicator of the impairment status of leprosy patients. Change in impairment status is quite well reflected in change in the EHF Score. It is concluded that the EHF Score is a reasonable indicator for monitoring POD activities in a field programme.

Objective: To evaluate the management of chronic neuritis in the multidisciplinary neuritis clinic and compare it with that of treatment under fixed guidelines.

Subject: 32 patients treated at a specialist neuritis clinic (run by a leprologist, a surgeon and a nurse trained in nerve assessment) and 31 patients treated with steroids according to fixed guidelines in the general OPD. Results for additional patients will be presented in the poster.

Results: 29 of the patients treated at the neuritis clinic and 15 of the routinely treated patients, had chronic neuritis, with two or more previous episodes of steroid treatment. At the neuritis clinic, variable doses of steroids were given and surgical nerve release was undertaken, if indicated; 28 of the 29 patients showed some improvement in impairment status. 11 of the 15 patients given routine treatment showed some improvement in impairment status. The difference in this small study is not statistically significant.

Conclusion: These preliminary results indicate that combined nerve release and steroid treatment could be more beneficial than steroids alone in some patients with chronic neuritis. A prospective, randomised, controlled study is required to define clear guidelines for the management of chronic neuritis.

OPTIMISATION OF A MONOFILAMENT TEST FOR SENSIBILITY FOR USE IN A FIELD PROGRAMME OF PREVENTION OF IMPAIRMENT.

Monofilament testing for reduced sensibility in hand palms and foot soles of leprosy patients can provide information for diagnosis and monitoring of sensory nerve function impairment.

To provide useful information for clinical decision making, diagnostic tests should be subjected to assessment of reliability( inter-tester agreement). The diagnostic cutoffs used should be relevant for the population under test and the availability and type of possible treatment To be useful under field conditions, a test should be simple and quick enough to ensure that testing of patients is likely to be done by field staff.

Monofilament testing with a set of five 'pocket filaments' was subjected to inter and intra tester reliability testing in groups of staff of differing ability and experience. Databases from reliability testing using leprosy patients, testing of normal subjects and a longitudinal study of neuritis patients were used to explore empirically the interaction of theoretical probability considerations, reliability, number of sites tested per nerve and diagnostic cutoff, within the test.

A monofilament test using a maximum of five sites on each hand palm and foot sole was found to detect at least 95% of patients whose loss of sensation had been detected by a longer test using up to twelve sites. A cutoff set at a score of 'minus three points per nerve' (three sites one level above normal, or one site two levels above normal and one site one level above normal etc.) gave a test with a acceptable rate of expected false results, when the reliability of the test was taken into consideration. Using a composite test of this type appeared to give substantial savings in time, and reductions in complexity, with minimal loss of performance compared with the larger test.

AGE SPECIFIC NORMAL THRESHOLDS FOR SENSIBILITY TESTING WITH MONOFILAMENTS IN A NEPALI POPULATION

Semmes-Weinstein monofilaments can be used to provide a graded (quasi-quantitative) measure of sensibility. The test can be used for diagnosis and monitoring of sensory nerve function impairment in leprosy. For diagnostic use, if treatment is provided because of subnormal test results, appropriate normal thresholds must be derived. Previous work has suggested that factors such as age, gender and occupation must be taken into consideration in deriving thresholds.

A cross sectional survey of more than 600 apparently healthy Nepalis was undertaken. The study was designed (in terms of size and stratification) to provide sufficient subjects in each age decade to allow exploration of differences due to age, gender, occupation, shoe wearing habits, hand dominance and terrain in which the subjects lived. The size was sufficient to allow calculation of normal thresholds by age and gender, if the differences noted were statistically and clinically significant.

Six sites were tested on each hand palm and foot sole. Pilot studies were used to choose two sets (one for hands, one for feet) of ten monofilaments covering the expected range of the normal threshold, from the twenty available.

Non-parametric statistical methods were used and normal thresholds were calculated from the 95th percentile of the observed data.

Testing showed significant differences between age groups. In the decades 20-29, 30-39 and 40-49 years the 95th percentile of the data was approximately constant. Outside this age range a statistically and clinically significant change in sensibility was observed.

For diagnostic use in leprosy, most commonly the 'pocket set' of five filaments is used. The results of this study suggested that, from the pocket set, filaments giving forces of 200mg, 2g and 10g are close to the normal thresholds for hands, forefoot and heel respectively, for subjects aged approximately 20-50 years. Younger people have a normal threshold at a lower force, and older people at a higher force, for both hands and feet.

INTERVENTIONAL STUDY OF A SELF CARE CAMP FOR THE LEPROSY PATIENTS WITH DISABILITY

With the introduction of MDT by WHO in 1982 all over the world, the leprosy patients are being cured medically but their personal and social problems continue to exist due to anaesthesia and the stigma attached to the deformities. Self care is taught to the patients with disability, but very few of them practise these skills at home. This two year project was started in March 1997 with an objective to promote participation of community leaders in supervising self care activities of leprosy patients at their respective homes. In order to achieve this a self care camp was organised in the project area where scientific facts about leprosy were displayed through exhibition and puppet show and self care was demonstrated to the patients, their family members and the community. Following the camp, volunteers were selected and given responsibility of 3-4 patients. Now at the end of one year, 13 volunteers are involved in this supervising work. 37 out of 45 disabled patients are doing self care at home regularly. There has been a reduction in the occurrence of sole wounds by 50%. Thus involving the community and family members in self care activities will bring down the incidence of ulcers and will lead to better patient care.

PREVENTION OF DISABILITY THROUGH MEASUREMENT OF UNDERLYING PERIPHERAL NERVE INVOLVEMENT

Judith Bell-Krotoski, Clinical Research Therapist/Chief, Hand and Occupational Therapy. Gillis W. Long Hansen's Disease Center, Carville, LA; Linda Lehman. ALM Advisor and Consultant for Prevention of Disability and Rehabilitation Programs. Belo Horizonte. Minas Gerais; Robert Jerskey. OTR ALM Disability Consultant. Peripheral Nerve Project Consultant. India

A multicenter project was launched in 1990. "International Project to Measure the Peripheral Nerve Involvement Underlying Disability of the Hand in HD" in order to address objective measurement of peripheral nerve involvement. Measurement of disability alone docs not provide direct measurement of nerve involvement sufficient to allow consideration of early treatment and intervention of nerve damage that would prevent disability. Disability is secondary, and varies with injury, deformity, and psychosocial factors.

Included in the formal study are patients treated at the U.S. Public Health Service Hospital at Carville, LA; seven sites in Brazil; and five sites in India. Other sites were additionally included out of interest. An overall prevelance of peripheral nerve involvement will be reported with disability measurement along with significant variables. The nerve involvement as it varies with treatment is analyzed by correlating the change (worsening or improvement) in the period reviewed, with specific chemotherapy received Both new patients receiving MTD and patients who have received other treatment are included in the study to allow comparison.

Without a doubt the largest result of this project to date has been the transfer of technology to international treatment programs. The introduction and use of Semmes-Weinstein Monofilaments enabled measurement that is 1) sensitive, 2) repeatable, 3) simple, and 4) comprehensive enough to allow monitoring of patient nerve involvement as it varies with disease and treatment The filaments were found suitable for field situations as well as for hospitals and clinics.

OCCURRENCE OF LOWER EXTREMITY VENOUS ULCERATION IN HANSEN'S DISEASE - EITIOLOGY AND TREATMENT

Physical Therapy Dept., Gillis W. Long Hansen's Disease Center. Carville. Louisiana USA

Lower extremity venous ulceration is a relatively common occurrence in patients seen in the Physical

Therapy Department at the GWLHDC . These ulcers may be sensate and painful for some, while insensate for most others. A venous incompetent extremity coupled with neuropathy and the possible presence of plantar foot problems is a twofold problem and a challenge for treatment is created. In the event of trauma, a lower extremity with edema and a loss of sensory feedback can mean instant breakdown of skin integrity and resulting months or years of persistent wounds. Various diseases causing venous insufficiency is well documented. The purpose of this presentation is to discuss the relationship between venous insufficiency ulceration and Hansen's disease, along with other possible contributing factors. Additionally, treatment regimens including various forms of compression therapies and wound care dressings will be presented.

Footwear is recommended in persons with plantar anaesthesia to prevent ulcers. Footwear from 8 different projects in different countries 'was studied to analyse the distribution of pressure at different sites on the plantar surface of feet. These pressures were compared with pressures on bare-feet. The study showed that irrespective of the model of footwear, materials used for its production, cost, etc as long as it has an adequate insole, it results in diminuition of pressure at the big toe, 1 MTH and heel.

Prakasam District in Andhra Pradesh (A.P) with a population of 36 lakhs, harbouring 1722 leprosy disabled cases was adopted for experimenting a unique field based disability care programme in 1991. The methodologies adopted were simple and easy to practise by any leprosy worker. The training provided to the staff of NLEP by the expert trainers from Bombay Leprosy Project was practical and task oriented.

136 field leprosy staff of the NLEP, Govt, of A.P practised disability care after receiving task oriented training in conducting disability survey using a simple survey proforma and in applying simple adaptations like pre-fabricated splints, grip-aids for hand deformities and MCR footwear, mini plaster, 'Foot Care' kit besides the conventional physiotherapy. Assessment of 454 disabled leprosy patients at the end of 4 years indicated that:

The sustainability of results in spite of withdrawing the surveillance after 2 years demonstrates the possibility of extending disability care along with routine MDT programme in the background of declining endemicity of leprosy.

Abraham Meima¹. Paul Saunderson², Shibru Gebre² Ketsela Desta², Dik Habbema¹

2) All Africa Leprosy, Tuberculosis and Rehabilitation Centre (ALERT), Addis Ababa, Ethiopia

Objective: To study changes in the impairment status of leprosy patients over time.

Material and methods: This study reports on 284 leprosy patients from the prospective ALERT MDT Field Evaluation Study in central Ethiopia (AMFES). The Eye-Hand-Feet impairment score (EHF Score) is the main outcome measure.

Results: 138 (49%) out of 284 new patients had EHF-scores of 2 or more at start of MDT treatment. At review between 2 and 4 years after release from treatment, this number was 120 (42%). 42 (15%) patients improved and 18 (6%) deteriorated by two EHF-points or more during treatment. These numbers are 21 (7%) and 32 (11%) respectively for the period after release from treatment. Initial improvement was sometimes followed by deterioration and vice versa. Overall, 47 (17%) patients improved and 28 (10%) patients deteriorated by two EHF-points or more.

Conclusion: The preliminary results indicate that the impairment status at intake is the main determinant for the impairment status a few years after release from treatment. The question is whether the risk of deterioration of the impairment status, both during treatment and after release from treatment can be reduced. Answering this question requires further study, in which patients who did not complete treatment or did not present for re-examination after release from treatment are involved as well.

While great strides have been made toward a cure for Hansen's disease, it remains a fact that damage can occur to one or more of the peripheral nerves. If permanent, nerve damage can result in deformity that perpetuates the stigma of the disease. This poster presentation is designed to encourage prevention of disability in the hand and foot. The poster highlights each extremity at the sites commonly involved and depicts visual progression of potential deformity. Early and regular peripheral nerve monitoring is recommended with intervention techniques to stop nerve involvement underlying the progression to disability. A pamphlet with the information contained in this poster is intended for distribution to clinics and hospitals to be utilized as a tool for health care worker and patient awareness and education. This project is made possible, in pan, by support of American Leprosy Mission.

Provision of protective shoes and training on self-nursing were applied in 284 leprosy patients with simple sole ulcers or soles without sensation. Before implementation of this project, there were 36 chaps and 162 ulcers in these patients. In the first 2 years of a 6-year trail, protective shoes were distributed and supervision of self-nursing was stressed with a consequent disapperance of 91 ulcers (56%) and 12 chaps (23%). The occurrence rate of new ulcer in simple insensitive feet was 2.75%; the rate of recurrence after cure was 8.4%. In the next three years when no shoes were provided, the number of ulcers increased to 144 and chaps to 30. When in the 6th year protective shoes were provided and supervision was stressed again, the number of ulcers and chaps decreased once more. It was believed that provision of protective shoes and supervised self-nursing were helpful in healing existing ulcers and preventing patients from the occurrence of new ulcers. These findings were obviously observed even in the three years when shoes were used and supervision stressed. The effect in the first year was the best, but once no longer had distribution of shoes and supervision, the number of ulcers and chaps increased year by year. This suggested that it would be a long-term and hard job to help patients to form a good self-nursing habit.

CHANGE OF DISABILITY GRADING IN LEPROSY PATIENTS BEFORE AND AFTER MDT/WHO (A CASE CONTROL STUDY OF 847 RFT CASES IN A URBAN LEPROSY CONTROL PROGRAM IN THE SOUTH WEST OF BANGLADESH)

YUTAKA ISHIDA SR. LORELLA PICORINI. SR. ELENA GUGIELMELLl AND BIDHAN CHANDRA MONDOL

DHANJURI LEPROSY PROJECT-KHULNA BRANCH(PIME SISTERS) DASS PARA ROAD. BORO BOYRA. KHULNA, 9.000. BANGLADESH

A case control study was done to evaluate the effectiveness of prevention of disability of leprosy patients during implementation of MDT/WHO. Disability gradings and some other related indicators of 847 cases who completed MDT/WHO in 1995/1996 at our urban leprosy control project were studied retrospectively. In total the disability- grading after completing MDT got a little bit better than that before starting( 1.6% in G=1, 1.0% in G=2).

There is no statistical difference between these changes. Disability gradings of BL cases got worse after MDT by 5.3% in G=2, while TT, BT and PN cases got recovered a little bit. 38.7% of MB regimen got steroid therapy during MDT, while only 5.5% of PB cases did.(P<0.01)

PROFILES OF NERVE FUNCTION IMPAIRMENT AND PREVENTION OF DISABILITY ACTIVITIES AT THE H.D. CLINIC. LAC+USC MEDICAL CENTER. LOS ANGELES. CALIFORNIA

Hansen's Disease Clinic. Los Angeles County+ University of California Medical Center. Los Angeles. California. U.S.A.

The Hansen's Disease clinic at LAC+USC Medical Center In Los Angeles Is one of 10 regional clinics of the National Hansen's Disease Program. Over 500 registered patients attend clinic for treatment and monitoring of nerve function Impairment. Nearly all these patients reside throughout the greater Los Angeles metro area. The vast majority of these patients are immigrants who have relocated from Mexico. Southeast Asia, the Pacific Islands and other parts of the world.

A primary goal of the National Hansen's Disease program Is to prevent disability and deformity through early diagnosis which would eliminate the potential for stigma. However, for those patients who have already been found to have nerve function impairment, disability, or deformity. It Is vital that Impairments are reversed or prevented from worsening, that disability is addressed to promote patient independence in his/her dally living activities, and that deformity Is corrected whenever possible. Prevention of nerve function Impairment and prevention of disability activities are Integral to a successfully operating program, such as at the LAC+USC H.D. clinic.

STEROID THERAPY AND THE MANAGEMENT OF SEVERE SENSORY LOSS IN HANDS AND FEET OF LEPROSY PATIENTS: FINDINGS AND RECOMMENDATIONS.

Sacred Heart Leprosy Centre. Kumbakonam. T.N., INDIA Gillis W. Long Hansen's Disease Center. Carville. USA

In testing with Semmes-Weinstein nylon monofilaments, norms of touch pressure thresholds were determined for hands and feet of urban and rural residents of South and Central India, and presented at the previous Congress In Orlando.

One of the above authors. D. Samuel Thomson Sugumaran. previously conducted a recently published study Involving the use of prednisolone for the treatment of paralytic deformities of <6 months duration. Significant restoration of nerve function was demonstrated. In both motor and sensory components. The results of this study revealed a higher incidence of motor recovery than sensory recovery.

The current study, funded in part by the American Leprosy Mission. Involves a larger patient population sample and Includes monitoring of the sensation of the plantar surface of the foot. This study plots the sensory changes of the patients' hands and feet over time and the response to steroid therapy. Sensation Is monitored with Semmes-Weinstein nylon monofilaments.

The results of this current study include tables depicting the recovery from severe sensory loss. i.e.. those with suspected loss of protective sensation and therefore at risk of injury. Concise tables of the determined Indian norms are also presented for easy reference.

NERVE FUNCTION IMPAIRMENT IN LEPROSY - A REPORT F ROM NATIONAL POD PILOT PROJECT

J. Jiang, J.M. Watson, X.Y. Wei, G.C. Zhang Institute of Dermatology, CAMS & PUMC, Nanjing, 210042, China

As a part of the national pilot project of POD and rehabilitation for leprosy patients, a pilot study including early detection and treatment of recent neuritis (the duration of neuritis within 6 months) was carried out in 9 provinces with different leprosy prevalence. All the new cases, newly relapsed cases, active cases and PALs on the first year of surveillance who were available for follow up were involved. A regular nerve function assessment was conducted by the field staff and supervised by provincial, national and TLMI supervisors. Once a nerve function impairment was confirmed, a standardized regimen of prednisolone was given. The data between May 1995 and September 1997 were analysed.

During follow-up, 902 cases were assessed, in which 69 cases (7.6%) were diagnosed of having recent neuritis. Out of 69 cases, 40.6% of nerve function impairment occured pre-MDT, while 56.5% occured during or post-MDT. The prevalence of each nerve fuction impairment is as follows: facial 6 cases, ulnar 28 (3.1%) cases, median 17 (1.9%) cases, radial 5 cases, lat. popliteal 17 (1.9%) cases, posterior tibial 34 (3.8%) cases. For each nerve, the prevalence and the response to prednisolone of sensory and motor impairment are analysed seperately. The factors affecting the early detection of neuritis and recovery of nerve function are discussed.

WHO has recommended that the "Prevention of disability activities should be incorporated with MOT programmes to the extent possible keeping in view the cost effectiveness". Disability care is generally considered to be expensive by experts who have looked into the problem from an institutional base, leading to a belief among donors that highly trained salaried are to be employed. We believe that innovative low cost technology for offering disability care at the doorstep of the leprosy disabled is possible. We report our experience in an urban slum in Mumbai, housing 25,000 population using donor friendly low cost strategies for disability management

An ongoing MDT programme in the slum had identified 35 disabled leprosy patients who were offered disability services through volunteers living in the slum, working under the supervision of a trained para-medical worker. A weekly clinic situated in the same slum acted as a referral centre to manage complications. It was observed that the disability care techniques developed by Bombay Leprosy Project could be easily practised at the field by the volunteers following a task specific training in a cost effective manner. The cost of offering regular disability services at the door step of disabled leprosy patients for one year was US $ 1000.

Considering that donor funds are scarce and even declining, cost effectiveness will be the major component of any disability care strategy that may be adopted by the voluntary agencies working for leprosy. This study has not only revealed how cost for the donor can be saved, but also indicated the future possibility of reaching the goal of "Community Based Rehabilitation" provided non-leprosy handicapped in the community can be involved in a similar fashion.

This cross sectional study is undertaken to quantify the impairment and deformity in a given population to help us in understanding the pattern of impainnent and deformity and to plan customised home based seifcare.

All the living disabled leprosy patients of 3 TLM leprosy control units covering a population of 8.10.539 (91 census) were assessed by a qualified Physiotherapist and Para medical worker after a standardisation workshop at Salur.

The data was recorded on special individual records. The total number of disabled assessed are 2.855 inclusive of Grade-I deformity.

MULTIDISCIPLINARY APPROACH FOR PREVENTION OF DISABILITY IN NEPAL LEPROSY REFERRAL CENTRE

Surkhet Leprosy referral centre. Tuberculosis Leprosy Project. International Nepal Fellowship, Mid western region, Nepal

Cost-effective programmes for the prevention of disabilities in leprosy require active involvement of the patients and their families as well as all the centre staff approach This paper presents the specific objectives and strategies that the referral centre used for the prevention of disability programme from 1996 to 1998. Implementation of this programme involves more than one aspect and more than one professional. The four aspects are detection and treatment of neuritis, self care of eyes, hands and feet; footwear programme; and health education in the community. Two small retrospective studies were done on the patients who were involved in this programme for two years. The team approach is needed, the success of the programme depends mostly on the patient who should be participatory with other workers for preventing disability.

CR Revankar. A N Joshi, S Kingsley and R Ganapati Bombay Leprosy Project, Sion-Chunabhatti, Bombay - 400 022, lndia.

As a result of effective MDT campaign in Thane district since 1988, the registered prevalence rate of leprosy declined from 76 to 11 per 10,000 population in 1993. Though the MDT has minimized the risk of development of new disability, a field solution to the problem of disabilities is still not understood. An operationally feasible disability care programme using the existing infrastructure and manpower is called for.

In order to improve the compliance rate for disability care, an interventional study was initiated, using the existing leprosy staff in Ulhasnagar block of Thane district, Maharashtra, where the prevalence was 11 per 10,000 population. Baseline survey of the existing disability services indicated that, out of 419 deformed leprosy patients, only 25% were able to secure the disability services, The compliance for disability care was less than 50%. Lack of training to the leprosy staff, non-availability of aids and materials and lack of motivation on the part of patients and families were the reasons for poor compliance. Following a task oriented training to leprosy staff, a well planned disability care programme was implemented at the field level. 100% service coverage was achieved in six months and compliance rate improved from 50% to 90% in post-interventional phase.

An evaluation on the impact of training to leprosy staff showed statistically significant improvement in upgrading their knowledge and skills to deal with the disabled leprosy patients. A questionnaire study of 116 patients randomly selected, revealed that this intervention improved the physical (88%), functional (54%) and social (30%) status.

The short term results were very encouraging; however long-term follow up is necessary to determine the sustainability of the outcome of this study.

A COMPARATIVE STUDY OP OCULAR MORBIDITY AMONGST THE LEPROSY AFFECTED HOSPITAL INDOOR PATIENTS A THE RESIDENTS OF AFTER CARE LEPROSY COLONIES.

Now-a-days most of the Leprosy affected patients got admitted in the Leprosy Hospital with any one or more of the disease related complications like reaction relapse, ulcer on the extremeties, abscess or blinding eye diseases. On the other hand, being out casted from the society due to social stigma, many 'RFT'leprosy sufferers with deformities are still staying in the after care leprosy colonies. Both these group of sufferers have got potentially sight threatening lesions. Amongst hospital indoor leprosy patients the prevalence of ocular lesions varies from 55% to 65% whereas in the after care leprosy colony it is around 30%. The common ocular lesion are corneal hyposthesia, lagophthalmos cataract, exposure Keratitis and Uvietis. Blindness (corrected vision less than 3/60 in the better eye) is 15% amongst the first group and 7% in the second group. In the hospital all the patients are under ophthalmic supervision & in the after care colonies the affected population is totally unsupervised and many of them being unaware of the blinding factors turn blind due to neglect and improper management.

Objective: To measure the degree of disability (as defined in the ICIDH: WHO, 1980) in previously-treated leprosy patients from a rural population, and establish any association with the EHF Score.

Subjects: 329 previously-treated patients in one supervisory area in central Ethiopia with a total population of appr. 500,000. Design: The disability status was assessed using a structured questionnaire, which addressed ability to carry out activities of daily living, eg. eating, counting money, walking. Outcome measures: Disability was said to be moderate if any of the basic activities of daily living could only be performed with difficulty, and severe when any basic activity could not be performed.

145 subjects had moderate disability, (EHF Scores: less than 8 in 92 (63%); 8 or more in 53 (37%). 43 subjects had severe disability, (EHF Scores: less than 8 in 5 (12%); 8 or more in 38 (88%). Of the 141 without disability (as defined above), none had an EHF score of more than 6, while 86 (61%) had a score of less than 4.

Conclusion: The remaining lifelong disability in some people who have completed their treatment is a major health problem. This study indicates the range of disability experienced by people affected by leprosy and the prevalence in the general population in central Ethiopia. It has also shown that the EHF Score gives a fair indication of the disability experienced by any individual person and that a knowledge of these scores for all previously treated patients in a community would give valuable information as to the burden of disability faced by that community.

Objective: To measure the intra- and inter-observer variation in the assessment of the EHF Score.

Subjects: Eight leprosy supervisors examined 50 leprosy patients with a wide range of impairment, including eye damage, over a 2-day period. On the 3_rd day, 15 patients were examined a second time.

All observers performed similarly and agreed with the consensus in 74 - 85% observations. Kappa statistics were calculated for each pair of EHF Scores; the weighted kappa was also calculated (this takes more account of widely differing results):

The relative unreliability of sensory testing is described in the literature and appears to account for most of the variation in the EHF Score described here. The degree of inter- and intra-observer variation is shown to be within acceptable limits. The inclusion of the eyes in the score does not change the reliability significantly in the Ethiopian context, because eye damage is rare.

P.O.Box 165. Addis Ababa. Ethiopia
* INF Leprosy Project. P.O.Box 5 Pokhara, Nepal

The EHF (Eyes. Hands and Feet) Score measures severity of impairment in persons affected by leprosy. It can be used to monitor prevention of impairment and disability activities, at programme, region or country level.

This poster discusses the basic characteristics of the "EHF Score" and the reasons for using the 0-12 scale rather than the 0-8 scale. The latter has been used in the past, but excludes the eyes from the assessment. The major reason for including the eyes is to emphasise that eye damage is an important, treatable complication of leprosy, which should be watched for.

The EHF Score is calculated by adding together the WHO Disability Grades (more correctly called Impairment Grades, which may be 0. 1 or 2) for each of six sites, namely, right and left eye. right and left hand, right and left foot. The maximum score is therefore 12. which indicates severe impairment. The resulting 0-12 scale is not linear and. when looking at populations, is usually not normally distributed. In statistical computations non-parametric methods should therefore be used. The EHF score can either be used for cross-sectional comparisons between affected people or patients groups, or cohort-based calculations.

Although the idea of the EHF Score is not new, it has not been tested for its biometric properties, such as validity and repeatability. In the accompanying posters, we report studies of intra- and inter-observer variation and validation of the EHF Score against a more complete assessment of impairment. The relationship with the International Classification of Impairments, Disabilities and Handicaps (WHO, 1980) is also explored.

TECHNIQUES FOR ASSESSMENT OF IMPROVEMENT IN CLAW HAND AND ITS RELEVANCE TO DISABILITY MANAGEMENT

The major problem in disability management is the difficulty in assessment of results in improvement of claw deformity. For long term substantiation of lasting improvement it is necessary that simple field level techniques combined with necessary functional results is adopted. The extensive follow-up in field areas demonstrates the versatility of Shah's Ink-Impression Technique. Drawing of the deformity on a paper is another technique but is difficult to manage in long run. Another method for surgical cases would be the angle measurement which has limitations and is preferred only by the qualified physiotherapists. The photographic documentation in standard positions is excellent but expensive and need training. The usefulness and pitfalls of these various techniques will be presented for standardisation of disability data management.

EFFECTS OF EYES. HANDS AND FEET SELF-CARE IN LEPROSY DISABLED PATIENTS FOR SIX YEARS

Three hundred and thirty seven leprosy disabled patients have been trained in doing self-care and have put it into practice lor 6 years. It has been found that the self-care skill mastering rate of patients ranged from 48.1% to 95.57% and regularity rate of self-care ranged from 28.27% to 99.37%. The numbers of red eyes declined from 66 to 15. hand cracks from 126 to 28, hand wounds From 4 to 0. toot cracks from 93 to 3 and sole ulcers from 67 to 28. The authors considered that the frequency of supervision and provision of self-care facilties dominateed the regularity and effect of long term self-care, which, of course, also related to disability and economic conditions of patients, the consciousness of self-care of patients and their family members, busy season, the method of training, etc. In this paper disability worsening cases were discussed and some advices such as making a practicable disability prevention project, changing the focus of training. intensifying the intervention in busy season, providing econmic support etc., were recommended.

Tofurther investigate the orbicularis oculi muscle lesions in leprosy and the relationship between it and keratopathy or vision reduction, thus more rationally select priority cases for blindness prevention, a study of orbicularis oculi muscle, cornea and visual acuity was carried out in a sample of 187 lagophthalmoses caused by leprosy. The results showed that the orbicuaris oculi muscle lesion in lagophthalmoses were incompletely paralysed, frequently with a lid gap width of 4mm, 8mm and 6mm in gentle close. The keratopathy rate was 44.39% (83/187) and the vision reduction rale was 27 81% (52/187) which were positively related to the extent of motor loss of orbicularis oculi muscle and corneal exposure, especially in lagophothalmoses with normal corneal sensation. The lagophthalmoses with impaired corneal sensation accounted for 31.55% (59/187). Its keratopathy rate and vision reductiom rate were significantly higher than those with normal corneal sensation; The orbital section of orbicularis oculi muscle less frequently involved in lagophothalmoses, amounting to 17 65% (33/187) with a keratopathy rate and a vision reduction rate of 66.67% and 45.45% respectively, more significantly different from in those without involvemont of the orbital section. Lagophothalmoses with paralytic ectropion reached 24.06% (45/187) with a keratopathy rate and a vision reduction rate of 88.89%(40/45) and 73 33% (33/45) respectively, significantly higher than those without ectropion. The authors suggested that the lagophthalmoses with corneal exposure in gentle close, those with impaired corneal sensation, those with orbital section muscle failure and those with paralytic ectropion must be given prioity in order to use the limited resources for blindness prevention more reasonably and effectively.

During the past three years we have approached the self care and ocupational therapy with more emphasis. With systematic education by new and old leprosy patients, a new classification was developed to identify and apply ocupational therapy, and a strict system to convince staff and patients for self care

The admissions for patients with ulcers dropped 45%. The average admitted time for these patients dropped 9%. The global admitted days/year due to ulcers dropped from 11,815(1993) to 5,973 (19971) = 50% less.

Foot ulceration in patients with Diabetes MelIitus is a major public health problem. The minister of health estimates there are 3 million people in Turkey affected by diabetes. 107 male, 77 female total 184 diabetic cases were investigated whom were evaluated in Istanbul Leprosy Hospital. The average age was 61.2, and the average duration of disease was 18 years. 98% of them were seen to have loss of sensation, 17% to have weakness of muscles. 10% have had peripheral vascular disease. 67% of them have ulcers on their feet due to neuropathy. 30% to have local amputation and 2% to have below knee amputation. 5% of the patients have Charcot joint.

We have given them health education about neuropathic foot care and protective shoe.

The poster will show experiences from Istanbul Leprosy Hospital where diabetics can get foot care and rehabilitation.

EFFECTIVENESS OF PROTECTIVE ORTHOPAEDIC SHOES IN NEUROPATHIC AND DEFORMED FEET IN LEPROSY

The orthopaedic shoe workshop was initiated in our hospital in Bakirkoy. Istanbul in 1980. The objective of this workshop is to help prevent fool injuries as a result of loss of protective sensation, also to provide protective and corrective footwear and orthoses to patients with deformities.

681 leprosy patients were studied in this survey and they were evaluated according to their age. sex, level of education the regions they live, as well as the condition of their feet and the type of shoes they required. 74% of these patients were male and 26% were female, the average age was 55.10%. 86% of these cases came from rural areas, 62% were illiterate, 67% of them were unemployed. 30% of them were seen to have loss of sensation, 53% to have claw toes, healed ulcer, drop-foot. 27% to suffer severe disability.

33% of them have had two pairs slippers and protective shoes in a year, 40% have had orthopaedic shoe when they need it. 21% of them wears commercial shoes and we follow them. 2% refuse to use special shoe for them. 4% of them arc very old and we give them only orthopaedic slippers for home.

All the other results will be analyzed and the advantages of orthopaedic shoes will be discussed at the congress.

Zhi-ju Zheng, Guo-cheng Zhang, Liang-bin Yan, Jun Jiang, Di-sheng Zheng and Watson Institute of Dermatology. CAMS and PUMC. Nanjing City. China

The final evaluation results of eyes, hands and feet in the Stage 1 Collaboration Protect between MOH and TLMI were summarized. Among 856 people with eye. hand and foot disability. 70% of eye injection (red eye) disappeared, 80% of cracks on hand and foot disappeared. 40% of plantar ulcers healed. 18 wounds on 15 patients' hands healed, and 80% of people affected by leprosy (PAL) formed self-care habits showing that self care was acceptable for PALs and disability could be prevented only if health care and supervision were carried out well and intensively

The Leprosy Mission - Sankuru Leprosy Control program. Democratic Republic of Congo

Sankuru (Democratic Republic of Congo), is located in the dense tropical rain forest, where people are usually practising traditional medicine

This is a story of Mr. Dienena, a sixty years old man, known previously as a leprosy healer, and who finally got leprosy

Many years ago he treated leprosy patients by applying local medicine on the skin, in order to regain normal skin condition. When he found that he was not able to treat propely himself, he came to our clinic where he received proper treatment.

Today he is helping us in finding new cases as a health worker, and is bringing to health units his previous patients for right treatment (MDT) and health education.

In the other hand, we arc experiencing the use of a tree resin for the treatment of leprosy ulcers One of our patients was applying that resin, locally called "TSHO" It's orginal name is "Austranella". which is as well used by the Catholic church as incense. The substance is known to have a medical effect on wounds We still need to produce a pharmaceutical ointment, taking in account the guidelines of Dr. Hans Martin Hirt's "Topical Medicine" The results obtained by applying the ointment after having soaked and trimed the ulcer, are encouraging.

Success in healing ulcers requires all the attention of the health worker, to train patients in self-care, changing behaviours in getting family support.

¹MILEP2 Study Group. Richardson Leprosy Hospital, Miraj. Maharashtra. India. ²Dept.of Public Health, University of Aberdeen, Aberdeen AB9 2ZD. Scotland

The problems of identifying sub-clinical infection and those of in vitro cultivation of M. leprae have limited study of the transmission of leprosy infection in endemic communities. Early studies have demonstrated the high rate of discharge of M leprae from the nose in bacilliferous leprosy patients and the presence of early lesions in the nasal mucosa. The ability to use polymerase chain reaction (PCR) techniques to identify small numbers of M. leprae now gives potential to study transmission in endemic communities.

A leprosy endemic village (population : 1442) in South-West India where leprosy control activities have been underway for more than 20 years was selected for study. A survey of residents was conducted in 1997 where individuals were examined and nasal swabs taken from 1298 subjects to test for the presence of M leprae using PCR methods. The house location of old and current patients in the village is known from the leprosy control records. The leprosy cases (old and current) have been plotted on the map of the village along with the location of those identified as having PCR positive nasal swabs. The spatial distribution of cases and PCR positive individuals is presented in this analysis and hypotheses of the transmission discussed based on these findings. Two more villages will be surveyed as pan of this ongoing study.

PATIENT CONTACT IS THE MAJOR DETERMINANT IN INCIDENT LEPROSY: IMPLICATIONS FOR FUTURE CONTROL

¹ Dept. of Biomedical Research, Royal Tropical Institute, Meibergdreef 39, 1105 AZ Amsterdam. The Netherlands. ² Dept. of Microbiology, Hasanuddin University, Ujung Pandang, South Sulawesi, Indonesia.

Notwithstanding the elimination efforts, leprosy control programmes face the problem of many leprosy patients remaining undetected. Leprosy control focusses on early diagnosis through screening of household contacts, although this high risk group generates only a small proportion of all incident cases. We explored the extent to which other contact groups contribute to incident leprosy. We examined retrospectively incident leprosy over 25 years in a high endemic village of 2283 inhabitants in Sulawesi, Indonesia by systematically reviewing data obtained from the local programme and actively gathering data through interviews and a house to house survey. We investigated the contact status in the past of every incident case. In addition to household contact, we distinguished neighbour and social contact Of the 101 incident cases over a 25 years period 79 (78%) could be associated to contact with another leprosy patient Twnety-eight of those 101 cases (28 %) were identified as household contacts, 36 as neighbours (36%) and the remaining 15 (15%) as social contacts. Three patients had not had a previous contact with another leprosy patient and no information could be gathered from 19 patients. The median span of time from the registration of the primary case to that of the secondary case was 3 years; 95% of the secondary cases were detected 6 years after the primary case. Thus, contact with a leprosy patient is the major determinant in incident leprosy, whereby the type of contact is not limited to household relationships, but also includes neighbour and social relationships. This finding can be translated into a valuable and sustainable tool for leprosy control programmes and elimination campaigns by focussing case detection and health promotion activities not only on household contacts but also on at least neighbours of leprosy cases.

AN EPIDEMIOLOGICAL STUDY OF M. LEPRAE INFECTION AND DISTRIBUTION OF LEPROSY BACILLUS IN THE ENVIRONMENT OF ENDEMIC VILLAGES IN NORTH MALUKU. INDONESIA.

Shinzo Izunny, Masanri Matuoka , Teky Budiawan . Noboru Nakata and Keisuke Saeki

1) National Leprosarium Oshima Seisho-En, Kagawa. Japan, 2) Leprosy Research Center. National Institute of Infectious Diseases, Tokyo. Japan. 3) Ternate Leprosy Hospital. North Maluku, Indonesia.

It is well known that the geographic distribution ot leprosy is highly heterogeneous. There are relatively small areas with very high prevalence and incidence. Little is known, however, about the reasons why leprosy is so prevalent in the area. We conducted, therefore, a series of epidemiological survey in such an area to estimate the rate of M. leprae infection by serological techniques. and distribution of leprosy bacilli in the environment by polymerase chain reaction. The selected district was North Maluku, Indonesia, where estimated prevalence was 2.5%.

It was tound that about one third of the healthy villagers had anti- M . leprae specific phenolic glycolipid-I IgM antibodies without evidence of direct contact with leprosy patients, suggesting that epidemiologically important sources of M. leprae infection is not the leprosy patient but non-human source(s).

As the first step of searching the possible sources in the living environments, we examined all water sources for washing clothes, bathing and drinking in the villages. It was found that 13 out of 27 samples contain M. leprae specific DNA by nested-primer gene amplification technique (PCR). The 347bp PCR product was proved to have the same base sequence with M. leprae DNA fragment.

Our results are the first epidemiological observation to suggest that environmental M. leprae may play an important roles in the infection of leprosy bacillus and the transmission of leprosy in the endemic areas.

SEROREACTIVITY OF 102 NONHUMAN PRIMATES TO PGL-I OF MYCOBACTERIUM LEPRAE IN THE REPUBLIC OF BENIN

Ministère de la Santé and Agence Béninoise pour I'Environnement, Cotonou, Bénin; Institute of Tropical Medicine, Antwerp, Belgium, and Armed Forces Institute of Pathology, Washington DC, USA.

Naturally-acquired leprosy prevails in armadillos in the USA, and afflicts mangabey monkeys and chimpanzees in West Africa. Evidence in the US suggests that humans occasionally acquire leprosy from M. leprae-infected armadillos or their products. Thus, leprosy can be zoonotic, making the total eradication of leprosy exceedingly difficult. We conducted a serological survey for antibodies to PGL-I of M. leprae in nonhuman primates in Benin to obtain data relevant to the question of extrahuman reservoirs of leprosy in West Africa.

All animals originated from the wild and were either pets or sentinels at their owner's residence. Each animal was anesthetized on site with Ketamine via blowgun and dart. After clinical examination, venous blood was taken. No animal died or was injured. Sera were analyzed by a gelatin particle agglutination test (SERODIA-Leprae, Fujirebio Inc Tokyo) for antibodies to M. leprae PGL-I. Of the 102 animals the origin of 53 was known; 51 from Benin, 2 from Togo.

Ten animals (9.8%) were positive for antibodies to PGL-I: 9 of 48 baboons (19%), 1 of 23 patas monkeys (4%), none of 31 vervet monkeys. One positive baboon originated from Togo. We found no lesions consistent with leprosy.

We conclude that the data suggest nonhuman primates in West Africa may be reservoirs for M. leprae; however, additional studies are needed to establish the specificity of the test employed for PGL-I of M. leprae in the animal species examined.

IMPLICATIONS OF ENVIRONMENTAL MYCOBACTERIAL INFECTIONS FOR THE EPIDEMIOLOGY OF LEPROSY

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK

Most human populations are exposed to a variety of "environmental" or "atypical" mycobacterial infections. There is much evidence for cross-immunity between different mycobacterial infections, the most obvious examples being the protection by BCG (a derivative of M bovis) against human leprosy, tuberculosis and M avium infections. In addition, animal experiments have shown that exposure of mice or guinea pigs to a variety of different mycobacteria imparts varying levels of protection against subsequent challenge with M leprae and M tuberculosis. Such exposure in natural settings may explain several important features of leprosy, including geographic clustering (reflecting local variations in environmental mycobacterial exposure), regional differences in the observed efficacy of BCG (whose protective action may be masked by the protection provided by other mycobacterial infections) and perhaps also regional differences in disease type (though the evidence here is more speculative). The large number of different species of environmental mycobacteria, and the fact that many are non-cultivable, has inhibited research on this subject, but extensive skin testing in Malawi with a variety of mycobacterial antigens has provided evidence that exposure to agents which share antigens with M leprae imparts protection against leprosy. This paper will examine the global evidence and provide detailed analyses for the involvement of environmental mycobacteria in leprosy.

EARLY DETECTION BY ELISA AMONG 33 NEW CASES OF LEPROSY IN HOUSEHOLD CONTACTS OF MULTIBAC1LLARY PATIENTS IN CEBU (1985- 1997).

James Douglas¹. Paul. Klatser². Roland Cellona³ Rudy Abalos³. Tranquilo Fajardo. Jr.³, Ma. Victoria Balagon³ and Gerald Walsh³.

¹ Univ. Hawaii. Honolulu, HI.² KIT. Amsterdam, Netherlands, ³LWM Ctr. for Lepr. Res., Cebu. Philippines..

To assess the value of ELISA in early detection of leprosy we conducted a blinded prospective study among 601 household contacts(age x=29,267 male, 334 females) of multibacillary cases in Cebu, Philippines. The study started in January 1985. Using the ND-OBSA antigen we found 1.4% of 401 endemic controls(age x=34. 202 male. 199 female) and 91% of 193 multibacillary index cases were ELISA positive. During the study MB patients and their contacts were enrolled as MDT treatment was started. All contacts enrolled were screened to be free of leprosy. Any contact who developed disease was immediately treated with MDT. The diagnostic team was not given ELISA results. Serum samples were collected at six month intervals until 1989, then another survey was done in 1991. Between 1989 and 1991 and after 1991, passive surveillance was used to detect cases. Of the 601 contacts enrolled 559 were bled and followed for two or more times. The average duration of ELISA follow-up for the 559 contacts was 4.2 ± 1.6 years until 1991. The 33 new cases came from 27/186 households: 6 household had two each and the remaining 21 households one case per household. The average duration in the for development of disease after enrollment was 3.7 + 3.1 yrs for 15 MB cases and 3.6 + 1.9 yrs for 18 PB patients. Since the contacts had no sign of leprosy at enrollment and the index patient was on MDT, a contact who became a case was most likely was incubating the disease at intake. The last reported case was detected in 1996 with 9 years in the study as an MB with BI 4.0 and ELISA positive(+) in 1991. In 1994, a second MB case, BI 4.2, was detected after 9 years in the study. He was ELISA(+) at entrance to the study in 1985 These cases have the longest duration in the study prior to the development of disease. The mean duration for household exposure of new cases to the index was: PB 19.3 + 8.8 yrs and MB 20.5+ 6.6 yrs , as determined by interview. Of new MB cases 93%(14/15) and 33.3%(6/18) PB cases were ELISA(+). Of these five MB and three PB cases remained ELISA (+) from start of monitoring through 1991. Nine MB and three PB cases became ELISA(+) during the study. Eighty percent of ELISA (+) cases have other contacts in the house hold that are also ELISA positive. These findings and our earlier studies indicate that the ELISA was effective in identifying the subsets of household contacts who have a very high risk of developing leprosy and an even higher risk of developing multibacillary disease (RR> 40) and that being ELISA positive carries a long term risk for developing MB disease. Application of this test to household contacts combined with traditional diagnostic methods could assist control programs in early detection of leprosy and especially multibacillary disease. Application of these findings to chemoprophylaxsis is a next step logical step, keeping in mind that the most likely disease to develop in ELISA(+) contacts is MB.

MONITORING PROPHYLACTIC TREATMENT OF ELISA POSITIVE CONTACTS OF LEPROSY PATIENTS IN CULION.

Univ. of Hawaii. Honolulu: Res. Inst. for Trop. Med., Manila. Culion Found. Inc., Manila.

Multibacillary leprosy (MB) is difficult to diagnose unless frank signs have occurred, when MB patients are found they are usually detected with high bacterial index(BI) of 3,4 or 5. This observation suggests that high BI individuals are not recognized as cases of leprosy for some time before signs occur. Since transmission is associated with MB (BL and LL) patients, it is reasonable to assume that among these strongly BI positive incubating cases, some will serve as an undetected reservour of transmission. The incubation period prior to onset of clinical symptoms is thought to last several years alter infection. Since the ELISA based on the PG-I antigen of M. leprae is known to be positive in MB patients both before diagnosis, and is also associated with declining ELISA values during treatment, we decided to use this test as a marker for candidates for chemoprophylaxsis. In studying 6.837 contacts of leprosy patients Culion, we found positive serology correlated with a high risk of developing leprosy, RR= 23(95%Cl=12-45). The relative risk of developing MB disease increased among ELISA positive contacts of patients to a RR = 48( 17-132). With this background information, we monitored 37 ELISA positive contacts of leprosy patients with the ELISA during preventive chemotherapy in a double blind trial. These contacts had positive ELISAs with OD readings greater than 0.2 on at least two consecutive tests. The treatment group of 19 was given rifampin daily every other month for three months and three doses a week of Clofazimine on alternate months for three months. Dapsone was given daily. The control group of 17 was given a placebo. ELISA monitoring at six month intervals measured OD values within the two groups. The age, sex, starting OD values were similar for both groups. Significant declines in ELISA values were found in the treatment group, compared to the placebo group. Chi square values were: 5.8 at six months, 4.2 at 12 mo. and 5.6 at 18 mo., p= 0.03, 0.04, 0.02. No significant changes were found in OD values for the placebo group comparing initial values with 6, 12, 18 month values by Ttest.. The Ttest values for the treated group drop significantly at 6, 12, 18 mo., p<0.01, p< 0.02 and p<0.01. No side affects were detected with treatment clinically or by monitoring of liver function. These results demonstrate the value of serological selection and monitoring in its application to chemoprohylaxis in leprosy, where there is no other means of identifying incubating disease. These findings also indicate the potential of focal use of the ELISA in eliminating foci of infection in the community.

DETERMINANTS IN THE DEVELOPMENT OF LEPROSY AMONG HOUSEHOLD CONTACTS OF LEPROSY PATIENTS IN CULION ISLAND, PHILIPPINES

Observations made from incidence .studies among household contacts (HHC) of leprosy patients have established that HHC of leprosy have the higher risk of developing leprosy infection and disease. To investigate further this data, a longitudinal seroepidemiological survey covering 80% (7547/8508) of the islands accessible population was conducted. One of the objectives of the study is to identify the determinants associated with the development of leprosy among HHC who have intra-familial contact with currently and/or previously infected hansenite. Over the 5 years duration of the study 34/2012 HHC developed clinical leprosy. Sociodemographic profiles and other determinants including positivity to IgM antibody to PGL-1 were analyzed among HHC who develop the disease compared to HHC who did not developed the disease. The following factors were found to be significantly present among HHC who developed leprosy: age .when first stayed in Culion, duration of stay in Culion, age of exposure with index case, number of index case in the household and positive serology. This study was able to establish an epidemiological data bank that could be used as a database for designing intervention strategies by the National Leprosy Control Program of the Department of Health in the future.

MILEP 2: SUB-CLINICAL LEPROSY INFECTION AMONG HEALTHY CONTACTS IN ADDIS ABABA, ETHIOPIA

G. Mengistu*. D. Beyene*, N. Gebre*, L. Tesfa*, S. Britton*, M. Macdonald@, I.A. Cree@ and W.C.S. Smith@ for the MILEP 2 Study Group

* P.O.Box 1005. Addis Ababa, Ethiopia
@ Inst. of Ophthalmology, Bath Street, London. UK

With the advent of multi-drug therapy (MDT) for leprosy, the prevalence of the disease has come down tremendously. However, despite effective MDT, the incidence of the disease has remained static in areas where the MDT program has been going on for the last 10 years or more. The possible explanation for the incidence not coming down, could be the presence of people with sub-clinical infections in the community who can serve as reservoirs, of whom only a few become overt clinical cases.

To explore this possible transmission route and also to elucidate the pathogenesis of primary nasal infection in leprosy, pilot studies on a small number of newly diagnosed, untreated leprosy patients (n=20) and healthy contacts or family members of leprosy patients who were released from treatment in the past years (n=15), were conducted. Using polymerase chain reaction to detect Mycobacterium leprae DNA from nasal swab material, 2 of the patients and 2 of the healthy contacts were positive.

Anti- M. leprae IgA antibody was also detected in saliva by ELISA. Eighty percent (16/20) of the patients and 33% (5/15) of the healthy contacts had Anti- M. leprae IgA antibody.

The results of this study to date are consistent with results from the MILEP 2 study in India using similar methods and suggest that such methods may be useful for investigation of transmission and immunity in leprosy in Ethiopia.

SEROLOGICAL AND PCR MONITORING OF THE EFFECTS OF PREVENTIVE THERAPY AGAINST LEPROSY

¹Dept. of Microbiol., Yonsei Univ. Coll. of Med., Seoul. Korea; ²Leonard Wood Memorial. Cebu. Philippines; and ³Dept. of Microbiol., Colorado State Univ.. Fort Collins. Colorado. USA.

A WHO-Special Action Project for Elimination of Leprosy has been implemented in the Federated States of Micronesia (FSM). in which one dose of rifampicin 600 mg, ofloxacin 400 mg, and minocycline 100 mg were given to residents without any sign of leprosy. Serum and nasal swab specimens from the residents were obtained before and on year after one-dose preventive therapeutic drugs and used for detection of antibodies and of Mycobacterium leprae by PCR. respectively. Of 1.725 serum samples obtained from three states of FSM before starting preventive therapy. 240 (13.3%) had elevated antibodies to phenolic qlycolipid I (PGL-I), the M. leprae specific antigen. The seroprevalence to PGL-I was the highest among the teenage school students (19.1%). followed by the age group pi 21-30 years old (15.1%). Surprisingly, 15 (13.3%) of 112 samples from young children (age <10) were seropositive to PGL-I. indicating the active transmission in the community. Serum samples from students from whom paired sera were obtained before and one year after preventive therapy were analyzed. Among 80 sera, there was no change in the seroprevalence of anti-PGL-l antibodies before and one year after preventive therapy at 23.8%. There were four residents who had seronegative conversion one year after therapy, but other four had seropositive conversion even after preventive therapy. There was also no change in seroprevalence to M. leprae soluble antigen and lipoarabinomannan one year after preventive therapy. However, the mean absorbance to PGL-I in seropositive serum samples decreased by 15% one year after preventive therapy. In addition, of 629 nasal swab samples obtained before preventive therapy. 12 (1.9%) were PCR-positive for M. leprae, while 9 (1.4%) of 622 samples obtained after preventive therapy were PCR-positive. The results thus failed to show statistically significant decrease in seroprevalence to M. leprae antigens and in PCR-positive rate one year after preventive therapy. Further evaluation of long term effects of preventive therapy against leprosy is undertaken.

National Leprosy Eradication Program(NLEP) monitoring statistics routinely collected from leprosy endemic area shows a declining trend in prevalence after the introduction of Multi Drug Therapy(MDT). The assessments based on visual interpretation of NLEP monitoring data or any other data have several pitfalls; therefore the impact on leprosy situations in these areas should be adjudged with extra care. An attempt has been made to examine the leprosy situation and its associations with the type of case detection strategies practiced in different areas.

The data from 3 areas with different case detection strategies has been used for this study. We reanalysed the same data using indepth epidemiological analysis and found that Rapid case detection approach covering entire population in short periods is more closely associated with favourable changes in leprosy situations in an area compared to the other areas where conventional total population survey at an interval of 3 years or more are in practice.

Hence the visual approach to the analysis of NLEP monitoring data although seemingly convincing, can be misleading. It is evident from indepth epidemiological analysis that prevalence though higher in certain areas, the leprosy situations is favourable compared to other endemic areas with different case detection approach.

Culion Sanitarium. Culion Palawan 5315 Philippines¹. Res Ins. for Trop. Med . Alabang. Philippines²and University of Hawaii. Honolulu. HI 96822 USA³.

Culion Sanitarium is the oldest existing sanitarium in the Philippines, est. 1906. An island-wide MDT program was started in 1987 and found new cases and prevalence rate of 75/10.000 and 260/10.000 respectively. In 1991 there were 13 new cases, from 1991 to 1997 the average annual number of new cases was 7.9. with 6 new coses in 1997. The population of the Island expanded from 11.070 in 1987 to 18.590 in 1997. In 1997, the incidence was 3.2.10.000 and prevalence 9/10.000. The decline in prevalence was the result of removal of treated cases from registration after MDT and an increase in the over all population by 68%. Most of the population growth was in the community contacts. To investigate the persisting emergence of new cases after the completion of the MDT. occurring at a rate similar to the early 1980's, a new survey was started in 1990 to 1991 covering 90% of stable Culion Island population over 5 years of age. This population was followed from 1991 to 1997. Contacts were placed in two groups: household (HHC) and community( CCC) contacts depending on presence of index cases at home. They were clinically and serologically examined regularly every 6 months. Thirty seven new endogenous cases were diagnosed from 1991-1997: 34(92%) HHC and 3(8%) CCC. A total of 6837 contacts were included in the study of which 54% were female. The contacts were: CCC = 4750( 69.5%) and HHC = 2087(30.5%). The ELISA was positive for 400(5.9 %) contacts: 118 HHC and 282 CCC. The relative risk (RR) of HHC developing leprosy was 26 times greater than CCC with a 95% Confidence Interval of ( 8. 84). The RR of HHC to develop MB disease was 43( 6.323) times greater and for PB 17(4.74) greater than CCC. The distribution of ELISA (+) reactions in new cases was: MB 15/20 (75%) and PB 7/17 (41%). The risk of ELISA (+) HHC and CCC of developing any type of leprosy (MB/PB) was RR=24 (12.45) when compared to ELISA (-) contacts. The risk of ELISA (+) HHC to develop MB disease is 47(17.127) times greater than ELISA negative HHC, with a RR=15(5,40) for PB HHC. In addition, the risk to develop MB leprosy in ELISA (+) HHC was a RR+ 133(52,348) compared to all CCC and ELISA(-) HHC. We found the major risks for developing leprosy were being a HHC and/or ELISA (+). These findings show that household contacts should be a focus of attention of control programs, when ever a new case appears and that most new cases come from households with index cases. The application serology allows the focus of control of transmission to be refined to about 6% of HHC, who are at the greatest risk of developing MB disease.

ESTIMATING HIDDEN PREVALENCE OF HANSEN'S DISEASE COMBINING TWO RELATED VARIABLES DIAGNOSIS DELAY AND GRADE OF DISABILITY AT TIME OF DIAGNOSIS

We have analysed a database of 4142 Hansen's disease (HD) patients, diagnosed in Rio Grande do Sul State (RS). Brazil, between 1970 and 1991. Out of these 4142 cases. 3291 had their grade of disability (GD) evaluated at time of diagnosis and had recorded the information given by the patient about the time elapsed between the beginning of the symptoms and the moment when HD was identified by a physician (diagnosis delay - DD) The mean time, in yean of DD was 1.51 for grade zero of disability. 2.14 for grade 1; 4.46 for grade 2 and 9.64 for grade 3

We propose a simplified model to estimate hidden prevalence (EHP). taking into account only 2 strata of GD and expressed by the following formula:

the values 2.0 and 5.0 correspond to an approximation of the mean time, in years, of diagnosis delay in each respective stratum of GD.

We have conducted a multivariate analysis, using a logistic regression model: it was observed that besides DD, other variables, such as clinical form, age group, sex and mode of detection were independent risk factors for having disabilities. In addition, we found two significant effect modification factors: DD vs. clinical form and DD vs. age group. We have performed a more complex model to calculate EHP, with 16 strata, taking into account clinical form, age group and GD from zero to 3. We have found an EHP of 485 cases for RS with this more complex model. This result differs only 5% from that of the simplified model: so. we conclude that the simplified model could be indicated for field uses.

ARE THE PROPORTIONS OF NEW CASES BY AGE GROUP AND BY CLINICAL FORM USEFUL INDICATORS TO DISCRIMINATE BETWEEN LOW ENDEMIC AND MEDIAN ENDEMIC REGIONS ?

The relationship between the Mean Annual Detection Rate (MADR) of Hansen's disease and two other epidemiological indicators - Proportion of Newly Detected patients under 15 years old (PR< 15) and Proportion of Newly Detected Multibacillary Patients (PRMB) - is analyzed, in order to evaluate the usefulness of these two indicators to discriminate between low endemic regions (LER - with MADR under 0.2/10000) and median endemic regions (MER - with MADR between 0.2/10000 and 1.0/10000)

A database of 4142 cases was studied, corresponding to all Hansen's disease patients diagnosed in Rio Grande do Sul State, Brazil, between January 1970 and April 1991 and notified until April 1994. Out of the 24 geographic regions of the State. 11 could be classified as LER and 13 as MER: subnotification is probably very low, because the control program presents very good operational indicators, covering 100% of the population.

Two kind of analysis were made : 1) bivariate analysis, comparing the distribution of patients, by age group and by clinical form, in the LER group and in the MER group; 2) multivariate analysis (weighted multiple linear regression), using each geographic region as a sample unit, in an ecological approach. In this multivariate analysis. MADR was the independent variable: PR <15 and PRMB were the dependent variables in two different models, which include many potential confounding factors.

All statistics tests have shown no significance, for α = 0,05. In conclusion, this study did not show reasonable evidence that PR<15 and PRMB adequately discriminate between low endemic and median endemic regions: in consequence we should consider alternative indicators to validate the achievement of Hansen's disease elimination goals in those regions where register prevalence is under 1,0 cases 10000 inhabitants.

HISTORICAL SERIE OF THE LEPROSY PREVALENCE ON THE STATE OF AMAZONAS, AN EPIDEMIOLOGICAL AND OPERATIONAL EVALUATION - F ROM 1982 TO 1997.

Institute de Dermatologia Tropical e Venereologia "Alfredo da Malta" Rua Codajas, 24 - Cachoeirinha

Leprosy remains endemic within Brazil particularly within the slate of Amazonas.

Since the adoption in 1982 of the WHO recommended multidrug therapy (MDT), in the state of Amazonas has been observed variations on its prevalence along 16 years when reached a peak of 24,510 cases, a rate of 128.63/10.000 inhabitants that declined to about 80% if compared to the current prevalence.

In the retrospective study, it was used data of the Amazonas Leprosy Control Program and estimated population based on official census. From those data prevalence rates were calculated and the historical serie of leprosy prevalence described for the stale of Amazonas, from 1982 to 1997.

In this study the authors intended to evaluate the influence on behaviour and important leprosy prevalence reduction at the studied area and period due mainly to the introduction and implementation of the MDT with its well-known effectiveness and also some other operational measures carried out such as: elimination of the 2 and 5 years follow up period after the patient released from the MDT regimen for Paucibacillary (PB) and Multibacillary (MB) respectively, later change on the MDT?MB regimen duration period to 24 months, besides norms applied to release defaulter patients from active register recommended by the Brazilian National Coordination of Sanitary Dermatology.

Xin-sheng Wu, Yong Ning, Ling Shu, Zheng l.e and Jian-wen Yang Sichuan Provincial Institute of Dermatology, Chengdu City, Sichuan Province. China

Sichuan province was one of the most serious leprosy endemic areas in China. Through leprosy surveillance system established in 1990's the authors analysed the epidemiology of leprosy from 1951 to 1996. The results showed that by the end of year 1996, the total number of registered cases was 32 772, the highest incidence rate was 2.44/100 000 in 1958 and then declined gradually. The annual average progressively decreasing speed (AAPDS) of the number of new cases, incidence rate, incidence rate in children, the number of newly detected patients, detection rate, the number of registered cases, registered prevalence rate were 4.7% (Ng=0.9534). 5.9% (Ng=0.9407). 74%. 6.7%(xg=0.9326). 8.1% (xg=0.9195). 11.5% (Ng=0.8853). 12.4% (Ng=0.8763) respectively Among newly detected cases the proportion of children gradually reduced year by year with an AAPDS of 2.9% (xg=0.9712), but that of household contacts gradually increased year after year, showing a gradual decline of source of infection the MB rate among new cases. newly registered cases and active cases increased also gradually year after year. The MB rate of children cases was much lower than that of adults (X=102 7. p<0.01). The disability rates of two periods of 1986-1990 and 1991. 1995 were significantly lower than overall average disability rate of the whole observation period (X-60.9, p<0.01, X=103.5, p<0.01) 20-30 age group was the peak of age at onset with an average age at onset of 31.92 years. Average age at onset gradually increased to 34.19 years in the period of 1991-1995. The average delay time of diagnosis was 4 89 years and reduced gradually to 3 24 years in the period of 1991-1995. The authors concluded that: 1) the epidemiological status of leprosy in Sichuan province showed an obvious trend of decline. 2) the case-finding activities were improved and intensified year after year, but 3) the disability rate of newly detected cases was still as high as more than 20% in recent years and the average delay time of diagnosis was still as long as 3.24 years suggesting that early case finding was far from satisfactory and more efforts to leprosy control should be made.

AN EPIDEMIOLOGICAL ANALYSIS OF NEWLY DETECTED LEPROSY CASES IN RECENT TEN YEARS IN HUBEI PROVINCE. CHINA

Long-ai Wu . Rui He and Wei-dong Luo Institute of Dermatology . Hubei Academy of Medical Sciences

An epidemiological study of 904 newly identified patients with leprosy in 1986-1995 was made in terms of year of detection. sex. age at onset, classification, disease duration . clinical skin lesions . disability rate and ulcers, infection sources, case-finding methods, distribution . social . economic and living conditions. The results showed that the annual number of new cases decreased year by year and that of 1995 decreased by 84.3% as compared with that of 1986, the sex ratio was 3.03 to 1 showing no significant change as compared with that of the highest incidence year, the age at onset showed a marked right shift as compared with that in 1960's, and the proportion of children patients among the total number of registered cases decreased from 10% to 3.3% . while that of aged patients (>60 years) increased from 3.4% to 9.5%. The proportion of MB cases among the total number of registered cases increased from 42% in the 1960's to more than 90% in the 1990's, 48.7% of the cases had a disease duration of less than 2 years, the disability WHO Grade II or III rate at diagnosis was 28.3%. much lower than that of 57 62% in 1960's, 39 6% of them were detected by active case-finding modes including clue survey, household contact examination, locus survey. 60 4% of them were detected by passive case-finding methods including case-reporting, making diagnosis in leprosy professional out-patient clinics and general hospitals or health centers; case distribution was uneven, more than 80% of them lived in three previous high leprosy endemic regions, namely Jingzhou prefecture. Enshi prefecture and Wuhan district, incidence rate was closely related to social, economic and living conditions, more than 90% of them came from very poor families with poor living conditions.

Suggestions on how to strengthen future leprosy control and surveillance were made by authors.

Xiao-hau Di and Dun-wen Tan Wangdu Hospital for Skin Disease. Hebei Province. China

From 1955 to 1996 . 125 patients with leprosy were detected in (??????) area. One hundred and six of them were males 19 were females. As regards their classification. 55 were MB. 22 were PB and 18 unknown due to had records. The average disease duration was 2 93 years Among 117 clinically cured cases 15 relapses were identified There were o children (0.14 years) patients. Four cases had not been followed up because of death or unknown reasons Four active cases remain at present.

Benign is a non-endemic area of leprosy The highest incidence period was from 1956 to 1960and the highest prevalence rate period was from 1958 to 1962 Ninety percent of the registered patients were immigrants from different parts of the country. only 10% of them were natives of Biejing.

Sixty four percent of the mentioned 125 patients were diagnosed by the Institute of Dermatology. the Chines Academy of Medical Sciences and departments of dermatology of other famous hospitals in 1950s and 1960s and most of the patients were diagnosed in early stage The profession of the patients in Beijing was significantly different from that in other provinces. 34% were industry workers, 10% were college or university students. 9% were army people and 4% were students from foreign countries, such as Tailand. Myanmar and Indonesia.

The results showed that the periods of the highest incidence and prevalence rates of leprosy in Beijing were similar to those in other provinces of China, and were almost the same to the decrease of both two rates in Beijing area and in remaining areas of the country.

Medical-Scientific; Center of Dermatology and STDs.
Yerevan, Republic of Armenia

Leprosy on the territory of historical Armenia existed in remote antiquity. The first leprosorium was founded in the end of the third century (290-291). Antileprotic organizational measures, as well as scientific analyses of leprosy epidemiology in Armenia was leaded after 1921. We analyzed the dynamics of incidence and epidemiology of leprosy from 1921 to 1995, on the structure, clinical types, age, gender, cartographic distribution and other epidemiological givens. During the past period 370 primary patients were reported in 111 populated areas. The analysis showed, that peak of incidence was observed in the first 2-3 decades, after which there was a gradual decrease of the incidence rate, with simultaneous decrease of lepromatous type, as well as incidence among children and adolescents. The last primary patient was registered in 1982. During those seven decades full and obligatory isolation of lepromatous patients and 80% of other types was implemented. Mass and selective inspections of population were implemented, as well as monitoring health of leprocontacts, BCG vaccination of risk groups, dispensary services, and treatment of leprosy cases. The implemented measures, the improvement of socio-hygienic and cultural levels of population brought to the lowering of the activity of leprosy endemy and to its decrease. The organization of antileprotic measures are still being continued.

Mesfin Hunegnaw, M.D.; Krishnan S.A.R., M.D.; Shibru Gebre, M.D., All Africa Leprosy & Rehabilitation Training Centre (ALERT); Sven Britton, M.D. Armauer Hansen Research Institute (AHRI)

The study was conducted to appreciate the influence of MDT on the incidence of Leprosy in Central Ethiopia

File study was conducted in 4 districts of Central Ethiopia with an estimated population of 600.000. From each district 3 to 5 schools were selected by cluster sampling. A total of 6.453 children of 5 to 12 years age range in 15 elementary schools were examined for evidence of leprosy. A public health physician, two dermatologists and one leprosy supervisor were involved in the study. The clinical diagnosis of leprosy was agreed and skin slit smear examination was carried out. Each patient was referred to the nearby leprosy treatment centre for standard WHO/MDT.

The diagnosis of leprosy was confirmed in seven primary' school children. Five of them had PB leprosy and two had MB leprosy. All cases were within the age range of 7 and 12. A single patient was female and showed complications of leprosy. 3 patients had in determinate leprosy and were subjected to regular follow up

Excluding the 3 cases of early leprosy, the incidence rate in the study group is 10 85 per 10.000 primary school children. This rate is very high in an area where leprosy control programme is operating especially after the introduction of MDT in 1983. There has been no active school survey in the region but the reported passive case detection rate in the region in 1997 is 9.65 per 100,000. Although. MDT has decreased individual sufferings and prevented the emergence of drug resistant strains, it doesn't seem to influence the incidence rate of leprosy. Other measures like effective vaccine have to be included along with MDT if leprosy is to be eradicated in the year 2,000.

National Hansen's disease sanatorium Hoshizuka-Keiaien, Kanoya, Kagoshima JAPAN 893-8502

In Japan, number of leprosy patients based on WHO criteria had not been reported, which made the international comparison difficult. In December 1995, a nation-wide study to survey all the leprosy patients under medical care was performed. This survey was purposed to provide sound scientific data to the government's council of leprosy prevention law. The law was finally abolished in April 1996.

5303 cases were reported from 12 national Hansen's disease sanatoria (4918 cases) and 9 clinics (385 cases), among which WHO-criteria matched patients were 213 (4.0%). Among 213 cases, 23 were fresh MB, 10 were fresh PB. 63 were relapse MB, 25 were relapse PB, and 92 were under treatment more than 5 years and still need therapy. On the other hand, clinically cured cases (based on Japanese criteria in 1988) were 4498 (84.8%), among which grade 2 deformity was observed in 3424, grade 1 in 561. and grade 0 in 513. Remaining 592 cases (11.2%) were between WHO-based patients and clinical cure.

These data indicate that new cases are rare (10-20/year), and 85% of the leprosy patients are relapse or under long time therapy. In addition, overall deformity rate is high, which forces the cured patients to stay in sanatoria.

Ministry of Public Health, China
National Center for STD and Leprosy Control,
Nanjing. 210042, China

Based on the data of 471,254 leprosy cases from the National Leprosy Surveillance System, the epidemiological trnds of detection and prevalence rates in China from 1949 to 1996 were analyzed. The detection rates were higher in 1950s and 1960s with a peak rate of 5.01 cases per 100,000 population in 1958-1959. This rate decreased to less than 1/100,000 in 1980s, less than 0.5/100,000 after 1986 and 0.15/ 100,000 in 1996. The prevalence decreased from the peak of more than 2/10,000 in 1960s to 0.06/10,000 in 1996. Between 1986 and 1996, a steep reduction in detection rate (66.1%) and prevalence rate(82.3%) can be observed. However, while the prevalence rate continued to decrease in the recent years, the number of the newly detected cases remained steadily ranging from 1,500 to 2,000 with a detection rate of less than 0.2/100,000. In 1996, the WHO elimination of leprosy as a public health problem has been achieved totally in terms of the country or province/region, and in 98.4% of counties or cities. However, the national criteria for elimination of leprosy defined as prevalence rate of less than 1/100,000 remained not to achieve in 337 (13.7%) counties or cities where the active cases accounted to 66.5% of the national load and the special attention for reaching the elimination goal on time will be needed in future.

Astrakhan region located in the delta of Volga-river to the north of Caspian Sea was and remains the most active focus of leprosy in Russia. With 0,7% population living in Astrakhan region here 40 to 70% of leprosy cases detected in Russia were registered. This fact may be partly explained by ancient centuries-old close economical ties with the countries of SouthEast and Middle Asia and Near East (the Great Silk Way). In total during the period from 1923 (beginning of State Program of Leprosy Control in the USSR) to 1998 about 2800 leprosy cases were registered on the territory of Astrakhan region, more than 90% of them falling on 1923-1962, or by decades: 578 cases - in 1923-1932; 234 - in 1963-1972; 552 - in 1933-1942; 40 - in 1973-1982; 644 - in 1943-1952; 22 - in 1983-1992,610 - in 1953-1962; and only 8 new cases in 1993-1998. Regular and significant decrease in leprosy incidence, beginning since the 70th years, was achieved through active case-finding and coverage of all the patients with multi-drug therapy (MDT) implemented in the USSR in 1965-1970, regular surveys of leprosy contacts, implementation of preventive chemotherapy, special measures of financial support for leprosy patients and their families, rise in hygienic and sanitary standards. Among leprosy cases detected in the last 25 years women prevail (55%), more than 50% of leprosy cases are over 60 years old and there no children under 14 years old. Duration of incubation period in 75% of all these cases exceeds 10 years. Data Bank on ex leprosy cases is on record since 1923. A retrospective analysis of distribution and activity of leprosy foci is being carried out.

Zhi-zheng Xie. Ning Chen and Lian-hua Zhang
Jiangsu Provincial Institute of Dermatology. Nanjing. Jiangsu Province. China
Hou-zun Wang
Dongtai hospital for Skin Diseases Control

MDT has been implemented in the whole province of Jiangsu since 1985 By the end of year 1996. a cumulative number of 4 313 cases had received MDT with a coverage rate of 99 1 ... % and a regularity rate of 99 13%. Of these patients. 3 832 cases were cured with MDT. The data of leprosy epidemiology available of a period of 12 years before and alter the implementation of MDT were compared live results showed that the average annual incidence has decreased from 1 01 / 100 000 to 0 21/100 000, the proportion of children patients (0-14 years) dropped from 4.33% to 2.04% and the average annual prevalence dropped from 26.56/100 000 to 1.46/100 000, all with significant difference (p<0 01) Turthermore, the proportion of MB cases among newly detected patients and that among active cases have increased from 28.97% to 47.55% and from 29.84% to 73.29% respectively The relapse rate has reduced from 3.05% of cures by DDS-monotherapy to 0.13% of cures by MDT The authors suggested that a very high coverage rate of MDT. effectively operated casefinding activities, well organized county-township-village network for control and deep-going health education observed in Jiangsu were the explanations of a big difference of the impact of MDT on leprosy epidemiology between this province of China and other reported countries in the whold.

PHRASING TARGET ON PREVALENCE FOR ELIMINATION OF LEPROSY BY 2000 AD - JUSTIFICATION

M.Subramanian, Inder Parkash and K.V.Krishnamoorthy Central Leprosy Teaching & Research Institute, Chengalpattu - 603 001, India.

There have been conflicting views on phrasing target on prevalence(PR) rather than incidence for elimination of leprosy as a public health problem by 2000 AD. Prevalence is a composite indicator influenced by many factors viz. New case detection. Registration for treatment. Duration of treatment. Regularity of treatment etc... The New Case Detection Rate(NCDR) is also depends on case detection activities, knowledge and attitude of people's etc.. Since it is difficult to obtain precise information on incidence of leprosy of a given area, new case detection rate considered as proxy indicator of incidence. During the initial period of MDT implementation, a rapid fall of prevalence was observed due to the clearance of back-log cases(i.e. PB cases on register for more than one year and MB cases more than 3 year on register). The fall of prevalence in the latter period has been closely related to NCDR. An attempt has been made to examine the influence of NCDR on prevalence by varying the other parameters such as Proportion of MB cases and Treatment Regularity.

Data collected from Tamil Nadu and Andhra Pradesh States of India has been used as empirical data for testing the methodology of analysis. The epidemiological formula Prevalence = Incidence X Duration of disease is used to study the relationship between PR and NCDR.

If 6 and 24 months duration of treatment for PB and MB cases are continued, the NCDR should be reduced to the level of 1.2 to 0.7 per 10000 population to reach the elimination level prevalence depends on MB proportion among new cases. The target set by WHO on prevalence for elimination of leprosy encompasses both reductions of backlog cases and incidence of leprosy.

IMPACT OF MDT ON LEPROSY WITH A SPECIAL REFERENCE TO MONOLESIONS AND SMEAR POSITIVITY AMONG THE NEW CASES

The impact of MDT on the prevalence and incidence rate of Leprosy is studied in a project area of 1 lakh population over a period of 10 years with a special reference to new monolesional cases and those presenting as smear positive cases. The prevalence rate showed a fall from 23 per 10,000 in 1986-87 to 2.6 per 10,000 in 1996-97. The number of cases presenting with single lesion however showed downward trend from 63.69% in 1986-87 to 40.94% in 1996-97. The cases showing smear positivity among the new cases detected showed an ascent from 3.91% in 1986-87 to 6.45% in 1996-97 with a peak of 25% in 1995-96. A similar trend was seen in the analysed figures of the 4 general surveys done.

EVALUATION OF TEN YEARS OF THE LEPROSY CONTROL PROGRAM IN THE STATE OF SÃO PAULO, BRAZIL- 1986 -1996

Mite Tada L.R.F. Brasil (1), Mary Use C. Marzliak (1) , Tanya Lafratta (1), Wagner Nogueira (2) Otilia J. G. Simões (2) (1) Leprosy Surveillance Division, (2) Leprosy State Coordination, Epidemiological Surveillance Center of São Paulo State Health Secretariat

The prevalence of leprosy in the State of São Paulo, Brazil, shows a declining trend, mainly in the last 5 years. The prevalence was 38,958 registered cases in 1996 and the prevalence rate was 13 01/10,000. The situation observed in 1996 was quite different: the prevalence rate was 2.9/10,000 and the number of the registered cases was 10,013 patients. Although the prevalence of leprosy shows an important decline, the detection trend of new cases has been stable over the last ten years. In 1986, the detection rate was 0.83/10,000 and in 1996 the rate was 0.85/10,000. The proportion of initial clinical types has remained stable over this period. The geographic distribution of leprosy, comparing 1986 and 1996, shows an important change in the prevalence distribution. The number of counties with no patients has increased dramatically. Nevertheless, the geographic distribution of new cases has not changed if one compares 1986 to 1996. The epidemiological factors that influence the maintenance of the detection level during this period is one of the research objective of the surveillance service. Migration is an important factor to be considered. The theme of this presentation is the important reductions in the prevalence and the operational component parts of the elimination program that are responsible for this result These component parts are: organization of health services to attend the program activities, personnel training, intensification of the educational activities with the community participation and the organization of the State leprosy's surveillance system.

EPIDEMIOLOGICAL SURVEILLANCE SYSTEM OF LEPROSY RELAPSES -STATE OF SAO PAULO, BRAZIL. - 1990 - 1997

Mitie Tada L.R.F Brasil (1). Mary Use C. Marzliak(1). Dittor Opromolla (2) (1) Leprosy Surveillance Division of Epidemiological Surveillance Center and (2) Lauro de Souza Lima Institute. Sao Paulo State Health Secretariat.

The implementation of MDT/ WHO in the State of Sao Paulo. Brazil, started in 1986 as special projects, was fully implemented from 1992 on. The introduction of fixed duration MDT originates a great number of cured cases out of active records. So. many persons were even released with positive skin smear or some cutaneous lesions. After releases, medical teams started questioning the criteria of cure due to the fact that several cases returned with din»cal signs suggesting relapses. To avoid premature questioning of the efficacy of the fixed-dose regimen and to get minimum reliable data, the leprosy surveillance has defined a set of procedures. They are: implementation of Regional Reference services, standardized clinical procedures and special standardized forms. This system started in 1995. in a experimental basis, and was effectively adopted from 1996 on. Available Information were analyzed since 1990.

In the State of Sao Paulo. Brazil, from 1990 to 1997, 53.711 patients were released after completion of the treatment. Among those. 27.491 were treated with MOT/WHO regimen. 26.220 were treated with DDS monotherapy or "DNDS regimen". This was the standardized anti leprosy treatment in Brazil since 1975 until the MOT adoption in 1990. It recommended, for the MB patients. Rifampicin daily during 3 months plus DOS daily until the skin smear become negative or the disappearance of the clinical lesions. For the PB patients, it recommended DOS daily for at least 2 years or until the disappearance of the clinical activity. During this same period, 1.035 relapses were notified. Of these. 460 were investigated. Among them. 304 cases were considered relapses. The relapses were classified as: 9 cases were treated with MOT/WHO. 224 were treated with "DNDS Regimen" and 71 were treated with DOS only. The 196 cases discarded as relapses, were diagnosed as Leprotic Erythema nodosum, reversal reactions or some kind of physical disabilities. The operational difficulties to confirm relapses were caused by health services dispersion, troublesome access to references services, and difficulties to get laboratory tests for all patients. Besides that, the clinical and laboratory criteria to confirm relapses are not equally clear to all medical teams In order to fulfill operational requirements and to settle medical questions, the leprosy surveillance service was motivated to implement a special leprosy relapse study. Preliminary results of this research are prompted in this presentation.

1) The Danish-Bangladesh Leprosy Mission, Nitphamari, Bangladesh
2) Department of Public Health. Erasmus University Rotterdam, The Netherlands
3) Department of Public Health. University of Aberdeen. Scotland

BANDS is a prospective cohort study designed to investigate epidemiological, therapeutic and operational aspects of acute nerve function impairment (NFI) in leprosy. It is a unique study with respect to the number of patients included and detail of information gathered prospectively in a cohort of leprosy patients. A total of 2.665 consecutive, newly detected leprosy patients were recruited during 1 year (starting in 1995) in a highly endemic area of Bangladesh with a population of approximately 5.5 million people. This represents a new case detection rate of 0.5 per 1.000 per year.

Risk factors under study include age. sex, leprosy classification (Ridley-Jopling). leprosy group (MB, PB), skin smear result, skin lesion count, mode of detection, distance to clinic, duration of symptoms before diagnosis. NFI (motor and sensory), nerve enlargement, leprosy reactions, pregnancy, delivery, lactation, chronic disease status, and leprosy treatment. The follow-up period is 5 years from the beginning of treatment, with assessments at regular intervals. This includes examination of skin and nerves, nerve function tests and identification of specific risk factors.

An epidemiological description of the BANDS cohort at intake will be provided, together with a discussion of the research questions concerning the occurrence of NFI in leprosy that will be addressed in the study. Results at 24 months follow-up will be presented in different reports.

NERVE FUNCTION IMPAIRMENT AND REACTIVE EVENTS IN A PROSPECTIVE COHORT OF LEPROSY PATIENTS AT 24 MONTHS-FOLLOW-UP

Richard Croft¹, Peter Nicholls¹, Jan Hendrik Richardus², Alison Anderson¹, and Cairns Smith⁴

1) The Danish-Bangladesh Leprosy Mission. Nitphamah. Bangladesh
2) Department of Public Health. Erasmus University Rotterdam. The Netherlands
3) INF RELEASE Project. Pokhara. Nepal
4) Department of Public Health. University of Aberdeen. Scotland

The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study aimed at investigating the epidemiology of acute nerve function impairment (NFI) in leprosy, its risk factors and response to treatment. A total of 2.665 new leprosy patients have been recruited in the cohort. This paper reports on the results of follow-up at 24 months.

Incidence, timing and severity of episodes of NFI and other reactive phenomena will be presented and discussed. The contribution of the various risk factors under study will be analysed by means of regression analysis. The risk factors include age. sex. leprosy classification (Ridley-Jopling), leprosy group (MB. PB). skin smear result, skin lesion count.

mode of detection, distance to clinic, duration of symptoms before diagnosis. NFI (motor and sensory), nerve enlargement, leprosy reactions, pregnancy, delivery, lactation, chronic disease status, and leprosy treatment.

SENSITIVITY AND SPECIFICITY OF SIMPLE METHODS OF CLASSIFYING LEPROSY WITHOUT THE USE OF SKIN SMEARS

1) Department of Public Health. University of Aberdeen. Scotland
2) The Danish-Bangladesh Leprosy Mission. Nilphamari. Bangladesh
3) Department of Public Health, Erasmus University Rotterdam. The Netherlands

Over the past few years a number of simplified methods of classifying leprosy into Paucibacillary (PB) and Multibacillary (MB) disease have been developed and recommended. Classification is of importance to the selection of the MDT chemotherapy to be used to treat patients. The simple methods are important where basic health or primary health workers who have had minimum training in the diagnosis and treatment of leprosy. Methods which do not require the use of skin smears are also important for use in situations where skin smears are not available or can not be performed reliably. However it is important to know the sensitivity and specificity of these new methods in order to understand the size and direction of any misclassification.

Data from a cohort of 2665 consecutive, newly diagnosed leprosy patients recruited over one year in an area of north west Bangladesh were analysed. These patient data contained the results of skin smears at diagnosis. Ridley-Jopling classification and details of the numbers and distribution of nerve and skin lesions. The WHO 1988 MB/PB classification was used as the gold standard and different methods based on counting skin lesions assessed. In this data set a cut off of 6 skin lesions misclassified a small percentage of smear positive patients. Varying the number of skin lesions required to diagnose MB affects the sensitivity and specificity of the method.

The classical picture of peripheral nerve impairment in leprosy is that sensory impairment develops first, followed by motor impairment and in the established peripheral nerve damage there is both sensory and motor deficits. This is usually explained by the stating that sensory nerves are more susceptible to pressure and inflammation so that sensory deficit appears first. However a number of studies report, although not always commenting, on the fact that some patients have motor impairment with out sensory impairment.

We have analysed a dataset of 2665 consecutive, newly diagnosed leprosy patients from north west Bangladesh which included detailed nerve function assessments using the modified 5-point MRC scale for motor assessment and the ball point method of assessing 12 standard points on each palm and 11 standard points on the sole. The data set shows that 15% of patients have some sensory impairment and 12% have some degree of motor impairment and indeed there are patients who have motor with no sensory loss in the same nerve trunk as reported in other studies. These findings may be explained by differential recovery between motor and sensory fibres, misdiagnosis, or the insensitivity of sensory testing or they may hold clues to the pathogenesis of nerve damage in leprosy.

FACTORS IN DELAYING DIAGNOSIS AND TREATMENT OF LEPROSY - FINDINGS F ROM THE BANDS STUDY

1) Department of Public Health, University of Aberdeen. Scotland
2) The Danish-Bangladesh Leprosy Mission, Nilphamari, Bangladesh
3) Department of Public Health, Erasmus University Rotterdam, The Netherlands

It is generally held that early diagnose and treatment of leprosy leads to better outcome of treatment, particularly in terms of nerve function impairment. It is therefore important to recognise the factors which are associated with delay in diagnosis of leprosy and to understand the underlying issues.

Each of 2665 consecutive, newly diagnosed leprosy patients in a field project in north west Bangladesh was asked about the duration of skin lesions and the duration of nerve damage at detection. Around 55% reported that the lesions present for up to one year prior to diagnosis where 9% reported that the lesions had been present for more than 5 years. The delay in diagnosis has been analysed by factors such as age. sex. classification, and disability so that the characteristics of those with long delays to diagnosis can be described. These data can also be used to identify true incident cases from so called backlog cases. The validity of self reported delay to diagnosis can be challenged, with possible under-estimation in those reported only short duration of lesions.

GENDER. CASE DETECTION AND DISABILITY IN LEPROSY IN BANGLADESH: A TREND ANALYSIS

1) Department of Public Health. Erasmus University Rotterdam. The Netherlands
2) The Danish-Bangladesh Leprosy Mission. Nilphamari, Bangladesh

A trend analysis is presented of all newly detected leprosy cases over a 18-year period (1979 to 1996) in a highly endemic area of Bangladesh. A total of 23.678 new cases were registered, with an average of 860 new cases per year in the first 12 years, and increasing to around 3.000 newly detected cases in 1996. This increase primarily reflects intensified case finding efforts.

The male:female ratio decreased from 2.5 to less than 1.5. and annual new case detection rates per 10.000 general population increased from 3 to 6 and from 1 to 4 for males and females respectively. The proportion of newly detected cases with MB leprosy decreased over time, from 60% to 10% in males and from 45% to 5% in females. The proportion of newly detected cases with disability also decreased over time, from 65% to 20% in males and from 55% to 10% in females. The decline was primarily attributable to decline in grade 2 disability.

Together with more or less equal benefits of the intensification of case finding in terms of disability for males and females, these data also show an overall reduction in the gap in case detection between males and females. But comparison of the age-specific new case detection rates reveals that in the period 1991 to 1996. females in the age between 15 and 29 years were considerably under-represented compared to males in the same age group. This is probably due to the particular sociocultural circumstances of Bangladesh, where (young) women are less likely to report possible symptoms of leprosy in fear of not being able to get married. or to be divorced.

M. Macdonald. I.A. Cree. V.K. Edward. R.S. Jadhav. J.R. Rao. A. Fernando. V. Shinde. P. Raiborde. P. Klatser. J. Ryon and W. C. S. Smith for the MILEP 2 Study Group.

MILEP 2 Study Group. Dept. of Pathology. Inst. Of Ophthalmology, Bath Street, London. ECIV 9EL. UK and Richardson Leprosy Hospital. Miraj. MS. 416410. India

As part of the MILEP 2 study, a large survey of the mucosal immunology of leprosy. we have developed a procedure for the detection of small numbers of M. leprae bacteria on the nasal mucosa, utilising polymerase chain reaction (PCR) coupled with a specific, sensitive and robust detection strategy which uses novel peptide nucleic acid (PNA) probes. This study (funded by E.C. grant ICI8-CT96-0047). follows on from the MILEP I study previously undertaken by our group (Ramaprasad et al. Lep. Rev 68 301-315 (1997)).

The MILEP 2 survey team from Richardson Leprosy Hospital. Miraj, collected samples from all inhabitants of a nearby village. Two nasal swabs, sampling the dorsal surface of the nasal mucosa, were obtained from each individual; over 1200 subjects have been tested in the study to date. PCR analyses of material from nasal swabs were performed in the Stanley Browne Laboratories of Richardson Hospital Reactions were performed using "Ready-to-Go" PCR beads (Pharmacia. UK), under conditions similar to those recommended by the manufacturer, the PCR strategy is specific for the proline rich antigen ( pra) gene of M. leprae: in our hands. DNA equivalent to as few as 5 bacteria could be detected by this method (de Wit et al. J. Clin. Microbiol 31. 502-506 (1993)). Confirmation of the presence of pra -specific amplicons was achieved using a fluoresceinated PNA probe (Perseptive Biosystems. UK) complementary to an internal sequence of the pra gene PCR products were heat denatured in the presence of this probe and allowed to anneal. The DNA-PNA complex was bound to streptavidin-coated 96 well plates by virtue of biotinylation of one of the PCR primers. This was followed by colourimetric detection of binding of the PNA probe to the PCR product by HRPO conjugated anti-fluorescein antibody.

By this method, it was apparent that approximately 5% of individuals in the clinically normal population tested were positive for nasal carriage of M. leprae, this is in agreement with previous studies. Studies of these "PCR positive" individuals are continuing, to ascertain the progression of their M. leprae PCR status over time

THE EPIDEMIOLOGY OF M.LEPRAE PCR POSITIVITY IN AN ENDEMIC COMMUNITY - PRELIMINARY FINDINGS F ROM THE MILEP2 STUDY

WCS Smith. CM Smith. VK Edward. JR Rao. RJ Jadhav. A Fernando. M Macdonald. P Klatser. J Ryon. IA Cree for the MILEP2 Study Group

MILEP2 Study Group. Department of Public Health. University of Aberdeen. Aberdeen AB25 2ZD. Department of Pathology. Institute of Ophthalmology. Bath Street. London ECIV 9EL. UK and Richardson Leprosy Hospital. Miraj. Maharashtra. India 416410

The MILEP2 Study is an investigation into transmission of leprosy and protection within leprosy endemic populations. The study is funded by the European Commission and is a partnership including researchers in India. Ethiopia. United Kingdom, the Netherlands and Norway The development of laboratory methods for the detection of small numbers of M leprae on nasal mucosa utilising polymerase chain reactions (PCR) coupled with a specific, sensitive and robust detection strategy have been established in both India and Ethiopia. Details of the techniques are presented elsewhere.

The initial part of the study is to conduct surveys of endemic villages, examining all inhabitants and collecting nasal swab and saliva samples, in both India and Ethiopia The target is to examine 3.500 individuals over the first year of this 4 year project. A total of over 1200 have been recruited into the study so far and we have preliminary analysis of the first 600 samples available. The percentage of the population who are PCR positive is around 5% which is similar to that found in previous studies in India and Indonesia. The rates appear higher in women than in men There are few positive under the age of 15 years and over the age of 65 years. The PCR positivity rate is slight lower in those who have a BCG sear but further analysis of the effect of age and BCG is to be undertaken. The rate of PCR positivity in household contacts is around lour times higher than the rale among non-household contacts

These findings are the result of preliminary analysis of the initial results from this large scale investigation. Further analysis are being undertaken but the initial results reveal some important and interesting leatures of the epidemiology of M. leprae in nasal mucosa in a population. The potential significance of these findings will be discussed

MILEP2: DEFINITION OF LEPROSY TRANSMISSION AND PROTECTION WITHIN LEPROSY ENDEMIC POPULATIONS

C. M. Smith. I.A Cree. V. K. Edward. J Ryon. G. Bjunc. P. Klatser. W.C.S Smith for the MILEP2 Study Group

MILEP2 Study Group. Dept. of Public Health. University of Aberdeen. Medical SchooI. Foresterhill. Aberdeen AB25 2ZD. UK. Richardson Leprosy Hospital Miraj. India 416410 and Amauer Hansen Research Institute. PO Box 1005.Addis Ababa. Ethiopia

The incidence of leprosy in many endemic countries has remained static despite the success of MDT in reducing the prevalence of the disease Studies of transmission of M leprae infection have been limned due to the inability to cultivate the organism in vitro. The recent development of sensitive polymerase chain reaction (PCR) methods lor the detection of small numbers of M leprae should enable the estimation of infection rates within a population. Saliva IgA responses can also be used to reflect exposure to M leprae. The laboratory methods for these techniques have been established during a previous European Commission funded project in India (MILEP1).

The presentation will describe the design of a 4 year project in India and Ethiopia which will use these established techniques to study the transmission of M leprae and protective immunity in endemic populations.

The objectives of the study are: To establish the relationship between M.leprae infection and the development of immunity in a community in which multiple drug therapy (MOT) has been used for more than l0years; to elucidate the pathogenesis of primary infection in leprosy: and to develop and test a chemotherapy based intervention strategy for the interruption of leprosy transmission.

Three villages in India and one in Ethiopia were selected and matched for socio-economic status and size. Complete household surveys for detection of leprosy and BCG status are being performed and two Nasal swabs and saliva sample collected from each member. ENT examination and nasal biopsy is being performed on all PCR positive subjects, follow-up will continue for 3 years.

University of Hawaii John A Burns School of Medicine and Hansen's Disease Community Program. Department of Health. Honolulu, Hawaii

Hansen's disease has been endemic in Hawaii since the 1830's. Following initial importation, the disease became well established in the native Hawaiian population. Since the middle of the twentieth century. the number of cases in Hawaiians and the number of cases acquired in Hawaii have fallen progressively and in recent years the vast majority of cases have been imported. Two major factors have determined the sites from which cases come. These are 1) the number of immigrants coming from a particular country and 2) the prevalence of Hansen's disease in that country. While screening of immigrants for communicable disease may eliminate the importation of some cases of Hansen's disease, several factors limit the effectiveness of this type of screening. Among these are the nonspecific appearance of some of the skin lesions, the appearance of lesions long after exposure and infection in many individuals. and the long period of time required for successful treatment Most of Hawaii's cases in the last few decades have come from the Philippines, with the next largest number coming from Samoa. In the last decade, however, an increasing number of cases have come from other Pacific island nations.

The Republic of the Marshall Islands had a prevalence rate of 15.5 cases of Hansen's disease per 10.000 and a case detection rate of 20.4 per 10.000 in 1996. This nation of 55.000 residents signed a Compact of Free Association with the United States of America in 1986. Under this compact. Marshallese citizens are free to travel to the U. S. without any health screening. Hawaii is the preferred destination for Marshallese travelling to the U.S. and the port of entry for many of those who settle elsewhere.

In 1996 a case of Hansen's disease was identified in a 19 year old Marshallese man hospitalized on the island of Hawaii. Contact investigation revealed a number of individuals with skin lesions suspicious for Hansen's disease. The Hansen's Disease Community Program of the State of Hawaii Department of Health established a program to screen Marshallese residents of nearby communities. The screening of about 235 people detected 11 cases of Hansen's disease confirmed by clinical findings and skin biopsy. This report gives details of that investigation.

CLINICAL RISK FACTORS IN LEPROSY REACTIONS: AN EPIDEMIOLOGICAL REVIEW OF RECORDS F ROM NORTHERN THAILAND

McKean Rehabilitation Center, Chiang Mai, Thailand; Aberdeen University, Aberdeen. Scotland; Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, USA

A previous small study of selected new cases suggested that leprosy patients who develop erythema nodosum leprosum (ENL) have an earlier age of disease onset than patients who develop reversal reactions (RR) or no reaction. To confirm this and look for other possible risk factors affecting lerposy reactions, we analyzed medical records of all 7881 patients seen at McKean Hospital. Chiang Mai, Thailand, from 1965 through April, 1996. Of the 7881, 4324 received care entirely at McKean. and 4241 (98.1%) had complete data. Of the 4241, 21.8% developed ENL, 10.0% developed RR, and 68.1% had no reactions. The median (25th-75th percentiles) age of leprosy onset for patients who developed ENL: 22 (14-34) years, RR: 30 (18-45) years (P<000l), and no reaction: 29 (17-43) years (P<.000l compared to ENL, P=0.34 compared to RR). Moreover, as the median age of onset steadily increased from 18 (12-26) years in the 1950s to 34 (23-44) years in the 1990s (P<0001 for trend), the proportion developing ENL declined steadily from 41.5% of patients with leprosy onset in the 1950s to 11.9% of patients with leprosy onset in the 1990s. The proportion developing RR increased steadily from 7.7% of those with leprosy onset in the 1950s to 16.0% of those with leprosy onset in the 1990s (P<.000l for both trends). As expected, the incidence and types of reactions were related to leprosy type and severity: Only 8.9% of those with paucibacillary leprosy developed any reactions (0.9% ENL, 8.0% RR), while 55.1% of those with multibacillary leprosy developed reactions (42.4% ENL. 12.7% RR) (P<.0001). Among patients with no deformities, 16.6% developed ENL and 11.9% developed RR, while among those with at least 1 grade 2 limb deformity, 21.8% developed ENL but only 7.0% developed RR (P<.0001). There was no relationship between sex or between family history and incidence (or types) of reactions. We conclude that the risk of RR and ENL is strongly related to age of leprosy onset which is changing over time; to type and severity of leprosy; but not to sex or family history. The age relationship may point to important clues regarding the pathogenesis and epidemiology of leprosy.

EPIDEMIOLOGICAL SURVEILLANCE OF THE OCULAR DISABILITIES IN LEPROSY, SÃO PAULO STATE. BRAZIL Norma Helen Medina(1), Mitie Tada L. R. F. Brasil(2), Mary Lise C. Marzliak(2), Hannelore Vieth(3).

(1) Sanitary Ophthalmology Service and (2) Leprosy Surveillance Division, Epidemiological Surveillance Center - São Paulo State Health Secretariat, (3) Leprosy Control Program of Maranhão State Health Secretariat - Brazil

Evaluation of available data on the ocular disabilities of registered leprosy cases in 1989 in the State of São Paulo, Brazil, revealed a need to change the criteria of diagnosis of such disabilities to improve its sensibility at the time of detection. Since 1990, the Leprosy Program together with the Ophthalmology Service intensified training in the detection, prevention and treatment of the ocular disabilities. At the same time a group of experts designed new standardization of the procedures and criteria for grading ocular disabilities based on WHO guidelines. The suggested changes were also adopted by the National Leprosy Control Program of the Ministry of Health of Brazil.

To evaluate the new criteria, data recorded on São Paulo State Leprosy notification forms was analyzed for the years 1989, 1993 and 1996.

There was notification on 3,210 leprosy cases in 1989. Of these, there were 72 (2.2%) with ocular disabilities, of which 20 (1.1%) were PB and 52 (3.8%) were MB cases. In 1993, there was notification on 2.927 leprosy cases of which 40 (3.0%) were PB and 90 (8.1%) were MB cases. The number of cases notified in 1996 was 2,915. Ocular disability was present in 164 (6.9%) of which 48 (3.7%) were PB and 116 (10.7%) were MB cases.

The increase in number of cases with ocular disabilities (from 1989 to 1996) reflects the result of changes in criteria and the notification forms to document ocular disability, as well as training of personnel. Increases were primarily noted in Grade I (corneal hypostesia) and Grade III (visual acuity less than 207200). The MB cases showed a greater proportion of ocular disability than the PB case (p < 0.005)

Leprosy seems to be an interfamilial disease in Turkey. Many patients has ansestors affected with leprosy in the past stories. On the other hand it is a typical fact to get married among the patients. In this study we wished to learn the relationship of the patients and male female ratio in a given group.

We have already datas of the 2607 leprosy patients who arc alive and who are under the control of the our center at the end of the 1997(Male=1695 (65.02 %). Female=912 (34.98 %)). If we documéntate al the previously registered patients this number comes to 5298. When we examine them, 3449 arc male (65.10 %) and 1849 are female (%34.90 %).

Among this group we were able to find information about the familial relationship of only 1481 patients. In this study we arc giving the documetation of the relationship of this 1481 cases as a model in Turkey.

RAPID GEOGRAPHICAL INFORMATION ASSESSMENT FOR LEPROSY SURVEILLANCE IN LARGE URBAN AREA

Celina MT Martelli¹, Ana Lúcia SS de Andrade¹, Otaliba L Moraes Neto¹, Simonne A Silva¹, Marília D Turchi¹, Euclides A Castilho², Fabio Zicker

¹ Departamento de Saúde Coletiva, UFG/ Brasil;² Fundação Oswaldo Cruz, Rio de Janeiro, Brasil;

³ Special Programme for Research and Training in Tropical Disease, Geneva, Switzerland

ln the present study, a georeferenced leprosy surveillance system was built-up in a large urban setting of central Brazil to define cut-off levels of endemicity and to establish inner city migration patterns. Sis hundred newly detected leprosy cases were interviewed to record their socioeconomic status, rural-urban origin and residential history in the last 10 years. Rates were calculated according to district level and the threshold for discriminating high risk areas were defined by exploratory data analysis and by the distribution of the pediatric cases. Our results showed that most of the leprosy cases were city residents in the last decade despite of their rural origin, suggesting infection transmission within the city. Around 33% of the cases had changed addresses in a decade in a well defined centre-periphery flow. The exploratory method used in this paper through the graphic representation of stem & leaf and box-plot allowed to discriminate pocket areas inner city taking into account the variability of the local leprosy rates. The appropriateness of this methodology was to provide rapid assessment of leprosy critical areas, feasible for leprosy control interventions.

Vera Andrade(1) , Paulo Chagastelles Sabroza (2), Maria de Fátima Militao de Albuquerque(3), Celio da Paula Motta (4)

(1) Ministry of Health-Secretariat of Health Care/ SAS / MoH,(2)Samuel Pessoa Department/ENSP/ FIOCRUZ -RJ.(3) Colletive Health Studies Department/ CPqAM / FIOCRUZ-Clinical Medicine Department/Universidade Federal de Pernambuco-Recife, (4) Rio de Janeiro State Health Secretary

A decreasing trend in the prevalence rate of leprosy was observed in Brazil only after the introduction of the WHO /MDT implementation in 1990. This paper analyzes prevalence rate, and its utilization in monitoring the progress towards leprosy elimination in Brazil. Since this indicator is influenced by changes of definitions, comparisons from different endemic countries or different periods of time within the same country calls for caution. In Brazil, the current prevalence rate of 6.34/100,000 inhabitants could be considered high as compared to rates from other countries, but it is important to note that defaulters and patients being treated with old regimens are kept in the active registers, while in some other endemic countries they are not.

A STUDY OF 97 LEPROSY CASES F ROM KNOWN PATIENTS' HOUSEHOLD CONTACTS IN WUWEI COUNTY. ANHUI

Wuwei county was a mid-endemic area of leprosy that reached the target of basic eradication of leprosy in 1994 . By the end of 1995 , 902 leprosy have accumulatively been detected (MB 284 and PB 618; female 161 and male 741) There were 97 cases of attacked household contacts (MB 45 and PB 52; female 29 and male 68) involving 44 families, among them the female percentage (29.9%) and MB percentage (46.4%) were significantly higher than that of other non-household leprosy patients (17.8% and 31.5% respectively). Though the detection rate of new patients has been decreasing gradually, the household patients show a relatively increasing trend. The household patients diagnosed in the recent 10 years made up 30.6% of all newly detected ones during the same period, significantly higher than that 10 years ago (9.3%). The author emphasized the importance of regular surveillance of household contacts of known patients in detecting early leprosy in low-endemic situation.

LEPROSY DISEASE IN MINORS 15 YEARS OF AGE AND UNDER THE INFLUENCE OF DETECTION PROCEDURES ON CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS. Duppre NC. Nery JAC. Garcia CC. Pereira RMO. Sarno EN. Leprosy Laboratory. Oswaldo Cruz Foundation. Av Brazil. 4365 - Manguinhos. Rio de Janeiro - RJ. Brazil.

The clinical characteristics of leprosy in childhood are similar to those in adulthood but with certain peculiarities. It is known that children constitute a high risk group in families with MB leprosy patient because of greater risk of contagion by M. leprae

One-hundred-twenty (120) leprosy patients between the ages of 0 to 14 were included in this study. Their clinical and epidemiological characteristics were analyzed according to detection procedure and then divided up into two groups, as follows Group 1: Detection through examination of household contacts: and Group 2. Passive detection (self-referal or referral by others)

Among the 51 children included in this group 28 (58%) were from 0 to 9 years of age. 44 (86%) developed paucibacillary forms. 16 (36%) of whom presented the Infantile Nodular form. Among those whose degree of disability was evaluated 35 (97%) presented 0. Group 2: 49 (68%) of the 69 children included in this group were between the ages of 10 and 14. Twenty-three (33%) developed multibacillary forms, and the disability grading for 11 children (17%) was between 1 and 3.

The examination of household contacts made it possible to diagnose children in the 14-and-under age group and to detect early forms of leprosy, including the Infantile Nodular form (TT single lesion children)

Zhong-dong Duan, Yan-Fer Kuang, Xian-dan Di, Jie-xiao Wang and Xiao-lin Gao Hunan Provincial Institute of Dermatology and Venereology. Changsha City. China

512 children suffered from leprosy had been detected during the period of 1950 to 1995 in Hunan province, among them 470 cases(91 8%) were detected before 1985 and 42 cases (8.2%) after 1985 (including 1985) The proportion of children patients with a disease daration of less than 2 years was 66%. Most of the cases (59.6%) were household contacts of known leprosy patients and the main source of infection way active MB cases. The illiteracy rate of children cases was 42%, and 73.1% of them were unable to go to school after diagnosed as leprosy patients. The first skin lesion more frequently appeared in MB and PB cases was erythema with a frequency of 43,7% and 38.1% respectively. The main location of the first skin lesion was face (42.2%) in MB and upper limbs (30,7%) in PB. The Grade II and III disability rate was 31.8%. There were remarkable differences between MB/PB value, detection rate of early leprosy, modes of case detection, incidence of household contacts, illiteracy rate, rate of deprivation of education after diagnosed as leprosy and Grade II and III disability rate of children with leprosy identified before and after 1985.

Tibel Ieprosy Association and Tibet Autonomous Regional Institute for Prevention and Treatment of Skin Diseases. Lhasa city. Tibet Autonomous Region. China

Tibet Autonomous Region was previously a medium leprosy endemic area with an endemic history for more than 1 400 years leprosy patients were identified in 58 of 75 counties (cities)

Through comprehensive leprosy control activities implemented for more than to years, especially with the introduction of WHO MDT since 1987, the prevalence and incidence rates reduced from the highest (060 ‰ in 1980 and 12.62/100 000. In 1970) to 0,027 ‰ and 0,20/100 000 in respectively No children cases were detected in the recent 3 years. The proportion of county and village with registered leprosy patients also remarkably dropped by 63.7% and 82.5% respectively Epidemicity of this disease has been effectively controlled from the whole autonomous region point of view. By the end of the year 1997 there were only 66 active cases in the whole region.

S.K. GHEI,S.R.QAMRA,U.SENGUPTA & B.K.GIRDHAR CENTRAL JALMA INSTITUTE FOR LEPROSY TAJGANJ, AGRA-282001, INDIA

Of late, the significance of genetic mechanism in leprosy has been highlighted to account for the unexplained vagrancy of its incidence in endemic population. The epidemiological studies of the disease have contributed in this regard to some extent. Our previous studies on blood groups, Dermatoglyphics and other genetic markers have shown the association with leprosy in one way or the other. In the present study, we have taken two important genetic markers Taste deficiency for phenyl-Thio-Carbamide (P.T.C.)and Colourblindness in order to find the association, if any, of these markers with leprosy. For the Taste deficiency for P.T.C.,409 leprosy patients (212 BL/LL type and 197 TT/BT type) were compared with 200 normal healthy individuals taken as controls. For the incidence of Colourblindness 600 leprosy patients (311 BL/LL Type and 289 TT/BT type) were compared with 199 controls.

Investigations reveal that both TT/BT and bl/ll type of leprosy patients differ significantly from controls with regard to the frequencies of Tasters and Nontasters in them. On the other hand, no significant difference was observed between patients and controls with regard to the frequencies of colourblindness. Yet another important finding was that 2 TT/BT type of female patients(out of 56 TT/BT female patients) were colourblind.

INTRODUCTION - Regarding number of leprosy cases Brazil ranks second in the world. Epidemiological indicators, as of 1995 (Brazilian Ministry of Health), are: prevalence rate: 8.82/10.000 population; detection rate: 2.30/10.000 population; detection rate below- age -fifteen: 0.63/10.000 population. All these data are thought of as high according to WHO standards.

OBJECTIVE - To investigate clinical, hystopathological, bacteriological and epidemiological patterns within the below -age -fifteen leprosy patients group treated in HUCFF (University Hospital), a reference center for Rio de Janeiro metropolitan area.

METHODS - Transverse survey of below -age -fifteen patients records, treated in HUCFF from 1990 to 1997.

RESULTS - 26.08 percent were multibacillary. In 65.2 percent the index case was unknown. 43.47 percent came from "Baixada Fluminense", a group of poor dormitory towns in the neighborhood of Rio de Janeiro, and 40 percent were from the same district as our hospital - both areas considered endemical ones. Two cases came from "Vila do João". a shantytown close to our hospital. Both were investigated in their homes and surroundings, and it has been possible to determine the index cases (one in his own family, and the other one in the neighborhood, both Lepromatous leprosy).

CONCLUSION - The epidemiological studies point out that one of the main indicators in order to define a risk area for leprosy is the detection rate among below -age -fifteen. Considering leprosy incubation period (2-6 yrs.) every diagnosed case in this age range should result in epidemiological investigation of origin area and near home focuses research.

MOTIVE OF PRESENTATION - Discussion of these results, based upon bibliographical data.

THE DETERMINATION OF IgM ANTIPHENOLIC GLYCOLIPID-1 ANTIBODIES IN CURED LEPROSY PATIENTS

Zhi-cheng Li, Hua Yu, Feng-hou Zhang and De-ying Wang Gansu Provincial Institute for Prevention and Treatment of Endemic Diseases. Lanzhou City. 730030, Gansu Province,China

In order to develop a surveillance approach to be effectively used in the field, this study was carried out in 8 high, medium and tow endemic counties to determine IgM antiphenolic glycolipid-l antibodies in 359 leprosy cases cured with DDS monotherapy and to assess its role may have to play in predicting leprosy relapses. Positivity of IgM antibody to ND-O-BSA/ELISA(OD value > 0,16) is regarded as a hazardous factor. During the three years of monitoring 14 relapsed cases were detected including 12 in IgM positive group and 2 in the negatives, and the relapse rates were 26,09% and 0,65% respectively. The relative hazard degree was 40,17. The sensitivity and specitity of the test for MB were 91.6% and 90.16% respectively with a relative hazard degree of 70.28, and those for PB were 50%. 89.54% and 7.80. The results showed that the antibody has been disappearing gradually in cured individuals as time goes on. The authors consider that those who had gone through longer time after cure with higher IgM level or with an IgM level suddenly elevated alter its reduction should be given a more careful attention and more longer time for surveillance.

THE DYNAMICS OF LEPROSY PATIENTS FAMILY AND EPIDEMIC FOCUS OF LEPROSY -A PRELIMINARY ANALYSIS

Hospital for Skin diseases and STD, Nandan County, Guangxi Autonomous Region, China

Six hundred and seventy three patients with leprosy from 524 families and 310 villages were detected from 1958 through 1996 in Nandan County, Guangxi Autonomous Region. The results showed:

ANALYSE DE LA TENDANCE TEMPORELLE ET DE LA DISTRIBUTION SPATIALE DE LA LÈPRE DANS LA VILLE DE RECIFE - ÉTAT DE PERNAMBUCO - BRÉSIL

Entre les états brésiliens, celui de Pernambuco, situé dans la région nord-est du Brésil, présent une situation des plus atypiques étant donné sa croissante tendance à une être prévalent de 12.93 / 10000 habitants, tandis que les autres états présentent cette tendance décrassante. Les taux de détection sont de 3.55/ 10.000- habitants contre 1.45 /10.000 habitants moins de quinze ans après. La concentration urbaine et les conditions socio-économiques de cet état font que 90% des cas se concentrent en zone métropolitaine de Récife, avec une population de 45% du total de l'Etat

Face à cette réalité sévissante, on a essayé d'étudier, dans le présent travail, certains indicateurs, comme par exemple le coefficient de détention de la maladie en moins de 15 ans, par local de résidence en cherchant à identifier les événements dans lesquels ce phénoméne-la intensifierait les actions de contrôle.

Ce travail, a travers une recherche opérationnelle, anlyse la tendance temporelle de la Lèpre et utilize les tecniques du système d'Information Géographique, que permet de vérifier la variation spatiale des cas de Lèpre à Recife, en relation aux aspects opérationnels des services de santé et de la condition socio-économique de la population.

INCIDENCE RATES AND USE OF A LOGISTlC REGRESSION MODEL TO CHARACTERISE RISK FACTORS IN COHORT STUDY. Matos, HJ. Duppre. N. Alvim. MFS: Vieira. LMM: Sarno. EN: Struchiner. CJ.

Leprosy Section/Scientific Computation Program Fiocruz. Rio de Janeiro. Brazil Medical Informatics Section General Pathology Medical School State University of Rio de Janeiro, Brazil.

Leprosy household contacts have a greater risk in developing leprosy than general population. In a recent study (1993). Chanteau et al. have calculated a risk ratio of 30.8 for acquiring leprosy in Household contacts in comparison to general population. So, contacts surveillance is as necessary as understanding basic mechanisms related to the transmission and developing of frank disease. In fact both become important in a perspective of control and in an effort to eliminate this disease.

The main objective of this study was to answer to the following question: Among a set of factors, which are most important to influence development of disease in a cohort of household contacts? This way, a dynamic cohort of leprosy household contacts has been followed since 1987, at Department of Leprosy front Fundação Oswaldo Cruz, in Rio de Janeiro. Up to now. this cohort includes 2225 subjects, and a set of data have been collected, from three levels of analysis: family, person and individual immunologic status. The present study analyses data from 1987 to 1991. In this period o time 670 healthy contacts have been followed. Incidence rate, in person year of follow-up was calculated as 0.01694 at the end of observation time. Nevertheless, there was variation in this rate related to the time of follow-up for each subject in the cohort. For subjects at the end of the tint year of follow-up, for instance, the incidence rate was 0,06385: in contrast if we consider all subjects up to the end of the second year of follow-up it was 0.03299: up to end of the third year it was 0.02370, up to the forth it was 0.018622, and as was mentioned, up to the end of the period of observation it was 0.01694. For modelling risk from these data, it was proposed a stepwise multivariate logistic regression model. The software used was EGRET^®. In this model, co-prevalent cases have been included, totalling 758 contacts. In the final logistic regression model, the risk of developing leprosy was related to a negative Mitsuda cutaneous test (the cut-off adopted was that recommended by WHO. as 3.0 mm), with OR of 3,093 (C195%=1.735-5.514). also it was related to a previous vaccination with BCG. OR of 0.3802 (C195%= 0.2151-0,66719), and finally it was related to a multibacillary clinical form of primary case (either BB. BL or LL), with OR of 2.547.(C195%= 1,249-5,192). Although this model is dependent to a set of assumptions, among these cut-offs used, it shows that both, sufficient amount of bacilli, as well as specific immunologic status are useful indicators of risk of developing leprosy in a cohort of household contacts.

Dept. of dermatology,Kyoto University Hospital,Kyoto,Japan
*Wilson Leprosy and Rehabilitation Hospital, Director,Korea
**Anandahan Hospital (previous) ,RN,Nepal

It is widely accepted that the high ratio of child leprosy suggests that leprosy is still endemic there.

K.Saikawa had carried on the follow-up survey of the age specific distribution in Okinawa prefecture since just after the retrocession from the U.S.A., comparing with the other part of Japan. He traced how the pattern of the age specific distribution changed with the lapse of time. His conclusion is that the peak of the curve shifts toward the right (to older ages) accompanying with a decrease of new cases. The peak splits into one or two lower peaks and the curve becomes bimodal. A.Obara et al also observed a similar phenomenon in Korea. On the other hand, there are different patterns in other areas, as S.K.Noordeen mentions to in his article. The patterns in Nepal and in Haiti are different from ones observed in Japan and in Korea, where the elimination of leprosy has been achieved relatively in a short time. In the areas where leprosy is chronically endemic, the peak at ages below 14 (child leprosy) persists rather for à long time.

Impression: These different patterns look to reflect the endemicity in each area related with socio-administrative backgrounds.

THE PREDICTIVE VALUE OF NERVE ENLARGEMENT FOR NERVE FUNCTION IMPAIRMENT IN LEPROSY

1) Department of Public Health, Erasmus University Rotterdam, The Netherlands
2) The Danish-Bangladesh Leprosy Mission. Nilphamari, Bangladesh
3) Department of Public Health, University of Aberdeen. Scotland

The presence of nerve enlargement is considered as almost pathognomonic for leprosy. Suspected leprosy patients are usually examined for the presence of enlarged nerves, yet little is known about the sensitivity and specificity of this sign as indicator of nerve function impairment (NFI) in leprosy. The development of disabilities can be prevented successfully by treating recent NFI with corticosteroids. It is therefore important that NFI in leprosy patients is diagnosed easily, safely and effectively in field conditions. Palpation of peripheral nerves is a simple, cheap and safe test This study examines its effectiveness as a diagnostic tool for NFI.

Included in the study are 2,665 new leprosy patients who were recruited in the Bangladesh Acute Nerve Damage Study (BANDS). This is a prospective cohort study aimed at investigating the epidemiology of acute NFI in leprosy, its risk factors and response to treatment All patients were examined for the presence of enlarged peripheral nerves and sensory and motor function impairment at the time of diagnosis and at 12 months follow-up.

Nerves included in the study are the ulnar, median, radial, common peroneal, and posterior tibial. The following values win be presented and discussed: 1) the predictive value of nerve enlargement for the presence of NFI. and 2) the prédictive value of nerve enlargement for the occurrence of NFI within the following 12 months.

THE EFFECTIVENESS OF THE BCG4D VACCINE AMONG HOUSEHOLD CONTACTS OF MULTIBACILLARY LEPROSY PATIENTS A RETROSPECTIVE STUDY. Duppre NC. Nery. JAC. Wanzeller SH. Mattos H. Sarno EN. Struckiner CJ. Leprosy Laboratory Oswaldo Cruz Foundation. FIOCRUZ. RJ - Brasil

The degree of protection conferred by the BCg-ID vaccine against leprosy continues to be investigated worldwide. Studies are constantly being carried out to evaluate the degree of protection that BCG confers against both leprosy and tuberculosis. In this connection, it has regularly been demonstrated that BCG provides a more consistent protection rate against leprosy (20 to 80%) than against tuberculosis (0 to 80%). The present study was developed in the Clinical Unit of the Leprosy Laboratory. Oswaldo Cruz Foundation (FIOCRUZ). Rio de Janeiro. RJ. BRAZIL. The health care center takes care of leprosy patients from all over the State of Rio de Janeiro who have been referred either by doctors or other patients.

Six- hundred* twenty (620) contacts of MB leprosy patients were included in the study, 468 of whom had a BCG sear (exposed to BCG) and 152 did not (not exposed to BCG), all between th ages of 0 to 28.

These contacts were introduced into the study at different times from June 1987 thru December 1992. Medical exams were carried out on these contacts for a consecutive five-year period as of the date of the first examination at the clinic.

The results showed a cumulative rote of infection of 7.05% among those exposed to BCG and 15.13% among those that had not been exposed to BCG. A variation in the incidence rate was seen during the five years the contacts were under surveillance. In the first year, the incidence rate for those with a BCG scar was 0.49/100 persons versus 4.07/100 without 4 BCG sear. In the second year, the rate was 0.41 100 for those with a BCG scar as opposed to 1.08/100 for those without.

In the third year. 0.13/100 with a scar became infected with the disease versus 1.44/100 without. In the fourth year, however, the incidence rate was zero for both groups and remained so in the fifth year of surveillance. As a whole, the protection rate conferred by HCG-lD provided a greater degree of protection against the multibacillary forms (BB/BL/LL), which was 85.6% (53.8-95.5%) than against the paucibacillary forms (HI/TT/NI/BT), which was 52.6% (23.0 - 70.9%). Moreover, it was shown that other factors contributed to contraction of the disease. These factors included the presence of two or more MB patients in the family. type of relationship of the household contact with the patient (s), and the number of inhabitants per room in place of residence.

IMPACT OF HIV INFECTION ON SURVIVAL OF LEPROSY AND TUBERCULOSIS PATIENTS IN MWANZA. TANZANIA. J. van den Broek. S Mfinanga. C. Moshiro. R. O'Brien, et al Royal Tropical Institute. Amsterdam, The Netherlands

Long term survival of 120 consecutively diagnosed leprosy and 561 tuberculosis patients, with and without HIV infection, enrolled in 1991 in Mwanza Tanzania, after 56 months observation, was as follows:

Leprosy: 5 patients died during and 5 after treatment. The mortality of leprosy in this cohort was 33% (3/9) for HIV+ and 6% (7/111) for HIV- patients. Death after treatment occured in HIV negative patients only. The risk of dying was significantly associated with HIV infection (HR 8.3. 95% conf. int. 1.9 - 35.6), controlling for age group, sex and disability grading. In this study. HIV infection was associated both with MB disease and mortality.

Tuberculosis: 56 died during and 51 after treatment. Mortality of tuberculosis in this cohort was 35% (51/146) for HIV + and 13% (56/415) for HIV- patients. The risk of dying was significantly associated with age group above 35 years 1.5(95% conf. int. 1.03 - 2.1). and HIV infection 3.7 (95% conf. int. 2.6 - 5.2).

Kaplan Meier survival analysis for HIV- and HIV+ leprosy and tuberculosis patients, adjusted for age group, sex, disability grading (for leprosy) and type of tuberculosis (for tuberculosis) was as follows:

Conclusion: leprosy and tuberculosis patients with HIV infection have a high mortality: in leprosy during the treatment period and in tuberculosis both during the treatment period and the years following.

J van den Broek. Fr. van der Steen. J. Rubona. A. van Wijnen Royal Tropical Institute. Amsterdam. The Netherlands

Variables used in a model to estimate the burden of leprosy disabled grade 1 +2:

Model: the disabled prevalence (DP) equals the sum of survivors (S) and new or additional disabled, in 10 year age groups (i) and over 10 year periods (t):

Conclusion: the proportion of disabled among new cases and their age distribution, everything else kept equal, are the most important determinants of the level and trend of disabled prevalence.

Vijayakumaran, P., Manimozhi.N., Jesudasan, K. Schieffelin Leprosy Research & Training Centre, Karigiri. India PIN 632 106.

Multi Drug Therapy (MDT) programme with WHO recommended treatment regimen has given the hope of early case detection and rendering a leprosy patient especially Multi Bacillary (MB) non infective within a short duration. Hence duration of exposure for household contacts to infection is expected to be remarkably less when compared to MB leprosy patients on DDS monotherapy. During the period from 1984 to 1994, a total of 360 MB (previously untreated & skin smear positive) leprosy patients were treated with Multi Drug Therapy (MDT). The household contacts were examined once year. The incidence of leprosy among these contacts was about 14 per 1000 PYR during the first three years of surveillance. It declined to 4.6 per 1000 PYR during 7^th 8^th and 9^th years. Overall incidence of leprosy among all these household contacts was 9.8 per 1000 PYR. Other factors like duration of the disease, coprevalent cases, etc will be discussed. The incidence during Dapsone monotherapy period was reported to vary between 4.2 per 1000 to 29.5%. Though it was less during MDT, still the incidence seems to be high. Combined chemotherapy seems to be effective in reducing disease transmission among household contacts. But still the incidence is higher when compared to that of total population. Effective intervention needs to be introduced to reduce the risk of contacts developing leprosy.

EPIDEMIOLOGlCAL CHARACTERISTICS OF LEPROSY IN LOW ENDEMIC AREAS ALONG THE MIDDLE-LOWER REACHES OF YANGTZE RIVER

• Health and Epidemic Prevention Station, Jiujiang City. Jiangxi Province, China
•• Station for Schistosomiasis and Endemic Diseases Control. Jiujiang City. Jiangxi Province, China

Jiujiang city, administratively divided into 14 counties and districts, was a low endemic area. The prevalence has dropped from 0.222 ‰ in 1971 to 0.03 ‰ in 1995 and the average incidence rate for every 5 years from 0.32/100 000 to 0.02/100 000 having reached the goal of basic eradication of leprosy. By the end of 1995. 167 leprosy patients have been diagnosed, most of them lived in the south part of this city. The age at onset of the disease was 8-74 years including 15 cases of less then 15 years. The average detection age, average age at onset, the proportion of MB patients amongst newly detected cases and average medium time of delay increased as the time goes on. Seventy (41.92%) of 167 registered patients were immigrants mainly living in 7 counties/districts along railway and arterial highways. The index cases of 86 counties/districts of above mentioned seven were immigrants.

Early casefinding has been the key of leprosy control particularly in low endemic area. It needs participation of the whole health system and its personnel. Clue survey is consided as the best mode of case detection, which largely depends upon the qauality of training of personnel at peripheral level and their conscientious service for the community.

THE CHARACTERISTICS OF EPIDEMIOLOGICAL DISTRIBUTION AND STRATEGY DURING THE PERIOD OF POST ELIMINATION OF LEPROSY

• Hospital for Skin Disease. Fuchuan Yaozu Autonomous County, 542700 Guangxi Autonomous Region, China
•• Hospital for Skin Disease, Hezhou Prefecture,Guangxi Autonomous Region, China
••• Hospital for Skin Disease, Zhongshan County, Guangxi Autonomous Region, China

Seven counties of Wuzhou prefecture with a population of 3 672 300 and an area of 20 113.97 kilometers in the East Guangxi Autonomous Region where leprosy was medium endemic were selected for investigation. One thousand two hundred and eight three leprosy patients have been detected in 788 of 16 756 villages. Every five years from 1956 through 1955 was considered as an endemic period for observation. The method consist in linear correlation analysis and multiple regression coefficient test using average incidence of each period (AIP) as independent variable, unknown-cause incidence (UCI)X, incidence by extra-familial infection (IEFI) and incidence by familial infection (IFI) as dependent variables. The results showed that as regards the average period incidence (API), there is a significant correlation between UCI. IEFI and IFI, a very significant dependence relation between UCI and no linear regression correlation between IEFI and IFI indicating a potential change from coexistence of incidence by irregular UCI and incidence by extra-familial and familial clustered infection to clustered incidence by extra-familial and familial infection. It also demonstrated that intimate and repeated contacts with patients still remain as a risk factor of familial incidence and of extra-familial incidence as well.

and only 8 new cases in 1993-1998. Regular and significant decrease in leprosy incidence, beginning since the 70th years, was achieved through active case-finding and coverage of all the patients with multi-drug therapy (MDT) implemented in the USSR in 1965-1970, regular surveys of leprosy contacts, implementation of preventive

chemotherapy, special measures of financial support for leprosy patients and their families, rise in hygienic and sanitary standards. Among leprosy cases detected in the last 25 years women prevail (55%), more than 50% of leprosy cases arc over 60 years old and there no children under 14 years old. Duration of incubation period in 75% of all these cases exceeds 10 years. Data Bank on ex leprosy cases is on record since 1923. A retrospective analysis of distribution and activity of leprosy foci is being carried out.

For Karakalpakstan leprosy is an ancient heritage, but regular efforts towards leprosy control were initiated since 1933 after national health protection and leprosy service had been organized. To intensify antileprosy activity in 1962 Karakalpak Leprosy Control Branch of Uzbek Institute for Study of Dermatovenerology was opened and two outpatient clinics and six leprosy units were organized. Since 1957 active case-finding through regular sample and mass surveys with annual coverage of up to 100 000 inhabitants were carried out, identified foci of leprosy were put under surveillance with chemotherapy of both leprosy cases and their contacts, and just in 1960-1964 these efforts resulted in finding 490 new leprosy cases. Rates of leprosy incidence sharply contrasted between north and south parts of the country. Thus, in 1960 when the highest rate of total incidence for the country was observed (30,4 per 100 000) it was 43,7 in the north districts, approaching 185,6 in Muinak while in the southern parts it reached only 2,8 per 100 000. This difference is due to various factors, including genetic, besides living and economical conditions (Abdirov Ch.A. et al., 1973, 1977). Successful combined chemotherapy resulted in gradual decrease in leprosy incidence. By 1980 a tendency towards sporadic incidence began to be observed, ranging from 0,83 to 0,7 per 100 000 in 1987. In recent years only single cases of leprosy have annualy been registered in the north territories, and Karakalpak focus acquired features of disappearing endemicily. Meanwhile, difficult ecologycal and economical situation, long incubation period, absence of antileprosy vaccine and high susceptibility of a part of the population to leprosy could induce hurst of leprosy incidence on Karakalpak territory.

Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523 U.S.A.

Basic biological research on Mycobacterium leprae and on the immunology and pathogenesis of leprosy conducted over a period of the past 20 years has contributed little to the present optimistic state of global leprosy. Indeed, proceedings from the recent historical joint workshop of ILEP and WHO/LEP (July 1997) made no mention of a role for such research in identification/confirmation of the still appreciable numbers of new leprosy cases, or in gauging the extent of sub-clinical leprosy in the community, or in the ultimate eradication of the disease. Yet, there is the need for new diagnostic and epidemiological tools, for a deeper understanding of the bacteriological and immunological basis of pathogenesis, perhaps resulting in new treatment for reactions, for probes and assays for drug resistance and, possibly, for a vaccine for ultimate eradication of the disease. Those principles are still the driving force behind small, poorly funded but enthusiastic and well coordinated research groups throughout the world. Recent watershed meetings in Bangkok (March 1996) and Addis Ababa (February 1998) have identified disease-related issues to be addressed, most promising immunological and molecular approaches to follow, and shared centralized resources required to fulfill the mission. The International Leprosy Congress provides the ideal forum for the exposition and promulgation of a shared, interdisciplinary, interdependent global research strategy.

AN MALIES IN NEUROFILAMENTS PROTEINS SOME CLUES TO MOLECULAR MECHANISM OF PASSIVE NERVE DAMAGE IN LEPROSY.

Mechanisms of nerve damage in leprosy remains very poorly understood. In a recent morphological study, it was noted that, a decrease in axonal caliber precede paranoial demyelination which in turn precede nodal demyelination in human leprous nerves (Shetty and Antia,1995). As a logical extension of this observation, the biochemical basis for such a reduction in diameter of the myelinated fibres that leads to secondary demyelination was sought in the present study.

Neurofilaments (NTs) are the important constituents of the axonal cytoskeleton and C-terminal phosphorylation of NF. H is known to govern the axonal caliber (Hoffman et al 1984). Therefore the state of NTs and its phosphorylation were investigated in human and in experimental mouse leprous nerves, using immunocytochemical technique. SDS-PAGE and Western blot analysis

Reduced SMI-31 staining, decrease in NF protein in triton insoluble fraction and a corresponding increase in total protein in triton soluble fraction were noted in minimally involved human leprous nerves as well as in sciatic nerves of mice injected in foot pads with live and heat lulled M. leprae as compared to normal nerves. Protein bands corresponding to NF triplet were not seen in SDS-PAGE and immunoblotting. Results indicate alterations in the 3-D structure of NF protein as well as in NF phosphorylation. The results will be presented and discussed.

He-ying Wang, Wei-yun Zhang, Oin-Xue Wu. et al lnstitute of Dermatology, Chinese Academy of Medical Science and PUMC, Naming, China

In order in explore the variation of the specific anti-ND-O-BSA lgM antibodies in the mice which were infected with M leprae, the authors tested 50 serum specimens from normal mice and 131 from the M. leprae infected mice. The results indicated that the IgM level of infected sera was significantly higher than that of normal sera (p<0,01) And there was a significant difference between untreated and treated mice (p<0,01). In addition, the specific antibody levels showed distinct differences among the mice which had taken different drugs or different dosages of the same drug (p<0,01 or p<0,05). The results also suggested that IgM antibody levels of mice ran parallel with bacilli load and were related to the degree of infection and effect of chemotherapy.

THE LIMITED DIVERSITY IN RESPONSES TO LEPR0MIN-A AMONG ARMADILLOS IN THE SOUTHERN UNITED STATES.

¹G.W. Long Hansen's Disease Center. Baton Rouge, LA., USA ²St. Thomas Hospital, Tamil Nadu, India

Though sylvan leprosy is rare or absent in most locales it is highly prevalent among armadillos in the southern Mississippi river valley and contiguous coastal marshes. We examined the histological responses of 392 armadillos taken from various locations in Florida, Louisiana, Mississippi and Texas to determine if armadillos in different locales preferentially express different forms of the disease or if variations in host resistance to leprosy might influence this distribution. After adapting to captivity 1x10' heat killed M. leprae prepared as Lepromin-A were inoculated to the abdominal skin and the site biopsied after 21 days. Many of the animals were later experimentally infected with M. leprae. The Mitsuda reaction was described as Multibacillary or Paucibacillary and further sub-classified by the Ridley-Jopling scale as LL, BL, BT, or TT. The percentage of animals classified as different types varied significantly ( p < 0.05) between groups. Animals from non-enzootic areas in Florida showed the lowest Multibacillary percentage (65%) but those from another non-enzootic area in central Texas showed the highest (95%). The main variation seen was in the percentages of animals classified as either BL or TT and may have been influenced by the reaction of animals already exposed to M. leprae or harboring the agent. The Multibacillary rates of animals from enzootic areas and non-enzootic areas were identical (82%). The minor variations in Lepromin reactivity seen here could not underlie the major geographical disparities seen in the distribution of leprosy among wild armadillos. Results of experimental infections show that the majority of Multibacillary spectrum armadillos succumb to leprosy but 10-20% of the animals reliably resist the disease. The relationship between Mitsuda reactivity and resistance is complex and should not be confused as an indicator of susceptibility.

•Dela Cruz, E. C. •Balagon. M. F. •Villahermosa, LG, Fajardo, T.T. Jr . •Cellona, R. V. •Tan. E.V , • Abalos. R M . •Walsh, G. P. #Watson. J. D

•Leonard Wood Memorial Leprosy Research Center, Cebu, Philippines
#Genesis Research and Development Corporation. Auckland. New Zealand

The study aims to determine the effect of M. vaccae immunization on the growth of Myco leprae in mice

Preliminary results of a pilot study conducted at the LWM Laboratory indicated significant reduction of M. leprae growth in vaccinated mice compared to non-immunized controls. An expanded study using acid fast bacilli from histoid, BL relapsed and untreated LLs patients were used to infect inbred CBA/J mice. These were immunized with I mg of M vaccae LP. at day 0.3 weeks later infected with 5.000 AFB into each hind footpads and re-immunized with M. vaccae 90 days post infection. A non-immumzed group was used as control. Mice in both groups were sacrificed at 6.9. and 12 months post-infection. Hind pads from individual mice were harvested, pooled, stained and the AFB enumerated.

When compared with controls, results of harvest in the treated group inoculated with AFB from LLs patient showed a percent inhibition (P.I.) of 99.15%, 72.4%, and 62.4% at 6,9,12 months respectively. Those inoculated with AFB from the histoid patient showed a P.I. of 83.9%, 65.9% and 43.4% at 6,9,12 months. In the BL relapsed group a 95.6% and 92.8% P.L was noted at 6 and 9 months, and a 83.8% and 68.7% P.L was seen at 6 and 9 months in the other LLs patient.

This investigation is funded by Genesis Research and Development Corporation. Auckland. New Zealand and Leonard Wood Memorial-American Leprosy Foundation (LWM-ALF)

Previosly we found out that intensity of phagocytic responses of granuloma macrophages of from lepromatous leprosy patients towards M. leprae is directly related to the activity their of myeloperoxidase (MPO). The main function of MPO is binding of H₂0₂, thus, interfering its intracellular accumulation. Enzyme therewith becomes inactive. Mice were introduced 0,03-0,05 ml of 0,6% H₂0₂ solution into their foot pads. Then, 1-2 hours later, the animals were inoculated with passed M. leprae at a dose of 10⁴ into the same foot pads. An introduction of H₂0₂ activated multiplication of M. leprae in foot pads. By 5 month after the inoculation of M. leprae mycobacterial counts in foot pads of test-animals exceeded control values (without previous introduction of H₂O₂). At this time a few leprosy mycobacteral were discovered in lungs of test-mice. In 7 months a generalization of leprosy process was observed (M. leprae were found in large numbers in lungs and in less numbers - in spleen). By 9 month a large number of M. leprae was found out in spleen of test animals with decrease of mycobacterial counts in lungs. Electron cytochemically a decrease in MPO activity was found out in phagocytes of test-mice. The data obtained should permit a further elucidation of leprosy pathogenesis and will be used in attempts of new therapeutical approaches.

BALB/c mice, bred and maintained under SPF conditions, were administered Mycobacterium leprae soluble antigen from which lipoarabinomannan had been extracted (MLSA-LAM), M. leprae cell-wall antigen (MLCwA) or MLCwA-LAM subcutaneously in the flank, the antigens had been suspended in incomplete Freund's adjuvant (IFA) or aluminum hydrogel (AIOH), an adjuvant suitable for use in humans

After one month, the mice were challenged in the right hind footpad, each with 5000 freshly harvested M. leprae of the "Thai 53" strain. Harvests of the organisms four months later yielded the following results:

Thus, all three skin-test materials appeared to protect the mice when suspended in IFA, whereas no protection by these materials could be demonstrated when they had been suspended in AlOH.

Recently an association between goats and prevalence of leprosy in Indian villages was reported. It is well known that these animals live in close proximity to humans in this environment. Following this report a histopathologic study of biopsies from ears of over 300 goats and domestic pigs were studied. No evidence of leprous infection was detected. In this experiment 3 one-month-old baby goats and 2 one-month-old Yorkshire pigs were intradermalIy infected in the ears with saline suspensions of 10⁷ M. leprae and the animals were followed up for 12 to 18 months. Finding of a nodule showing granulomatous inflammation at the infected site will be described and its significance discussed.

INVESTIGATION OF THE POSTANTIBIOTIC EFFECT OF RIFAMPIN AGAINST MYCOBACTERIUM LEPRAE USING A BACTEC SYSTEM.

The postantibiotic effect (PAE) is defined as a measure of the suppression of bacterial growth following exposure and removal of an antibiotic. Although M. leprae cannot be cultured, its viability can be maintained for some time in artificial media. We have recently investigated the postantibiotic effect of rifampin against M. leprae by measuring ¹⁴CO₂ release with a BACTEC system and the concomitant incorporation of 1-¹⁴C-palmitic acid (substrate for BACTEC system) into the M. leprae -specific glycolipid, phenolic glycolipid-I (PGL-I).

Previous reports in the literature have shown that 3 hours after an oral administration of 600 mg rifampin, a mean peak serum concentration of approximately 15 μg/ml was observed, M. leprae harvested from the footpads of experimentally-infected athymic nude mice were incubated for 3 hours at 33ºC in the presence of 10 μg rifampin and 30 μg rifampin (a concentration approximating the area under serum concentration vs time curve). After incubation, the samples were centriruged and the pellets washed 2x with medium. The final bacterial pellets were resuspended in fresh drug-free medium and transferred to BACTEC vials. Growth Index (GI) readings were taken at prescribed intervals for 14 days. The contents of the vials were then frozen and lyophilized. After total lipid extraction, PGL-I was separated by column and thin-layer chromatography and radioactivity enumerated.

Although the GI (¹⁴CO₂ evolved) and the ¹⁴C-palmitate-PGL-I incorporation values were lower in the rifampin-exposed organisms, when compared to controls, there was no discernible postantibiotic suppression observed at either concent rat ion of the drug. Two factors may influence the postantibiotic effect of rifampin on M. leprae: exposure time and drug concentration. Future experiments will attempt to address these variables. However, this investigation demonstrates a radiometric procedure of determining PAE for M. leprae and may be helpful in considering dosage regimens for drugs to be used against M. leprae.

AN IN-VITRO MODEL OF HUMAN CELLS PHAGOCYTOSING M. LEPRAE BE USED TO ASSAY THE EFFECT OF ANTILEPROTICS

Ju-shi Oiu, Sheng Quan, Hong-mei Qiu, et al Department of Pathology, Sun Yat-sen University of Medical Sciences, Guangzhou City, China

In order to establish a model of Schwann cells phagocytosing M. leprae in vitro, the Schwann cells taken from the human peripheral nerves were cultured and identified by electron microscope and immunohistochemistry detecting S-100 and liposome in the cultured cell, then enabled them to phagocytose the M. leprae taken from skin leison of lepromatous leprosy patients. For the purpose of assaying the effect of antileprotics, we used them to treat the model respectively. after 10 to 20 days, double color fluorescent stain method was utilized to demonstrate the live or death of M. leprae. The results have indicated that Rifampin and Ofloxacin had a strong effect on M. leprae, the death rales were 91.08% and 90.9% respectively. Under the electron microscope. M. leprae underwent degeneration and necrosis. However, the death rates of M. leprae in Dapsone and the control group were 29.25% and 27.8% respectively. there was no difference between them. These results showed that Dapsone only had weaker effect on M. leprae. In conclusion, the above results have suggested that the model mas be used as an assaying method tor scanning and detecting sensitivity of antileprotics.

IMMUNOLOGICAL POTENTIAL OF SCHWANN CELLS AND ITS IMPLICATIONS IN REACTIONS IN LEPROSY

The Foundation for Medical Research, 84-A. R.G.Thadani Marg. Worli. Bombay 400 018, India.

The nature and origin of the aignal that invites an immunological attack on the peripheral nerves is largely unknown. The documentation on localized reactions in nerves, the immuno competence of peripheral nerve glial cells and the selective entry and multiplication of M. leprae in Schwann cells favors it as an initiator of an inflammatory reaction in nerves. This was investigated in murine dissociated Schwann cell cultures (DSC) to which viable M. leprae or its subcellular antigens (r-65KD/LAM) were added in the presence of lymphoid cells. Evidence from lymphoproliferative and multiple functional assays could conclusively demonstrate the immunological potential of Schwann cells albeit there were differing requirements for accessory cells and sensitization levels of lymphoid cells. The time-Kinetics of co-culture and the presence of fibroblasts and endothelial cells revealed significant modifications in patterns of DSC induced sensitization.

The observations raise doubt about specific reaction- precipitating antigens and restrict their role to differential activation requirements, genetic restriction and tissue distribution rather than in their effector potential. The role of the blood-nerve barrier, pre-inflammatory markers in nerves and the role of CNS will also be highlighted

MYCOBACTERIUM LEPRAE INFECTION RESULTS IN DIFFERENTIALLY TRANSCRIBED GENES IN CULTURED RAT SCHWANN CELLS

Biological Sciences Department, Louisiana State University, Baton Rouge. Louisiana¹ and Molecular Biology Research Department. Laboratory Research Branch, GWL Hansen's Disease Center. School of Veterinary Medicine. Louisiana State University, P.O. Box 25072, Baton Rouge, Louisiana 70894²

Invasion and destruction of Schwann cells (SCs), the principle support cells in the peripheral nervous system, by Mycobacterium leprae is the hallmark of leprosy and the major cause of disability. However, the interaction of M. leprae with SCs and the events which result in nerve destruction have not been fully elucidated but may be augmented by certain inflammatory cytokines. A better understanding of the direct effect of M. leprae infection on SCs may provide information to identify early nerve damage and potentially serve as a rationale basts for the development of therapeutic strategies that interrupt the M. leprae- SC interaction. To determine the potential effects of M. leprae infection on SCs we have employed the use RT-PCR and differential display technologies to study differential gene expression in infected cells. A rat SC line (33B) was infected with mouse footpad-derived M. leprae at an MOI of 100. After 24 hr exposure total RNA was obtained from infected and non-infected SCs and mRNA was reverse-transcribed into cDNA. Optimal conditions for semiquantitative RT-PCR analysis of gene transcripts encoding the myelin proteins, peripheral myelin protein (Po) and myelin basic protein (MBP) were developed. These myelin gene transcripts were present in the sciatic nerve preparation but MBP was not transcribed in detectable levels in 33B cells and was not up regulated in 33B cells 24 post infection. The gene encoding Po was transcribed in cultured 33B cells, however, there was no apparent effect of M. leprae infection on transcription of this gene 24 hr post infection. Longer time periods post infection are being analyzed. The effect of M. leprae infection on the transcription of other genes in 33 B cells was assessed using Differential Display (RNA fingerprinting). cDNA from M. leprae- infected and non-infected cells was amplified by PCR using arbitrary and poly(dT) primer combinations. Polyacrylamide gel electrophoresis of products demonstrated that several gene transcripts were differentially transcribed in M. leprae- infected cells 24 hr post infection. These transcripts have not yet been been identified. In conclusion, this 33B SC/M. leprae infection model has limited use for the study of myelin gene regulation. Presently, a rat SC/neuron co-culture system is being established in our laboratory. Since myelin genes are expressed in this system it will be used to study the direct effect of M. leprae infection on myelin sheath production, maintenance, degradation and repair, as well as, the expression of other genes.

MYCOBACTERIUM LEPRAE BINDS TO A 25 KDa PHOSPHORYLATED GLYCOPROTEIN OF HUMAN PERIPHERAL NERVE.

Dept. of Molecular Biology and Biochemistry Institute of Genetics, Begumpet, Hyderabad -500 016, India and

Neurochemistry Labs, Christian Medical College and Hospital, Vellore - 632 004, India.

Mycobacterium leprae, the causative agent of leprosy, specifically invades and destroys the peripheral nerve, which results in the main clinical manifestation of the disease. Little is known about the bacteria-nerve protein interaction.

We show in the present work that when Gamma [32 P] phosphorylated rat and human peripheral nerve proteins were used in binding assays, M leprae was found to bind to a 28-30 KDa protein of rat and a 25 KDa protein of human peripheral nerve. Partial characterisation of these binding proteins revealed that they are glycoproteins whose biochemical identify is similar to the 'P zero' protein.

Pre-treatment of M leprae resulting in proteolytic digestion, delipidification or carbohydrate removal resulted in decreased binding suggesting that structural integrity of M leprae is essential for binding. These M leprae - protein interaction could be important in the pathogenesis of leprosy.

The Foundation for Medical Research, 84-A, R.G.Thadani Marg. Worli. Mumbai 400 018. India.

In peripheral nerve lesions. Schwann cells (SCs) actively participate in nerve repair where they are aided by macrophages.

Therefore any alteration in SC functions would hamper regeneration. The aim of the present study was therefore to determine the effect of M. leprae infection on the regenerative functions of SCs and their modulation by macrophages which form a major proportion of the cells that infiltrate the nerve. Observations in 2 strains of mice, Swiss White (SW) and C57BL/6 were compared in view of their divergent responses to M. leprae infection.

M leprae infected SCs from SW mice showed a decrease in proliferation and expression of NgCAM and nerve growth factor receptor p⁷⁶. In addition, they responded to infection with an increase in laminin and collagens type I, III and IV. In contrast infected C57BL/6 SCs showed a decrease in expression of p⁷⁴ and secretion of fibronectin.

Macrophages, modulated SC response to infection by enhancing proliferation and the expression of NgCAM and p⁷⁶and decreasing extracellular matrix (ECM) secretion in both strains. The decrease in ECM was a function of protein breakdown by macrophage derived protease and also active regulation by macrophage secreted cytokines.

A similar modulation on SC metabolism in leprous nerves would have major ramifications on damage and repair activities. In addition ECM proteins would also influence the composition of the infiltrating cell population in lepromatous and tuberculoid nerves. The strain variation in Schwann cell response to M. leprae infection suggests diverse mechanisms of nerve damage in tuberculoid and lepromatous leprosy patients.

Mycobacterial Research Laboratory, Anandaban Leprosy Hospital. PO Box 151, kathmandu, NEPAL

Dapsone resistance has been recognised as a problem in leprosy treatment since 1064. In Nepal, dapsone monotherapy was introduced in 1056 and Multi-drug therapy (MOT) in 1083. However MDT coverage has only recently exceeded 95%. At Anandaban Leprosy Hospital, a mouse foot pad (MFP) laboratory was established in 1081. New previously untreated multibacillary cases and relapses presenting at the hospitals clinics are screened for dapsone and nifampicin resistance by MFP culture.

In the period 1987-1993, among 157 cases, there was a 6% dapsone resistance among new cases and 47% dapsone resistance among previously treated cases. In a new scries of 60 patients presenting between 1993 and 1997, the rate of primary dapsone resistance was found to be 10.5% and the secondary dapsone resistance rate was 8%. Whereas in the first cohort all primary dapsone resistant cases were resistant at low (0.0001%) dapsone, the new cohort include one high (0.01%) DDS resistant case. All secondary DDS resistant cases have been previously treated with dapsone monotherapy. No cases of rifampicin resistance were found. It is vital that surveillance of resistance to drugs used in MDT should continue at sentinel centres.

EZZAT M. NASR, SAWSAN EL TAYEB AND ABDEL HAMID MOHAMED FACTUALITY OF MEDICINE (GIRLS AND BOYS) ASYOUT & ALAZHAR UNIVERSITY, EGYPT

Diagnosis of leprosy is essentially clinical based on finding one or more signs of disease and supported by observing in some cases acid fast bacilli (mycobacterium) is slit skin smear.

Hyperimmune sera of different mammalian species including the human were mixed with dead staphylococcus aureus strain rich protein A content, the immunoglobulins attach to protein A by there Fe portion leaving the Fab region free to bind the homologous antigens.

Urine was collected from patients with lepromatous leprosy and tubercloid leprosy, concentrated and freezed at - 20 C.

The work is currently in progress and the results, statistical analysis and interpretation will be presented

INHIBITION OF LIPID SYNTHESIS IN MYCOBACTERIUM LEPRAE BY THE ANTIBIOTIC CERULENIN.

Cerulenin is an antibiotic isolated from the fungus, Cephalosporium caerulens and was found to be the first specific inhibitor of fatty acid synthesis. Fatty acid synthesis has been proposed as a possible target for antimycobacterial drugs. M. leprae has a lipid-rich envelope which contributes to virulence and antibiotic resistance. We have tested the effect of cerulenin on the synthesis of the M. leprae- specific lipids, phenolic glycolipid-l (PGL-I) and phthiocerol dimycocerosic acid (DIM).

Exogenous ¹⁴C-palmitate is readily incorporated into the specific lipid fractions of M. leprae maintained, but not growing, in axenic medium. M. leprae harvested from the footpads of experimentally-infected athymic nude mice was dispensed into Bactec vials containing l-¹⁴C-palmitic acid in 7H12 medium and cerulenin (5μg/ml). Vials without cerulenin served as control. The vials were incubated at 33ºC and at prescribed time intervals the ¹⁴CO₂evolved was measured in the Bactec radiometric system and the contents of the vials lyophilized. After total lipid extraction of the lyophilized media, PGL-I and DIM fractions were separated by column and thin-layer chromatography and the radioactivity enumerated.

Cerulenin totally inhibited the incorporation of 1-¹⁴C-palmitic into the PGL-I and DIM fractions of M. leprae. Although the presence of cerulenin resulted in a reduction of ¹⁴CO₂ evolved, the inhibition was not comparable to that seen in the lipid fractions. This indicates that the oxidation of palmitate was not adversely effected. Mycocerosic acid is an integral part of both the PGL-I and DIM structures and is formed by a condensation reaction involving long chain fatty acids and propionic acid. We can hypothesize from this data that the condensation reaction is inhibited by cerulenin. Further studies with cerulenin may provide an insight into the synthesis of these characteristic lipids found in M. leprae and the suitability of using this compound as an antimycobacterial agent.

A chronobiological approach is increasingly used in studies of pathogenic mechanisms of different immune-mediated diseases, including infections, as well for improvement of available methods of therapy. Our preliminary data on changes in biological rhythms of some blood counts in rats given a long-time therapy with dapsone were presented at the XIV International Leprosy Congress (1993). We continued studying the influence of DDS-therapy on biorhythrns of red and white blood picture in mice (circadian rhythms), in rats (season rhythms) and, retrospectively, in leprosy patients under therapy of long duration (perennial rhythms). It was found out that one-time administration of dapsone to mice resulted in changes in chronostructure of red and white blood counts. The effect was dependent on the time (morning-evening) and season of administration. In rats continuous administration of dapsone resulted in changes in perennial fluctuations in chronostructure of lymphocyte count and other blood indices, including biochemical ones. In long treated leprosy patients the most significant changes were noted in annual rhythms of lymphocyte counts. Thus, it may be concluded that if while short-term administrations of DDS cause dissimilar chronostructural changes in blood picture, these changes arc abated in prolonged treatment with dapsone, probably, in the course of adaptive process. The most significant changes are noted in chronostructure of lymphocyte count that might be due to immunotropic activity of the drug.

CHROMOSOMAL ABERRATIONS IN BONE MARROW AND GERM CELLS OF MICE TREATED WITH ANTI-LEPROTIC DRUGS.

K. Kalaiselvi¹, P. Rajaguru¹, N. Elangeswaran², H. Vinodkumar², Ooman², S. Murugan³, M.V.Usha Rani⁴.

1 Dept. of Environmental Science, PSG College of Arts & Science. Coimbatore, India.
2. CLT & Rl, Tirumani, Chengalpattu. India
3. CULEC, Coimbatore, India.
4. Dept. of Environmental Science, Bharathiar University, Coimbatore, India.

The frequencies of chromosomal aberrations (CA) caused by antileprotic drugs (Dapsone-D. Rifampicin-R. and Clofazimine-C) used in the multidrug therapy in bone marrow(BM) and germ cells (GC) of Swiss albino mice, with or without M Leprae inoculation, were studied. It was shown that the drugs under study caused CA both in BM and GC. In the M. Leprae inoculated animals (treated and untreated) both mitotic and meiotic cell division appeared to be inhibited as shown by low mitotic and meiotic indices. The mean frequencies (100 metaphase/animal) of major CA (chromosome rings and dicentric) in BM of M. Leprae inoculated (MLI) and non-inoculated (MLN) mice after 2 months of treatment with 2 drugs (D+ R) were in MLI - 0.18 and in MLN - 0.27 and with 3 drugs (D+R+C) in MLI - 0.15 and in MLN - 0.25. In GC of drug treated MLI mice, in addition to chromosome rings and dicentric, more numbers of fragmented chromosomes were also observed. After 2 months of drug treatment the mean frequencies of CA in GC of MLI mice were D+R -0.27 and D+R+C - 0.14 and of MLN mice, D+R - 0.16 and D+R+C - 0.14. The prolongation of drug treatment to 10 months showed a decrease in CA both in MLI and MLN animals. The antileprotic drugs and M. Laprae caused CA types which are likely to result in cell killing of both BM and GC.

REACTIVITY OF A POPULATION OF ARMADILLO LYMPHOCYTES WITH AN ANTIBODY TO HUMAN T, Δ T-CELLS.

D. M. Scollard, G. Lathrop, & M. Dietrich. GWL Hansen's Disease Center at LSU, & LSU School of Veterinary Medicine.

Background. Inability to identify distinct lymphocyte populations in the nine-banded armadillo (Dasypus novemcinctus) has hindered immunologic studies of M. leprae infection in this animal model.

Design. Leukocytes from 47 armadillos were screened by flow cytometry with a panel of 16 monoclonal antibodies (mab) against human or murine leukocyte antigens.

Results. The only reactivity observed was with antibody TCRδ1, directed against an epitope on the human δ chain. Among circulating lymphocytes, this mab identified a distinct, bright population in all animals, accounting for 2.0 - 47.1% of lymphocytes (median 10.6%). Compared to blood, the percentage of γ,δ-reactive lymphocytes was smaller in lymph nodes and greater among intestinal intra-epithelial lymphocytes; the percentage was variable in the spleen, thymus, bone marrow, and in cutaneous lepromas. Armadillos with disseminated M. leprae infection had a significantly greater percentage of circulating γ,δ-reactive lymphocytes than did naive or resistant armadillos (P<0.05).

Conclusion. This is the first described reactivity of armadillo lymphocytes with an antibody to a lymphocyte surface antigen. The percentage andistribution of γ,δ-reactive lymphocytes is similar to that of sheep and bovines. The role (if any) of these cells with M. leprae infection in armadillos remains to be determined.

FATE OF M.LEPRAE INJECTED INTRANEURALLY IN A MURINE MODEL: ITS VIABILITY. FOLD INCREASE AND CLEARANCE IN THE SCIATIC NERVE OF SWISS WHITE MICE.

In an experimental study.freshly harvested M. leprae inocula containing around 10⁷ bacilli were microinjected into the sciatic nerves of normal and immunosuppressed (TR) mice. Massive but localized predominantly epitheloid and macrophage granulomas were readily obtained in normal and TR mice respectively. In order to determine the fate of M. leprae within the neural granuloma, its load, viability and clearance if any were investigated sequentially using semiquantitative measures.

The average M. leprae yield per nerve assessed at regular intervals beginning 0,24, 72 hours and 2, 3, 4, 12 and 24 weeks showed neither a significant increase nor a decrease. Viability of M. leprae derived from the intraneural compartment were tested

using the standard mouse foot pad method. There was a marginal decrease in viability as compared to baseline growth, effective at 24 hours and remained more or less static till six months. There was no significant difference in the morphological index of M. leprae. These findings were reaffirmed in 3 independent experiments and using histopathology as well as electron microscopy. One of the most important future application of this model lies in assessing the efficacy of vaccine/ immunomodulators in clearing and killing the bacteria from within the nerve.

Research Associate, (CSIR), Dept. of Molecular Biology & Biochemistry, Institute of Genetics, Begumpet, Hyderabad-16, India and

Neurochemistry Labs, Christian Medical College and Hospital, Vellore 632 004, India.

Protein phosphorylation mediated by protein kinases play an important role in the regulation of cellular signalling mechanisms. Protein phosphorylation plays a role in uptake of pathogenic bacteria by host cells.

1. To study protein phosphorylation in normal human peripheral nerve and in patients affected with leprosy.

2. To study the effect of M. leprae on peripheral nerve protein phosphorylation.

ii) Purified M. leprae inhibits phosphorylation of the 28-30 KDa protein of rat/mouse peripheral nerve and the 25 KDa protein of human peripheral nerve.

The significance of these results in the pathogenesis of leprosy and nerve damage will be discussed.

Dept. of Molecular Biology and Bio-chemistry Institute of Genetics, Begumpet, Hyderabad -500 016, India and

Neurochemistry Labs, Christian Medical College and Hospital, Vellore - 632 004, India.

Bacterial protein kinases are shown to regulate cell cycle, metabolite transport and sporulation. Protein phosphorylation studies in M. leprae have not been reported. The present study has been taken up to observe the existence of protein phosphorylation by intrinsic protein kinases in purified mycobacterium leprae derived from human leproma skin biopsies.

Reaction mixtures in which M. leprae homogenate was incubated with gamma [32 P] ATP under normal assay conditions were subjected to SDS gel electrophoresis and autoradiography. The autoradiogram showed two prominent high molecular weight proteins 200 K and 150 K phosphorylated. The other bands are 100K, 70 K and 45 K. The phosphorability of these bands reduced significantly with time after isolation.

When M. leprae was used as a substrate for cyclic AMP dependent protein kinase it phorphorylated 220 K, 150 K, 100 K, and 70 K protein bands. Alkali treatment of the polyacrylamide gel to distinguish the serine, threonine and tyrosine residues suggested that protein phosphorylation is mainly on serine residues.

THE SUSCEPTIBILITY TO MYCOBACTERIUM LEPRAE OF NF-IL6 KO MICE AND INDUCTION OF CYTOKINES

Yasuko Yogi¹⁾. Masumi Endoh¹⁾. Takashi Tanaka²⁾. Sizuo Akira²⁾. Haruki Okamura²⁾ and Hiroko Nomaguchi¹⁾

1: Leprosy Research Center, National Institute of Infectious Diseases. Tokyo. Japan 2: Hyogo College of Medicine, Hyogo, Japan

Transcription factor, NF-IL6 recognizes the same nucleotide sequences as C/EBP and it is predominantly expressed in macrophages Tanaka et al. reported that NF-IL6 KO mice are highly susceptible to Listeria monocytogenes and Salmonella typhimurium. due to impairment of bacteria killing by activated macrophages. We have tried to see the susceptibility for Mycobacterium leprae infection in the NF-1L6 KO mice and also we examined the cytokine gene expression and induction of cytokines such as TNF-α . lL-1-α. IL-6. IL-10. IL-12 and lGIF-7IL-18 in the peritoneal macrophages and then IFN- y and IL-10 by splenocytes.

NF-lL6 KO mice was found many leprosy bacilli in the peritoneal macrophages on 30 days after inoculation while that of the wild(NF-lL +/+)mice was showing disappear. Besides TNF-α lL-1-a and 11-12 production were observed stronger in culture supernatant of peritoneal macrophages of NF-IL6 KO mice than that of the wild mice. NF-IL6 KO mice shows predominantly multiplication of M. leprae on the abdomino-organs, such as omentum and also scroturn on 10 months after intraperitoneal inoculation.

Department of Dermatology. Sun Yet-sen Hospital attached to Zhenang Medical University Hangzhou City, Zhejilang Province, China

In order to study the cytokine level in multibacillary (MB) leprosy patiens and get more knowledge of the probable correlation between the cytokine secretion as anti-infection immunological response and that due to specific cellular imnuno deficiency in leprosy patients, the authors measured the serum SIL-2R and TNF-α level in to active MB patients (including 7 relapses). 18 cured persons affected by MB leprosy and 19 normal local subjects in. Lanxi and Tongxiang cities of Zhejiang province.

The results showed that the serum SIL-2R and TNF-α levels were markedly higher than those in normal individuals and clinically sures of MB leprosy (p<0,01-0,001), and there was a positive correlation betwee SIL-2R level and TNF-α level in MB patients (t=2.536, r=0.667) The SIL-2R level in active LL patients and the TNF-α level in relapses of MB were the highest as compared with those in others, but the SIL-2R and TNF-α levels in cures of MB were lower than those in normal controls. The authors suggested that there were abnormal cytokine secretion of SIL-2R or TNF-α and inhibited immuno function in MB patients. High TNF-α level was not prutective to the patients Serum SIL-2R and TNF-α levels were closely associated with the seventy of the disease of MB patients and with relapse of the disease as well. It told us that determination of SIL-2R and TNF-α levels may be of some value to predict the patient's immuunological status and prognosis of their disease.

Negussie Gebre, Mesfin Hunegnaw, Yohannis Negesse, Genet Amare and Sven Britton

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The mode of transmission of M. leprae is not well understood and thus improved skin test reagents for the detection of infection with M. leprae would be of considerable benefit for leprosy control programs.

The available skin test reagents for leprosy, like lepromin, contain cross-reactive mycobacterial antigens and it is therefore not possible to know if skin test positivity to lepromin is due to exposure to or infection with M. leprae, vaccination with M. bovis BCG, or exposure to other mycobacteria.

For the study, 19 synthetic peptide pools each containing 10 or 11 peptides were provided by WHO GPV/VRD & TDR. The peptides were then tested for their ability to induce T-cell proliferation and interferon-gamma secretion in vitro using blood samples from tuberculoid leprosy patients and healthy leprosy contacts.

Our results showed that many of the peptide pools induced good T-cell responses, but that no single peptide pool was immunodominant. Four synthetic peptide pools containing 40 to 43 peptides were selected for further testing. The results of the present and the future studies with the selected peptides will be discussed.

H.M. Dockrell¹, R. Hussain², F. Shahid², T. Chiang², P. Roche³, R. Butlin³, C. Pessolani⁴, E. Sampaio⁴, E. Sarno⁴, N. Gebre⁵, M. Hunegnaw⁵, Y. Negesse⁵, G. Amare⁵, S. Britton⁵, L. Murrillo⁶, F. Guzman⁶, B. Robertson⁷, J. Thole⁸, D. Young⁷, U. Fruth⁹.

¹London School of Hygiene & Tropical Medicine. Keppel St. London WC1E 7HT, UK; ²Aga Khan University. PO Box 3500, Stadium Road. 74800 Karachi. Pakistan: ³Anandaban Leprosy Hospital, P.O. Box 151, Kathmandu, Nepal; ⁴Oswaldo Cruz Foundation, av. Brasil 4365, Manguinhos, Rio de Janeiro 21045, Brazil; ⁵Armauer Hansen Research Institute. P.O. Box 1005, Addis Ababa, Ethiopia; ⁶lnstituo de Immunologia, Hospital San Juan de Dios, Santafe de Bogota. Colombia; ⁷Imperial College, St. Mary's Hospital Medical School. Norfolk Place, London, W2 IPG; ⁸Div. Immunological & Infectious Disease, TNO Prevention & Health. P.O. Box 2215,2301 CE Leiden. The Netherlands: ⁹Global Programme for Vaccines & Immunization. World Health Organisation, CH-1211 Geneva 27, Switzerland.

The overall objective of the WHO IMMYC Synthetic Peptide Skin Test Initiative is to develop a new, synthetic peptide-based skin test reagent which would allow the identification of individuals infected with, or exposed to, Mycobacterium leprae. A total of 193 synthetic peptides were selected for testing, based on 5/15 amino acid mismatches between the M. leprae and M. tuberculosis sequences, or sequences from the M. leprae genome predicted to contain DR binding motifs. Initial screening of 19 peptide pools, each containing 10-11 peptides, was performed in 4 centres. Lymphocyte proliferation and IFNγ production using PBMC from tuberculoid leprosy patients or healthy staff contacts revealed broad T cell recognition of the peptide pools. In the second round, individual peptides from 8 pools will be screened. We hope this approach will identify leprosy-specific peptides which could be pooled for use as a new skin test reagent.

EVALUATION OF A RAPID ML DIPSTICK ASSAY FOR DETECTION OF IgM ANTIBODY IN LEPROSY

University of Hawaii. Honolulu. Hawaii¹ and Department of Biomedical Research. Royal Tropical Institute, 1105 AZ Amsterdam, The Netherlands²

Although the ELISA has been well established for leprosy, there is no rapid and simple serologic test to measure antibody to M. leprae in developing countries where the disease is endemic. The ML Dipstick Assay was recently developed at the Royal Tropical Institute to meet this need by detecting binding of human IgM to a semi-synthetic analog of M. leprae phenolic glycolipid - I (PG-I). a well known ELISA antigen. The result of this phenomena, is a dichotomy where the technology dependent assays like ELISA are most effective in developed countries or central laboratories far from the point of transmission and occurrence of leprosy. The recent push to eliminate leprosy as a public health problem has intensified the focus on the endemic countries, bringing control efforts to local levels often located in remote regions distant from central laboratories where the ELISA might be applied. Detection of antibody to PG-I can enhance local control programs by serving as screening test for the ELISA, and assisting in recognition of potential multibacillary ( MB) cases among household contacts. Since this test has important potential in the "end game" of control at the local level, we evaluated the assay against a variety of 140 known sera from leprosy patients and individuals free of leprosy living in endemic and non-endemic environments. The sera were grouped according to ELISA results. ELISA positive sera were from 69 MB leprosy patients with range 0.16 to >0.90 OD units. The ELISA values of the 19 sera were from treated patients, 21 sera from endemic negative controls from Cebu, and 31 sera from non-endemic population in Chicago, were less then 0.15 OD units. Both of the endemic and non-endemic negative control sera were obtained from individuals known to be free of leprosy. There was no significant difference between the negative control sera from the endemic and non-endemic populations( p>0.68) Also, the 96% of the leprosy cases were detected. In addition, the assay correctly interpreted 96% of the negative control sera, showing that the specificity is good. The treated cases did not give any conclusive results, since 53% of the treated cases showed a low positive result in the dipstick assay. In conclusion, the dipstick assay is a simple alternative to the ELISA assay, which can be used remote areas. It is quick, specific, and low in cost and effort, not requiring extensive training. It can be used in the field to identity household contacts with the high potential of incubating and developing MB disease.

(MLPA) TEST AND ENZYME LINKED IMMUNOSORBENT ASSAY (ELISA) ON DISTRIBUTION AND PERSISTENCE OF IGM ANTIBODIES AMONG INDIVIDUALS IN LEPROSY ENDEMIC AREA, SOUTH SULAWESI, INDONESIA.

Mochammad Hatta 1). Shinzo Izumi 2), Masanori Matsuoka 2), Stella M van Beers 3), Paul R Klatser 3).

1. Department of Medical Microbiology. Faculty of Medicine, Hasanuddin University, Ujung Pandang. Indonesia.
2. Department of Bioregulation. National Institute for Leprosy Research. Tokyo. Japan.
3. Department of Biomedical Research. Royal Tropical Institute. Amsterdam. The Netherlands.

In this study, we applied a Mycobacterium leprae particle agglutination (MLPA) test and ELISA that detected a IgM against Phenolic Glycolipid-I (PGL-I) of M. leprae on sera collected through a total population survey and longitudinal study from individuals in leprosy endemic area. South Sulawesi Indonesia.

Among the total tested population of 1496 people. 40.4 % (604/1496) were found to be seropositive using MLPA test in the first survey (survey I). Seropositivity was shown to be randomly distributed among the population and the seropositivity rates in female were significantly higher than in males.

To evaluate the persistence of seropositivity, we followed up some persons every 6 months during one year (three times examination). These results suggested that there was no significantly different results in seropositivity rates in three times examination among individuals (survey I and survey II and III or survey I and III).

Also, we compared a MLPA test with the conventional ELISA to detect IgM PGL-I in the same person. Percentage of concordance between MLPA and ELISA for positive or negative results was satisfying and there was no significant difference in positivity rates between MLPA test and ELISA.

A SIMPLE DIPSTICK ASSAY FOR THE DETECTION OF ANTIBODIES TO PHENOLIC GLYCOLIPID - I OF M. LEPRAE.

Samira S. Buhrer1, Henk L. Smits1, George C. Gussenhoven1, Cor W. van Ingen2 & Paul R. Klatser1.

1 Department of Biomedical Research, Royal Tropical Institute, The Netherlands. 2 Foundation for the Advancement of Public Health and Environmental Protection (SVM), Bilthoven, The Netherlands.

Among the many reported applications of the detection of antibodies to phenolic glycolipid 1 of M. leprae, in particular the use of seroprevalence as an indicator of the magnitude of the leprosy problem may turn out to be very useful to leprosy control programmes. An operational function of serology within the leprosy control services requires a simple test system. We have developed a simple dipstick assay for the detection of antibodies to PGL-I and we compared its performance with that of ELISA. A high degree of agreement (97.2%) was observed between ELISA and the dipstick assay when tested on 435 sera; the agreement beyond chance (Kappa value) was 0.92. No significant difference was found between the dipstick assay and ELISA when seropositivity rates obtained in groups of leprosy patients, household contacts and controls were compared The interpretation of the dipstick results as positive or negative was unequivocal as illustrated by the high agreement between different persons reading the test (kappa values X).88). An agreement of 94.9% (kappa=0.87) was found when dipstick results obtained with whole blood were compared with ELISA results obtained with the paired scrum samples. Storage of the only reagents required, the dipsticks and the stabilized detection reagent, up to 3 months under "tropical" conditions of high temperatures, high humidity and exposure to light did not influence the results of the assay. The dipstick assay described here is an easy-to-perform method for the detection of IgM antibodies to PGL-I of M. leprae; it docs not require any equipment and the highly stable reagents make the test robust and suitable for use in tropical countries. An internal control validates the performance of the assay. This dipstick assay may be the method of choice for epidemiological mapping of leprosy.

Rukeslh Manandhar and Paul Roche
Mycobacterial Research Laboratory, Anandaban Leprosy
Hospital. PO Box 151, Kathmandu, NEPAL

New tools to detect leprosy exposure in the community will be necessary for the eradication of leprosy. A simplified blood test has been applied to determine whether exposure to leprosy can be detected by the production of the cytokine, interferon y after stimulation of whole blood cultures with leprosy proteins. First we investigated whether the production of interferon y after 24 hours was associated with lymphocyte proliferation and interferon y production after 5 days, and which of the leprosy protein antigens available were the most potent. A recombinant 35kD protein and preparations of native proteins such as sonicates of armadillo derived M. leprae were found to be potent in inducing the production of interferon y at 24 hours and this was significantly associated with high levels of cytokine at 6 days and with lymphocyte proliferation.

24-hour cultures of whole, undiluted blood from leprosy patients and contacts and healthy subjects without exposure were incubated with r35kd, MLS. MLS-LAM, and MLCwA antigens. A IFNγ response was detected in contacts to MLS-LAM antigen. This response was significantly higher in leprosy health workers than in healthy non-exposed subjects. These results indicate the utility of measuring leprosy exposure by a new simple overnight blood test.

Department of Microbiology, Colorado State University, Fort Collins. Colorado 80523 U.S.A.

A major challenge of current research is to provide new tools of sufficient sensitivity and specificity to identify subclinical infection and facilitate epidemiological monitoring of the disease. Serological and gene amplification approaches have not met the needs. A remaining hope lies in new skin test antigens. Past products--the lepromins, the Rees MLSA and Convit SDA--have their place in leprosy control but fail as universal diagnostic/epidemiological tools. We have produced under prescribed pilot-plant conditions two new skin test reagents. M. leprae- soluble antigens devoid of LAM and other immunosuppressive carbohydrates (MLSA-LAM) and M. leprae cell wall antigens (MLCwA). Those have been submitted to a full gamut of biochemical and immunological analyses to identify the inherent immunogens; in vitro assays to confirm the absence of endotoxin; in vivo safety tests in mice; assays for potency, sensitivity and specificity in M. leprae -sensitized guinea pigs; and further in vitro assays for potency in stimulating T-cell proliferation and the evocation of y-IFN and other cytokines in blood from appropriate patient groups. We are now awaiting approval by regulatory authorities for Phase I human trials in the U.S. before formulation of Phase II trials towards application of these products in leprosy endemic areas in order to test in field settings their actual potency, specificity and suitability for wide-scale application. Separately, we will report on studies of MLSA-LAM and MLCwA as subunit vaccines. Supported by NIAID/DMID Contract NO1 AI 55262.

INSA S.N. Bose Research Professor, Dept. of Biotechnology, All India Institute of Medical Sciences, New Delhi, India, *Department of Medical Dermatology, Safdarjang Hospital, New Delhi, India, and **Leprosy Mission Hospital, Shahadra, New Delhi, India

Leprosy patients suffer from clinical episodes associated with tissue damage which are designated as Type 1 (reversal reaction) when localised to the lesions and Type 2 (erythema nodosum leprosum, ENL) when accompanied by systemic involvement. We had reported earlier that stable, non reaction lepromatous leprosy subjects show Th2 and Th0 but not Th1 like responses in the peripheral blood. To further understand the development of Th like responses during disease, 32 lepromatous patients undergoing reactions were studied using cytokine specific RT-PCR and ELISA in peripheral blood and some skin biopsies. Of interest was the emergence of Th1 like response with presence of interferon-gamma (IFN-gamma) and absence of interleukin-4 (IL-4) mRNA in the PBMC of 85% and 64% of Type 1 and 2 reaction patients respectively and in all reaction sites. Whereas Th0 was seen in some, Th2 like response was absent. IL-12p40 mRNA was seen in 21/25 ENL and all Type 1 reaction subjects irrespective of the Th phenotype. IL-12p40 and IFN-gamma were detectable in unstimulated PBMC suggesting an in vivo priming during reactions. IL-10 was mainly associated with adherent cells and showed a differential expression in the two reactions. It was present in the PBMC of ENL but not in reversal reaction patients. Moreover, it was not detectable in the skin lesions of either type of reactions. Th1 like cytokine profile was associated with immunopathology and persisted up to 6-7 months after the onset of reactions.

IMMUNOITISTOCHEMICAL ANALYSIS OF MYCOBACTERIAL ANTIGENS IN SKIN LESIONS OF LEPROSY PATIENTS RELATED TO REACTIONS

Claudia Verhagen¹², William Faber¹, Paul Klalser², Anita Bulling¹, Ben Naafs¹ and Pranab Das¹, ¹Department of Dermato-immunopathology, Academic Medical Center. University of Amsterdam;² Biomedical Research Unit. Royal Tropical Institute. Amsterdam and ¹Department of Dermatology. University Hospital Leiden. The Netherlands (ILEP no: 7020242).

At present identification of antigenic recognition by T cells derived from leprosy patients across the clinical spectrum, including the reactions, are still lacking. The strategy of the present study is to demonstrate in situ presence of the immunodominant mycobacterial antigens (both m. leprae specific and cross reactive) in relation with the local cell mediated immune status in the lesional skin specimens and systemic humoural immunity of patients. Towards this goal, we applied immunohistochemical (THC) methods using mAbs to m.leprae specific phenolic glycolipid-l (PGL-1) and lu cross reacting mycobacterial antigens (CKMA) of 30KD, 36KD. 65KD and lipoarabinomanan (LAM). In addition, we also studied the association of the in situ presence of antigens with the presence of viable bacilli by NASBA as well as with the circulating m.leprae specific antibody levels in serum. Results: The staining patterns with mAbs to all the protein CRMA were heterogeneous that could also be seen in the lesions of other skin diseases. However, in situ staining of PGL-I and LAM could only be seen in leprosy. These antigens are abundantly present in infiltrating macrophages in the lesions of untreated multibacillary (MB) patients whereas only PGL-I was occassionally seen in scattered macrophages in some untreated paucobacillary (PB) patients. During treatment clearance of PGL-I from granulomas in MB lesions was seen before that of LAM. although the former persisted in scattered macrophages in some treated patients. lite pcrsistance of PGL-I in the lesions paralleled high scrum anti PGL-I antibody tilres and was not indicative for ihc presence of viable bacilli in the lesions. Interestingly, we also observed that the dynamics in the expressions of PGL-I and LAM in the lesions of patients with the presence of acid fast bacilli during the course of the disease are associated with the reactional states of the patients. Hie implications of the present study indicate that the IHC study for in situ presence of mycobacterial antigens in conjunction with the estimation of anti PGL-I antibody litres in leprosy patients will be valuable in (he future Leprosy containment protocol.

Gilla Kaplan. Ph.D., The Rockefeller University 1230 York Avenue, New York, N.Y. 10021, USA

Erythema nodusum leprosum (ENL) is an acute inflammatory state of lepromatous leprosy characterized by painful cutaneous lesions, severe systemic symptoms and accelerated, irreversible nerve damage. Ue and others have reported that ENL is associated with high levels of plasma TNF-α which fall precipitously following treatment with thalidomide. The drug has been shown to inhibit the production of TNF-α but not IL-1β, IL-6 or CM-CSF. We have recently shown that thalidomide stimulates T cells in vitro, particularly the CD8+ T cell subset. The drug Increases T cell proliferation and also the production of THI 1 cytokines IL-2 and IFN-γ. The effect of thalidomide on T cells in vivo is currently being evaluated in patients with ENL. We are also examining the biologic effects of a number of newly synthesized analogues of thalidomide which have increased TNF-α inhibitory activity compared to the parent drug. If found to be more efficient and less toxic than thalidomide, it is hoped that the drugs will provide alternative therapies for ENL.

A DISTINCT Thl/Th2 PAITKRN OF CYTOKINE mRNA EXPRESSION IN LEPROSY PATIENTS UNDERGOING REACTIONAL EPISODES Moraes MO. Sarno EN. Almeida AS, Saraiva BCC Nery J AC. Sampaio EP. Leprosy Laboratory. Osvvaldo Cruz Foundation. Av. Brasil. 4365 - Manguinhos. Rio de Janeiro - RJ. Brazil.

Leprosy reactions are still a major health problem. Patients during the natural course of
the disease may undergo reactional states that can be characterized by immunoinllammatory episodes. Our previous studies base indicated that TNFα play a key role in the inflammatory process mediating tissue damage during erythema nodosum leprosum. Since the role of other cytokines in the regulation of the inflammatory response in leprosy is not fully understood. we decided to evaluate the cytokine profile of blood and tissue samples obtained from patients among the clinical spectrum of leprosy, by using RT-PCR. We analyzed 20 blood samples (BL/LL = 5; BT/TT = 5; ENL = 5; RR = 5) and 14 skin biopsies (BL = 4; ENL = 7; RR = 3). For a qualitative approach. we analyzed the presence of a PCR product for each cytokine tested in agarose gel electrophoresis. We observed that there is an increase of mRNA synthesis of IFNγ , GM-CSF, p55 and perforin in patients during the reactional episodes in blood samples. On the other hand, in biopsy specimens. we were able to detect both IFNγ and IL-10, in LL or ENL and RR lesions. Moreover, IL-6 mRNA is observed only in the reactional biopsies. The sensitivity of the approach did not allow a distinction among patientss group for most cytokines tested. Then, we performed a semi-quantitative RT-PCR. and verified that there is an up-regulation of TNFα, IFNγ and IL-6 mRNA during the inflammatory episodes. The data reported so far suggest a distinct Th1/Th2 pattern observed in, leprosy reactions. Besides, a more complex mRNA cytokine profile showing IFNγ . IL-10, TNF, IL-4 and IL-6 is detected. This pattern results probably from an immunological reactivation that might lead to the acute inflammatory response in these patients.

A POSSIBLE ROLE FOR IFNγ AND IL-12 IN THE PATHOGENESIS OF ERITHEMA NODOSUM LEPROSUM Sampaio EP. Moraes MO. Saraiva BCC Almeida AS. Teles RMB, Sarno EN. Leprosy Laboratory, Oswaldo Cruz Foundation. Av. Brasil, 4365 - Manguinhos, Rio de Janeiro - RJ. Brazil

Acute inflammatory episodes can occur during the natural course of leproxy. A classification of these reactional states is obtained according to the clinical status of the patients. The type I or reversal reaction (RR) is described as an activation of the immune response that is triggered info a previous unresponsive patient. The mechanisms that are involved in the development of erythema nosodum leprosum (ENL) or type II reaction is not fully understood, although a pivotal role for TNFα has already been demonstrated. It has been previously described high TNFα levels in ENL patients' sera, as well as an increase of TNFα mRNA and protein expression in the tissue during ENL. In order to understand the immunological reactions that can lead to the acute inflammatory response, semi-quantitative RT-PCR for IFNγ and IL-12 was employed in the skin biopsies of leprosy patients undergoing or not reactional episodes. Samples of the same patient were collected before and during ENL (n=2) or after thalidomide (n=3) and pentoxifylline (n=4) treatment. As a control, tissue samples from patients undergoing RR and alter being treated with prednisone (n=3) were also included. IFNγ mRNA was up-regulated during the reactional episodes and it was observed that after anti-inflammatory treatment. IFNγ mRNA was down-regulated. Besides, IL-12 mRNA was intensely expressed in the skin biopsies during the reaction, and was negatively regulated after thalidomide and prednisone administration. These results together suggest that IFNγ and IL-12 could be participating in the establishment and development of ENL reactions

LYMPHOCYTE-MACROPHAGE CONTACT PROVIDES A POTENT STIMULI AMPLIFYING TNFα PRODUCTION IN LEPROSY. •Sampaio EP., •Oliveira RB., ••Warwick-Davies J., ••Griffin GE., •Hernandez MO., •Sarno EN. ••Shattock RJ • Leprosy Laboratory. Oswaldo Cruz Foundation. Av Brasil. 4365 - Manguinhos; 21.045-900 Rio de Janeiro - RJ, Brasil.

••Division of Infectious Diseases. St. George's Hospital Medical School. Cranmer Terrace. London SW17 ORE.

During the natural course of disease, leprosy patients may undergo reactional states which represent immunoinflammatory episodes in response to the mycobacterium. Our previous studies have indicated that TNFα plays a key role in this process mediating local and systemic symptoms mainly in type II reaction (ENL), Increased interest has developed to define the cells and or secreted mediators that are involved in the amplification of TNFα production in leprosy. Previous reports have demonstrated that engagement of integrin receptors regulated both mRNA expression and production of inflammatory mediators. In the present study, we investigated whether T cell-macrophage contact had any role in amplification of TNFα secretion in leprosy.

Co-cultures of activated (PMA 5 μg/ml and PHA 1 μg/ml) paraformaldehyde fixed T-cells (HUT-78 T-cell line) and human monocytes prepared by centrifugal elutriation were established in vitro in the presence or absence of M. leprae (0.3 - 10 μg ml), and supernatants harvested after 18-20 hours for determination of TNFα levels (Elisa, R&D Systems).

Interaction of the T-ccll line wilh monocytes up-regulated M. leprae- induced TNFα secretion by monocytes. Cell contact between T-cells and monocytes was required since physical separation of these cells abrogated this response. Pre-activation of human monocytes with IFNγ also lead to enhanced TNFα secretion induced by M. leprae. In this context, we have observed that PBMC obtained from ENL patients released increased TNFα compared to purified monocytes obtained from the same individuals Moreover, if purified monocytes were reconstituted in vitro with lymphocytes. TNFα release was similar to that released in the original PBMC cultures from the same individuals. In summary, direct contact between T-cell and monocytes amplifies production of TNFα by monocytes in response to M. leprae. This finding is relevant to the observation of increased expression of TNFα in the reactional leprosy lesion where lymphocytes and macrophages are in close proximity, a phenomena not seen in the unreactional tissue.

ROLE OF INTERLEUKIN-12 (IL-12) AND IL-12 RECEPTOR SIGNALLING IN PATIENTS WITH DISSEMINATING INFECTIONS WITH M. LEPRAE AND OTHER MYCOBACTERIA

Dept. of Immunohematology and Bloodbank. Leiden University Medical Center. P.O. Box 9600. 2300 RC Leiden. The Netherlands

IL-12 plays a crucial role in immunity to mycobacterial pathogens by promoting T helper-1 differentiation, IFN-γ production and natural killer cell function Lepromatous leprosy patients' specific T cell nonresponsiveness to M. leprae could be overcome effectively by the synergistic action of IL-12 and IL-2 in vitro In addition, patients with disseminated, nonleprous mycobacterial infections appeared to produce strongly reduced levels of IFN-γ . This was due to genetic mutations in the IL-12R complex, which led to lack of IL-12R expression and function. These findings document a novel immunodeficiency and highlight the crucial role of IL-12 in immunity to mycobacterial pathogens in man.

LEPROSY PATIENTS WITH LEPROMATOUS DISEASE RECOGNISE CROSS REACTIVE T CELL EPITOPES IN THE M. LEPRAE 10KDA ANTIGEN

*Department of Microbiology, The Aga Khan University. P.O. Box 3500, Karachi, Pakistan, ** Marie Adelaide Leprosy Centre, Karachi, Pakistan and ~London School of Hygiene and Tropical Medicine, Dept of Clinical Sciences, London, U.K.

T cell responses play a critical role in determining protective responses to leprosy. Patients with self limiting tuberculoid leprosy show high T cell reactivity while patients with disseminated lepromatous form of the disease show absent to low levels of T cell reactivity. Since the T cell reactivity of lepromatous patients to PPD, a highly cross reactive antigen, is similar to that of tuberculoid patients we queried if lepromatous patients could recognise cross reactive epitopes in M. leprae antigens as well. T cell responses were analysed to a recombinant antigen 10kDa (a heat shock cognate protein) which is available from both M. tuberculosis (MT) and M. leprae (ML) and displays 90% identity in its amino acid sequence. Lymphoproliferative responses were assessed to ML and MT 10kDa in newly diagnosed leprosy patients (lepromatous; N=23; tuberculoid; N=65;). Lepromatous patients showed similar lymphoproliferative responses to ML and MT 10kDa while tuberculoid patients showed much higher responses to ML 10kDa compared to MT 10kDa suggesting that the tuberculoid patients may be recognising both species specific and cross reactive epitopes in ML 10kDa while lepromatous patients may be recognising only cross reactive epitopes. This was further supported by linear regression analysis. Lepromatous patients showed a high concordance in T cell responses between ML and MT 10kDa using (r= 0.658; p<0. 0006) not observed in tuberculoid patients (r=.203; p>0.1). Identification of cross reactive T cell epitopes in M. leprae which could induce protective responses should prove valuable in designing second generation peptide-based vaccines.

T CELL AND CYTOKINE REACTIVITY TO THE Mycobacterium leprae 45 kDa ANTIGEN BY LEPROSY PATIENTS. CONTACTS. AND ENDEMIC CONTROLS

Anne MacFarlane, Rafael Mondragón*. Octavio Flores*. Francisco Vega-López*. B Wieles**, Obdulia Rodriguez*, Josefina de Peña*, and Hazel Dockrell.

London School of Hygiene and Tropical Medicine. UK. *Centro Medico Nacional INSS. Centro Dermatológico Pascua SSA, Mexico City **Leiden University Hospital. The Netherlands.

Peripheral b!ood mononuclear cell (PBMC) proliferation and interferon y (IFN) production by leprosy patients, household contacts, and endemic controls to the M. leprae 45 kDa antigen and other mycobacterial proteins were compared. A total of 48 leprosy patients (34 lepromatous and 14 paucibacillary) were diagnosed and recruited in Mexico according to the Ridley & Jopling entena. The contact group consisted of 17 individuals living in the same house as die leprosy patients, and 20 healthy subjects were studied as leprosy endemic controls. T-cell proliferation assays and ELISA for the detection of IFN in culture supernatants were performed following standard protocols in our laboratory. A Mann-Whitney U test was used for the statistical analysis. All patients, household contacts, and endemic controls gave strong proliferative responses and IFN production in response to the mitogen PHA. The majority of TT/BT cases responded to the M. leprae 45, and 30/31 kDa antigens, whereas the lepromatous, household, and endemic control groups showed significantly lower responses to these proteins. A similar pattern was observed with the IFN production. Our results demonstrate that the M leprae 45 kDa protein is a potent T-cell antigen. The responses to the M. leprae 45 kDa were on average higher than those obtained with the 65. 30/31, and 10 kDa leprosy antigens. The 45 kDa antigen was recognised by a high proportion of leprosy cases and household contacts but not by healthy endemic controls or patients with other mycobacterial disease This antigen may have potential as a reagent for skin testing.

HEAT SHOCK PROTEIN AND APOPTOSIS OF PERIPHERAL BLOOD MONOCYTES IN LEPROSY PATIENTS AND HEALTHY INDIVIDUALS

Samia Nassar•, Farid Badria ••, Eman EL-Nashar •••, Samia Hawas••••, Hamdy M. Hassanein §, and W.E.G. Muller §

Department of Dermatology•, Tanta Faculty of Medicine; Department of Pharmacognosy••, Faculty of Pharmacy, Histology•••, Microbiology•••• Departments, Mansoura Faculty of Medicine.

§Institute for physiologische chemie, Abteilung Angewandte Molekularbiologiei, Universitat, Duesbergweg 6, 55099 Mainz, Germany.

Factors determine the outcome of exposure of human immune system to Mycobacterium leprae antigen are poorly understood. Estimation of heat shock protein (Hsp) 65k J and 70 kd which may represent one of the major targets of cell mediated immune response were evaluated by Western blot in skin biopsies of 46 untreated leprosy patients, 15 reactional leprosy patients and 25 age and sex matched healtlhy control. Results showed that 65 kd Hsp was significantly higher in reactional state groups, multibacillary leprosy and baucibacillary. Seventy kd Hsp was significantly lower in control group than other groups. Reversal up grading reaction (type I) showed highly significant expression of 65 kd and 70 kd Hsp.

The possible involvement of apoptosis or programmed cell death (PCD) of peripheral blood mononuclear cells (PBMC) was evaluated in leprosy patients. The peripheral blood mononuclear cells were prepared and incubated for 24,48 and 72 hours in tissue culture medium. The percentage of apoptotic PBMC at 0 time, 24, 48 and 72 hours of each culture media was assessed by both morphology and DNA fragmentation. There was significant increase of percentage of apoptotic cells with aging in culture medium from normal control subjects, paucibacillary, multibacillary and reactional groups (type I, II).

There was no significant difference in the percentage of apoptotic PBMC between paucibacillary and healthy control subjects. On the other hand there was higher significant difference in multibacillary than other groups. Interestingly patients with upgrading reversal reaction (type I) snowed inhibition of PBMC apoptosis in comparison to other groups. These results suggest that prompt death of PBMC in multibacillary leprosy may be due to decrease cell mediated immune response also could be considered as protective mechanism against highly replicated bacilli. It could be concluded that the increased expression of 70 Kd and CD5 kd Hsp increase resistance to apoptosis in leprosy.

DICHOTOMY AND PARADIGM OF THE AND TH2 SUBSETS IN RELATION TO THEIR CYTOKINE PROFILE IN LEPROSY PATHOLOGY.

P. K. Das¹, C.E. Verhagen¹, E.A. Wierenga¹, A.A. Bulling¹, AM. Chand¹. L.A Aarden² and W.R. Faber¹: ¹ Academic Medical Center University of Amsterdam and ²Central Blood Transfusion Laboratory, Amsterdam, The Netherland (ILEP no. 7020242)

Changeable immunostatus of borderline leprosy patients during the course of the disease represent an unique model to investigate the paradigm of Th1 and Th2 in humans. During the course of the disease, some of these patients show excerbated immune activities in the form of reversal reaction (RR) and erythema nodosum leprosum (ENL). In order to explore the role of T cell subsets in relation to their cytokine profile, we generated T cell clones (TCC) from the lesional skin of 7 untreated patients and again from 3 patients undergoing RR during treatment. Both ml responsive (mIR) and non-responsive (mlNR) TCC were generated with minimum selection. TCC consisted of all phenotypes (CD4', CD8', TCRγδ) that had similar distribution pattern of in vivo situation. In respect to the ratio INF-γ/IL-4 secretion profile. TCC were Th1, Th0 and Th2 irrespective of the clinical status of the patients. Interestingly, in 3/7 patients who (re)experienccd RR a polarised shift to Th1 among mIR TCC were seen whereas this shift did not occur among mIR TCC. Further analysis of a broad range of cytokines, showed a positive correlation in the co-production of INF-γ/TNF-α (xr = 0,81) and in that of IL-4/IL-5 (r = 0.83), IL-4/IL-13 (r = 0,80) by the mIR TCC. Furthermore, Th1 and Th2 mIR TCC can be characterised by the co-production of INF-γ/TNF-α and IL-4/IL-5/IL-13 respectively. Such clear cut correlated co-production of these cytokines was not seen among mlNR TCC of distinct isotypes of mIR Th1 and Th2. Interestingly, isotypic forms of both mIR Th1 and Th2 TCC can be recognised further by differential expression of these cytokines including IL-10 and IL-6. The present results suggest that distinct isolypes of mIR Th1 and Th2 characterised by a panel of cytokine profile reflect a pathogen associated characteristic of T cell subset, furthermore, in the context of future leprosy containment programme in the next millennium, we hypothesise that monitoring the in vitro INF-γ/IL-4 section of primary isolates of lesional T cell lines could be useful for the diagnosis of reactions versus reactivation of the disease.

GRANULOMA FORMATION AND GROWTH OF MYCOBACTERIUM LEPRAE IN INOS DEFICIENT MICE.

GW Long Hansen's Disease Center, Laboratory Research Branch at Louisiana State University, Baton Rouge, LA, USA

Production of nunc oxide (NO), a free radical generated from L-arginine by cytokine inducible nitric oxide synthase (iNOS), is a major anti-microbial mechanism of activated macrophages (ACT MФ) To study the effects of NO on Mycobacterium leprae infection in mice, C57BI/6 (B6) control mice, B6 mice given drinking water supplemented with 2.5% aminoguanidine (AG), an inhibitor of iNOS, and iNOS gene knockout (KO) mice were infected via two routes with freshly harvested, viable, nu/nu mouse-derived M. leprae. iNOS deficient mice inoculated in the foot pads exhibited a marked enlargement of the foot pads. Immunostaining for CD4 and CD8 differentiation antigens showed an enhanced infiltration of CD4+ cells into the foot pads of iNOS KO mice compared to controls. In mice infected intravenously, liver tissue from control mice showed slow development of granulomas, with moderate sized, non-organized inflammatory infiltrates surrounding the bacilli. However, AG mice and iNOS KO mice exhibited large, focally organized granulomas, many of which contained multinucleated giant cells. iNOS mRNA was detected in granulomatous liver tissue from control mice, but none was found in iNOS KO mice. Interestingly, high levels of iNOS mRNA were detected in AG mice. Immunostaining revealed a pattern similar to that seen in human tuberculoid granulomas, with many CD4+ cells dispersed throughout the granuloma and fewer CD8+ cells located at the periphery. In vitro, ACT MФ from iNOS KO mice, as well as B6 ACT MФ treated with AG, produced negligible nitrite and were incapable of killing M. leprae. Like ACT B6 MФ, though, ACT iNOS KO MФ generated elevated levels of TNF-α . Intracellular mycobacteriocidal events may thus be suppressed in vivo in the absence of NO, and perhaps in compensation, granuloma formation is greatly enhanced. These data suggest that NO, generated by iNOS, is an important regulator of cell mediated immunity to M. leprae.

THE ROLE OF TRANSFORMING GROWTH FACTOR - β (TGFβ) AND INDUCIBLE NITRIC OXIDE SYNTHASE IN LEPROSY REVERSAL REACTIONS: AN IMMUNOHISTOLOGICAL STUDY

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine. Keppel Street, London WCIE 7HT

Inducible nitric oxide synthase (iNOS) synthesises reactive nitrogen radicals which have a role in mycobacterial killing. Expression of iNOS is induced during macrophage activation. Transforming growth factor β (TGF-β) antagonises Th1, mediated macrophage activation and promotes fibroblast activity.

Using immunocytochemical techniques iNOS and TGFβ were localised in paraffin embedded skin biopsies from lesions in 33 patients across the leprosy spectrum and a further in 15 patients with reversal reactions.

iNOS expression was highest at the tuberculoid pole of the spectrum and increased during reversal reaction. TGFβ was detected throughout the leprosy spectrum but was highest at the lepromatous pole. Levels of TGFβ decreased during reversal reaction.

We propose that reduced levels of TGFβ may contribute to unregulated inflammatory responses during reactional episodes.

Bi-zhong Zheng et al Station for Skin Diseases Control. Lanzi City. Zhenang Province. China

In order to study the immunofunction and cytokine's role m clinically cured persons affected by leprosy and get more knouledge of immunophathogenesis of leprosy. serum TNF-α level and SlL-2R level were measured in 62 cures of leprosy. 28 their lineal relatives and 28 randomly, selected locaI normal persons in Lanzi City, Zhenang Province. The results showed that the TNF-α level in all cures of leprosy was marked lower (p<0,001) and the SIL-2R level in cures of MB leprosy was lower than those in controls (p<0,002). The TNF-α and SlL -2R levels in cures of LL leprosy were the lowest (p<0,001, p<0,005). This suggested that there were still abnormal cytokine secretion and macrophages function disturbance in cured persons affected by leprosy. It also suggested that there were some disturbances in T cell's activation function in cures of MB leprosy. The persistence of lower TNF-α level and SlL-2R level may be correlated with the sensitivity of leprosy patients to M. leprae and may play an impontant role in immunopathogenesis of leprosy

Indian Council of Medical Research conducted a large scale BCG trial in Chingleput district in South India to study efficacy of BCG in preventing tuberculosis from 1968 to 1985. Leprosy component was added in 1978 and apart from the baseline survey, which covered about 200.000 available individuals from the "vaccinated" cohort, four follow-up surveys were conducted at 2.5 years' intervals. This study was a placebo controlled double blind study, involving 2 different strains (French and Danish) of BCG and 2 different doses (0.1 mg and 0.01 mg) of BCG in a factorial design. Initial screening of the population was done by paramedical workers and confirmation of diagnosis was done by medical officers. Analysis of this study has been recently completed.

French and Danish strains provided similar levels of protection. Usual dose of BCG (0.1 mg) consistently gave higher protection (24.4%), compared to the lower dose of 0.01 mg (17.4%) over 5-15 years of follow-up. Females were somewhat better protected (26.7%) than males (22.8%), but the difference was not statistically significant. Children in the age-group 0-4 years were protected best. However, the protective efficacy waned from 58% to 18% from 5 to 15 years after BCG vaccination. BCG provided protection against all clinical forms of leprosy. However, smear positive leprosy was not prevented. A total of 121 new smear positive cases were distributed uniformly over the three arms. Protective effect was also observed during the first 5 years based on the results of the baseline survey conducted 5 years after vaccination.

Mycobacterial Research Laboratory. Anandaban Leprosy Hospital. PO Box 151, Kathmandu, NEPAL and * Centenary Institute of Cancer Medicine & Cell Biology, Locked Bag 6 Newtown 2042, AUSTRALIA

Two plasmid Constructs containing the gene for the 35kD leprosy protein were constructed incorporating a cytomegalovirus (CMV) promoter and with or without a tissue plasminogen activator (TPA) leader sequence to give a membrane expressed or secreted 35kD protein.

Swiss albino mice 6-8 weeks were immunised with 3 doses of 100μg of DNA intramuscularly, at intervals of three weeks. Control mice received either 10⁷ heat-killed M. leprae or 10⁶ live BCG intradermally or three doses of PBS or control plasmid without the gene insert intramuscularly. One month after the last immunisation, all mice were infected in the hind foot pads with 10⁴ live M. leprae. The effect of the immunisation was measured by the growth of M. leprae six months after infection.

Bobby J. Gormus, Keyu Xu. Michael Murphey-Corb, Louis N. Martin, Gary B. Baskin, Pamela A. Mack. Marion S. Rattenree. Peter J. Gerone, David M. Scollard and Thomas P. Gillis

Tulane Regional Primate Research Center. Covington, LA and Gillis W. Long Hansen's Disease Center, Baton Rouge, LA USA

Seven of eight rhesus monkeys (RM) coinfected with Mycobacterium leprae (ML) and simian immunodeficiency virus (SIV, 8-10 months pre-ML) harbored acid-fast bacilli (AFB) at sites of dermal inoculation and/or at disseminated sites (nasal mucosa) at times of humane sacrifice (up to 270 days post-ML inoculation) due to SIV-induced debilitation or, in one long term survivor's case, to date over 3 years post-ML inoculation. Detectable AFB were cleared in biopsies of inoculation sites of RM inoculated with ML alone after 63 days postinoculation: these sites have, so far. remained AFB-negative, thereafter.

Compared to animals infected with ML alone. RM coinfected with SIV plus ML showed: 1) completely suppressed serum antibody responses to ML-specific phenolic-glycolipid-1 and to mycobacteria-common lipoarabino-mannan antigens, but strong anti-SIV Gp120 antibody responses; 2) impaired sensitization of blood mononuclear cells (MNC) to in vitro recognition of ML-specific antigens in blastogenic stimulation assays; 3) impaired in vitro responses of blood MNC to nonspecific (ConA) blastogenic stimuli and 4) early post-ML inoculation, there was a significant incremental diminution of percentages of blood CD4+CD29+ T-cells in addition to the existing SIV-induced diminished percentages of the CD4+CD29+ subpopulation of T-cells.

A follow-up study in groups of 6 RM showed that SIV given at the same time as ML is significantly more lethal than SIV inoculated 2 weeks prior to ML; both of these inoculation procedures are effective in inducing increased susceptibility to leprosy. Differences in relative timing of inoculation with the 2 agents result in differing degrees of modification in immune responses to ML antigens.

The results indicate that humoral and cellular immune responses to ML antigens are compromised in ML-inoculated RM that are coinfected with SIV and provide an immunologic basis for the demonstration of enhanced ML persistence or leprosy susceptibility in SIV-ML coinfected RM.

SIMIAN IMMUNODEFICIENCY VIRUS (SIV)-ASSOCIATED DELAY OF CD4 CELL ACCUMULATION AT M. leprae SITES IN VIVO IS ACCOMPANIED BY A DELAY IN LYMPHOCYTE RESPONSES IN VITRO.

D. M. Scollard¹, T. P. Gillis¹, B. J. Gormus¹, G. Lathrop¹, and M. Murphey-Corb². GWL Hansen's Disease Center at LSU, Baton Rouge, LA; and Tulane Regional Primate Center, Covington, LA.

Background. The mechanisms by which immunity to mycobacteria is deranged in HIV Infected individuals (and SIV-infected rhesus monkeys) is not known. HIV is reported to have little or no effect on leprosy.

Objectives: To assess T-cell subsets and cytokines at M. leprae inoculation sites in normal (SlV-)and SIV+ monkeys.

Methods. Biopsies were taken at cutaneous M. leprae inoculation sites in 4 SIV[-] rhesus monkeys and 8 SIV[+] rhesus monkeys (Macaca mulatta). CD4+ and CD8+ cells were counted in immunostained frozen sections, or in blood by flow cytometry. Lymphocyte transformation (LTT) was measured by ³H-thymidine uptake in 6 day cultures with M. leprae sonicate antigen (MLS). mRNA for IL-2 and TNFα were evaluated by RT-PCR using primers & probes developed for rhesus monkeys.

Results. The percentage of CD4 lymphocytes In skin peaked at 5 days in healthy, SIV[-] monkeys, but was delayed until 27 days in the SIV[+] animals. In the SIV[-] group, IL-2 mRNA was detected in all animals by day 5 and the percent reacting in LTT increased steadily from 3 weeks onward. In SIV[+] animals, the percent of animals positive for IL-2 mRNA increased slowly until day 63; LTT reactivity was not observed until 5 weeks and only 4/5 were responsive at 15 weeks. TNFα expression was observed at inoculation sites in all animals, similar in both groups.

Conclusions. (1) CD4+ T-cell participation in situ in SIV[+] animals is delayed. (2) Robust mechanisms of recruitment appear to remain in SIV[+] animals: the percentage of CD4+ cells at inoculation sites ultimately reaches levels similar to the maximum in SIV[-] animals. (3) The delay in CD4 recruitment appears to be associated with a delay in the initiation of specific immunity to M. leprae in SIV[+] animals, as indicated by a delay in expression of IL-2 mRNA and in LTT. (4) M. leprae infection in rhesus monkeys may be a useful model in which to study the early immunologic aberrations induced by SIV, as a model for abnormal responses to mycobacteria in HIV-infected patients.

IMMUNOCHEMOTHERAPY (M.D.T.+Mw vaccine) AND CHEMOTHERAPY (M.D.T.+PLACEBO):- A comparitive assesment.

Pankai Sharma*. R.S Misra#. H. K. Kar^. Rajani Rani*. Harvinder Kaur* & Rama Mukherjee.*

# Deptt. of Skin &. STD. Safdarjung Hospital. New Delhi-110029 ^ Deptt of Skin & STD, Dr. R.M.L. Hospital, New Delhi-110001

In clinical trials with Mycobacterium w (Mw) anti-leprosy vaccine, (materials & methods discussed breifly in the abstract of immunotherapy paper) the data pertaining to 300 cases (155 vaccine & 145 placebo group) is available which have been followed up for 8 years with respect to thier lepromin status. Better response has been observed in vaccine group as compared in the two groups taking into consideration the 3 parameters viz. (a) percentage of conversion from lepromin negativity to positivity, (b) actual measurement of lepromin response in mm and (c) the duration for which the lepromin positivity was sustained. The average duration of positivity observed in LL, BL & BB types was 2 years, 1.9 year and 3.75 years in vaccine group. The corresponding figures for placebo group were 0.3, 1.0 and 2.5 years respectively. Overall, 16 out of 162 (9.8%) cases in vaccine group failed to convert to lepromin positivity and remained lepromin negative through out, as compared to 92 of 148 (62.1%) cases in the placebo group. The average lepromin response was 3.39 mm at the end of 1 year in LL type as compared to 1.1 mm in placebo group, the difference being highly statistically significant (p<0.001). Similar difference was observed up to 4 years from commencement of therapy in LL leprosy, and up to 3 years in BL type.

IMMUNOTHERAPY WITH Mycobacterium w VACCINE IN MULTIBACILLARY LEPROSY ACCELERATES B.I. DECLINE, REDUCES THERAPY DURATION FOR SMEAR NEGATIVITY: A 7 years experience.

Pankaj Sharma*, R.S. Misra#, H. K. Kar^, Rajani Ram*, Harvinder Kaur* & Rama Mukherjee.*

* National Institute of Immunology, New Delhi-110067
# Deptt. of Skin & STD, Safdarjung Hospital. New Delhi-110029
^ Deptt. of Skin & STD. Dr. R.M.L Hospital, New Delhi-110001

The clinical trials for evaluation of immunotherapeutic effects of Mycobacterium w (Mw) anti-leprosy vaccine have been in progress since 1986. at Urban Leprosy Centres of two hospitals of Delhi Out of 422 patients of multibacillary leprosy inducted. 315 have persued a regular course of treatment. Initially all cases were untreated, lepromin negative and bacteriologically positive and divided randomly into vaccine and placebo groups. Both groups received MDT as per NLEP regimen for a minimum period of 24 pulses and continued thereafter till the skin smear negativity. The vaccine group received, in addition, Mw vaccine given intradermally, at 3 monthly interval, till a maximum of 8 doses. The rate of bacteriological fall in the two groups showed statistically significant difference in LL and BL types during first 3 years of therapy (2 years immunochemotherapy followed by chemotherapy alone). Among 300 (155 vaccine & 145 placebo) cases, the number of patients released from therapy (RFT) after 24-29 months of treatment in LL & BL types were 84 out of 133 (60.3%) in vaccine group, and 30 out 120 (25.0%) in the placebo group, the difference being statistically significant (p<0.01). No statistically significant difference was observed in the two groups with respect to incidence of type-1 and type-2 reactions, episodes of neuritis. The addition of vaccine to MDT did not lead to any rise in the incidence of disabilities of all grades over & above those encountered with MDT given alone. In post-RFT follow up for varying durations (from 1-8 years) in different patients, there has not been any case of bacteriological or clinical relapse in both the groups.

RESPONSES OF ACTIVATED ARMADILLO MACROPHAGES TO CHALLENGE WITH MYCOBACTERIUM LEPRAE.

GW Long Hansen's Disease Center, Laboratory Research Branch at Louisiana State University, Baton Rouge, LA, USA

Upon inoculation with Mycobacterium leprae, the nine-banded armadillo (Dasypus novemcinctus) often develops lepromatous leprosy, and extensive histopathological studies have been done. However, due to a lack of reagents, little work has been done to evaluate immune responses in vitro. In this study, macrophage activating factor (MAF) was prepared by incubating armadillo spleen cells in medium containing Concanavalin A (ConA) for 48 hr. Control MAF (cMAF) was prepared by incubating the spleen cells in medium and adding an equivalent amount of ConA at the end of the culture period. Peripheral blood was collected from armadillos and the monocytes were cultured for 6 days. These monocyte-derived MФ were stimulated for 24 hr with cMAF or MAF, infected with M. leprae, and reincubated with cMAF or MAF. The infected MФ were then lysed and the viability of the released M. leprae was evaluated in a ¹⁴C- palmitic acid oxidation assay. As a control for anti-microbial activity, similarly treated MФ were evaluated for the ability to kill the intracellular protozoan, Toxoplasma gondii. MAF-treated armadillo MФ exhibited increased spreading compared to cMAF-treated cells, and were capable of killing T. gondii. In contrast, MAF-treated armadillo MФ did not consistently inhibit the metabolic activity of M. leprae. In addition, no nitrite, an end-product of the L-arginine-dependent production of reactive nitrogen intermediates (RNI), was detected in the supernatants of MAF-treated MФ. This profile of RNI-independent killing of T. gondii and an inability to inhibit mycobacteria is similar to that seen with IFN-γ-treated human monocyte-derived MФ.

STUDIES ON LYMPHOCYTE PHYSIOLOGY - STUDY OF MARKER ENZYMES OF METABOLIC PATHWAYS

Central Leprosy Teaching & Research Institute, Chengalpattu - 603 001, Tamil Nadu. India.

Infection with M. Leprae, diagnosis and the reasons behind occurrence of the reactions and relapse all the things remain scientifically obscure although we are nearing the goal of global elimination of leprosy. Although the abnormality may be the result of defect in CMI and variations in number, quantity and functions of T-Lymphocytes and certain cytokines. The changes that occur in the physiology of lymphocyte might be one of the physiology of hinphocyte might be one of the reasons for their depressed functions, specially in the effector limb. We have studied a number of enzymes to elucidate different metabolic pathways like Arginase (an enzyme associated with one cytokine which is basically a LPS in nature). Iso-enzymes of LDH and Aldolase, SOD and Peroxidase, Adenosine deaminase and rate of translation by labeled aminoacids. Lymphocyte Arginase showed an increase of activity in LL (5.48 units/mg), BB and BT (2.54 units/mg), TT (1.81 units/mg) in comparison to healthy controls (0.87 units/mg). ADA shows a reversal of this trend as in LL (265 units/mg), TT (375 units/mg) which is common in immunoproliferative disorders. Activities of all other enzymes also varied throughout the spectrum of the disease, which is well correlated with LTT and LMTT. Enzyme induction studies have been carried out to rectify the defects in lymphocytes which showed varying responses to different antigens including M. Leprae.

Tulay Cakiner, Fatma Savran Oguz, Mural Karcorlu, Gulumser Dolgun, Turkan Saylan, Mahmut Carin

This study was planned to investigate the role of HLA-DRB1 and DQB1 alleles in Turkish patients with uveitis.

The subjects were 27 Turkish leprosy patients (15 uveitis and 13 non uveitis). Controls were 27 healthy subjects.

We have performed DR and DQ "low resolution" typing by the PCR-SSP technique. We used 32 primer mixes for per sample. Twenty one PCR reactions were performed for identifying DR1-DR18. in addition. 3 PCR reactions were performed for the DR51,52, 53 superspecifities, 8 PCR reactions were performed for identifying DQ1-DQ9.

There was no significance difference between leprosy patients with and without uveitis and healthy controls with any of HLA-DRB1 and DQB1 alleles except DR16 (p<0.05).

The authors compared the natural trisaccharide of PGL-1 conjugated USA (NT-P-BSA) with the three recombinant antigens (TRA)-M. bovis BCG 85B (BCG85B). M. kansasii 85B (KAS85B) and M. leprae 85B (ML85B) to observe the distribution of the antibody titers in leprosy patients, leprosy household contacts, tuberculosis patients, pregnant women and controls and evaluate the value of the TRA in the serodiagnosis of leprosy.

The results indicated that. 1) in the 95% of specificity, the sensitivity of the TRA was lower than that of NT-P-BSA, but the sero-positive rates of the antibodies against the TRA in leprosy patients was relatively high reaching 82.3%-87.5% in lepromatous patients in particular and significantly higher than that of non-leprosy patients and controls; 2) among 138 leprosy household contacts with anti-NT-P-BSA antibody positive, only 0.0%-4.3% of them had positive anti-TRA antibody levels, but among 57 leprosy household contacts with high liter of anti-NT-P-BSA antibody, 4.3% had the antibody against the TRA.

The authors believed that the TRA should and could be considered as an alternative to NT-P-BSA in the serodiagnosis of leprosy, but could not replace it entirely. It appeared not be useful for detection of subclinical infection and high risk group in leprosy.

STUDY OF AFFINITY OF ANTI-PGL-I ANTIBODIES IN THE LL PATIENTS WITH TYPE I AND TYPE II REACTIONS

¹University College of Medical Sciences, Delhi, ²National Institute of Communicable Diseases. Delhi. ³V.P. Chest Institute, Delhi.

This communication describes the differential response of anti-PGL-I antibodies in the sera of leprosy patients suffering from type I and type II lepra reactions. Both IgG and IgM classes of antibodies in the serum samples obtained from the lepromatous patients and the patients during acute onset of both reactions and following clinical remission of the same after steroid therapy were quantified and their binding constants (K) determined. It was observed that the mean K of IgM antibodies in both types of reactional patients got markedly reduced in comparison with LL patients without reactions. However, the affinity of IgG class (K) of anti-PGL-l antibody in the sera of patients during episodes of both type I and type II reactions increased drastically with respect to control LL patients. The decreased K of 1gM antibodies during lepra reactions is likely to suggest switching of IgM synthesis to IgG variety. Immunological implications of the present findings will be discussed.

IMMUNOASSAYS WITH 29/33KD DOUBLET AND 65KD ANTIGENS OF MYCOBACTERIUM TUBERCULOSIS FOR SERODIAGNOSIS OF BORDERLINE LEPROSY PATIENTS

Pranab Das¹. Claudia Vaharon¹, Jan Dirk Burggraaf¹, Sila Yong¹ William Faber¹ and Anura Ramhukkana¹^●, Departments of Dermato-immunopathology. Academic Medical Center. University of Amsterdam. Amsterdam. The Netherlands (ILEP no. 7020242)

Immunologically unstable borderline leprosy patients, classified as borderline tuberculoid (BT). mid borderline (BB) and borderline lepromatous (BL) patients, often undergo reactions such as reversal reaction (RR) and erythema nodosum leprosum (ENL) in the course of the disease. It is often difficult to discriminate between BT and BL patients because of previous treatment. Moreover, differential diagnosis of these patients is essential in order to monitor the risk for developing distinct types of reactions. Presently known all serologic assays are only applicable in discriminating multibacillary (MB) and paucibacillary (PB) patients and there are no immunoassays for distinguishing between BL and BT patients.

In the present retrospective study we examined a total of 121 serum samples (40 TT. 22 BT. 26 BL and 33 LL) of leprosy patients for the antibodies to mycobacterial antigens using immunoblotting and enzyme linked immunosorbent assays (ImBA and ELISA, respectively). The ImBA showed seroreactivities to 29/33 KD doublet bands of m tuberculosis (RIVM 7611 strain) in 99% and 77% of LL and BL patients respectively, whereas none of TT, BT and control patients did not show such specific antibodies. However, most of the TT and BT patients' sera (94% and 63% respectively) reacted to 65KD antigen(s) but not in disease specific manner when compared to controls. Interestingly, by ELISA mean, serum IgG antibody levels to either gel purified 29/33 kd doublet and 65 KD antigens were found significantly higher in lepromatous (LL/BL) and tuberculoid (TT/BT) leprosy patients respectively as compared to control sera consisting of tuberculosis, Crohn, sarcoidosis patients and patients with different skin diseases. After establishing a cut off point. 97% and 88% sera of LL and BL patients were positive with the 29/33 KD doublet as compared to the positivities of 41% and 20% of BT and TT patients respectively. In contrast 86% TT and 82% BT patients' sera showed high positivity for high antibody levels to 65 KD antigens as compared to 50% BL and 14% LL patients' sera. The present study showed that the measurement of antibody activities to 29/33 KD and 65 KD mycobacterial antigens by ImBA and ELISA could clearly discriminate BL and BT patients from the respective polar forms. We recommend that the presently described immunoassays should be used in a field investigation as an additional supportive tool for clinical classification of leprosy spectrum.

IN SITU EXPRESSION OF IFN-γ AND IL-4 IN THE LESIONAL SKIN ACROSS THE IMMUNOPATHOLOGICAL SPECTRUM OF LEPROSY: REFLECT DISEASE ACTIVITY

Claudia E. Verhagen¹², Anita A. Buffing¹², Robert Slebos², Chris M. van der Loos², William R. Faber¹ and Pranab K. Das¹² Departments of ¹Dermatology and ²Pathotogy and Division of Cardiovascular Pathology, Academic Medical Center. Universtity of Amsterdam, Amsterdam. The Netherlands (ILEP no. 7020242).

The dynamics of immune responses in leprosy patients display a clinical and histopathological spectrum from the paucibacillary (PB) type of polar tuberculoid leprosy (TT) to the multibacillary form (MB) of polar lepromatous leprosy (LL). Between the two polar forms of leprosy, the majority of the patients are the immunologically unstable borderline patients. A considerable number of these patients (20-30%) show changing clinical status in the course of the disease, known as reactions, resulting in clinical and pathological alterations accompanied by tissue damage. The reversal reaction (RR) is accompanied by augmented m. leprae specific CMI-DTH responses that often parallels the destruction of peripheral nerves. In the erythema nodosum leprosum (ENL) reaction, tissue damage appears to be mediated by the local deposition of immune complexes and complement fixation. Type 1 - and type 2-like m. leprae responsive T cells, characterised by a predominant production of either IFN-γ or IL-4, are recognized in vitro to parallel CMI-DTH or humoral immune responses within the immunopathological spectrum of leprosy. In the present study we assessed the in situ presence of IFN-γ and IL-4 both at protein and mRNA levels in lesional skin biopsies of untreated leprosy patients, and in patients during a RR or an ENL. as well as after treatment. We observed that both IFN-γ and IL-4 were present in varying amounts in the lesions of untreated paucibacillary (PBland multibacillary (MB) leprosy patients. Moreover, no significant differences were seen in regard to the protein level of both of these cytokines in one individual lesion. However, high levels of in situ protein of IFN-γ and IL-4 were seen in all lesions with RR, and in ENL lesions the IL-4 protein was relatively higher than IFN-γ. Interestingly, m situ protein expression of IFN-γ and IL-4 was found significantly lower in the lesions of PB and MB patients who were released from treatment. Similarly, both cytokines decreased in the lesions of patients with RR or ENL with treatment. Using a RT-PCR method, the in situ expression of IFN-γ and IL-4 mRNA. relative to the same amount of T cell mRNA also did not differ between untreated PB patients, untreated MB patients, and those patients experiencing an ENL. However, similar to the immunohistochemical findings, the lesions of patients experiencing RR showed high level of both IFN-γ and IL-4 mRNA as compared to the other groups of patients. These data implicate that although in vivo expression of IFN-γ and IL-4 in leprosy lesions may not necessarily reflect the role of discrete type 1- or type2-like in leprae responsive T cells in the pathology of different types of leprosy. The monitoring of lesionai cytokines will be useful for the evaluation of disease activity (particularly in regards to the development of reactions) of patients in a leprosy control programme.

SAWSAN H. M. EL TAYEB Elizabeth RICH AND MOHAMED M. SADEK. FACULTIES OF MEDICINE ALAZHAR UNIVERSITY EGYPT AND CLEVELAND, USA

Alveolar macrophages (AM) obtained from the bronchoalveolar lavage and adjusted to 10⁶ cell/ml, mononuclear cells (PMN) were prepared and adjusted to 10⁷ cell/ml Both AM and PMN were infected with Mycobacterium tuberculosis (MTB) adjusted to 10⁷ cfu/ml. AM and PMN were stimulated with soluble mycobacterial preparation PDD and lipopolysacchande (LPS) and serve as control

The concentration of chemokines IL-8, Rantes, MCP and MIP. Alpha were assayed in the supernatant by ELISA. The migratory activity for MN and Lymphocytes in supernatant of MTB infected PMN and AM containing the chemokines was measured. Northern blot analysts of RNA extracted from AM and PMN was performed. The results and statistical analysis will be presented.

CELL MEDIATED IMMUNE RESPONSE IN HEALTHY EXPOSED INDIVIDUALS SETTLED IN NON-ENDEMIC AREA - A PILOT STUDY

¹ Stanley Browne Laboratories. Richardson Leprosy Hospital. The Leprosy Mission, Miraj-416410. India ² Institute of Ophthalmology, Bath Street, London ECIV9EL

Introduction: It is believed that upon infection with M. leprae the nature of the T-cell immune response in the exposed individual determines whether leprosy will develop or whether protection will be induced.

Aims and Objectives: To investigate the lymphoproliferative responses to leprosin A in the exposed individuals.

Experimental Procedure: Venous blood samples were collected from 10 subjects (8 with previous exposure and 2 with no known contact with leprosy). Lymphocytes were isolated and 3-4 day culture experiments were performed stimulating the cells with PHA.PPD and Leprosin A. The degree of lymphocyte growth was determined initially by ATP assay and later by an ELISA for gamma-interferon.

Graphical representation of ATP counts: Encouraging results with good lymphocyte growth and gamma-interferon is seen in subjects with previous leprosy exposure. Controls for the assay show no such response.

Conclusion and Discussion: The frequency of the reactive T-cells in the peripheral circulation at the time of sampling may influence the immune status of the host toward the antigens.

A POSSIBLE LINK BETWEEN TIMING OF DEVELOPMENT OF MUCOSAL AND SYSTEMIC IMMUNITY - APPARENT PROTECTION??

Leprosy Mission. Miraj-416410. India ² Institute of Ophthalmology. Bath Street. London ECIV9EL

sources is more important than infection from active clinically apparent cases. Since the primary lesion of leprosy is thought to be in the nose, it is possible that mucosal immunity plays a major role in protecting exposed individuals from developing the disease. Little known about the early lesion of leprosy there is some evidence that they may heal by the induction of a CMI with concomittant induction of an IgA response

Lymphocytes were isolated from venous blood samples collected during a period of time from subjects belonging to different groups including a) family contacts, b) individuals from non-endemic countries & c) fresh hospital contacts. The mononuclear cells were stimulated with a mitogen. PPD and Leprosin A. The degree of the cell growth was determined by an ELISA for gamma-interferon. Tuberculosis patients served as positive control to assess the response against PPD.

Good lymphocyte growth and production of gamma-interferon showed a strong T-cell response to M. leprae in some exposed individuals. Mucosal IgA responses at different time intervals alongside will help to determine the possible link between humoral and CMI and its putative role in protection.

Departments of Pathology. Pharmacology and Internal Medicine (Division of Dermatology). Faculty of Medicine of Ribeirão Preto-USP. São Paulo, Brazil.

The aim of this study is to determine the presence of Nitric Oxid and TGF-βl in the skin lesions of patients with leprosy, in an attempt to correlate the presence of both with the clinical forms of the disease that progress with a specific immunosuppresion to Mycobacterium leprae. The presence of NO and TGF-β1 were perfomed in biopsies from patients with lepromatous (LL, N=8) and tuberculoid (TT, N=8) leprosy. Normal skin samples (N=8) were used as control. The sections were submitted to NADPH-diaphorase activity a surrogate marker for NO-synthase and to Immunohistochemical studies using an anti- TGF-β1 and anti NOSi polyclonal antibodies and the avidin-biotin-peroxidase (ABC complex method). For the NADPH-diaphorase activity and to NOSi immunoreactivity, seven LL cases presented mild (+/++) staining and one case did not present reactivity in the dermal lesions. All TT cases were positive, five with moderate intensity (+++) and three cases presented intense (+ + + +) staining. Immunoreactivity to TGF-β1 protein was present in the dermal lesion of all LL cases. In contrast, it was absent in all TT cases. The immunoreactivity to TGF-β1 and to NOSi were usually observed in the cytoplasm of mononuclear cells with macrophage/histiocyte morphology (CD68+). Conclusion: In the lepromatous form M. leprae multiplies in the cytoplasm of macrophages inducing the production of TGF-β1. Its immunosuppressive activity inhibit the differentiation and activation of these cells perpetuating the infection. In the tuberculoid forms TGF-β1 absence cause intense differentiation of macrophage cells and NADPH-diaphorase activity which eliminates most of the bacilli.

PRODUCTION OF TGF-β1 BY BLOOD MONOCYTES F ROM PATIENTS WITH DIFFERENT CLINICAL FORMS OF LEPROSY

Departmente of Internal Medicine, Faculty of Medicine of Ribeirão preto. University of São Paulo, and •Department of Internal Medicine and ••Pathology. Federal University of Uberlándia, Brasil

It has been demonstrated that there is a clear correlation among the clinical forms of leprosy and the state of mononuclear phagocyte activation in the lesions which are also associated with the presence of cytokines such as IL-2. IFN-γ, TNF-α and IL-12 in tuberculide form and IL-4, IL-5 and IL-10 in lepromatous form. The cytokine TGF-βM (transforming growth factor-beta 1) has been described as a macrophage-suppressing factor in diseases caused by intracellular parasites and in dermal lesions of patients with BL and LL forms of leprosy.

In the present investigation, we determined the concentration of TGF-βl secreted in the adherent cell supernatants from human monocytes stimulated in vitro with PGL-l. LPS or media only. The cells were obtained from untreated patients with different clinical forms of leprosy and healthy individuals, as controls. The peripheral blood mononuclear cells were isolated by Ficoll-Hypaque and platelets were removed from monocytes by washing in Versene buffer and differential centrifugation. Monocytes were cultured in RPMI 1640 in presence of 2.5% heat-inativated human AB serum at 37º C for 1 h. The adherent monolayers were then cultured in presence of RPMI 1640 only. TGF-βl concentrations were determined by ELISA in cell free supernatants harvested after culture of 48 h. Our results demonstrated that the adherent cells exhibited spontaneous release of TGF-βl in all clinical forms of leprosy and in healthy individuals. However, adherent cells from patients with the BL and LL forms with erythema nodosum leprosum (ENL) displayed significantly higher concentrations of TGF-βl when stimulated with PGL-l (p < 0.0124), or LPS (p < 0.0445) or media only (p < 0.0362) than patients with other clinical forms of leprosy or healthy individuals. In addition, when stimulated with PGL-l. the cells from ENL patients exhibited high concentrations of TGF-βl as compared with LL (p<0.0069). BT (p<0.0173) or healthy individuals (p<0.0124).

Comparing these observations with our previous data studying the TGF-βl in dermal lesions, it appears that this molecule probably play different rotes in leprosy, presenting a supressive action locally and features of pro-inflamatory cytokine when secreted systemically by monocytes.

Division of Dermatology-School of Medicine of Ribeirão Preto São Paulo University-Brazil

Considering that the different clinical manifestations visualized in the spectrum of leprosy can be related with the immunological response, we have investigated serum cytokines levels in 35 leprosy patients and 10 normal individuals(controls).The patients were subdivided into LL(7). BL + BB(8). BT(7), TT(6) and ENL(7). All patients were classified by clinical, bacteriological and histological criteria. It was include only untreated patients. The scrum levels of IL1, IL4, IL6 and TNFα were measured by ELISA (R&D Systems). The results showed significantly higher IL4 levels in multibacillary leprosy-MB(62.0pg/ml in LL.BL.BB), when compared with paucibacilIary-PB(1.3pg/ml in HBT,TT) patients and control group(0.0pg/ml) In contrast, the ILl and IL6 levels were significantly lower in MB patients(1.6 and 5.6pg/ml) when compared with the levels of PB patients(33.7 and 12.7pg/ml). In patients with ENL the TNFα Ievels(101.5pg/ml) were significantly higher than in controls(30.5pg/ml) and were associated with decreased concentrations of IL4(59.9pg/ml). In conclusion, we suggest that the capacity of immune response in leprosy is related to the ability of cytokines IL1,IL6 and TNFα, to induce the activation and modulation of the response of phagocytic cells(macrophage) and effector cells(Tlymphocites) and the immunosuppression observed in LL could be maintained by IL4 activity, through the supression of macrophage activation.

CYTOKINE Th1 AND Th2 PROFILE. TGFβ₁ AND IMMUNOSSUPRESSION OF LEPROMATOUS LEPROSY.

Norma T. Foss, Meire A. S. Oliveira, Andrea M. Zangrande, Célio L. Silva, Floréncio Figueiredo.

The aim of this study is to verify whether the correlation between peripheral cytokines levels, "in vitro" production, and inflammatory cells pattern in cutaneous biopsies from patients is related with the evolution of the polar forms of leprosy. Cultures of PMNBC from 21 leprosy patients (11 lepromatous leprosy-LL. and 10 tuberculoid leprosy-TT) were treated during 24-72 hrs with LPS (10 mg/mh, PHA (20 mg/ml) and lepromin (2 x I0⁷ bac/ml). The supernatant and serum citokines (IL1, IL2, IL4, IL6 and TNF), were measured by ELISA (R & D Systems). In the cutaneous lesions the presence of T cell (PANT-T4, T8), macrophages (CD68) and TGF-β1, were determined by immunohystochemical assay (ABC-peroxidase), using frozen skin biopsies. IL1, IL6 and a TNFα levels in the serum and in the supernatant were higher in TT (37.5; 13.5 and 84.5 pg/ml; 63.1; 22.0 and 166.5 pg/ml; p < 0.05) than those levels of LL patients (0,0; 3.4; 0,0 and 15,7; 5,8; 14,4 pg/ml). IL2 was detected only in the lymphoproliferative supernatants of TT patients showing elevated levels (129.3 pg/ml) when compared to LL patients (10,4 pg/ml). IL4 was observed only in LL (89.2 e 51.2 pg/ml, serum and supernatant). It was observed predominance of macrophage (CD68) in the cutaneous inflammatory infiltrate from both leprosy patients groups. TGF-β1 was found in 85% of CD68 cells from LL patients and it was absent in TT infiltrate. 80% of T cells of TT infiltrate showed CD4+ pattern, whereas only in 10% of LL patients CD4+ pattern was observed. These results may suggest that IL4 and TGF-β1 are correlated with the immunossuppressive

mechanisms observed in LL. Since both cytokines can be induced by M. leprae and/or correlated antigens, we can suppose that this mechanism should explain, in part, the maintenance of the supressive response.

Reactional states in leprosy can be defined as the clinical manifestations of alterations in the immunological balance between host and infecting organism. There are two types of them: Type 1 reaction or reversal reaction-RR. frequent in paucibacillary leprosy is associated with an increased cellular immune response. Type 2 reaction or erythema nodosum leprosum-ENL. occurs in lepromatous leprosy patients and characterize a systemic inflammatory reaction. Forzen skin lesions biopsies from 15 patients (9 in ENL and 6 in RR), were immunostained to evaluate the inflammatory cells phenotypes, expression of IFN-γ, TNFα, TGFβ1 and the were negative for TGFβ1. Memory lymphocytes. CD3+CD45RO +expressed IFN-γ in their cytoplasm. The presence of iNOS was detected in the cytoplasm of pratically all CD68 + cells. In ENL cases the CD68 + macrophages positively immunostained for TGFβ1 and TNFα and were negative for iNOS. However, presence of iNOS was detected in the cytoplasm of neutrophils cells (CD15+). This TNFα detected in lesion site was correlated with increased concentrations in serum of ENL patients (105.6±9.8 pg/ml), while in RR patients the TNFα levels were lower (57.3±5.0 pg/ml). The presence of IFN-γ, TNFα and iNOS in skin lesions of reactional states in leprosy may induce local production on nitric oxide leading to mycobacterium killing.

Tsuyoshi Fujiwara, Koichi Fukase¹, Shoichi Kusumoto², Fumishige Minagawa², James T. Douglas³

Institute for Natural Science, Nara University, ¹Department of Chemistry, Graduate School of Science,

Osaka University, ²Hansen Disease Research Center, National Institute for Infectious Disease, ³Department of Microbiology, University of Hawaii

To study the mechanism in which antibodies recognize antigens, anti-PGL-I monoclonal antibody DZ 1 was employed, because of that DZ 1 had unique characteristics which recognized inner part of the sugar chain of PGL-I. The activity of purified DZ 1 was tested by ELISA for synthetic sugars related to PGL-I. DZ I was active to the inner disaccharide 3-OMe-2-(2', 3'-di-OMe-α-L-Rha)-α-L-Rha (ID). DZ 1 had no activity to the inner monosaccharide.

DZ 1 had greatly reduced activity to 4-OMe, 3-OH, 3'-OH or 2',3'-di-OH derivatives of ID. But, DZ 1 was activity to 2'-0H derivative of ID. DZ 1 recognized two anomeric configurations in ID. These results showed that DZ 1 recognized the inner disaccharide, 4-OH, 3-OMe and 3'-0Me of ID.

Computer modeling and structural analysis by NMR of the trisaccharide suggested that two types of the cluster (Conformation A and B from lower energy level) were present in about 46.2% and 50.3% within 10Kcal/mol. They were in very similar conformation on the inner disaccharide

which were recognized by DZ 1. NMR spectroscopy (NOE HETLOCK and pHMBC spectra) supported conformation B strongly. NMR study showed also that conformation B was dominat in solution. In confomation B the trisaccharide chain vented between Rha-Rha linkage, forming the surface open to the outside. 4-OH, 3-OMe And 3'-OMe, which were recognized by DZ 1, were present on this surface, and 2'-OMe and non-reducing-end glucose residue were oriented to 90 degree directions. Thus, it was concluded that DZ 1 bound to the trisaccharide from this direction. This is why DZ 1 recognized the inner part of the sugar chain.

St. Thomas Hospital and Leprosy Centre, Chettupattu - 606 801, Tiruvannamalai District, Tamil Nadu, India.

There have been several reports about AIDS patients easily acquiring tuberculous infection saying that it is one of the common causes of death. Particularly in USA the prevalence of TB since the advent of AIDS has considerably increased. However M. leprae which belongs to the same species as M. tuberculosis does not seem to affect the HIV patients with the same virulence as evidenced by the available reports. In reports where leprosy and HIV infection are associated, most of the patients belong to borderline variety rather than lepromatous type. The prevalence of HIV infection among leprosy patients is not higher than any general population. Lepromin test is one of the important tests which even now we use to measure the CMI to M. leprae in HD patients and in the general population. This study is undertaken to find out the lepromin reaction of HIV positives in 3 HIV positive individuals and discuss its significance.

AN EXPERIENCE OF USING LEUCINFERON FOR TREATMENT OF LEPROMATOUS LEPROSY PATIENTS

Not infrequently leprosy patients, after some period of prolonged improvement against the background of antileprosy therapy, show stabilization of the process: clinical, morphological picture and immunological profile do not improve further. In such cases addition to the standard therapy of immunomodulators might be rather effective. We present our experience of using leucinferon - a combination of alpha-interferon and other cytokines ("Intecor", Russia) for the treatment of LL patients with no signs of further improvement of their disease. The results were estimated by the dynamic of clinico-morphological and immunological indices. Histological investigations were based on morphometry with using 100-point ocular system (Avtandilov, G., 1991). Antibodies to Dis-BSA and protein antigens of M. leprae were determined in ELISA. After a course of leucinferon therpy there was a marked improvement of clinical manifestations. Morphological pictuare of infiltrates changed as follows: macrophages decreased by 31,3%, fibroblasts and tissue basophils increased by 9,2% and 9,6%, correspondingly. Solid forms of M. leprae disappeared. Initial high levels of anti-M. leprae antibodies fell to normal values during 2 months of the therapy. Thus, using of leucinferon might be useful in treatment of leprosy patients inresponsive to standard therapy.

DEFINITIVE ROLE OF LEPROMIN POSITIVITY IN BACTERIOLOGICAL CLEARANCE IN MULTIBACILLARY LEPROSY.

Pankaj Sharma*. R.S. Misra#, H. K. Kar^, Rajani Rani*, Harvinder Kaur* & Rama Mukherjee.*

* National Institute of Immunology, New Delhi-110067
# Deptt. of Skin & STD. Safdarjung Hospital, New Delhi-110029
^ Deptt. of Skin & STD, Dr. R. M. L. Hospital. New Delhi-110001

In clinical trials with Mycobacterium w (Mw) anti-leprosy vaccine, the role of lepromin status on B.I. decline was studied. From LL, BL and BB leprosy types there were 83, 48 and 24 patients respectively who received immunochemotherapy (MDT+Mw vaccine), and 81.41 and 23 patients respectively, who received chemotherpy (MDT+placebo). All patients, in both groups, were lepromin negative initially. In LL and BL types, the rale of BI decline in the vaccine and placebo groups showed a statistically significant difference from 6 months therapy onwards. Analysed with respect to lepomin status, by segregating the patients in vaccine and placebo groups into lepromin positives and negatives, this statistically significant difference was observed only in patients converting to positive lepromin status. The difference was non-significant among cases remaining lepromin negative throughout, although slightly higher rate of BI decline was observed in vaccine group.

Apart from the well recognised role of lepromin positive status in imparting protection against contracting leprosy (immunoprophylaxis), its role in bacteriological clearance also seems definitive (immunotherapy).

G.W. Long Hansen's Disease Center, Laboratory Research Branch at Louisiana State University, LA, USA

Multibacillary lepromatous leprosy is characterized by enormous numbers of Mycobacterium leprae in the lesions and a potent antibody response, but little cell mediated immunity. M. leprae engorged granuloma macrophages (MФ), harvested from the foot pads of experimentally infected athymic nu/nu mice, as well as MФ infected in vitro with high numbers of bacilli, are refractory to activation by interferon-gamma (IFN-γ). This suggests that any killing of M. leprae in infected tissues would likely be due to newly-arrived, competent MФ activated before or shortly after their traffic into the leproma. Therefore, we have developed an in vitro model to simulate the turnover of MФ in a lepromatous lesion. Murine target MФ, infected with varying doses of viable M. leprae freshly harvested from the foot pads of nu/nu mice, were challenged with normal or activated (ACT) effector MФ. At various times, the bacilli were recovered and, since M. leprae cannot be cultured in vitro, assayed for ¹⁴C-palmitic acid oxidation to assess viability. M. leprae recovered from target MФ possessed high metabolic activity. Bacilli from target MФ challenged with normal effector MФ displayed metabolism which was often greater than that of bacilli from unchallenged targets, suggesting that turnover may actually sustain M. leprae viability. Bacilli recovered from infected target MФ challenged with ACT MФ, however, exhibited a markedly decreased metabolic activity, implying that M. leprae residing in normal target MФ are not protected from the microbicidal effects of ACT MФ. Thus, the state of the MФ infiltrating a granuloma may markedly affect the viability of M. leprae residing in MФ in the lepromatous lesion.

COMPARISON BETWEEN ANTI-PGL-I SEROLOGY AND MITSUDA'S REACTION (CLINICAL READING, MICROSCOPIC FINDINGS AND IMMUNOHISTOCHEMICAL ANALYSIS)

MAEDA, S.M.¹; CRUAUD, P.²; SUNDERKOTTER, C³; MICHALANY, N.S.¹; TOMIMORI-YAMASHITA, J.¹; ROTTA, O.¹

1-UNIFESP- EPM, São Paulo- Brazil 2-Hôp. Jean-Verdier, Bondy- France 3-Univ. of Münster - Germany

A quantitative relationship between anti-PGL-I IgM levels (ELISA) and Mitsuda's reaction was studied in 44 leprosy patients (10 TT, 11 BT, 5 BB, 15 BL and 3 LL). We have performed the clinical reading and histological analysis of Mitsuda's reaction. Histological examination of lepromin reaction was classified into 6 categories. A correlation was found between clinical reading and microscopic findings. The antibody titers against PGL-l antigen increased from tuberculoid to lepromatous pole, although individual variations were found in the spectrum. When multibacillary patients presented high antibody levels, the clinical reading of Mitsuda's reaction were low (< 3,0mm) and the histological findings were an incomplete tuberculoid granuloma or absence of granuloma. Tuberculoid patients showed low anti- PGL-I titers. The Mitsuda's reaction in these patients was > 6,0 mm and the histological analysis presented a tuberculoid granuloma development. CD4+ lymphocytes were found throughout epithelioid cells and CD8+ cells were predominantly in the mantle surrounding the compact granuloma as it had been demonstrated in other tuberculoid granulomas as sarcoidosis and rhinoscleroma (MODLIN et al., 1983).

LYMPHOCYTE AND CYTOKINE RESPONSES TO SUBFRACTIONS OF THE LEPROSY BACILLI IN PATIENTS WITH TYPE I REACTIONS

The biological basis of Type I reactions (TIR) is poorly understood. To investigate the immunological responses in TIR, whole blood cultures were stimulated with leprosy antigens (MLS, WML, MLS-LAM, MLCwA) for 24 hours and levels of cytokines in the supernatants were measured by ELISA. Patients with untreated TIR had significantly higher levels of interferon-gainma (IFNγ) and tumor necrosis factor alpha (TNFα) but not interleukin 10 (IL-10) in response to leprosy antigens when compared with non-TIR controls. The levels of IFNγ and TNFα showed a marked decline within one week of commencing steroid therapy. The antigenic specificity of the lymphocyte proliferation in patients with neural and cutaneous forms of TlR was also investigated.

ANALYSIS OF CITOKINE mRNA PROFILE- IN LEPROSY LESIONS DURING ACUTE INFLAMMATORY EPISODES: IMPACT OF PENTOXIFYLLINE. THALIDOMIDE AND PREDNISONE TREATMENT. Moraes MO. Samo EN. Almeida AS. Saraiva. BCC, Nery JAC, Sampaio EP. Leprosy Laboratory Oswaldo Cruz Foundation. Av. Brasil. 4365 - Manguinhos. Rio de Janeiro - RJ. Brazil.

Cytokines play a crucial role in the establishment and development of immune response against intracellular injections. In this regard, a cytokine profile resembling a Th1 pattern in related to the resistance. while Th2 responses may lead to susceptibility to the pathogen. The clinical features of leprosy comprise a spectrum of immunological response including the tuberculoid (TT-responsive) and lepromatous (LL-unresponsive) poles. Besides, during the natural course of the disease, patients may undergo reactional episodes that are characterized by an acute immunoinflammatory response to Mycobacterium leprae, that can be correlated to tissue and nerve injury. They are clinically classified as type I (reversal reaction-RR) and type II (erythema nodosum Ieprosum-ENL) reactions. Despite of the amount of knowledge accumulated in the past few years, very little is known about the molecular mechanisms that lead to reactions in leprosy. Moreover, the understanding of cytokine balance in the development of leprosy reactions and its modulation by anti-inflammatory drug therapy is poorly understood. Our previous studies suggest that I'NFα is involved in mediating the local and systemic pathophysiological events during those episodes Furthermore, the inhibitory effects of thalidomide (THAL) and pentoxifylline (PTX) on TNFα mRNA expression and protein secretion in the sera from ENI, patients have been demonstrated Recent data from our group and others suggest that these drugs are acting in a broader range of cytokine regulatory pathways. We decided to employ semi-quantitative RT-PCR to determine the cytokine profile at the site of the lesion of leprosy patients undergoing or not reactional episodes. The effects of drug treatment were also evaluated. Skin biopsy specimens were collected from 6 unreactional (5-LL and I-TT) and 13 reactional (10-LL undergoing ENL and 3-LL undergoing RR) patients Biopsies were collected at the time of leprosy diagnosis, at the onset of the reactional episode, and 3-30 days after drug administration. ENL patients underwent pentoxifylline (n=8) or thalidomide (n=2), while RR patients were treated with prednisone (n=3). We observed that patients undergoing reactions present a more prominent expression of TNFα. IFNγ and IL-6 mRNA in situ. In addition, message for IL-2, IL-10 and IL-4 was also noticed. So, leprosy patients during reactions seems to present a Th0 response. Whenever the impact of the anti-inflammatory drugs was evaluated, we verified a drastically inhibition of TNFα. IFNγ, and IL-6 mRNA expression. However, the impact on IL-10 and IL-4 gene expression was dependent of the immune status during the reaction

Fatixis M. M, Guillen V. C., Navarro F. S., Morales O. R*. Armendariz-Borunda J**. Centro de Investigacion en Inmunologia y Dermatologia. ••Instituto de Biologia Molecular. C.U.C.S. Universidad de Guadalajara. •Instituto Dermatológico de Jalisco. Guadalajara, Jalisco MEXICO

The pattern of specific cytokines produced has been used to define subsets of T lymphocytes in diseases caused by intracellular pathogens. This subsets of T lymphocytes (TH1, TH2) has been associated to the different poles of leprosy (lepromatous LL and tuberculoid LT).

Previous reports indicate that LL patients can be classified in responden (R ) and non responders (NR), according to their activity under rnitogenic stimulation. Our previous reports showed that lymphocytes from NR patients release threshlod IL-2 as compared with R patients and healthy subjects. On the other hand there is an ongoing controversy concerning to the correlation of cytokines production, and the general status in leprosy patients.

In this work we attempted to elucidate the serum levels of EL -1β, IL- Ira and TNFα in LL-, LT- patients and healthy subjects. Furthermore, we analyzed the production of EL-4, EL-6 and IL-10 in culture of T lymphocytes from LL- patients.

Our results showed no differences in the pattern of TH1 and TH2 cytokines released by lymphocytes from LL-patients and healthy subjects. This was the same for cytokines serum levels. Nonetheless, EL-1ra serum levels were dramatically higher in LL- as compared to LT-patients and healthy subjects. This could explain the lack of microbicidal activity displayed by macrophages in LL- patients.

DO γ/δ T-CELLS PLAY A ROLE IN LEPROMIN SKIN REACTIONS IN HANSEN'S DISEASE-NAIVE VOLUNTEERS?

Tomasz F. Mroczkowski,¹ David M. Scollard,² Edward J. Shannon,²and Wojciech A. Krotoski,³

¹Tulane University School of Medicine, New Orleans; ²GWL Hansen's Disease Center at LSU, Baton Rouge; and ³Louisiana State University School of Medicine (LSU), New Orleans, Louisiana, U.S.A.

Studies have indicated that mycobacterial antigens, including those of Mycobacterium leprae, evoke γ/δ T-cells: they were found in increased numbers in lepromin skin-test sites, and comprised a significant proportion of the T-cell population in Mitsuda reactions among patients with various forms of Hansen's disease. The purpose of this study was to evaluate the role of γ/δ T-cells in both Fernandez and Mitsuda responses in healthy, tuberculin PPD-negative volunteers who had never lived in leprosy endemic areas.

Volunteers were injected intradermally with standard lepromin A, tuberculin PPD, and lepromin diluent as a control. Biopsies were obtained at the time of injection (control), and after 48 h and 21-28 days. Suction blisters were produced over control and test sites at the same times, and blister contents were aspirated 24 h later for evaluation of cellular content. Blood was also obtained before lepromin administration, then after 48 h and 21-28 days, for fluorescence-activated cell-sorter (FACS) analysis.

As determined by cell analyses of biopsy specimens, monocytic infiltrates observed in Fernandez and Mitsuda reactions contained insignificant numbers of γ/δ T-cells, and the majority of lymphocytes were of CD4 + and CD8 + phenotype. The same results were obtained when cellular contents of supra-lesional suction blisters were examined. At 23 days, incubation of peripheral blood mononuclear cells with M. leprae or tuberculin PPD resulted in a significant increase in incorporation of ³H-TdR by cells exposed to the former, but not to PPD ( p = 0.04).

In conclusion, the results of our study indicate that, in contrast to published observations in patients infected with M. leprae, γ/δT-cells do not appear to play an important role in the early development of responses to M. leprae antigens evidenced by Fernandez or Mitsuda lepromin reactions in Hansen's disease-naive individuals.

IMMUNOLOGICAL RESPONSE OF N TT LEPROSY PATIENT POST BCG VACCINATION DURING DISEASE AND AFTER HEALING OF THE LEPROSY LESION, Monica C. B. S. Lima¹²³, Jorge L. Salgado⁴, Maria C. V. Pessolani¹, Geraldo M. B. Pereira ², Franklin D. Rumjanek², Nadia Duppre , Jose A. C. Nery , Luis C. M. S. Porto , Luciane F. S. Pontes⁴, Euzenir N. Sarno & Elizabeth P. Sampaio

I. Leprosy Laboratory. Oswaldo Cruz Foundation, Rio de Janeiro, R. J. Brazil, 2 and 4 Laboratory of Immunopathology (2) and laboratory of Histocompatibility (4). School of Medical Sciences. State University of Rio de Janeiro, Rio de Janeiro, RJ. Brazil, 3. Biochemistry Department. Federal University of Rio de Janeiro. Rio de Janeiro. RJ. Brazil

It has been shown that BCG is an effective vaccine against leprosy, and the aplication of multiple doses to leprosy contacts has been adopted as a regular protocol by the National Control Program in Brazil. In the present study, a clinical and immunological evaluation of a household contact of a multibacillary patient who developed a self-healing TT leprosy following BCG vaccination is presented, JSS, a female aged of 55. received 1 dose of BCG vaccine and 4 months later a single leprosy lesion was observed on her face. At this point, a lepromin skin test was performed and a reaction of 22 mm was detected. HLA-typing for this individual was A31-B35-Cw4-DR16. DR51-DQ7/A2-B51 PBMC from the patient was analyzed with regard to in vitro proliferation and cytokine production following stimulation with M. leprae and BCG at 4 different periods of the follow-up (at diagnosis, and after 7. 16 and 19 months). A positive T cell response and IFN-γ production was observed along the follow-up When PBMC from JSS were depleted of the CD4 lymphocytes, the proliferation and IFN-γ production to M. leprae stimulation were decreased by 44 and 34% respectively, suggesting a major participation of this population in this type of response. In addition, mononuclear cells from this patient were able to proliferate and produce IFN-γ in response to four major purified proteins of the leprosy bacillus (10 kDa/GroES homolog, 22 kDa/bacterioferritin, 35 kDa/MMPI and the secreted 85 complex). Finally, M. leprae and BCG were also able to induce IL-2. TNF-α, IL-10 and IL-5 production. In this study we then demonstrated an immunological type of response which was found to be associated with a self-healing case in leprosy.

EFFECT OF PHENOLIC GLYCOLIPID-I ON TNF-α PRODUCTION AND T CELL ACTIVATION, Pessolani MVC¹. Charlab R², Alvim IMP¹. Nery JAC¹. Esquenazi D^1.3, Sarno EN¹. & Pereira GMB^1.3 ¹Laboratorio de Hanseniase. Institute Oswaldo Cruz. FIOCRUZ, Rio de Janeiro. Brasil; ² CNPq/CBPF. Rio de Janeiro. Brasil. ³ Laboratory of Immunopatology, School of Medical Sciences. State University of Rio de Janeiro, Rio de Janeiro, Brazil.

PGL-I has been associated with the selective anergy observed in lepromatous leprosy patients. Experimental findings indicated that PGL-I interferes with the cellular immune response at the level of both macrophage function (measured by the release of inflammatory cytokines and by generation of oxygen radicals) and lymphocyte proliferation. However, little is known of the molecular events triggered by PGL-I in human cells, and that are responsible for the alterations seen in their physiology and metabolism. We have studied the effect of PGL-I on the production of TNF-α by human monocytic cells. We found that PGL-I alone was unable to induce TNF-α secretion, but acted as a co-signal for the production of this cytokine when associated with M. leprae or PMA, PGL-I was also able to inhibit the IL-2 dependent pathway of T cell activation. In PBMC Stimulated with anti-CD3 or ConA. PGL-I down modulated the expression on T cells of the α chain of the IL-2 receptor and the secretion of IL-2 itself. Moreover. PGL-I aKo affected the expression of CD69. suggesting that interferes at very early steps in the signaling pathways leading to T cell activation. Currently, we are working on the hypothesis that PGL-I exerts its modulatory effects by inserting its very large hydrophobic moiety into the membrane lipid bilayer, disturbing in this way, signaling pathways such as those dependent on protein kinase C

Maria Quintana•, Jesus Cuevas, Jose Terencio•
Hospital de Fontilles, Alicante, España• Hospital La Paz, Madrid, España.

A study was carried out on a group of cu red lepromatose leprosy patients who turrei spontaneously to Mitsuda's test, and it was compared histologically to tne granulome in Mitsuda's reaction from another group or also cured tuberculoid leprosy patients.

As parameters for the study, H-E tincture, the proteines S-100, CD-68_f MAC-387, Muramidase HLA-DR, CD-3, CD-4, CD-8, CD-19 and CD-20 were used.

The results obtained are compatible with the reaction or granulomatose type caused by Mitsuda's reaction in tuberculoid leprosy.

These patients of lepromatose leprosy snow an evident histological change, coming close to the tuberculoid pole and suggesting the possi bility of immunological change.

Maria Quintana, Mª Jose Enguidanos, Jose Terenci. Hospital Fontilles, Alicante, España.

A research was carried out on a group of 43 cured leprosy patients: 32 of them belonged to the lepromatose leprosy type, I6 of whom showed spontaneous positivity to Mitsuda's reac tion; the other I6, who remained negative, were used as a control group. The rest (11) was a group of patients of tuberculoid leprosy used as a control.

A group of 9 healthy, Mitsuda positive peo ple who lived with the patients was also taken as a control.

In cellular immunity, the parameters CD3, CD4, and CD19 were studied; as for humoral immunity, the immunoglobulines IgA, IgM, IgG and the subtypes lgGl, IgG8, IgG3 and igG4, as well as the interleukines IL-2, IL-4 and IL-10 and the Gamma-interferon were considered.

In spite of the causative agent being the same i.e., M. leprae, different individuals manifest leprosy in different forms ranging from paucibacillary tuberculoid pole to multibacillary lepromatous leprosy. To study the genetic factors which determine the immune response to an antigen or infectious agent, HLA-DRB1, DQA1 and DQB1 were studied in tuberculoid (TT), borderline lepromatous (BL) and lepromatous leprosy (LL) patients and compared with normal controls. While DRB1*1501 was significantly increased in patients of all types of leprosy, other alleles at DRB1, DQA1 and DQB1 loci seem to play a significant role in determining the type of leprosy one develops after infection. Since peptides presented by different MHC molecules have allele specific motifs, different peptides of M. leprae get presented by different HLA molecules, resulting in differential immune response to the causative agent and hence differential manifestations of the disease. The detailed analysis of hetero-dimers and trans-mers will be presented.

Paul Roche , Warwick Britton# and Robert Cole* Mycobacterial Research Laboratory. Anandaban Leprosy Hospital. PO Box 151, Kathmandu. NEPAL, # Centenary Institute of Cancer Medicine & Cell Biology, Sydney, AUSTRALIA and * ICT Diagnostics, PO Box 228, Brookvale. NSW, AUSTRALIA

A rapid immunochromatographic tests was devised for the qualitative detection of human antibodies to Mycobacterium leprae. The test consists of a folding cardboard device containing a nitrocellulose strip and anti-human IgG attached to colloidal gold particles. The 35kDa M. leprae protein expressed in recombinant M. smegmaus (Triccas et al 1996. Infection & Immunity 64:1571) was immobilised across the nitrocellulose strip. When 30 μl of serum or plasma is added to a pad it diffuses across the 35kDa protein and specific IgG antibodies bind. Upon closure of the test card, the anti-human IgG attached to colloidal gold particles binds to the bound IgG producing a distinct pink line within 15 minutes.

When tested with leprosy patients serum, 23% of PB and 100% of MB patients gave positive responses. When compared with a conventional ELISA using the 35kD antigen and a cut-off determined by the mean plus 3 SD of a pooled normal serum, the test cards had a 74% sensitivity and 100% specificity. This rapid and specific antibody test may be useful in countries with low endemicity of leprosy where delays in diagnosis are common.

NEUTROPHILS ISOLATED F ROM LEPROSY PATIENTS EXHIBIT ACCELERATED APOPTOSIS IN VITRO AND RELEASE TNFα AND IL-8

Oliveira, RB., Sarno, EN., Moraes, MO. Oliveira EB., Almeida, AS., Sampaio EP. Leprosy Laboratory. Oswaldo Cruz Foundation. Av. Brasil. 4365 - Manguinhos. Rio de Janeiro - RJ, Brazil.

This study demonstrated that poly morphonuclear neutrophils (PMN) participate in the acute inflammatory response in some way as effector cells. Reactional lepromatous patients (Type II reaction or ENL showed in the lesion intense infiltrate of neutrophils. Polymorphonuclear cells of nonreactional patients, health donors, and reactional patients were purified and analysed. Human neutrophils were purified from the peripheral blood by Ficoll-llypaque density centrifugation and dextran sedimentation. The cells were suspended in RPMI 1640 (Gibco BRL) supplemented with 10% fetal bovine serum. According to Trypan blue dye exclusion tests, upon purification around 100% of PMN was viable. The first phase of the study confirmed the short lifespan of these cells in culture in addition to progressive changes characteristic of apoptosis. Apoptosis was greatly accelerated in ENL patients as shown by morphologic analysis, which was later confirmed by DNA fragmentation and quantitative analysis. Analysis of TNFα production in culture supernatants was performed by specific Elisa after 18-20h of stimulation. It was observed that neutrophils stimulated with LPS synthesize and secrete TNFα and IL-8 in significant quantities. Thalidomide a drug known to inhibit TNFα synthesis on monocytes also exerted an inhibitory effect on LPS-induced TNFα secretion in neutrophils. It was also demonstrated that neutrophils stimulated with M. leprae e LAM-ML secreted IL-8. TNFα gene expression was analyzed by Northern blot hybridization. The capacity of neutrophils to synthesize and secrete cytokines after stimulation by mycobacterial products suggest that these cells participate in the regulation of the immune response. In addition, the ability of reactional these cells to release TNFα suggested that they could be involved in the amplication of TNFα production at the site of leprosy lesions (ENL).

CLOFAZIMINE INTERFERES WITH T-LYMPHOCYTE ACTIVATION IN VITRO. Martins MVBS. Sarno EN. Sampaio EP. Leprosy Laboratory Oswaldo Cruz Foundation. Av. Brasil. 4365 - Manguinhos. Rio de Janeiro - RJ. Brazil

Recent studies in our laboratory have demonstrated that clofazimine, an anti-microbicidal and anti-inflammatory drug, has a multiple effect on the regulation of the immune response firstly, clofazimine, but not thalidomide, showed in vitro an inhibitory effect on the in vitro proliferation of T cells, an effect which appeared to be irreversible. It was demonstrated that IFNγ production in these cultures was inhibited as well. The goal of the present study was to determine if clofazimine in any way interfered in the expression of activating molecules (CD25. CD69. HLA-DR. and B7) in PBMCs activated with PHA. It was shown that clofazimine was only able to inhibit the expression of CD25 (IL-2 receptor) In addition, it was decided to investigate whether either lymphocytes or macrophages were the target cell responsible for or that interfered with the action of this drug. As a first step, lymphocytes and macrophages were incubated separately for 1-3 hours with different drug concentrations (5. 25 and 40 μg ml). After the incubation period, the cells were washed reconstituted with lymphocytes and macrophages (without clofazimine) respectively and stimulated with 1% PHA (in the absence of the drug). The results showed that only the cultures which had the lymphocytes that were pre-incubated with clofazimine showed inhibited proliferation.

In the second part of the study, the effect of clofazimine on the secretion of inflammatory cytokines was investigated. The kinetic of TNFμ production in culture supernatants of monocytes and PBMC stimulated in vitro with LPS 1μg ml, in the absence or presence of clofazimine was determined. Inhibition of TNFα protein synthesis was noted within the first three hours of culture. Interestingly this effect was bypassed during longer periods and. at 20 hours, no effect of the drug on TNFα production was seen.

SERUM ANTIBODY TO A SYNTHETIC PEPTIDE ANTIGEN OF THE 85B MYCOBACTERIUM LEPRAE PROTEIN COMPLEX IN NEWLY DIAGNOSED LEPROSY PATIENTS

An ELISA for the quantitative determination of serum antibody to Mycobacterium leprae was developed using a synthetic peptide as antigen corresponding to the amino acid sequence 256 -280 of the 85B protein complex, a major and well conserved M. leprae antigen.

This test was applied to the sera of newly diagnosed leprosy patients, i.e. 14 multibacillary (MB) and 13 paucibacillary (PB) cases as well as to 11 healthy household contacts (HHC) and 11 endemic controls (EC) Results were compared to those of the PGL-I ELISA using phenolic-glycolipid disaccharide serum albumin (D-BSA) as antigen. Sensitivity of the peptide ELISA was 43% for MB leprosy and 46% for PB leprosy as compared to 100% and 23% respectively of the PGL-I ELISA. Using PGL-I ELISA the reactivity was 36% for HHC and 18% for EC, resulting in a specificity of 82% (EC only) and 59% if both HHC and EC are considered The respective specificity of the peptide ELISA was 64% for EC and 59% for HHC and EC combined

It is concluded that the detection of serum antibody directed against the 85B peptide is not useful in the diagnosis of leprosy because of the low sensitivity and specificity of the test.

EARLY LOCAL & REGIONAL EVENTS IN THE 2º RESPONSE OF RHESUS MONKEYS TO M. LEPRAE.

Thomas Lemarchand¹. Marion Ratterree². Bobby Gormus² and David Scollard³. ¹Department of Veterinary Pathology, Louisiana State University, Baton Rouge, LA.; ²Tulane Regional Primate Research Center, Covington. LA.; ³Research Branch. GWL Hansen's Disease Center at LSU, Baton Rouge, LA.

Background: Previous studies have indicated differences between simian immunodeficiency virus-infected (SIV+) and SIV- rhesus monkeys, with regard to T-cell recruitment and function during the first month after their initial exposure to M. leprae.

Objectives: The 2º immune response was studied in 9 animals inoculated 18 months earlier with M. leprae; 3 were also SIV+. The percentage of CD45RO+ 'memory' T- cells was determined at new M. leprae inoculation sites, in lymph nodes and in blood .

Design: Fresh M. leprae (10⁷/site) were injected intradermally at 12 sites (4 per limb). Biopsies were taken at 2, 5, 8, 12, 26 and 62 days post-inoculation; biopsies of lymph nodes and samples of blood were taken at days 0, 5, 26, and 62. Tissues were minced and filtered, and suspensions were analyzed by 3-color flow cytometry for CD45RO+/CD4+ and CD45RO+/CD8+ cells.

Results: A weaker granulomatous response was seen in the SIV+ group. In both SIV- and SIV+ animals, a small increase in CD45RO+ cells occurred in the skin at day 5 in both CD4+ & CD8+ subsets. A larger increase in CD45RO+ cells was observed in both subsets, in skin and lymph node, at day 62.

Conclusions: SIV+ animals are less capable of producing a granulomatous secondary 2º response to M. leprae and have lower CD4+ cell counts at inoculation sites, in draining lymph nodes, and in blood. Nevertheless, they are able to recruit CD45RO+ 'memory' T-cells to skin and lymph nodes in the 2º response to M. leprae, in a pattern comparable to that of healthy rhesus monkeys.

SEROLOGICAL DIAGNOSIS OF LEPROSSY USING FULL THICKNESS SKIN CULTURES IN VITRO: A PRELIMINARY STUDY,

Although specific serological assays using PGL-1 and 35kD antigens of M. leprae have been developed both of these specific assays fail to detect a significant level of antibody against M. leprae in clinically established cases of leprosy. It was noted that in early stages of infection (TT/BT leprosy) only 40 to 60% of patients show positivity to these assays. When the antibody levels against whole M. leprae was measured in such patients it was further noted that 40% of TT/BT leprosy do not show a significant level of antibody. This finding led us to look for antibody measurement locally in skin lesions. Methods were established to measure antigen and antibodies in skin smear suspensions taken from skin lesions of patients. It was noted that 100% of TT/BT patients were positive for antibody. To know the mechansim of local antibody secretion a full thickness skin culture has been established and all types of leprosy lesions were found to liberate antibodies in vitro in the tissue culture. The kinetic of antibody response in vitro from TT/BT and BL/LL skin lesions have been noted and the mechanism is being understood immunohistologically using B cell markers. These studies would further provide an insight into the mechanism of local immunity and in establishment of a diagnostic assay for early cases of leprosy.

IN VITRO THALIDOMIDE IS AGONISTIC TO THE SYNTHESIS OF IL-2 AND FREQUENTLY ANTAGONISTIC TO THE SYNTHESIS OF TNF-α IN ENL AND HIV SEROPOSITIVE PATIENTS.

Shannon. E. J, Pankey. G., Aseffa, A., Sandoval. F. Webster, K. Laboratory Research Branch. GWL Hansen's Disease Center at Louisiana State University, Baton Rouge, La., Ochsner Medical Center, New Orleans. La., Clinical Branch. GWL Hansen's Disease Center. Carville. La. U.S.A.

Recently, there has been a resurgence of interest in thalidomide (thal). Contributing factors to this renewed interest arc the numerous reports of thal's

successful use in the treatment of conditions other than INL such as aphthous ulcers in patients with AIDS. The mechanism by which thai attenuates these inflammatory conditions is unknown, but modulation of inflammatory cytokines like IL-2 and TNF-α possibly plays a key role.

Prior to treatment with thal, peripheral blood mononuclear cells (PBMC's) and plasma were obtained from 4 patients with ENL and 6 HIV seropositive patients. After the patients had ingested a cumulative dose of 800 mg of thaI (48h) a second sample of blood and PBMC's were taken . The PBMC's were exposed for 2 h to 4.0 μg/ml of thaI and stimulated with 50 ng/ml of staphylococcal enterotoxin A (SEA). After 16 h the culture supernatant was assayed for TNF-α and IL-2.

In the four patients with ENL, prior to ingestion of thaI, comparing the concentration of the cytokines in the SEA-stimulated cell cultures to those treated with thaI and SEA. the thaI and SEA cultures had an average increase of 163 pg/ml of IL-2 (range 397-9 pg/ml). TNF-α was decreased by an average of 95 pg/ml (range 154 to 71 pg/ml) in 3 patients and increased by 550 pg/ml in one patient. The concentration of IL-2 in the plasma prior to ingestion of thai was 10 ± 11 pg/ml and 15 ± 12 pg/ml at 48 h. The concentration of TNF-α was 60 ± 54 pg/ml prior to ingestion of thaI and 67 ± 49 pg/ml after 48 h. In a similar protocol in six HIV seropositive patients, the thai and SEA-treated cultures had an average increase of 182 pg/ml of IL-2 (range 392 to 58 pg/ml). TNF-α was decreased by an average of 78 pg/ml (range 215 to 62) in 5 patients and increased by 84 pg/ml in one patient. The concentration of IL-2 in the plasma prior to ingestion of thalidomide was 29 ± 15 pg/ml and 19 ± 15 pg/ml after 48 h. The concentration of TNF-α in the plasma prior to ingestion of thaI was 9 ± 5 pg/ml, and 4 ± 3 pg/ml after 48 h. After 48 h. when unhydrolyzed thaI achieved an average concentration of 2 ± 0.5 μg/ml in the plasma, the results from the in vitro studies on the cytokines from the cultured cells was highly variable.

ThaI, in vitro enhanced the ability of SEA-stimulated cells to produce IL-2, and it frequently suppressed the ability of the same SEA-stimulated cells to produce TNF-α.

THALIDOMIDE CAN MODULATE THE ABILITY OF MONONUCLEAR CELLS TO INCORPORATE [³H]-THYMIDINE WHEN STIMULATED WITH M. LEPRAE ANTIGENS.

Shannon. E.J.¹ Sandoval, F.¹, Harris. E.B.¹ Laboratory Research Branch, GWL Hansen's Disease Center at Louisiana State University, Baton Rouge. La.¹, U.S.A.

Thalidomide is capable of modulating the immune response. The exact mechanism by which it modulates and suppresses erythema nodosum leprosum (ENL) is unknown. In this study, M. leprae was incubated with mononuclear cells from a donor naive to M. leprae, a lepromin-positive, healthy individual and a patient with ENL. Four μg/ml of thalidomide was added into the cultures at the initiation of the incubation period and was replaced daily to maintain an estimated concentration of >0.5 μg/ml of unhydrolyzed thalidomide. After 6 days [³H]-thymidine was added into the cultures and the cells harvested the next day. When cells cultured in the absence of M. leprae and thalidomide were compared to those cultured in the presence of M. leprae, the M. leprae -exposed cells from the lepromin-positive individual and the ENL patient were stimulated in their ability to incorporate [³H]-thymidine. When cells cultured in the presence of M. leprae were compared to cells cultured in the presence of thalidomide and M. leprae, incorporation of [³H]-thymidine was dramatically inhibited in the cells from the lepromin-positive individual and significantly enhanced in the ENL patient. The presence of M. leprae or thalidomide had no effect on the ability of the cells from the naive individual to incorporate [³H]-thymidine.

THE POSSIBLE ROLE OF INTERLEUKIN (IL) 12 AND INTERFERON-γ-INDUCING FACTOR/IL-18 IN PROTECTION AGAINST EXPERIMENTAL MYCOBACTERlUM LEPRAE INFECTION IN MICE

Ram Pyare Singh, Masanori Kai, Masa-ichi Gidoh, Noboru Nakata, Masumi Endoh, Kazuo Kobayashi, and Hajime Saito

Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama-shi, Tokyo 189-0002, Japan

Cell-mediated immunity participates in host defense against mycobacterial infection. Both interleukin 12 (IL-12) and interferon-γ-inducing factor (IGIF/IL-18). produced mainly by macrophages, play a critical role in expression of cell-mediated immunity. To investigate the role of IL-12 and IGIF/IL-18 in vivo, we examined cytokine profile, bacterial growth and the potential benefit of cytokine therapy in genetically susceptible and resistant mice infected with M. leprae. The early expression of IL-12 p40 and IGIF/IL-18 at the site of inoculation was found in resistant mice 3-72 hr after the infection, but not in susceptible mice Both strains of mice did not show expression of IFN-γ and IL-4. IL-12 administration resulted in a significant reduction of bacterial loads in mice with XL leprae infection. The results imply that susceptible mice exhibit decreased expression of type 1 helper T (Th1) response without reciprocal increased Th2 response and show responsiveness to exogenous IL-12. IL-12 therapy may be a possible rationale for treatment of M. leprae infection.

ANTIBODY RESPONSES WITH RECOMBINANT SELECTIVE SEQUENCE BASED PEPTIDES IN HUMAN LEPROSY PATIENTS

Dept of Biotechnology, All India Institute of Medical Sciences @, Leprosy Mission Hospital #, New Delhi, 110029 India, and *Present address: Dept of Bioregulation, Leprosy Research Centre, National Institute of Infectious Diseases,Tokyo 189 Japan

Lepromatus leprosy patients(LL) and border line (BL) patients develop Type-2 and Type-1 reactions approximately 10-15% respectively. ENL (erythema nodosum leprosum) type 2 reactions are episodic, and are responsible for significant morbidity in lepromatus leprosy patients. These reactions are a prime source of morbidity and occurs before or during treatment with anti leprosy drugs. At present there is no method by which patients prone to reactions can be identified prior to onset of reactions. Such a distinction is mandatory for appropriate therapy. The aim of the present study is to evaluate MLS antigen and other sequence specific recombinant peptide as a predictor /marker of reactional states in leprosy using conventional ELISA.

To determine the immunological specificity between the different types of leprosy including ENL, we investigated the antibody responses to MLS ( M. leprae derived sonicated antigen), recombinant peptide 2 and peptide 3. These peptides are 10-15 mer overlapping peptides synthesised on the basis of LSR amino acid sequence. We have observed that there is a selective recognition of B cell epitopes with ENL as compared to control groups. Of significance was more than 90% patients of ENL sera were recognised by recombinant peptides 2 and peptides 3. The amino acid sequences of recombinant peptide 2 and peptide 3 were GVTYEIDLTNKNAA and IDLTNKNAAKLRGD respectively. MLS antigen recognised all most all of the patients sera The core sequences IDLTNKNAA arc common in both the peptide and this may be a major target of antibody responses in ENL and lepromatus leprosy patients in Enzyme-Iinked immunoabsorbent assay(ELISA). These recombinant sequence specific peptides may be useful as a markers in diagnosis of early ENL.

Mariane MA Stefjni; Celina MT Martelli; Otaliba L Morais-Neto; Pierpaolo Martelli; Maurício B Costa and Ana Lucia SS de Andrade¹

Instituto de Patología Tropical e Saúde Pública -UFG Brazil; ¹Communicable Disease Program, Pan American Health Organization-WHO, Washington D.C., USA.

Anti-PGL I assay is currently applied for leprosy conceited as an early marker of asymptomatic infection, early disease diagnosis and cure monitoring. Its use as prognostic marker of reaction is still a matter of controversy. We conducted a case-control study to investigate whether IgM and IgG anti-PGL I antibodies could discriminate patients at increased risk of developing reactions, Eligible cases were untreated leprosy patients at the onset of tvpe-1 and type-2 reactions recruited from among 600 concurrent newly detected untreated leprosy patients attending outpatient clinic in Central Brazil. For each patient with reaction approximately the same number of leprosy cases without reaction matched to bacilloscopic index (Bl), age and gender was randomly selected. Individuals without clinical leprosy were evaluated as healthy controls. Sera from type-l reaction patients (N=43) and type-2 reaction (N=26) were tested by ELISA using PGL I synthetic disaccharide - BSA antigen and 1:300 sera dilution (cutoff point S0.2 OD). Antibody profiles were evaluated by exploratory data analysis and reserse cumulative distribution curves. IgG anti-PGL I response did not have a defined pattern being detected in low levels. Our results indicate that leprosy patients, independently of their reactional status, produce high levels IgM anti-PGL I demonstrating a strong correlation between the magnitude of antibody response and bacilloscopic index (Bl). Patients with higher Bl were at least 3.4 times more prone to produce antibody response compared to healthy controls.

Frequency of ifnγ Secreting Cells in the Peripheral Blood of Leprosy Patients Depends on the Clinical form of the Disease and Show a Dominant cd4+ Phenotype. Salgado, JLF¹; Sampaio. EP¹ Hernandez, MO¹; Moreira, RO²; Ferreira, AP² ; Sarno. EN¹. Teixeira, HC²

1- Leprosy laboratory, FIOCRUZ. Rio de Janeiro-RJ
2- Immunology laboratory, ICB, UFJF. Juiz de Fora. MG

It is well known that IFNγ is a critical cytokine involved in controlling resistance to many intracellular pathogens In the present study. IFNγ production by peripheral blood mononuclear cells (PBMC) of leprosy patients in response to M. leprae antigens or mitogens, were investigated using the ELISPOT and ELISA methods. In vitro depletion studies using monoclonal antibodies (MACs method) were employed to determine the role of CD4^• and CD8^• cells in IFNγ production In addition, cytokine production was compared to the lymphoproliferative response of the PBMC studied. Our results show that: (i) frequencies of IFNγ producing cells in response to M. leprae antigens were high in PBMC of TT, BB and in reactive BL patients (fl/1000); (ii) increased numbers of IFNγ - SFC (ELISPOT) are correlated with the detection of IFNγ in the supernatants (ELISA) and. with on exception, with the in vitro proliferative capacity of the PBMC. (iii) in all individuals tested, numbers of IFNγ SFC were increased after in vitro stimulation with PHA; (iv) PBMC of LL patients failed to produce IFNγ in response to M. leprae antigens, in comparison to reactive BL patient; (v) in vitro treatment with anti-CD4 Mab but not anti-CD8 Mab reduced (2-fold) antigen specific IFNγ production in 4/4 reactive BL patients. Our results underline the important role of CD4 cells and the marginal contribution of CD8 cells to IFNγ production in leprosy patients; and suggest that M. leprae induced IFNγ production is selectively decreased in multibacilary LL patients, but is enhanced during reaction.

Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India, * Institute of Pathology, New Delhi, India and ** Department of Dermatology, Safdarjung Hospital, New Delhi, India

The role of antigen presenting cells was investigated in Th like responses in lepromatous leprosy patients. T cells, dendritic cells (DC) and monocytes (Mo) from PBMCs were separated on antibody coated magnetic bead columns using both positive and negative selection methods. Subsequently T cells were combined with 1 or 10 % DC or Mo, cultured for 24 hours in the presence of M. leprae antigen and assayed for mRNA expression of IFN-gamma IL-4, IL-10 and IL-I2p40 using RT-PCR to reverse transcibe for cDNA and amplify by specific primers using polymerase chain reaction. Concurrently, quantitation by means of 32 P labelled probes was undertaken for IFN-gamma and IL-4. The results indicate that dendritic cells promoted expression of IFN-gamma even at 1 % concentration. IL-4 mRNA was not detectable in the majority of cultures. Conversely it was not possible to detect IFN-gamma signal in parallel T + Mo cultures from the same subject.

CUTANEOUS DELAYED-TYPE HYPERSENSITIVITY RESPONSIVENESS IN LEPROMATOUS LEPROSY AS DETERMINED BY MULTITEST CMI

• Department of Immunology and Medicine, US Army Medical Component, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand, and Leonard Wood Memorial Center for Leprosy Research (American Leprosy Foundation), Cebu, Philippines

MULTITEST CMI is a disposable, plastic applicator with 8 sterile tines pre-loaded with 7 recall antigens and a glycerin control. To assess cellular immune function in lepromatous leprosy (LL), 37 patients were examined with the MULTITEST CMI to evaluate cutaneous delayed-type hypersensitivity (CDTH) responsiveness before or during therapy. Of 26 newly diagnosed patients who had a MULITEST CMI applied before therapy (Group 1), 11 were responsive (> 2 antigens positive) and 15 were hypo-responsive (< 1 antigen positive). Nine of the 15 were re-tested after therapy began and 6 eventually converted to a responsive state. Eight of 11 patients already on therapy (2 months to 1 year; Group 2) at first MULTITEST CMI application were responsive; 2 others eventually converted. Eleven of 12 community or household contacts without clinical evidence of leprosy were responsive.

The MULTITEST CMI applicator provided an efficient, safe, reproducible, and relatively inexpensive method to determine CDTH responsiveness in LL and control subjects. Our findings indicated that most LL patients are able to generate a CDTH response to standard recall antigens, some becoming responsive after therapy initiation. This suggests that CDTH abnormalities are neither predisposing causes nor necessary accompaniments of LL, but probably represent remote sequelae of the disease.

Accu- d ng to the WHO-MDT we have carried out this study to know the invoIvement of HLA in leprosy. Seventy-two Southern Chinese Leprosy patients and 120 health subjectts as tho control were particion-ted in this study. HLA-A. -8 and - C were serologically typed by using a standard iciucytotoxicity test, and HLA-DR2 sub-types and MHC class I chain-realted A (Ml CA) allels were typed at the DNA level by using the PCR-SSCP method.

The frequencies of HLA-B57 antigen were significantly increassed, and those of HLA-B46 antigen were significantly decroased, in the Ieprosy patients as compared with the control group (P<0, 01), The frequencises of HlA-DR2 antigen and its subtypes in the patients showed a higher tendancy than those in the controls, bat there were no significant differences. In addition, the freqq ... of MICA alieles were not significantly different. However. the patients with 957-MICAS. Y has ' ... were significantly increased. and those with B46- MICAS haplotyce were decreased, when compared with the control group (p<0.01).

This study slows that the leprosy is this district is significantly associated with particular HLA - B/ MICA haplotypos(positive assocition with 857-MICA5. I and negative assocition with 846-MICA5. These ... suggest that an HLA- linked disease - control gen for the leprosy in Southern China may be Iocated ... the HLA- S/MICA region and not in the HLA - DR Iocus.

ANALYSIS OF IN VITRO T-CELL RESPONSES TO CANDIDATE M. LEPRAE SKIN TEST ANTIGENS IN LEPROSY PATIENTS AND CONTROL SUBJECTS

London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK

²Department of Microbiology, Colorado State University. Fort Collins. CO 80523, USA

A sensitive and specific method for detection of subclinical infection in leprosy remains a priority for leprosy control. Development of a tuberculin-like skin test to identify M. leprae- exposed subjects would be the most practical approach for use in leprosy endemic areas. This may be achieved by isolation of M. leprae specific peptides, or by defined fractionation of the bacillus. A new approach to fractionation of M. leprae has yielded two fractions depleted of lipoarabinomannan (LAM). These fractions, derived from M. leprae cell cytosol (MLSA-LAM) or cell wall (MLCwA-LAM) were tested in a whole blood assay, to assess in vitro T-cell responses in Nepali leprosy patients, and in endemic and non-endemic (UK) control subjects. The fractions proved to be potent T-cell antigens, inducing high proliferation and IFNγ responses in paucibacillary leprosy patients and leprosy contacts. However, lepromatous leprosy patients did not respond. Responses in control subjects indicated that exposure to cross-reactive antigens in other mycobacteria may compromise the M. leprae specificity of these fractions. An alternative approach, to analyse differential responses to equivalent fractions derived from both M. leprae and M. tuberculosis was also explored. These field studies have demonstrated the utility of the whole blood assay in epidemiological studies as an indicator of T-cell responses, prior to in vivo skin test trials.

A STUDY ON THE METHODS FOR EARLY SEROLOGICAL DIAGNOSIS OF LEPROSY AND THEIR POTENTIAL USE

Oin-xue Wu, Xin-yu Li, Yue-ping Ying Hui-wen Su, Wan-hui Wei, Qi Liu and Ganyun Ye Institute of Dermatology, CAMS and PUMC, Nanjing City. China

The authors have established 11 methods for early serological diagnosis of leprosy, including FLA-ABS test, ELISAs with artificial products (ND-O-, ND-p-, NT-O-, NT-p-BSA, PGL-I, whole M. leprae and M. smegmatis), monoclonal antibody specific binding assay (McAB/SBA), latex agglutination test (LAT) and MLPA. These methods were compared each other on a large scale in leprosy patients in the field.

The results indicated that: 1)the excellent results were obtained when ELISAs were conducted with skim milk or egg albumin as blocking agent and by using blood from ear lobes instead of those from venipuncture; 2) according to 4 "S" standard (sensitivity, specificity, simplicity and speed), ND-O-BSA-ELISA (ND-ELISA) was proved the best and MLPA more suitable for use in the field due to its simple procedure and quick reaction; 3) in ND-ELISA, the increase or decrease of OD value was positively correlated with Bl, and the order of positive rates (PR) was LL>BL>BB>BT>TT and household contact > random population > normal control of endemic area > normal control of nonendemic area; 4) in population of subclinical infection with M. leprae, the highest risk group was 15 - 25 years age group with an increase or a persistance of high OD values prior to the onset of disease. 5) OD values were gradually decreased as the treatment goes on and these declines run parallel with the declines of BI. 6) in cases cured with DDS monotherapy, an increase or a persistance of high OD values in ND-ELISA occurred prior to the onset of leprosy relapse.

In conclusion, the authors have developed 11 immuno-assays and have proved ND-ELISA as the most practical one in investigating early detection of disease, in monitoring antimicrobial therapy and even in predicting relapse of leprosy.

ANTI-LEPROSY PROTECTIVE VACCINATION OF MONKEYS WITH BCG AND BCG PLUS HEAT-KILLED MYCOBACTERIUM LEPRAE: IMMUNOLOGIC OBSERVATIONS

Rudolf P. Bohm. Pamela A. Mack. Marion S. Ratterree, Sang-Nae Cho, Wayne M. Meyers and Gerald P. Walsh

Groups of rhesus and sooty mangabey monkeys (RM & SMM) were vaccinated and boosted with BCG or BCG + low-dose (LD) or high-dose (HD) heat- killed Mycobacterium leprae (ML) or were unvaccinated. Prior to and following vaccination-boosting and subsequent ML challenge, these and unvaccinated-unchallenged monkeys were observed longitudinally for several years. Paucibacillary (PB)-prone RM were significantly protected clinically by BCG or BCG + HKML; multibacillary (MB)-prone SMM were partially protected by BCG alone, but were rendered clinically more susceptible by BCG + HKML. Clinical interpretations were supported by phenolic glycolipid-I (PGL-I) antigen levels in plasma. Highly significant blastogenic responses (to lepromin, Rees antigen, ML 10Kd protein & tuberculin) were seen in all 3 vaccinated RM groups post-vaccination (PV), post-boosting (PB), immediately post-inoculation (PI) with ML and 2 years PI. Similar responses to ML antigens occurred mostly in BCG + HKML groups of SMM PV and PB; suppression of some responses occurred in SMM approximately 2 years PI. Blood lymphocyte subsets with the following phenotypes significantly changed in vaccinated vs unvaccinated ML-challenged SMM and RM: CD2, CD4, CD8, CD16, CD20, CD4CD29 and CD4CD45. Patterns of changes in the subsets differed between the 2 species. Serum IgG vs IgM anti-PGL-l responses supported our prior observations that serum IgG anti-PGL-l responses favor protection while IgM responses correlate with susceptibility to leprosy. Lepromin skin testing confirmed successful long-term immunization of RM and failure to induce significant responsiveness in SMM by these immunizations. SMM immunized with BCG + LDHKML had significantly suppressed lepromin skin-test responses 33 months post-ML challenge. The immune response to vaccination with HKML and/or BCG is complex, multifaceted and dose-dependent. BCG protects individuals who are susceptible to either PB or MB leprosy; BCG + HKML protects PB-prone and heightens susceptibility in MB-prone individuals.

IDENTIFICATION OF SPECIES-SPECIFIC ANTIGENIC DETERMINANTS OF M. LEPRAE IN CULTIVABLE MYCOBACTERIA

O.S.Salamatina, M. N.Dyachina, O. A. Kalynina, L.N Chernojusova. O.V.Kalyanina, M.Y.Yushin

Leprosy Research Institute, Astrakhan. Central Research Institute of Tuberculosis. Moscow. Russia

At the present stage of leprology in some countries great efforts are aimed at searches for cultivable mycobacteria having close antigenic relationship with M. leprae so to use them as vaccine and diagnostic preparations in leprosy. With using immunoblotting we studied antigens of mycobacteria isolated from tissues of lepromatous leprosy patients (M.01, M.011) and cultivated in vitro on Shkolnikova's nutrient medium modified with perfluorine decaline as well as antigens of M. lufu, known as highly susceptible to dapsone. For identification following six clones of MAbs to M. Ieprae antigens obtained from WHO Bank were used: anti-12KDa mc8908-MLO6-A. anti-18 kDa mc8026-L5, anti-36 kDa mc5828-F47-9-36, and mc9215-IIIE9. mc5205-11H9 and mc2404-IVD8 against three epitopes of 65kDa-protein. For reference, a sonicate of M. Ieprae isolated from nine-banded armadillos (WHO Bank) was used. The obtained results were following. In antigenic reference-preparation proteins of molecular weights 12, 18, 36 and 65 kDa (IIIE9) were identified. 36 kDA-protein was detected in M.01 and M. lufu. 12 kDa - in M.011 and M. lufu. MAb mc2404-IVD8 actively interacted with 65 kDa in M.01 and M.011. Presence of antigenic determinants specific for M. leprae in mycobacterial strains under study might suggest their antigenic relationship with M. Ieprae. hence, necessitating further investigation of their biological properties.

DETECTION OF MYCOBACTERIUM LEPRAE IN NASAL SECRETIONS OF HOUSEHOLD CONTACTS OF MULTIBACILLARY AND PAUCIBACILLARY PATIENTS

TP- Gillis¹, E.V Tan², D.L. Williams¹, M.F. Balagon², R.V. Cellona² and G.P. Walsh²

¹Molecular Biology Research Department, Laboratory Research Branch, GWL Hansen's Disease Center at LSU, P.O. Box 25027, Baton Rouge, LA and ²Leonard Wood Memorial Center for Leprosy Research, Cebu City, Philippines.

It is generally accepted that one mode of transmission of M.leprae is via aerosols originating from infected individuals shedding M. leprae through the nose. Workers have reported either acid-fast bacilli (AFB) or PCR-positive nasal secretions from MB and PB patients. To better understand the risk of exposure to M. leprae from index cases we evaluated nasal carriage rates among household contacts (HHC) of MB and PB cases in Cebu, PI. Two hundred and forty-two HHC of both treated and untreated MB and PB index cases were enrolled in the study. Evidence of M. leprae in secretions by PCR was found in 8 of the 242 HHC (3.3%). Two of 8 of the contacts were positive from both nasal swabs and their serum tested positive for PGL-I antibody. All

PCR-positive HHC were at least 18 years old and were contacts of either LL or BL index cases. PCR-positive contacts lived with their index cases between 2-21 years. Whereas 2 index cases of the positive HHC were untreated LL's, the remaining index cases had either finished WHO-MDT or were currently under treatment with the same or a combination of rifampin and ofloxacin. All contacts of PB disease tested negative by PCR. Further serial testing of nasal secretions from contacts is warranted in an attempt to distinguish a true carrier state from transient contamination.

USE OF PCR MEDIATED AMPLIFICATION OF MYCOBACTERlUM LEPRAE IN DIFFERENT TYPES OF CLINICAL SAMPLES AND SEROLOGY IN LEPROSY PATIENTS AND CONTACTS.

¹Torres P., Gómez J.R., Gimer.o V., Terencio J., ²Camarer.a JlJ., Nogueira J.M., Navarro J.C., Olmos A.

¹ Sanatorio San Francisco de Borja. Fontilles (Alicarte),
²Servicio de Microbiología. Hospital Dr. Peset. Universidad de Valencia.

The purpose of this study is to determine the usefulness of different clinical samples obtained from skin lesions with slit-skin smears before and after biopsy, ear lobes and nasal swabs together with serum samples in different stages of the disease and compare the results of each group with the less sensitive conventional methods.

Samples were obtained from 54 leprosy patientos (42 muItioacillary and 12 paucibacillary) and 37 contacts (12 household contacts and 25 leprosarium staff members). The smear and histopathological stainings were done by the classical methods. The PCR primers used were S-13 and S-62 (Hartskeerl et al.1989) that amplify specifically the 530 bp fragment of the proline-rich (pra) gene of M. Ieprae. The serological assays include detection of antibodies to phenolic glycolipid I (PGL-I), LAM-B and protein antigens by enzyme-linked immunosorbent assays.

The results reveal that PCR was more sensitive in detecting M. Ieprae in biopsy and slit-skin smears specimens with no or low bacterial loads than the conventional microscopic examination and that the serological assys also correlated well with decrease of the bacterial index (BI) suggesting their usefulness for following leprosy patients responses to therapy.

A COMPARATIVE STUDY OF THE DETECTION OF Mycobacterium leprae BY PCR-BASED METHODS

Two "freezing-thawing" methods were used to extract genomic DNA from M. leprae and compared. The primer combination of Rl & R2 and C6 & C7 was chosen for subsequent amplification by PCR. PCR reaction volume was reduced proportionally to 50, 20 and 10ul from the original volume of 100ul. Two PCR amplification methods (Woods and Cole, 1991; Jamil et al., 1994) were compared by using the purified M. leprae genomic DNA. Both methods were able to detect M. leprae in human skin punch biopsy samples with at least Bl = 3.0 and MI = 0.2, microscopic density count = 2+, and viability count = 1/85. Both methods had also detected M. leprae DNA in human skin punch biopsy samples that were kept at -20ºC for up to 7.5 years. Of 46 biopsy samples from leprosy patients. 45 were tested positive by the method of colorimetric OTN PCR. They had Bl from 0.7 to 5.6 and MI from 0 to 24.3; and their homogenates had microscopic density counts from 0 to 5+ and viability counts of 0/100 to 9/91. Of 33 biopsy samples collected from household contacts (with suspicious skin lesions) of leprosy patients, 19 were positive by colorimetric OTN PCR. This study showed that the bacterial suspension from human skin punch biopsy could be used as an alternative material in colorimetric OTN PCR, if the skin biopsy sample was not available. Finally, no correlation was found between the colorimetric OTN PCR and IgM-phenolic glycolipid (PGL) ELISA.

IDENTIFICATION OF STRAIN VARIATION IN M. LEPRAE BY AMPLIFIED RIBOSOMAL DNA FINGER PRINTING.

V.M.Katoch. V.D.Sharma, H.B.Singh, K. Katoch, M. Natrajan, D. Singh, R.K.Sharma and L.S.Chauhan

With the widespread use of MDT, there have been major changes in the epidemiology of leprosy. However, continued high incidence rates and persistent foci of disease point to the need of developing techniques for eliciting strain variation for studying the transmission of disease. Our earlier observations and data published by others suggested some strain differences within M. leprae. In this study different primer combinations targetting ribosomal gene region have been tested for eliciting these differences. Biopsies from different types of leprosy cases attending the OPD of our Institute belonging to different geographical locations were collected. Nucleic acids were extracted and fractionated by a physiochemical technique being used at our laboratory. Different stretches of rDNA gene region were amplified, restricted with different enzymes and probed with rRNA probes by our earlier published methods. One fragment encoding most part of 166 rRNA and spacer sequences has been finally selected as this showed maximum variation. Using this strategy different subgroups within M. leprae have been identified. Results indicate that amplified rDNA-RFLP analysis can be used as a tool for molecular epidemiology of the leprosy.

DETECTION OF MYCOBACTERIUM LEPRAE BY POLYMERASE CHAIN REACTION IN NASAL SPECIMENS OF LEPROSY PATIENTS AND HOUSEHOLD CONTACTS

The University of Texas Southwestern Medical School, G.W. Long Hansen's Disease Center, Baton Rouge, Louisiana

Several Hundred new cases of leprosy are diagnosed annually in the United States. The route of transmission is hypothesized to be by aerosolization of bacteria present in the nasal cavity. To investigate nasal carriage and transmission of M. leprae, nasal secretions were collected serially from patients, contacts, and controls. Samples were analyzed by standard microscopic technique to detect acid-fast bacilli. In addition, nasal samples were analyzed by a M. leprae specific PCR assay.

The test is based on the amplification of a 360-base-pair region of an 18-kDa protein gene of M, leprae. Use of a molecular assay with enhanced sensitivity and specificity will allow detection of M. leprae nasal carriage in individuals potentially with subclinical infection as well as patients with clinical disease. Preliminary results from 21 patients and 28 household contacts have been PCR negative.

To our knowledge, this is the first study that will provide data concerning carriage and transmission of leprosy in a non-endemic area.

Qin-xue Wu, Lao Li, Yue-ping Ying, Xin-xu Li. Wei Hou Jing-ping Zhang, Xiu-ling Chi, Gan-yum Ye Institute of Dermatology . cams and PUmc . Nanjing. China

Authors have conducted a comparative analysis of nested primer gene amplification assay (NPGAA), PCR basing on ML gene coded 65kd (ML-PCR) and PCR basing ML gene coded 16s rRNA (16s rRNA-PCR) for detecting infection with M. leprae (ML). In view of sensitivity, specificity, tune consuming, substrate saving and practical value. ML-PCR was finally selected as first choice.

Considering ML-PCR was the best one of three PCRs established by us, it was futher used for studying on the optimum conditions and the factors influencing sensitivity of ML-PCR. The results indicated that 1) the sensitivity of ML-PCR was increased 100 folds when this PCR's denaturation and annealing temperature to be changed into 91 C and 61 C respectively. 2) the repeated freeze-thawing is the best method to release DNA from ML several tests used in our laboratory. 3) MI and Bl were positively correlated with the detection rate of PCR ( DRP ). 4) the DRP was higher in slit-skin scrapings than those in skin lesion biopsies of leprosy; and 5) the DRP was decreased after chemotherapy in mice and nude mice.

The authors concluded that. 1) although all the mentioned PCR tests were highly sensitive and specific, comprehensive comparative analysis indicated that ML-PCR may be qualified as a representative method for detecting infection with ML. 2) although PCR technologies were advanced and their parameters basically were definited. it is still in need of studies on optimization; 3) DRP was influenced with many factors, for example. DNA amount releasing from bacilli, viability of bacilli, chemotherapy and modes of taking specimens from leprosy patients.

It has recently been shown that the immune system is capable of responding to oligonucleotide motifs which are present in bacterial DNA. These motifs contain "CpG" dinucleotides at their core. Since mycobacterial DNA is GC rich one would predict that such motifs would be relatively common and hence that mycobacterial DNA should have powerful adjuvant properties. We have studied the immunostimulatory effects of synthetic oligo-nucleotides based on mycobacterial "CpG" motifs in the priming of the immune response.

Because dendritic cells are the principal antigen presenting cell in peripheral tissue, we have studied the response of primary or conditionally immortalized dendritic cells following exposure to synthetic oligo-nucleotides based on mycobacterial sequences. We have detected the specific induction of cytokine genes including IL-12, IL-6 and interferon alpha/beta after exposure to such DNA. One of these motifs is present in the repetitive sequence which is found in multiple copies in the M. leprae genome. We have also shown that co-immunisation of mice with purified mycobacterial proteins and immunostimulatory oligonucleotides induces a strongly TH1-dominated response to the protein.

properties of mycobacteria are not confined to the cell wall, but also extend to the mycobacterial genome. Such properties are likely to play a key role in the immunopathogenesis of leprosy.

PCR ASSAY FOR THE DETECTION AND IDENTIFICATION OF M. leprae IN PATIENTS IN THE UNITED STATES.

Background: The differentiation of leprosy from other cutaneous granulomatous diseases is routinely based on characteristic histopathologic features and the demonstration of M. leprae by acid-fast staining. Increased ascertainment of other mycobacterial infections in the skin has made this task more difficult, but the distinction remains fundamental in selecting appropriate treatment.

Design: Experience with formalin-fixed & paraffin embedded tissues, frozen tissues, and tissue lysates referred for M.leprae- PCR during the past four years has been reviewed. PCR was performed using primers and probes previously developed (TPG & DLW) to amplify a 360 bp fragment of the gene for an 18 kD protein of M. leprae.

Results: Among 32 biopsies, PCR was positive in 8/16 diagnosed as leprosy, and in 0/13 diagnosed as non-leprosy by histopathologic criteria. PCR also identified M. leprae in 1/3 biopsies in which acid-fast organisms were seen but leprosy was not diagnosed histologically.

Conclusion: In a non-endemic population, the sensitivity and specificity of this technique recommend its use primarily to identify M. leprae when acid-fast organisms are discernable but atypical clinical or histopathologic features obscure the diagnosis.

Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523 U.S.A. and Fundação Oswaldo Cruz, 21045-900 Rio de Janeiro, Brazil.

Definition of the genome of M. leprae has been matched by similar progress in defining the in vivo expressed proteins. The genome project identifies open reading frames, i.e.. genes for potential proteins identified as such by comparison with genes in other organisms. However, the proteome project identifies actual protein end-products that govern the immunogenicity and pathogenesis of the organism and can provide antigens for assay development. The approach involves the separation of highly purified, armadillo-derived M. leprae into its subcellular components (cytosol, membrane, and cell wall). The proteins of these fractions are separated by 2-D PAGE and selected products excised for in gel digestion with site-specific proteases. The resulting peptides are resolved by reversed-phase HPLC, directly analyzed by electro-spray mass spectrometry, and the molecular ions of these peptides searched against existing databases, thus allowing for identification of the whole protein by way of matches to calculated molecular ions of theoretical peptide fragmentation patterns. To date, about 50 major expressed proteins have been identified, some previously recognized, for instance: 65 kDa/GroEL-2; 10 kDa/GroES; 28 kDa/Sod A; 18 kDa heat-shock protein; 18 kDa/ MMP Il/bacterioferritin; 35 kDa/MMP II; antigens 85 A,B,C; L7/L12 ribosomal protein; CysA/thiosulfate sulfur transferase/rhodanase; AphC/alkyl hydroperoxide reductase; the protein elongation factor EF-Tu; a homolog of the MtrA response regulator; and a 34 kDa pseudolipoprotein. Recombinant forms of these are being generated to provide a new array of tools applicable for study of the immunopathogenesis of leprosy and for diagnosis. Supported by NIAID/DMID Contract NOl AI 55262.

Morten Harboe and Harald G. Wiker Institute of Immunology and Rheumatology. Fr. Qvamsgt. 1, N-0172 Oslo, Norway

In mycobacteria secreted proteins represent a distinct group, probably of particular importance for immune responses following infection. Quantification of individual proteins in culture fluid and corresponding disrupted washed bacilli permits determination of a Localization index (LI) which is essential for identification of secreted proteins. LI is >5 for soluble secreted proteins and close to 0 for known cytoplasmic constituents like heat shock proteins. This procedure cannot be applied for M. leprae since secreted proteins are lost during isolation of bacilli from tissues. Occurrence of the secreted antigen 85 in M.l. was first shown by formation of corresponding antibodies in armadillos with systemic infection after inoculation with M.l . (Wiker, Int Arch Allergy 81:307, 1986) . We have now compared DNA sequences of the cloned secreted proteins of M. tuberculosis with the available sequences of M.l. The close proximity between the 85a and mpt51 homologues also occurs in M.l ., the distance being 185 and 167 base pairs (bp) in M. tb and M.l . respectively. Additional sequences are available in M.l. corresponding to the 85b, 85c, mpt32 (apa), and erp genes of M. tb. All contain typical signal sequences for secretion in M.l. In M. tb. the distance between 85b and mpt32 is 26,178 bp with mpt32 on the complementary DNA strand. In M.l. the corresponding genes are located on the same cosmid, B38, with a similar distance of 23,032 base pairs, and again on different DNA strands. The 24.1 kDa lipoprotein of M. tb. also has a homologue in M.l. The genomic organisation of the genes coding for secreted proteins is thus very similar in M.l. and M.tb, the homology being higher for the mature polypeptide chains than for the corresponding signal peptides.

Yue-ping Ying, Suzuki Yasuhiko, Makino Masanao. Qin-xue Wu, Wei Hou Institute of Dermatology. CAMS and PUMC. Nanjing. China

The α antigen gene is one of the dominant mycobacterial proteins that are secreated from the mycobacteria One of the most interesting features of α antigen is antigencity against T and B cells in patient infected with Mycobacteria The authors have locused on α antigen as antigens for sero-diagnosis of leprosy because of their antigenitity

In the course of this study. the authors have constructed the genomic library of M. leprae Thai 53 strain, cloned a new α antigen gene with a plaque hybridization method using DNA fragment of M. leprae α 1 antigen as probe which was characterised in the previous study, the authors termed it as α 2 antigen gene The α 2 antigen gene has been characterized by sequencing From the results, α antigen of M. leprae have turned out to be members of gene family like M. bovis, BCG and M. tuberculous By comparing of the deduced amino acid sequence of α antigen with 85 complex antigen of other mycobacteria, the authors have found the homology as 74,3% - 85%

Our previous investigations demonstrated a number of common biological properties in M. lufu, M. leprae and cultivable mycobacteria isolated from tissues of leprosy patients and designated as M.01 and M.011. The mentioned mycobacteria showed comparable indices of their sulphone susceptibility (MIC 1,1 and 4 mkg/ml, respectively). With using different methods, such as precipitation reactions. ELISA and tests on sensitized guinea pigs it was found out that M. Ieprae, M. lufu, M.01 and M.011 shared common antigens and had similar protein spectra. Intracutaneous injections of M. lufu, M.01 and M.011 in to mice 28 days before M. Ieprae inoculation resulted in a marked protective effect (the highest degree of protection (log10 average harvest in controls minus log10 average harvest in test groups) was 2,96 for M. lufu, 2,26 - for M.01 and 2,73 - for M.011. Blood samples from 158 subjects including leprosy patients along the whole spectrum of the disease, patients with other infectious diseases and healthy donors were investigated in ELISA and it was found out that preparations made of M. lufu and M. Ieprae had antigens interacting with specific antibodies from blood samples of leprosy patients suggesting antigenic similarity of M. lufu and M. Ieprae. A comparison between test-systems developed on the basis of antigens of M. lufu and M. Ieprae showed comparable specificity (98.5% and 97,0%) and effectivity (98,6 and 97,2%) of both tests at 100% sensitivity. The results obtained appear to be rather interesting and promising for further development of diagnostic and vaccine preparations based on M. lufu.

Gene Vaccination for M leprae hsp65 using plasmid DNA carrying ImmunostimuIatory Sequences.

Hiroko Nomaguehi , Tin Maung Aye , Yasuko Yogi , Haruki Okamura , Masanao Miyata and Yukio Sato

1)Leprosy Res. Center, NIIP, Tokyo Japan. 2)Eyogo Medical College, Hyogu Japan. 3) Fukushima Medical College, Fukushima, Japan.

Recently in has been popular using DNA vaccines. The method is more easier to manufacture, provide prolonged antigen expression and when co-delivered with costimulatory molecles, enhance the subsequent response to the DNA-encoded antigen compared with conventional protein vaccines.

We constructed the recombinant DNA for expression of M. leprae hsp65 using pACB which carry two immunostimulatory DNA sequences located within ampicillin resistance gene. The BALB/cA mice vaccitiated with the recombinant DNA were sacrificed for analysis of immune responses against M. leprae by splenocytes and macrophages cultivation. IFN-γ was produced from splenocytes culture of the vaccinated mice, and enhanced by co-cultivation with M. leprae lysate or hsp65 in vitro.

This result suggest that hsp65 is useful protein antigen against defense for M. leprae infection, and this method is a good technique for development of vaccines.

Calcutta University College of Medicine and # Jadavpur University, Calcutta, India

The basic problems of immunity in LL and non-TT cases of leprosy are highlighted by defects in the cell mediated immunity, a progressive hyperbacillimea, a harmful persistent immune-complex state which actually protects the lepra bacilli, rather than killing them, a macrophage granuloma reflecting a surrender to the leprosy bacillus, and massive bacillary invasion of almost ail tissues and organs. In theory and practice, experimental evidences show that immunological unresponsiveness of LL cases to leprosy bacillary antigens can be partly or wholly changed to a positive response by various permutations and combinations of BCG, other mycobacteria and leprosy bacillus, modulated by immuno-boosters. Such responses may also be long lasting. The immunological failure reflected by lepromin anergy, immune complex and macrophage granuloma formation, may be corrected substantially, firstly by reducing the bacterial load using chemotherapy and subsequently various combinations of immunotherapy ; this will help achieving lepromin positivity and conversion of the cases by recruiting appropriate subsets of the T-cells. An in vitro grown killed culture of the leprosy bacillus will be the most suitable ingredient of all combination vaccines. Our studies show that these in vitro cultures (CAN bacteria) have same immunological specificity

as the leprosy bacillus. Selective chemotherapy is a suitable adjunct based on in vitro sensitivity tests. As of today, all studies indicate that the CAN bacteria are in vitro cultivated forms of leprosy.

IN VITRO DETERMINATION OF ANTIMICROBIAL SUSCEPTIBILITY OF MYCOBACTERIUM LEPRAE BY THE MICROPLATE ALAMAR BLUE ASSAY

Laboratory Research Branch, Gillis W. Long Hansen's Disease Center, P.O. Box 25072, Baton Rouge, LA 70894

The Alamar Blue reagent, an oxidation-reduction indicator, was used to assess antimicrobial activity of drugs against the non-cultivable M leprae in axenic medium in 96-well plates. 10⁷ M. leprae/well were exposed to antimicrobial agents for 1-2 weeks at 33C under ambient or microaerophilic conditions. Alamar Blue reagent was added and the reduced form of the dye was measured fluorometrically after 48 hours incubation and compared to that of drug-free cultures. Marked dose responses were observed to rifampin and clarithromycin, both effecting a significant reduction in fluorescence at 39 ng/ml. Dapsone was also active at this concentration while sparfloxacin, minocycline and ofloxacin showed significant inhibition at 62.5, 125 and 500 ng/ml respectively; Alamar Blue is an inexpensive, non-toxic dye which can be used to rapidly determine the viability and drug susceptibility of M. leprae.

Stewart Cole, Nadine Honore, Andrea Thomas* and Paul Roche* Unite de Genetique Moleculaire Bacterienne, Institut Pasteur. Paris. FRANCE and * Mycobacterial Research Laboratory. Anamlaban Leprosy Hospital. Kathmandu. NEPAL

Rifampicin is the key bactericidal drug in multi-drug therapy (MDT) for leprosy. Resistance to rifampicin is rare in leprosy and measurement of rifampicin resistance is dependent on the mouse foot pad assay which is rarely applicable to the detection of resistance in patients relapsing after MDT. The mutations of the rpoB gene associated with rifampicin resistance in Mycobacterium leprae have been identified and employed in a novel line probe assay. PCR amplification of the rpoB gene from skin biopsies from reactivated/ relapsing leprosy patients was followed by hybridisation to oligonucleotides complementary with the wild-type gene and with 5 of the point mutations which account for 70% of the recognised mutation in rifampicin resistant leprosy. Binding to oligonucleotides was visualised by binding streptavidin-alkaline-phosphatase to the biotin labelled PCR product and incubating with chromagen. The application of this test to the detection of rifampicin resistance and preliminary results from relapse patients in India and Nepal will be presented.

Molecular Biology Research Department, Laboratory Research Branch. GWL Hansen's Disease Center. School of Veterinary Medicine. Louisiana State University. P.O. Box 25072, Baton Rouge, Louisiana 70894

Dihydropteroate synthase (DHPS), encoded by folP, is a key enzyme in the folic acid biosynthesis pathway of bacteria which catalyzes the condensation of para-aminobenzoic acid (PABA) and 7,8-dihydro-6-hydroxymethylpterinpyrophosphate to form dihydropteroate. Sulfonamides are a class of drugs that act as substrate analogues competing with PABA and thereby, exerting their antimicrobial effect. Dapsone (DDS). a sulfonamide analogue, is an effective antileprosy drug; however, resistance to this drug is quite high in some regions of the world with the potential for undermining current control strategies for leprosy. The mechanism of DDS resistance in Mycobacterium leprae is unknown, however, it is thought to be associated with DHPS. We have previously cloned the putative folP from a DDS-susceptible strain of M. leprae into a DHPS temperature sensitive mutant of E. coli (MC4100ts3) and showed that expression of this gene product complemented the folate pathway at 42ºC. Three possible mechanisms of DDS resistance directly associated with DHPS in M. leprae were investigated: 1) missense mutations in folP leading to an altered DHPS. 2) folP gene amplification leading to overexpression of DHPS and 3) mutations in promoter-like regions upstream of folP which may up regulate DHPS. Comparison of folP sequences from DDS-resistant and DDS-sensitive M. leprae strains showed no differences. Restriction fragment length polymorphism analysis using a folP probe and Stul digests of chromosomal DNA from DDS-resistant and DDS-susceptible strains of M. leprae showed that one copy of the folP gene was present in all strains, indicating that gene amplification was not a mechanism for DDS resistance in Si. leprae. Comparison of promoter-like regions upstream of folP from DDS-sensitive and resistant strains showed no sequence differences. Therefore, these data suggest that resistance of M. leprae to DDS is not directly associated with overexpression of folP based on gene amplification, altered promoter activity or an altered structural folP gene in the DDS-resistant strains analyzed in this study.

RIFAMPICIN RESISTANT MYCOBACTERIUM LEPRAE ISOLATE F ROM JAPANESE PATIENTS AND MUTATION IN rpoB GENE

Masanori Matsuoka,• Yoshiko Kashiwabara,• Masaichi Gidoh,• Masanori Kai, • Shinji Maeda,• Noboru Nakata,• Eiji Nagao •• and Kunihiro Kinjoh••

Many rifampicin resistant M. leprae have been detected and threaten the effective leprosy control. Genetic method might be useful for the early detection of resistant bacilli, since the mutation in the rpoB gene confers the rifampicin resistance. Two rifampicin resistant M. leprae were isolated from Japanese patients and nucleotide sequence of rpoB gene was deduced to clarify the causative mutation in the gene. Usefulness of the simple method for the detection of mutation was also apprised.

The nude mice were inoculated with 8.0 X 10⁵ or 1,0 x 10⁴ bacilli into the foot fad and fed on diets containing with rifampicin in the concentration of 0.01gm per 100gm of diet from 2months after infection. Bacillary growth in the rifampicin treated mice was compared to that in the untreated mice by 55 weeks after infection. The susceptibility to drugs was examined by mouse foot pad method or Buddemeyer system. One isolate was resistant to rifampicin, KRM 1648 and DDS. The mutation in the codon for serine-531 which resulted in the substitution to leucine was detected as in most resistant cases so far reported. Markedly different banding pattern in PCR-SSCP was depicted between wild type and the resistant isolate, Heteroduplex analysis revealed the two bands in the heterogeneous mixture of 305bp PCR products and single band in the homogeneous one. Another isolate was considered to be low resistant to rifampicin, however confirmation is in progress. The codon for glycine at 524 was changed from GGC to GGT, but no change in amino acid, silent mutation, was shown. Other point mutations were revealed in other regions of the gene. It is concluded that some genetic methods are applicable for detecting mutation in the gene, which confers rifampicin resistant, but susceptibility for the rifampicin must be confirmed by other methods such as sequencing.

K. Prabhakaran, E.B. Harris & B. Randhawa. GWLHD Center @ LSU, Baton Rouge, LA 70894-5072, USA

Mycobacterium leprae possesses a highly active enzyme that rapidly hydrolyses lysophospholipids. Lysophospholipids generated by host tissues are extremely reactive molecules that can lyse cell membranes and kill pathogenic organisms. The cell membranes of both prokaryotes and eukaryotes are mainly made up of phospholipid bilayers. Phospholipases that degrade phospholipids are classified according to the site at which each enzyme acts on the substrate molecule.

Phospholipase A₂ (PLA₂) comprises a diverse family of enzymes that cleave the sn-2 fatty acylester bond of glycophospholipids to yield a fatty acid and a lysophospholipid. PLA₂ has a central role in generating arachidonic acid that leads to the formation of thromboxanes and prostaglandins. We detected lysophospholipase in M. leprae by a sensitive radioisotopic method. Optimum activity was at 37ºC and at pH 6.0. Temperatures above 70ºC completely inactivated the enzyme. The compound AAC0CF3, a trifluromethylketone analog of arachidonic acid, inhibited the activity. The inhibition appeared to be of the uncompetetive type. The K_m of the enzyme was 2.5x10^-4M, suggesting a fairly strong affinity for the substrate. Lysophospholipids have been shown to be microbicidal to invading organisms. Possession of lysophospholipase by M. leprae apparently is one of the mechanisms which enables the bacilli to survive and proliferate in the phagocytic cells of the host.

STRUCTURAL ANALYSIS OP THE HIGH MOLECULAR MASS PENICILLIN-BINDING PROTEIN 1 OF MYCOBACTERIUM LEPRAE

Two high molecular mass multimodular penicillin-binding proteins (PBPs) of class A have been previously identified from the collection of ordered clones of Mycobacterium leprae, produced and characterized in Escherichia coli. PBPl behaves as a PBP of low penicillin affinity. Deletion of the N-terminal amino acids suggested that a region between residues 39 and 81 probably functions as a membrane association site. Deletion of the C-terminal 164 amino acids did not affect membrane association. Deletion of the non-penicillin -binding (n-PB) module led to production of a truncated PBP localized in inclusion bodies. The PBP was solubilized with guanidine-HCl and refolded in a renaturation buffer. Refolding was confirmed by measuring intrinsic fluorescence of unfolded and refolded forms. The truncated PBP showed kinetic properties similar to the intact PBP. This is the first report of a class A PBP retaining penicillin-binding activity after removal of the n-PB module. This PBP appears to be a low-affinity penicillin target unique to mycobacteria; since a protein with amino acid sequence similarity has recently been identified in a cosmid of M. tuberculosis. The fact that it retains activity as a soluble protein carrying the PB module only, should facilitate future X-ray crystallographic studies on this target.

SOME BIOCHEMICAL FEATURES OF THE INTERACTION OF MYCOBACTERIUM LEPRAE WITH LAMININ. Marques MAM. Brennan PJ* and Pessolani MCV. Laboratório de Hanseniase. Fundação Oswaldo Cruz. Rio de Janeiro. Brazil. 21045. *Department of Microbiology. Colorado State University, Fort Collins. CO. USA. 80523

The neural tropism of M.leprae has been recently attributed to the specific binding of the leprosy bacillus to laminin 2 (LN2). a LN isoform preferentially distributed on the Schwann cell basement membrane (Rambukkana et al., Cell 88: 811-821.1997). However, the molecule on M. leprae surface responsible for laminin binding is still unknown. In order to characterize the laminin receptor of the leprosy bacillus, we investigated several biochemical features of M. leprae -laminin interaction. By using microliter wells coated with the bacilli, we confirmed the capacity of soluble LN2 to bind to M. leprae. Enhanced binding capacity of laminin was observed with purified cell wall of the bacilli, indicating a surface location for this receptor. Also, binding of LN2 to M. leprae was reduced by treatment of the bacterial cells with proteinase K or trypsin, suggesting that the binding to this basement membrane protein is mediated by bacterial surface proteins Since phenolic glycolipid I (PGL-l) is abundantly present on the surface of M.leprae, we also investigated a possible role of this molecule on the interaction of LN2 with the bacteria. Preincubation of LN2 with PGL-1 resulted in significant enhancement of LN2 binding to the bacteria. These prelimmary results suggest that LN2 binds to proteins located on the surface of M.leprae and that PGL-I enhances the binding of LN2 to these proteins. Three independent approaches are currently being undertaken in order to isolate the laminin receptor(s) from bacterial extracts: i) far western (gel-overlay), ii) laminin affinity chromatography, and iii) immunoprecipitation of laminin-receptor complexes.

Department of Microbiology, Colorado State University, Fort Collins. Colorado 80523. USA.

Mycobacteria] cell wall polysaccharides include cell wall arabinogulaclan (AG) and peptidoglycan (PG). AG is esterified at the distal ends with mycolates and covalently linked to a peptidoglycan layer at the reducing terminus. In our effort to address the structures of these molecules in M. leprae, walls of M. leprae were purified on a discontinuous sucrose density gradient. Purified cell wall cores were subsequently treated with mild base to remove bound mycolates and mild acid to release PG from the covalently linked AG. The mild acid-solubilized AG was fractionated using size exclusion column chromatography and analyzed using chemical derealization and mass spectrometry.

We have also undertaken the formidable task of digestion of peptidoglycan (PG) of M.leprae , since mycobacterial PG are known to be notoriously resistant to lysozyme. The acid-released peptidoglycan is reduced and subjected to degradation using several methods (acid hydrolysis, mutanolysin digestion, trifluoromethane sulphonic acid treatment). We hope to assign the primary structure of M. leprae PG using an integrated approach of LC/ESMS (electrospray mass spectrometry). A comparative study is also carried out using M.tuberculosis cell wall in order to address subtle differences/modifications between the cell wall components of these two mycobacterial species.

We are also studying the non-covalent bound cell envelope polysaccharides of M. leprae, such as the secreted arabinomannans, glucans and lipoarabinomannans, by examining polysaccharides isolated from infected and non-infected armadillo livers.

COMPARISON OF ASSESSMENT OF VIABILITY BY NORMAL MOUSE FOOT PAD, ATP MEASUREMENT AND PCR ASSAYS.

Various techniques for the estimation of M. leprae viability have been described. Mouse foot pad (MFP) is one of the old and main techniques for this purpose. Besides MFP, bacilllary ATP measurements and PCR assay have been used in this study to determine the viability. In this investigation, an effort has been made to compare the usefulness of these techniques to assess the therapeutic effect of a newer drug regimen comprising of conventional drugs as well as newer drugs like ofloxacin & minocycline in smear positive MB cases in the beginning and after completion of one year of treatment. Biopsies were processed for viability assessment by normal mouse foot pad (Shepard et al), bacillary ATP measurement (Katoch et al) and PCR assay (Williams et al) by the techniques established at this Institute. Comparison of results by these techniques in untreated as well as treated patients suggests overall good usefulness of MFP & ATP measurement in assessing the effect of the MDT including this regimen. ATP assay has been found to be more sensitive in cases with low bacillary load. PCR assay appears to be suitable only for knowing the trends.

Jadavpur University and # Calcutta University College of Medicine. Calcutta, India.

The CAN bacteria or chemoautotrophic nocardioform bacteria (CANb) had been reproducibly cultivated and propagated continuously from human, mouse footpad and armadillo leprosy tissues ; these had been repeatedly isolated. The CANb, like the leprosy bacillus (LB) are non-cultivable on any of the known/acceptable media, but grow only on chemically defined media containing (NH₄)⁺², liquid paraffin, urea etc. These have an identical mycolate profile, long generation time (Ca. 44 hr), nocardioform, weak acidfastness, identical mouse footpad pathogenicity, lepromin response(s) across the LL-TT spectrum and presence of PGL-I. Its possession of collagenase and gelatinase further identifies it with the LB. Its guanine auxotrophy possibly explains it s selective preference of the macrophage nucleus for scavenging it. Multiple molecular biological parameters applied on the CANb viz-a-viz the LB show these as two converging on identical points.

CRAM-POSITIVE COCCOID MICROORGANISMS CULTIVATED F ROM THE HANSEN'S DISEASE PATIENT SPECIMENS, AND M. LEPRAE.

Since Hansen, G.A., after observing the Hansen's disease (HD=Leprosy) bacillus in the lesions, made the first unsuccessful attempts to cultivate it outside the host, as reported by Terni (1950) in a long time back, a great number of research workers have claimed that they have succeeded while others even now are doubtful that it has been accomplished.

It is said that the microorganisms most commonly isolated and known as the results of pioneer research works of leprosy bacilli are included in following categories: (a) strains belonging to diphtheroid bacilli which were either non-acid-fast or only weakly acid-fast, (b) chromogenic acid-fast bacilli, (c) non-chromogenic acid-fast bacilli and (d) anaerobic bacilli or actinomyces.

Amongst such microorganisms, the Gram-positive coccoid organisms are of compelling interest as observed and examined by Delville (1973) and Chatterjee (1976). The organisms are easy to be stained with Gram's method and to be cultured on media. From the bacteriological observations of their properties, they may be seen at a glance as the so-called contaminants or various bacilli, though they show a cyto-morphological change in state from cocci to rod - from rod to cocci.

The present report is a result scrutinized the bacteriological observations of the Gram-positive coccoid microorganisms cultivated from the HD patient specimens and the bacteriological mutual relation to HD bacilli varied from Gram-positive to Gram-ghost or Gram-neutral and examined as the acid-fast bacilli stain red.

Modem Science Clinic for Biomedical Research
Rm. 303, SPE Bldg, 302-46 Dongbuichon-Dong, Yongsan-Gu
Seoul, 140-031, Korea

I reported that colony forming acid-fast organisms are isolated from armadillo spleen and nude mouse footpad infected with M. leprae and that these two organisms maintain their multiplication in 3% Ogawa media containing recombinant human interleukin-2 (IL-2).

Continued cultivation trial showed that these two organisms maintain their IL-2 dependency up to 15^th and 16^th generation, in case of armadillo and nude mouse originated M. leprae, respectively.

Next step of experiment was to identify these organisms with polymerase chain reaction (PCR) using M. leprae specific primers C & D and primers L1-L4 (nested PCR). These showed that the template of armadillo M. leprae DNA prepared at Colorado State University, USA. the template of nude mouse M. leprae prepared at National Institute for Leprosy Research, Japan, the 11^th generation isolated from nude mouse at my laboratory, and the 10^th generation isolated at my laboratory from armadillo spleen infected with M. leprae, all these 4 templates amplified the expected and the identical sizes of DNA fragments (372bp in case of primers C & D; 347bp with primers L1-L4).

Quantitative PCR showed that 10⁹ fold multiplication of the 11^thgeneration (isolated at my lab from a nude mouse footpad infected with M. leprae) for 2 months after the inoculation. The control culture tube without IL-2 showed 10^-2 fold for the same time period.

Also, the M. leprae template prepared with the 10^th generation culture isolate from armadillo spleen amplified a 390bp DNA fragment in a PCR using γ3 & γ10 primers specific for human IL-2 receptor γ chain gene. This PCR product was sequenced successfully and further studies such as cloning and the DNA hybridization are under investigation to identify the full IL-2 receptor gene sequence in M. leprae.

A novel procedure in the cultivation of M. leprae in combined Dubos-Lowenstein-Jensen medium after addition of thyroxine sodium is being reported. This has been found to be successful as the organisms, after multiplying vigorously in thyroxine containing Dubos medium, have produced a visible colony on the surface of L.J. slant during 8-16 weeks of incubation at 37ºC. The enhanced growth of this recalcitrant organism is due to stimulating effect of thyroxine as well as supply of readymade basic nutrients in the Dubos medium. Intradermal inoculation of bacterial suspension from the subculture into the footpadof cortisone treated swiss mouse revealed an early appearance of specific histological lesion of leprosy with infiltration of nerve fibres by lepra cells. The methodology, described here for in-vitro cultivation of M. leprae, may open out a new era in preparation of purified vaccine, production of specific monoclonal antibody and study of in-vitro drug sensitivity, and as such ensure rapid eradication of leprosy.

INHIBITION OF METABOLISM AND GROWTH OF MYCOBACTERIUM LEPRAE BY GAMMA-IRRADIATION

L.B Adams,¹ N.A. Soileau,¹ R. Fajardo,¹ J.R. Battista,² and J.L. Krahcnbuhl¹

GW Long Hansen's Disease Center, Baton Rouge. LA, USA¹ and Louisiana State University, Baton Rouge, LA, USA²

Mycobacterium leprae is an extremely slow growing organism, having an in vivo doubling time of-12.5 days. In vitro, it is uncullivable on artificial medium, but viability can be maintained, without multiplication, for a limited time. Traditionally, incubation at 100ºC or autoclaving has been used to kill M. leprae for experimental use. Both of these methods cause extensive denaturation and damage to the bacilli. In this study, we evaluated gamma-irradiation (γ-rad) as a means to kill this slowly growing organism. Freshly harvested, viable athymic nu/nu mouse-derived M. leprae were exposed to varying doses (10² to 10⁶ Rad) of γ-rad in a Sheppard Model 484 ⁶⁰Co irradiator. The cultivable, environmental mycobacterium, M. lufu, was used as a control. To assay metabolic activity, both species were inoculated into the BACTEC 460 system which measures the oxidation of ¹⁴C-palmitic acid to ¹⁴CO₂. Growth of M. leprae was evaluated using the proportional bactericidal mouse foot pad assay. Growth of M. lufu was evaluated by plating serial dilutions on 7H11 agar plates for enumeration of colony forming units (CFU). γ-rad of both M. leprae and M. lufu resulted in a dose-dependent inhibition of metabolic activity, γ-rad of up to 10³ Rad had no effect on the oxidation of palmitic acid by either organism. With M. leprae, 10⁴-10⁵ Rad caused an intermediate inhibitory effect, whereas 10⁶ Rad yielded almost total inhibition of metabolic activity. With M.lufu, in contrast, 10⁵ Rad inhibited metabolic activity by 99%. However, culture of γ-rad M. lufu showed that while 10⁵ Rad caused > 2 log reduction in the number of CFU, ~ 10⁴ CFU/ml survived, γ-rad of 10⁶ Rad sterilized the culture of M. lufu as no CFU were recovered. The effect of γ-rad on growth of M. leprae is currently being evaluated. These data suggest that γ-rad may be an efficient way to kill M. leprae without causing extensive damage to the cell architecture, as opposed to boiling or autoclaving. Killing M. leprae by γ-rad may be preferable when comparing cellular responses to live versus dead bacilli in vitro and in vivo.

S. Suresh Babu and P.R. Mahadevan Malladi Research Centre, Ekkattuthangal, Chennai-600 097. India

Gene fusion expression technology has come a long way from the days of insoluble lacZ fusion constructs that were useful only as antigens. Today's fusion systems not only provide high levels of gene expression, but also often produce soluble and correctly folded fusion proteins that can be conveniently purified and efficiently cleaxed. Since mycobacterial transcription and translation signals are poorly functional in E.Coli, it is necessary to put the required gene under a strong and inducible promoter system to achieve the production of desired amount of the product If that expression system has a fusion partner, then, it provides high stability and solubility for the fusion protein with an opportunity to fold correctly instead of precipitating into inclusion bodies.

Delipidified Cell Component (DCC) of M. leprae has been shown to have immunomodulatory effect both in vitro and in vivo. By screening the λgt11 expression library of M. leprae with antibodies raised against DCC. various clones were selected. Out of these, one clone of 1.6 Kb length, expressing a protein of 25 kD showed functional properties similar to DCC

This gene was cloned into the E.coli gene fusion expression system with a fusion to Maltose Binding Protein (MBP) which is 42 kD. The fusion protein expressed was 67 kD indicating that the gene was coding for 25 kD protein. The expression level was high (~15-20% of the total soluble protein) and the purification was achieved by the affinity chromotography using Amylose resin. Factor Xa protease was used for cleaving at the junction of the fusion and the MBP was removed by repeating the Amylose resin affinity chromotography. The biotin-labelled Factor Xa was also removed from the sample by the immobilized streptavidin.

This purified product, which was part of the 65 kD hsp, was found to have similar immunomodulatory effect as DCC. By the use of internal restriction sites, this gene was further spliced into three distinct pieces, and cloned and expressed in the similar way as explained above. The MBP fusion system helped to make these peptides in large amount and by subsequent experiments the immunomodulatory effect of them was proved. Part of the work was done at the Foundation for Medical Research, Mumbai, India

Calcutta University College of Medicine and #Jadavpur University, Calcutta, India

Mycolate profile is used for identification of Mycobacterium spp. In this study, the pattern of mycolic acids have been studied in chemoautotrophic nocardioform bacteria (CAN b) derived from infected tissues of rat, human leprosy and tissues of epizootic ulcerative syndrome (EUS) - infected fish which also yielded a leprosy bacillus like pathogen. Closeness of the mycolate profiles of these 3 mycobacteria with that of different mycobacteria have been studied to distinguish these from each other, if possible, as well as other mycobacteria.

In this study, mycolates have been isolated from all the test bacterial samples by alkaline hydrolysis followed subsequently by thin layer chromatography. Spots were visualised by iodine vapour method.

CAN b, derived from human lepromatous tissues, showed the same profile as that of M. leprae and M. gordonae, containing three types of mycolic acids, namely, α , α' & β . Subsequently, CAN b derived from rat leprosy tissues and from tissues of EUS-affected fish showed α , α' & ω bands for mycolic acids, suggesting possible close proximities of these last 2 with that of M. avium rather than with M. leprae. The taxonomic value is evaluated.

MultimoduIar high molecular mass penicillin-binding proteins (PBPs), involved in bacterial peptidogrycan biosynthesis, are lethal targets of beta-lactam antibiotics. Peptidogrycan is one of the main structural component of mycobacterial cell wall. Identification of the genes of two high molecular mass PBPs in an ordered cosmid library of Mycobacterium leprae, overexpression of these genes in Eschericia coli and characterization of the expressed proteins reveal that these genes encode two PBPs, PBPl (M, 81 kDa) and PBP1* (M, 69 kDa). PBP1* is a high affinity PBP and is unstable at temperatures above 25ºC (Lepage et al ., 1997, J. Bacteriol 179, 4627-4630). PBPI is thermostable and binds penicillins with low affinity (Basu et al.. 1996, J. Bacuriol. 178, 1707-1711). This is reminiscent of the situation in E coli PBP. PBPla and PBPlb. Both M. leprae PBPI and PBPI* bear the nine motifs characteristic signature sequence of multimodalar bacterial class A PBPs at the same order and with the same spacing but their enzymatic and biochemical properties are markedly different. Critical analysis reveal that M. leprae PBPI contains an altered sequence in one of the domains of the penicilln-binding (PB) module. Similar altered sequence is also present in a low affinity PBP, PBP C of E. coli. This domain may be critical for penicillin sensitivity and the altered sequence may be related to the differences in the penicillin sensitivity and thermal stability of M. leprae PBPI and M. leprae PBPI*. The mycobacterial PBPs are the counterparts of the multimolecular class A PBPs, key components of morphogenetic networks. These studies are the first steps towards understanding the penicillin targets in mycobacteria at the molecular level. This knowledge is essential for future predictive studies on the interaction of new generation beta-lactams with the beta-lactam targets, and for the rational use of beta-lactams in antimycobacterial chemotherapy.

Arvind M. Dhople, Department of Biological Sciences. Florida Institute of Technology. Melbourne. Florida 32901. U.S.A.

We have presented earlier evidence on limited in vitro multiplication of M. leprae in DH medium. The growth has been extremely slow (about 20-30 fold increase in cell mass in 16-20 weeks), and terminated after 20-24 weeks. The growth was partly attributed to the presence of a growth factor that was demonstrated to be present in tissues of armadillos infected with M. leprae. The reason for the termination of growth was the accumulation of hydrogen peroxide in the growth medium during incubation. Addition of catalase in the DH medium did not alleviate the situation. Addition of ketonic acid, such as pyruvic acid, to neutralize hydrogen peroxide was also not helpful unless fresh pyruvic acid was supplemented every week. This resulted in extending the growth till 24 weeks with average growth of 55-65 fold. Still the growth was terminated after 24 weeks and subcultures were not possible.

Finally, the cultures were grown in Stirred Cells using 0.2μ membrane so that the fresh DH medium will be continuously supplemented at the same rate as the spent medium is removed from the chamber. This resulted in approximately 70 fold increase in cell yield in 24 weeks. The growth was enhanced further to approximately 100 fold by incorporating both catalase and pyruvic acid in the DH medium. Subcultures from these primary cultures in Stirred Cells could be achieved only when the growth factor was added to the DH medium along with catalase and pyruvic acid. However, the growth of subcultures in Stirred Cells could not be maintained beyond 10-12 weeks with maximum yield of 10-15 fold. Nevertheless, this is the first time we were successful in achieving subcultures of M. leprae. The studies are being continued further.

PRESENCE OF CALMODULIN-LIKE PROTEIN IN M. LEPRAE AND ITS IMPLICATIONS ON THE DEVELOPMENT OF NEW ANTILEPROSY DRUGS

Arvind M. Dhople. Department of Biological Sciences. Florida Institute of Technology. Melbourne. Florida 32901, U.S.A.

Calmodulin-like protein has been established as the primary receptor for calcium in eukaryotic as well as in prokaryotic cells. Calmodulin-calcium complex regulates a variety of enzymes including nucleotide phosphodiesterase. Recently, we have been able to show the presence of this protein in M. leprae harvested from armadillos infected earlier with human-derived M. leprae. Thus, studies were undertaken to evaluate the effects of calmodulin antagonists on the in vitro growth of M. leprae using the previously established DH medium. Among the six phenoihiazine-type calmodulin antagonists tested, trifluoperazine appeared to be the most potent in inhibiting the in vitro growth of M. leprae, with MIC of 10 μg/ml. Chlorpromazine, trifluopromazine and thioridazine were less active than trifluoperazine, with MIC of 20 ug/ml, while the other two, acetopromazine and fluphenazine were totally ineffective even at 80 μg/ml. These findings suggest that a methylpiperazinylpropyl group attached to the nitrogen at position 10 and trifluoromethyl group at second carbon confer the antileprosy activity to the phenothiazine molecule. Results from our preliminary studies based on the incorporation of ¹⁴C-acetate, ³H-thymidine and ¹⁴C-glycine indicate that the effect of trifluoperazine is on the synthesis of lipids. DNA and protein of M. leprae. (Supported through the funding from German Leprosy Relief Association).

MODELING ACTIVITY OF SINGLE DOSE COMBINATION REGIMENS BY SIMULATING HUMAN PHARMACOKINETICS IN MACROPHAGE CULTURES OF MYCOBACTERIUM LEPRAE

Since, with the exception of rifampin, the pharmacokinetics of the potent anti-leprosy drugs are markedly different in mice and humans, it is impossible to accurately simulate the drug concentration/time exposure in the latter by using a mouse model. Attempting to match the human AUC in most cases necessitates using a dose which results in a much higher maximum serum concentration (Cmax) than is possible in humans. The mouse model becomes even less representative when single doses of drug combinations are being assessed. The human pharmacokinetics of various combination regimens can be simulated by using M. leprae- infected mouse peritoneal macrophages. Cultures, in 24-well plates, are initially exposed to the expected drug concentrations following the customary doses of the corresponding drugs. At intervals of 4 hours or less, media is easily removed and replaced with fresh media containing drug combinations at concentrations which would be expected based on their respective serum half-lives. This process continues for several days until drug concentrations are at levels below the expected minimum inhibitory concentrations. After an additional week in macrophage culture without drugs, the macrophages are lysed and the viability of the released M. leprae are evaluated by radiorespirometry. Data will be presented on the relative inhibitory activities of combinations of rifampin, minocycline, ofloxacin, sparfloxacin and clarithromycin in addition to dapsone and clofazimine.

ELONGATION OF MYCOBACTERIUM LEPRAE IN MACROPHAGES CULTURED IN THE PRESENCE OF INTERLEUKIN-10

Y Fukutomi¹⁾, G. McCormick²⁾, J P Pasqua²⁾. J. L. Krahenbuhl²⁾, S. Toratani¹⁾, G. Matsuki¹⁾, and M. Matsuoka¹⁾

Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan¹⁾ and Laboratory Research Branch, GWL Hansen's Disease Center. Baton Rouge, LA, USA²⁾

Mycobacterium leprae, the causative agent of leprosy, is an obligate intracellular pathogen that prefers the mononuclear phagocyte as its host cell. Numerous efforts have been devoted to the in vitro cultivation of M. leprae since its discovery, yet the leprosy bacillus remains uncultivable. Difficulty in assessing the viability of M. leprae has also impeded leprosy research The availability of a constant supply of a large number of highly viable M. leprae from nude mice allowed us. to adapt radiorespirometry as a measure of the metabolic activity of M. leprae, affording a rapid (2 weeks), quantitative method to assess the viability of the leprosy bacillus in vitro.

In the present study mouse macrophages were infected in vitro with M. leprae from nude mice and were cultured Radiorespirometry data over 2 weeks showed M. leprae in macrophages at 31ºC to be more metabolically active than at higher temperatures, such as 37ºC Moreover addition of IL-10 to the cultures clearly sustained M. leprae metabolism in macrophages for 8 weeks. The apparent increase in number of M. leprae /macrophage was likely an artifact of loss and lysis of macrophage and re-phagocytosis of released M. leprae. Noteworthy, however, was the elongation of individual bacilli after 4 week-culture in macrophages maintained in media with IL-10 observed under light microscopy. Transmission electron microscopy also confirmed elongation of M. leprae in mouse macrophages sectioned after 4 weeks under the ideal culture conditions described above In addition armadillo macrophages cultured in vitro also supported metabolism as well as elongation.

GLOBAL EPIZOOTIC IN FISH BY A LEPROSY LIKE ACTINOMYCETE POSING A POTENTIAL HAZARD TO HUMAN HEALTH.

Presence of actinomycetic organisms have been reported in different varieties of fish affected with epizootic ulcerative syndrome (EUS) in India and elsewhere since 1988. The same organisms were isolated repeatedly from lesions of dermis, subcutaneous tissues, muscles and internal organs. Acid-fast bacilli, bacillary clumps, globi, mycelia, free acid fast bacilli (AFB) and 'Coccoid' bodies were present in the muscle tissues of fish, somewhat resembling human and rat leprosy bacilli. The characteristic macrophage granuloma surrounding these actinomycotic mycelia appeared to be consistent and compatible with actinomycetic pathogenicity. These isolates possessed fundamental similarities to the human isolates of chemoautotrophic nocardioform (CAN) bacteria, not cultivable in any common or conventional type of media. These could, however, grow easily on media for chemoautotrophy, composed of simpliest sources of C&N. These have been compared with the human leprosy bacilli on the basis of their morphological, staining, metabolic, and enzymological characteristics, lipid profile and PGL I specificity. All the above tests showed close parallelism between the CAN bacteria isolated from fish, rat and human leprosy infection. Thus EUS has not only posed a severe economic problem but also a potential hazard to fish handlers, fish mongers and even possibly fish eaters.

¹Molecular Biology Research Department, Laboratory Research Branch, GWL Hansen's Disease Center at LSU, P.O. Box 25027, Baton Rouge. LA and Infectious Diseases Section, Durham Veterans Affairs Medical Center, Durham. North Carolina

Nucleic acid sequence-based differentiation of microorganisms at the genus, species and strain level has fostered new approaches for comparative taxonomy, provided insight on mechanisms of microbial pathogenesis and exposed powerful markers for epidemiologic studies of infectious diseases. This approach has been informative for some mycobacterial species (MAC) and strains (M. tuberculosis). Systematic attempts to define DNA polymorphisms in M. leprae have met with limited success. While minor, independent polymorphisms have been identified in a few strains of M. leprae, a universal model based on genomic differences of M. leprae strains has not been demonstrated. We have applied restriction-fragment length polymorphism (RFLP) analysis, using numerous restriction enzymes and probes, as well as direct sequencing analysis of the 18kDa gene and the 16-23S rDNA internal transcribed spacer (ITS) region to evaluate similarities and differences between eleven strains of M. leprae. M. leprae strains originated from geographically distinct regions of the world (Philippines, Vietnam, US, Thailand, India) and the DNA from each strain was purified from bacilli either expanded in armadillos, nude mice or obtained directly from lesions of patients. In all instances RFLP patterns and DNA sequence comparisons between individually isolated "strains" showed exquisite homologies at all DNA sites studied, supporting earlier findings suggesting minimal divergence in M. leprae.

M. Ishaque. Institute Armand-Frappier. University of Quebec, Laval. P.Q; H7N 4Z3, Canada.

To determine the metabolically active state of various slow growing mycobacteria such as Mycobacterium leprae, M. lepraemurium and BCG, a rapid method was developed. M. phlei was used as a control. M. leprae bacilli were isolated from the nude mice foot pads while M.lepraemurium were recovered from C3H mice lepromata. BCG were grown on Sauton medium. M. Phlei were grown on Lowenstein-Jensen medium. Bacilli from various mycobacteria used in this study were purified by differential centrifugation and bacillary suspensions were prepared in 0.05 M phosphate buffer, pH 6.5. To determine the metabolically active state of mycobacteria two parameters namely oxygen uptake of bacillary suspensions and ATP content were used. By using this method, meaningful information concerning M. leprae, M. lepraemurium and BCG can be obtained in four hours while only one hour was required using M. phlei. The information gained could be very helpful for the in vitro cultivation trials as well as for the biochemical studies of slow growing M. leprae and M. lepraemurium. Bacillary suspensions which showed relatively higher rates of endogenous oxygen uptake and ATP concentrations were found to be in a better metabolically active state than suspensions exhibiting lower rates of oxygen consumption and ATP content. Suspensions showing higher rates of respiration when used for in vitro cultivation trials showed relatively better multiplication, though limited, of M. leprae and the bacilli maintained their morphology very well for 16-20 weeks.

Foot pad technique of M. leprae inoculation of mice (Shepard, 1960) permitted to study M. leprae survival in different environments. Through many years' experiments we succeeded in confirming a survival of M. leprae under the conditions when biopsies from untreated LL patients were put into 40% saline solution of glycerin (in refrigerator or at room temperature). In past this method was used for preserving viability of different organisms including M. lepraemurium (Marchoux, 1934; Chorine, 1934). At the moment of biopsy, then in three and subsequently in every six months M. leprae (10000) from lepromas were inoculated into 10 BALB/c mice by Shepard's technique. Inoculum and "harvests" were counted according to Shepard and McRae (1968). During the initial 12 - 24 months characteristics of M. leprae multiplication in mice foot pads (lag-phase, log-phase and plato phase) did not almost change in the most of cases. After 3-4 years of storing an amount of M. leprae increased more slowly. Preliminary results of these experiments were published in 1984. Maximal period during which it was succeeded to preserve M. leprae viability in 40% glycerin at room t was 12 years (longer experiments were not carried out). The results obtained could account for some unsolved questions of epidemiology and pathogenesis of leprosy. The method proposed is successfully used for transportation of infected tissues from leprosy patients without ice from any region of Russia to Leprosy Research Institute (Astrakhan) for studying. During a special study (Vishnevetsky & Juscenko, 1991) it was also proved that lepromas kept in 60-80% solution of glycerin at room temperature for 2-4 weeks remain suitable for enzyme and histochemical investigations.

DNA AMPLIFICATION FOR DETECTION OF LEPROSY AND ASSESSMENT OF EFFICACY OF LEPROSY CHEMOTHERAPY

Kowit Kampirapap, Paul R.Klataer, S. Wiriyawipart
Phra-Pradaeng Hospital, Samutprakarn, Thailand

PCR for the detection of M. leprae was applied to fresh skin biopsies and skin slit smears from 122 untreated leprosy patients. The PCR positivity rates in biopsies were 95.6% in MB cases and 44.2% in PB cases. Following 1 month of treatment MB cases declined by 54.3% and P3 cases by 61.8% of initial values. Six month values also declined from initial positivity rates to 50.3% and 53.8% of initial values in MB and PB,respectively. Larger declines in rate of positivity were seen for smear samples at 1 and 6 months in both MB and PB but overall PCR positivity rates were lower than biopsy rates for M. leprae.

CONFIRMATION OF DIAGNOSIS IN MONO LESION LEPROSY CASES BY GENE AMPLIFICATION TECHNIQUES

V.M.Katoch, V.D.Sharma, H.B.Singh, K.Katoch, M.Natrajan, D.Singh, R.K.Sharma, and D.S.Chauhan

With the successful use of WHO MDT there have been major changes in the profile of leprosy. Most of new emerging cases present with single lesions. It is difficult to diagnose these cases as the clinical features are vague in most of such cases and histopathology is of nonspecific type. Various gene amplification techniques developed during the last decade may help in confirming the presence of gene sequences in these lesions. In this study, DNA as well as rRNA targetting amplification techniques have been evaluated for their usefulness in the diagnosis of these early forms. Biopsies from these suspected early leprosy cases attending 0PD of our Institute were collected. Nucleic acids were extracted and fractionated by a physiohemical technique being used at our laboratory. A DNA targetting (Williams et al) and a RT-PCR targetting a part of 16S rRNA of M. leprae (standardised at our laboratory) have been tried to detect the presence of M. leprae sequences. Ribosomal targetting gene amplification assay was found to be slightly more sensitive (6 5%) than DNA targetting (5 5%) method. Results indicate a good potential for gene amplification techniques for confirmation of diagnosis of early leprosy.

ON THE NERVE LESIONS CAUSED BY A LEPROMA-DERIVED AND CULTIVATED MYCOBACTERIUM HI-75 PRODUCED IN MICE

The aim to make every experimental disease model has been the simulation of the pathognomonic lesion which characterize human disease by the simplest possible way. In leprosy, nerve lesions have been regarded as the one which characterize this disease. The present study was conducted to make the one modifying the methods to make experimental leprous lesions produced in nude and immunologically attenuated mice by Sasaki et al. by the inoculation of a leproma-derived and cultivated Mycobacterium HI-75 (HI-75) which was reported as M. leprae HI-75 by Skinsnes et al. including one of the present author (Matsuo E) in 1975 and was identified as M. scrofulaceum (MS) by Stanford et al. in 1977.

In this study 11 million in total of HI-75 mixed with hyaluronic acid were divided into two and injected into both upper hp of each female nude and SPF ddY(ddY) mice expecting the easier access of the bacilli to the sensory nerves and periodically examined the lesions in these portion histopathologically for a few months.

As the results, the lesions produced in nude and ddY were much different. In nude mice macrophages laden with abundant mycobacteria proliferated at the injection sites and in the limited cases and portions bacilli were seen in the endoneurium of tiny peripheral nerves. In ddY the abundant bacilli were often seen in the center of the granulomatous lesions which include the nerves with invaded AFB.

The questions arose from the results which should be solved to understand the pathologic mechanism of leprous neuropathy are firstly whether the mycobacteria other than the so-called M. leprae grow in nerves or not in certain conditions and secondly whether some of the mycobaceria might have the ability to transform into genetically different kind of those such as M. leprae or not.

LIMITED GROWTH OF MYCOBACTERIUM LEPRAE IN CELL-FREE LIQUID MEDIUM CONTAINING ADENOSINE

*Koga Hospital Medical Research Institute. Kurume 830-8577, Japan **National Institute for Leprosy, 189-0002. Tokyo, Japan.

No credible reproducible in vitro multiplication of M. leprae , either in a tissue culture or in a cell-free culture system has been reported to date, despite more than 120 years since the discovery of the bacilli by Hansen in 1873. Here we report the first evidence that the cells of the Thai-53 strain of M. leprae can multiply in a cell-free liquid system, when the cells are cultured in enriched Kirchner medium, at pH 6.8-7.0, containing adenosine, at 30 C. For cultivation, we employed two methods; inoculation of the bacillary suspension into the medium, and cultivation of slide glasses smeared with the suspension of M. leprae in the medium. The results obtained indicated that the number of the cells morphologically increased with increasing cultivation period. A 2 to 4-fold increase in the DNA content extracted from the cultured cells specifically amplified by the PCR method, was observed after 6-8 weeks of cultivation. Moreover, an approximately 2-fold increase in the intracellular ATP content was demonstrated after 2 weeks' cultivation, and an approximately 4-fold increase after 4 weeks' cultivation. However, the ATP content gradually decreased thereafter, and no further increase in the ATP content could be achieved. Either AMP, ADP or ATP could be substituted for adenosine obtaining the same results. From these results, it was evident that initiation of the growth of M. leprae in a cell-free system took place when the cells were cultured in the liquid medium containing adenosine. The limit in growth after 6 weeks' cultivation has remained difficult to clarify, and further studies are required.

THE ANTIMYCOBACTERIAL ACTION OF AMPICILLIN/SULBACTAM IN CELL-FREE AND INTRACELLULAR SYSTEMS

K. Prabhakaran, E.B. Harris & B. Randhawa GWLHD Center @ LSU. Baton Rouge, LA 70894-5072. USA.

We have demonstrated previously that ampicillin/sulbactam is bactericidal to drug-resistant Mycobacterium leprae multiplying in mice and Mycobacterium tuberculosis in vitro. Sporadic reports continue to appear of HD patients who relapse after undergoing multidrug therapy. Multidrug-resistant tuberculosis is becoming a world-wide problem now. A gene designated mdr, mediating multidrug resistance has been reported in bacteria. Recently, a bacterial protein LmrA that extrudes antibiotics from the cell was shown to be identical to the human multidrug efflux pump P-glycoprotein causing multidrug resistance in cancers. Drugs that kill multidrug-resistant microorganisms would be of use in controlling infections caused by them. β-Lactam antibiotics are the most widely used antimicrobial agents. Since mycobacteria, including M. leprae, synthesize β-lactamase, these drugs are inactive against them. Now, β-lactam/β-lactamase-inhibitors are being employed successfully to treat diseases caused by β-lactamase-positive organisms. We screened the action of three β-lactam/β-lactamase-inhibitors (ampicillin/sulbactam (Unasyn^R), amoxicillin/clavulanate (Augme^Rntin ) and piperacillin/tazobactam (Zosyn^R)l on four potentially-pathogenic (to humans or to animals) mycobacteria [ M.simiae, haemophilum,avium & microti ] in axenic cultures; the action of ampicillin/sulbactam was also tested against the mycobacteria phagocytized by macrophages. The mycobacteria were cultured axenically in 7H 9 medium with or without the drugs. The drugs suppressed the growth of the mycobacteria in the cultures; ampicillin/ sulbactam proved to be the most potent of the three drugs. In the acute phase of mycobacterial infections, the organisms multiply within macrophages. Peritoneal macrophages were harvested from BALB/c mice. The bacteria were exposed to monolayers of the cells in RPMI 10 medium. Unphagocytized bacilli were washed off. Three concentrations of ampicillin/sulbactam were tested. The drug killed 58-97% of the mycobacteria within the macrophages [assessed by CFU]. β-Lactam/β-lactamase-inhibitors, especially ampicillin/sulbactam might provide an alternative effective therapy against diseases caused by mycobacteria resistant to other drugs.

K. Prabhakaran. E.B. Harris & B. Randhawa GWL HD Center @ LSU, Baton Rouge, LA 70894-5072, USA.

Pathogenic bacteria have developed a variety of mechanisms to invade their hosts. Many intracellular microorganisms interact with host cell receptor molecules to induce their own internalization. Bacteria exploit eukaryotic protein kinases as part of a strategy to enter mammalian cells by stimulating these enzymes at the receptor sites in the host cells. Protein kinase inhibitors prevent cell infection by blocking bacterial internalization. M. leprae was purified from the foot pads of experimentally-infected nu/nu BALB/c mice. Peritoneal macrophages were collected from BALB/c mice, using heparinized Hanks' Balanced Salt Solution; the cells were sedimented by centrifugaron at 200xg for 10 min at 4ºC. The macrophages were suspended in a small volume of RPMI 1640 medium containing 15% heated fetal bovine serum, 20 mM HEPES, 2 mg/ml NaHCO₃, 2 mM glutamina and 50 μg ml gentamycin. The number of cells in the medium was adjusted to 4x10⁶ /ml. A round 13 mm coverslip was introduced into each well of a 24-well tissue culture plate; 0.5 ml of the cell suspension was added to each well. After 2h, nonadherent cells were washed off. The inhibitors tested (staurosporine, genistein and erbstatin) were dissolved in 0.25% DMSO. Medium with DMSO was added to one set of 3 wells. Each inhibitor solution (0.5 ml) was added to three wells each. After 60 min, the wells were washed with PBS and then with the medium; 0.5 ml medium was added to each well. In another group, the wells were replenished with medium containing inhibitor. M. leprae (2x10⁷/20 μl) was added to each well. After 2 h at 37ºC. the cover slips were washed in PBS. and stained by the Ziehl-Neelsen method. The coverslips were photographed under high power. The control macrophages and those exposed to genistem showed good internalization of M. leprae. Phagocytosis of the bacteria was suppressed in the cells exposed to staurosporine and erbstatin, even when the inhibitors had been removed after preincubation. Different inhibitors act on different types of protein kinases. Further work will elucidate this. The results suggest that protein kinase regulates phagocytosis of M. leprae by macrophages.

GENOMIC IDENTIFICATION OF THE LEPROMA-DERIVED. CULTIVABLE AND NERVE INVADING MYCOBACTERIUM HI-75 BY THE COMPLETE: DNA SEQUENCING OF 16S RIBOSOMAL RNA GENE

1)Dept Biochem. Molec Biol . and ²⁾ Dept. Pathol. Kyorin Univ. Sch Med . Tokyo. JAPAN

The complete sequence of 16S ribosomal RNA (16S rRNA) gene was analyzed with the leproma-derived and cultivable Mycobacterium HI-75 (M.Hl-75 ) in order to obtain its taxonomic characteristics by the direct sequencing of the polymerase chain reaction (PCR) products. The mycobacterium examined in this study was first isolated by Skinsnes et al. • in 1975 from a lepromatous type Hansen's disease patient and was maintained in Ogawa's medium enriched with glucuronic acid and N-acetyl-D-glucosamine in one of the authors' laboratory DNA extracted from the cultured bacilli was amplified by the PCR using five sets of primers. Thus obtained product was sequenced by the use of biotinylated and DyeAmidite-667 conjugated primers. The detected sequences of 16S rRNA were compared with the gene data base issued from GenBank and the published data by Rogall et al. The results revealed that the sequence of M.Hl-75 was most similar to that reported for M. scrofulaceum (MS) with 5 bases (0.35%) differences in the sequenced 1493 bases of 16S rRNA gene. M. leprae (ML) differed from M. HI- 75 with 47 bases (3.3%), Stanford et al. identified M.HI-75 as MS in 1976 from their biochemical characteristics. Sasaki and Hamit reported the nerve invasion and the growth of the inoculated M. Hl-75 either to the nude mice or the ¹³¹l treated immunocompromised Swiss mice. The results of this study indicates that M.HI-75 is one of the variant of MS possessing an ability to invade into peripheral nerve, claiming a nature of a pathogen in developing leproma-like lesions.

Ref) •Skinsnes OK. Matsuo E. Chang PHC. Andersson B. Int J lepr 1975;43:193-209

A METHOD OF CHANGING REVERSION OF IN VITRO MORPHOLOGY OF CAN BACTERIA TO IN VIVO FORMS OF LEPROSY BACILLUS

Calcutta University College of Medicine and #Jadavpur University, Calcutta, India

Leprosy bacillus (LB) in vivo shows the preponderance of acid fast bacillary bodies. However, when cultivated in vitro, they show a reduction in typical lepra bacillary forms and a preponderance of mycelia, spores and granules. This has, for a long time, confused recognition of the in vitro cultivated chemoautotrophic nocardioform (CAN) bacteria as the counterpart of the LB. We report on selective in vitro cultivation conditions which help revert the CAN bacteria to in vivo morphology.

Gelatin minimal (GM) medium supplemented with sodium palmitate was further supplemented with 5% Dextrin, 2% Fructose, Actinomycin D at 50 μg/ml concentration and this medium was inoculated with 10⁴- 10⁶CFU/ml of in vitro maintained CAN bacteria which was allowed to grow for 4-6 weeks. Morphology was studied every week by staining with acid fast stain. Gram stain and Giemsa stain. Control medium was GM without these supplements. The results showed unequivocal reversion of in vitro non-acid fast bacillary, mycelial and granular forms of CAN bacteria to typical acid fast bacilli seen in vivo in LL leproma. The role of individual factor by a process of elimination has been determined and evaluated.

OXIDATION OF ¹⁴C-PALMITATE AS AN INDEX OF INFECTIVITY AND VIABILITY OF 'FAST' AND 'SLOW' GROWING M. LEPRAE ISOLATES

Though there are as yet no recognized strains of M. leprae, variants which exhibit 'fast' or 'slow' growth in the mouse foot pad have been described. The factors which underlie these variant traits are not yet understood. We compared the metabolic activity and infectivity of different preparations of M. leprae including known 'fast' and 'slow' growing isolates. Inocula were compared between freshly harvested M. leprae with tissue preparations and suspensions preserved at different temperatures and times. A number of good handling practices are noted. Metabolic activity was assessed as the relative ability of 10⁷ M. leprae to oxidize ¹⁴C-Palmitate in Middlebrook 7H12 (BacTec) incubated at 33C and was expressed as a growth index (GI). Infectivity was determined using the mouse foot pad technique. Armadillos were inoculated with some preparations. The metabolic activity of M. leprae varied markedly by its tissue of origin, means of preparation, duration of storage, and general character of the tissue from which it was derived. The GI of freshly harvested preparations were roughly bimodally correlated with infectivity. Preparations with low GI tended to show poor to no growth upon reinoculation into animals while those with high GI usually achieved good growth results. Above or below a threshold, the GI was not proportional to growth rate and was not associated with 'fast' or 'slow' growth characteristics of different isolates. Preparations held at 4-33C showed first an increase and then a gradual decline in GI over a 4 week period, but infectivity was lost rapidly and generally eliminated by 3 weeks. Preparations held at 4C for less than 7 days retained best infectivity. Metabolic activity was not detectable following a single freeze-thaw of tissue or bacillary suspension and was generally associated with a 99% or greater decline in infectivity. Growth results achievable after inoculation of armadillos and mice were comparable. Oxidation of ¹⁴C-palmitate can be used effectively as a relative measure of the quality of M. leprae preparations. The lack of linear correlation between metabolic activity and 'fast' or 'Slow' growth characteristic suggests that differential growth rates are inherent and may be useful markers to help identify strain variants.

CULTURE AND PATHOGENIC CHARACTERISTICS OF THE MYCOBACTERIUM LEPRAE ISOLATE "THAI-53" IN ARMADILLOS (DASYPUS NOVEMCINCTUS).

Though no genetic variation has been detected in M. leprae from different patients, regions and animal hosts, some isolates can be distinguished by their differential growth rates the mouse foot pad. Thai-53- M. leprae is a well characterized "fast" growing isolate commonly propagated in athymic nude mice. To determine its pathogenic characteristics in another host we inoculated 2 groups of 10 armadillos with 1.9 X 10⁹ bacilli and compared their time course of serological, hematological and histopathological events of their infection with those of other animals inoculated with bacilli passaged from humans to armadillos. Thai-53 showed high metabolic activity for oxidation of ¹⁴C-palmitate. Consistent with its growth characteristics in the nude mouse, Thai-53 inoculated armadillos showed more a rapid progression of infection, developing fully disseminated leprosy within 8-12 months with all classical signs of the disease. Serological antibody profiles for infection with Thai-53 were low and inconsistent in comparison to that seen with other isolates and the bacilli did not commonly disseminate to distant somatic sites prior to the animals entering the terminal stages of disease. Necropsy examination showed that armadillos infected with Thai-53 had extensive neurological involvement. Interspecies transfer of bacilli do not effect their overt pathogenicity and similar culture characteristic can be observed in different hosts.

The relative importance in leprosy transmission of contaminated dust, droplets or fomites remain unclear. Mycobacterium leprae is an extremely slow growing obligate intracellular parasite which is yet to be cultivated on artificial media. Several environmental factors could limit its transmissibility and survival in nature including its tolerance to ultraviolet radiation (UV). In the laboratory, UV-C is generally recognized as a potent sterilizing aid but its effectiveness against M. leprae also has not been shown. We examined the influence of UV on the growth and metabolic activity of M. leprae. Temporary static cultures in 10x35mm polystyrene petri dishes with 500 ul 7H12 media containing 1x10⁸ M. leprae obtained from foot pads of nude mice were exposed to varying timed intervals of UV radiation generated from an artificial source. Exposure times ranged from 0-80 seconds and constituted doses totaling from 0-12.64x10⁴ ERGS/cm². The bacilli were immediately resuspended and 1x10⁷ organisms from each exposure dose were inoculated into BacTec 12B vials to assess for metabolic effects. Another 1x10⁴ bacilli from each exposure were inoculated into the foot pads of Balb/c mice (MFP) to assess long term effects on cell division. The growth index achieved in BacTec cultures showed an immediate dose response related decline to a minimum of about 50% of the control activity after exposure to 6.3x10⁴ ERGS/cm². MFP results assessing cell growth were similar and showed that doses of 3x10⁴ ERGS/cm² resulted in a 90% killing and 6.3x10⁴ ERGS/cm² killed 99%. M. leprae shows sensitivity to UV-C similar to M. tuberculosis and lacks mechanisms that might allow it to substantially avoid UV injury.

RAPID DETECTION OF RIFAMPIN RESISTANCE IN MYCOBACTERIAL PATHOGENS: EVALUATION OF PCR/UHG-RIF ASSAY

Rifampin resistance in Mycobacterium leprae and Mycobacterium tuberculosis has been attributed to missense mutations within an 81 base pair fragment of rpoB (Rif region), encoding the B -subunit of the DNA-dependent RNA polymerase. Using this information, we have developed and characterized DNA-based assays using heminested PCR and universal heteroduplex generator (PCR/UHG-Rif) for the rapid detection and rifampin-susceptibility of Mycobacterium tuberculosis and Mycobacterium leprae in clinical specimens. In a double-blind study. 655 sputum specimens were obtained from individuals suspected of having tuberculosis and analyzed for the presence of M. tuberculosis and rifampin-susceptibility using the PCR/UHG-Rif assay. Results of this study demonstrated that the PCR/UHG-Rif assay detected all smear-positive, culture-positive specimens containing M. tuberculosis. In addition, 50% of smear-negative, culture-positive specimens for M. tuberculosis were detected. This assay also correctly identified the rifampin susceptibility of M. tuberculosis from 98% of these specimens. All specimens containing only nontuberculous mycobacteria or no acid-fast bacilli were negative in the PCR/UHG-Rif assay. The presence of M. tuberculosis in culture-negative specimens from patients with previous culture-positive specimens but receiving anti-tuberculosis therapy when specimens were obtained for PCR/UHG-Rif testing was detected by the use of this assay. In addition, PCR amplification primers and conditions were modified to specifically amplify and detect the rifampin-susceptibility of Myxobacterium leprae in purified DNA samples and crude cell lysates of skin biopsy specimens from lepromatous leprosy patients. Even though, a small number of rifampin-resistant clinical specimens were available for analyses (no. = 4), the PCR/UHG-Rif assay correctly identified the rifampin susceptibility of these specimens. These assays require approximately six hours to run (post sample preparation) and should provide rapid tools for detection of the rifampin-resistant phenotype of these mycobacterial pathogens directly from clinical specimens.

The a antigen gene is one of the dominant mycobacterial proteins those are secreted from the mycobacteria. In the course of our study, we have constructed the genomic libray of M. leprae Thai 53 strain, cloned a new a antigen gene with a plaque hybridization method using DNA fragment of M. leprae al antigen DNA as a probe and termed it as a2 antigen gene. The a2 antigen gene was characterized by sequencing. By comparing the deduced amino acid sequence of a antigen with 85 complex antigen of other mycobacteria, the homology of 74.3%-85% was found.

The over expression system of M. leprae a2 antigen gene in Escherichia coli was constructed.

Recombinant a2 antigen was purified by amylose column chromatograph at the purity of more than 95%. More than 10mg of recombinant a2 antigen has been obtained from 200ml of liquid culture. Then we studied the serological activity of recombinant M. leprae a2 antigen using enzyme-linked immunosorbent assay (a2-ELISA) in sera from 100 leprosy cases and 50 normal persons, and determined the optimum conditions for a2-ELISA.The results indicated: the antibody titer to a2 antigen in leprosy patients was IgG>IgM>IgA>and there was same serological activity between a2-ELISA and ND-ELISA. These results suggested that the a2-ELISA may be useful for the serodiagnosis in leprosy.

Foot pad technic of M. leprae inoculation of mice(Shepard, 1960) permitted to study M. leprae survival in different environments. Through many years' experiments we succeeded in confirming a survival of M. leprae under the conditions when biopsies from untreated LL patients were put into 40% saline solution of glycerin (in refrigerator or at room temperature). In past this method was used for preserving viability of different organisms including M. lepraemurium (Marchoux. 1934, Chorine, 1934) At the moment of biopsy, then in three and subsequently in every six months M. leprae (10⁴) from lepromas were inoculated into 10 BALB/c mice by Shepard's technic. Inoculum and "harvests" were counted according to Shepard and McRae (1968). During the initial 12-24 months characteristics of M. leprae multiplication in mice foot pads (lag-phase, log-phase and plato phase) did not almost change in the most of cases. After 3-4 years of storing an amount of M. leprae increased more slowly. Preliminary results of these experiments were published in 1984. Maximal period during which it was succeeded to preserve M. leprae viability in 40% glycerin at room t⁰ was 12 years (longer experiments were not carried out). The results obtained could account for some unsolved questions of epidemiology and pathogenesis of leprosy. The method proposed is successfully used for transportation of infected tissues from leprosy patients without ice from any region of Russia to Leprosy Research Institute (Astrakhan) for studying. During a special study (Vishnevelsky & Juscenko, 1991) it was also proved that lepromas kept in 60-80% solution of glycerin at room temperature for 2-4 weeks remain suitable for enzyme and histochemical investigations.

¹St. Thomas Hospital and Leprosy Center. Chettaputtu; ²Leprosy Home and Hospital, The Leprosy Mission, Purulia; and ³S.L. R&T.C., Karigiri. INDIA

Cataract is found to be a common complication in lepromatous patients belonging to the older age group. During cataract surgery an iridectomy is performed as a routine procedure. The iris specimens obtained from lepromatous patients undergoing cataract surgery are studied histopathologically using hemoloxylin eosin stain and acid fast stain. Iris atrophy with evidence of chronic inflammation was found in a majority of patients even in the absence of acid fast organisms. In one specimen active inflammation with macrophage granuloma infiltrating the iris tissue including constrictor muscles was noticed. Acid fast organisms were present in large numbers inside macrophages and in bundles of smooth muscle cells regulating the pupil. Nerve fibers were not detected. Details of these findings will be presented and their significance will be discussed.

In severe ENL reactions we found acute necrotizing and exsudative vasculitis in deep dermis and subcutis. These vasculitis follow severe acute inflammatory reactions in the neighboring tissues. We describe in 10 lepromatous leprosy patients, many years after discharge, episodes of one or few erythematous nodules in the limbs. Microscopical examination revealed a exsudative and necrotizing segmentary vasculitis like Polyarteritis nodosa.

There are discrete inflammatory reaction in dermis and sub -Cutis and the clinical data, residual lepromatous infiltrate and Bacili in vessel's wall sugests a late ENL reaction

Theren't envolvement of Central nervous system, peripheral nervous systems, skin, muscles and lungs in secondary

amyloidosis in leprosy. In these sites the blood capillaries shows tigh junctions between the endothelial cells and the transport is made by pinocitosis. Otherwise in sites where blood capillaries are fenestrate (kidneys, bowel, endocrine glands) or sinusoids (liver , spleen , bone marrow) the Amyloid deposition is ever present and frequently massive. The amyloidogenic SAA protein is produced in the liver, their molecular weight is 250.000 and is found in the blood as a apolipoproteic complex. This suggests that there are a relationship between the size of the precursor protein molecule and capillary pattern in the distribution of amyloid deposition in leprosy

Acute cutaneous and neural lesions are the know signs of type I reactions. Theren't reports about visceral lesions during these episodes. We detected visceral tuberculoid granulomatous lesions in six patients that died during type I reactions. In these cases we considered these reactions as reversal reactions because all the patients developped previously cutaneous lesions and stigmata characteristic of lepromatous patients. We didn't found uniformity in the anatomic and clinic data of these patients. So, one patient presented both , ENL and type I reaction; na elderly patient presented a tuberculous lymmphadenitis that was follow by a generalized granulomatous lesions, with prominent granulomatous vasculitis in skin, nerves, synovial membranes and visceral sites ( liver, spleen, testis, larinx); other patient had a generalized tuberculoid granulomatous have followed a characteristic episode of sulphona syndrome M. leprae was found in the tuberculoid granulomatous lesions In all the patients , including in two patients the tuberculoid granuloma developped in kidneys . heart and salivary glands

HISTOLOGICAL CHANGES IN THE NASAL MUCOSA OF PATIENTS WITH PRIMARY NEURITIC LEPROSY

Sujai Suneetha, S. Arunthathi, Anand Job, Anand Date, Nisha Kurian, Chinoy JG Chacko.

Dhoolpet Leprosy Research Centre, LEPRA India, Hyderabad-6, INDIA.
and
Schieffelin Leprosy Research & Training Centre, Karigiri, INDIA.

The nasal mucosa of 39 cases of primary neuritic leprosy registered at the Schieffelin Leprosy Research & Training Centre, Karigiri were studied histologically to determine nasal mucosal involvement in PNL and its relevance to the pathogenesis of the disease. Specific changes of leprosy were seen in 20(51.3%) biopsies ranging from macrophage granuloma with acid fast bacilli, epithelioid granulomas and nerve inflammation. The remaining biopsies revealed chronic inflammatory changes of the mucosa or mild non-specific changes in small mucosal nerves.

These findings show that there are widespread effects of the disease even in PNL patients where the disease is believed to be confined to the peripheral nerves. The findings also show that early leprosy involvement can be found in the nasal mucosa even before lesions become apparent in the skin, nerve or other parts of the body. The nasal mucosa could be the site for the primary lesion in leprosy. Clinical and histological examination of the nasal mucosa may be useful and important in the early diagnosis of leprosy and especially in contacts.

Leprosy with varied clinical manifestations, necessities the establishment of a reliable classification for appropriate treatment and assessment of prognosis. The clinical presentation and the histology of skin lesions reflects the underlying immunological response against M leprae. This study aims at evaluating the significance of plasma cells in classifying leprosy histologically.

Biopsies of skin lesions from 70 untreated leprosy patients consisting of; 15 patients with indeterminate leprosy. 15 with tuberculoid leprosy. 15 with borderline tuberculoid leprosy. 10 with borderline lepromatous leprosy and 15 with lepromatous leprosy were studies The plasma cells in them were enumerated in 20 HPF in each biopsy The results of the study showed that plasma cell density was significantly high in multibacillary groups and declined towards the tuberculoid and indeterminate end of the spectrum

The high plasma cell count in histological sections of the skin of multibacillary patients may be a reflection of the underlying active humoral immune mechanism of the body against M. leprae. The increase numbers of plasma cells in association with other cellular infiltrates of lepromatous leprosy and high bacillary load may be an useful indicator in differentiating the various types of leprosy and arriving at a proper classification of the disease subtype.

LOCALIZATION OF M. leprae TO EPINEURAL BLOOD VESSELS IN EXPERIMENTAL LEPROSY NEURITIS.

Background. Infection of peripheral nerve by M. leprae is the histopathologic hallmark of leprosy and is a major factor in the deformity and social opprobrium of this disease, but the mechanisms by which the bacillus localizes to peripheral nerve are not known. We have shown that nerve involvement in experimentally infected armadillos is very similar to that in man.

Objective. Since the early neural accumulation of M. leprae in the armadillo is to the epineurium, we have used high resolution light microscopy and electron microscopy to determine the cellular location of epineural bacilli.

Methods. From 8 infected armadillos, 44 nerves were divided into 1 cm. blocks and processed in Spurr resin. Thick (1.5 μ ) sections were screened for acid-fast bacilli, and thin sections of positive specimens were examined ultrastructurally.

Results. Over 600 blocks were screened; 36% contained acid-fast bacilli, and 86% of these contained epineural organisms. Most epineural M. leprae were found in the endothelium of blood vessels or in histiocytes in the adventitia. Some were found in epineural lymphatics. Within nerves, M. leprae were found in the vascular endothelium as well as in Schwann cells and histiocytes. Conclusions. These results indicate that M. leprae localize to epineural blood vessels during the development of neuritis in leprosy. Specific interaction of neural vascular endothelium with M. leprae alone, or with infected monocytes, may therefore be a critical step in the pathogenesis of nerve injury in leprosy.

INFECTION OF DISTAL PERIPHERAL NERVES BY M. leprae IN ARMADILLOS: AN EXPERIMENTAL MODEL OF NERVE INVOLVEMENT IN LEPROSY.

D. M. Scollard, G. Lathrop, and R. W. Truman. Research Branch, GWL Hansen's Disease Center at LSU, Baton Rouge. La.

Background. No model has been developed to study the mechanisms by which M. leprae localizes selectively to peripheral nerve.

Objective: To determine the pattern and distribution of nerve localization of M. leprae in the armadillo model.

Design. Dissection of major peripheral nerves, from the spinal root to ramifications in the feet, was done in 6 exper-mentally infected armadillos. Nerves were divided into 1 cm blocks, and in Fite-stained sections were evaluated.

Results. Peripheral nerves were involved by M. leprae in 3 animals with disseminated infection. Infection increased in intensity as the nerve was followed distally. No M. leprae were found in 3 resistant animals. The extent of infection was greater epineurally than intraneurally, at all levels. M. leprae infection of nerves was associated with focal, interstitial, mononuclear cell infiltrates.

Conclusions. These results suggest that: 1) Armadillos offer a model for the study of neural involvement in leprosy, since the pattern of neural involvement is comparable in man and susceptible armadillos; 2) Early localization of M. leprae may be epineural; 3) Schwann cell involvement may be a late event; 4) Mechanisms involving the endothelium of epi- and peri-neural tissues may be important in the selective epineural localization of M. leprae.

¹St. Thomas Hospital and Leprosy Center, Chettupattu. India and ²MolecuIar Biology Research Department, Laboratory Research Branch, GWL Hansen's Disease Center at LSU, P.O. Box 25027, Baton Rouge. LA

Early detection of leprosy has become a major focus for improving control strategies for this disease. We evaluated a polymerase chain reaction (PCR) test for detecting Mycobacterium leprae in skin as an adjunct to standard clinical and histopathological evaluation of early lesions for diagnostic purposes. Skin biopsies of lesions from 39 patients suspected of early leprosy were taken and bisected. One piece was used for histologic examination and the other for PCR studies to detect M. leprae. The diagnosis of leprosy was made clinically in 14 patients and by histopathologic study in 26 patients. Acid-fast bacilli were seen in the histopathologic sections of only two patients and M. leprae were detected using PCR in 11 patients. In one patient the diagnosis of leprosy was made only because of the detection of M. leprae by PCR. Since even in endemic countries the profile of leprosy is changing, detection of leprosy in its early stages has become increasingly important. Since the finding of M. leprae is crucial in the confirmatory diagnosis of early leprosy, it is suggested that PCR studies to detect M. leprae be done wherever possible in conjunction with histopathologic examination. It is also recommended that the feasibility and the cost-effectiveness of both of these methods to find M.leprae be evaluated in other settings.

HISTOPATHOLOGIC CHANGES OF SKIN LESIONS IN RELAPSED BORDERLINE TUBERCULOID PATIENTS

Ten patients belonging to the paucibacillary group who had relapsed after receiving 6 months of multidrug therapy are chosen for the study. Clinically patients with renewed activity, extension of the original lesions and appearance of new lesions are considered to have a relapse of the disease. Skin biopsies from these active lesions are studied histopathologically using hemotoxylin eosin stain, acid fast stain and van Gieson stain. The appearance and the content of the granuloma and the appearance of skin adnexa especially the blood vessels and dermal nerves in relapsed skin lesions will be described. Distinguishing features of relapsed lesions will be pointed out. The role of histopathologic study of skin lesions in identifying relapse will be discussed.

HISTOLOGICAL EVOLUTION OF REACTIVATION OF HANSEN'S DISEASE DURINQ OR AFTER TREATMENT

Maria Angela Bianconcini Trindade, Raul Negrão Fleury, Maria Mercedes Loureiro Escuder, Cássio Cesar Ghidella, João Carlos Regazzi Avellera,

Francisco Reis Viana. Alfredo Bolchat Marques, Somei Ura
Instituto Lauro de Souza Lima, Bauru / Escola Paulista de Medicina. São Paulo. SP. Brasil

Reactivation in Hansen's disease has been reported since the dapsone era but after the introduction of MDT, with a prompt and effective cure, reactivation become an important research topic for control programs. Aiming to analyze the histological pattern of reactivation, the histological evolution of Hansen's Disease was studied in 179 biopsies of 66 individuals presenting reactivation during or after treatment. Such biopsies were examined in the Instituto Lauro de Souza Lima between 1987 and 1994. Relapse occurred in 9 individuals not treated with MDT and was solely detected by the bacillary index. The intensity of the reactivation episode seems to be related to the cell immune resistance of the individual and depends on the amount of accumulated antigen. The analysis of the biopsies in this study confirms the difficulty in to differentiate activity, reaction and relapse and the correct allocation of these cases in the spectrum of the disease. It was not possible to distinguish between relapse and acute reactivation (type I reaction) in histological and clinical terms. This fact lead to the conclusion that reactivations are bacillary proliferation due to drug resistance or multiplication of persisting M.Leprae.

Weng Xiao-Man Beijing Tropical Medicine Research Institute
Li Huan-Ying .. .. .. .. ..
Li Fu-Tian Shanghai Zun-Yi leprosy Hospital
Ran Shun-Peng Wenshan Prefectural Institute of Dermatology Yunnan Province

The diagnosis of relapse in leprosy can be difficult, if relying solely upon clinical examinations. In order to detect relapse early and to differentiate relapse from late reversal reactions, laboratory methods such as PCR. Dot ELISA/ECL were applied to detect M. leprae and PGL-I antigen in nasal secretions and slit-skin smears, as well as histopathological methods to detect PGL-I antigen and S-100 protein in skin biopsies. The results on 33 relapses from patients cured with dapsone plus rifampin therapy were found as follows:

1. PCR is more sensitive than acid-fast staining (PCR 27/29. 93.1%; AF 29/33, 87.9%), but PCR method basing upon DNA amplification, cannot differentiate live from dead bacilli.

2. PGL-I antigen can be detected in nasal and skin smears with Dot-ELISA/ECL and that PGL antigen appeared in 3 relapses from nasal secretion and slit-skin smear before oven signs of relapse developed.

3. Immuno-histochemical methods with PGL-I monoclonal antibody (DZ-l) and S-100 protein antibody can not only reveal clearly cutaneous nerve but also demonstrate the location of PGL-I antigen in relation to cutaneous nerve. In 89.5% of relapses (MB 16, PB 2, unclassified 1) . PGL-I were demonstrated in in skin smear by Dot-ELISA/ECL and/or immunochemical methods.

The combination of the above tests with routine clinical and AF examinations may be of advantage in the early diagnosis of relapse, as disagreement between slit-skin-smear and histopathology can occur in the early stage of relapse. Four suspected relapses suplemented with the above testes and negative findings were thus diagnosed as late reversal reactions. These preliminary results indicate that further testing on more samples are necessary.

RELATIONSHIP BETWEEN PATHOLOGICAL AND CLINICAL MANIFESTATIONS IN MB PATIENTS DURING MDT

Jia-ju Ma, Yun-shan Deng• , Cun-xin He, Xiu-lian Zhang, Yi Yin, Fa-de Men and Li-hong Sun Hanzhong Sanatorium, Hanzhong City, Shanxi Province, China • Xi'an Medical University. Xi'an City

Pathological, bacteriological and clinical changes and their relationships were prospectively studied qualitatively and quantitively in 104 MB leprosy patients alter MDT. They were grouped according to homologdus matched-pairs and different clinical results. Results showed that: a decrease of GF, BIG, LHI and BI negatively correlated with the duration of MDT treatment; area of pathological infiltration obviously shrank and number of Virchow cell infiltration reduced; clinical effect rate of MDT was 100% alter 24 months' treatment, of whom 12.5% reached the criteria of clinical cure. The authors recognized that pathological, bacteriological and clinical changes were closely identified each other alter MDT; regularity of bacteriological changes and effect of MDT were better reflected by GF and BIG; GF and LHI could reflect the effect of MDT only in a short period; MDT had good anti-bacteria and anti-inflammation functions, and can kill the bacteria in the beginning of this treatment; different clinical results were related to the different levels of pathological damages and the number of bacteria; the lower all the indexes were, more effective the treatment could be; measurement of infiltration area was helpful in evaluating the clinical effects and the number of Virchow cell was likely not related with the evaluation mentioned, localized granuloma and the degenerated specific infiltration cells will existed continueously after MDT, but was not likely important for the evaluation of clinical effects.

CLINICO-PATHOLOGICAL CORRELATIONS OF MACULAR LESIONS IN LEPROSY, BEFORE AND AFTER MULTI-DRUG THERAPY.

The clinical features and histopathology were studied in detail in 27 patients (24 new and 3 old) of bacteriologically negative macular forms of leprosy (macular tuberculoid or maculo-anaesthetic) with a view to clínico-pathological correlation before starting treatment here. In addition, repeat biopsies (one or more) were performed from the same lesions in 16 new patients and 2 old patients, who were taking regular multi-drug therapy here, usually after a variable period of daily rifampicin. In general, there was no absolute correlation of the type/severity of dermal infiltrate (round cell or granuloma) and intensity of cutaneous nerve infiltration between patients with and without deformities. However, out of 11 patients with deformities (8 new and 3 old) at least 7 patients had significant granuloma formation and nerve infiltration in their biopsies, in contrast to the group without deformities,in whom only a smaller proportion had such changes. A pronounced linear peri-vascular infiltrate in the papillary dermis was observed in several patients. In many patients the hypopigmented macules improved after treatment and the repeat biopsies usually showed decreasing dermal infiltrates.

EXPRESIÓN DE LAS CELULAS DEL SISTEMA MONOCITO-MACROFAGO EN EL ESPECTRO INMUNOPATOLOGICO DE LA LEPRA : ESTUDIO INMUNONISTOQUIMICO.

¹Cuevas Santos J., ²Contreras Rubio F., ³Gómez Echevarría J. R., Torres Muñoz P., Hernández Ramos J.

¹Hospital General Universitario, Guadalajara, Serv. Anatomía Patológica. ²Hospital La Paz, Madrid, Serv. Anatomía Patológica. Sanatorio San Francisco de Borja, Fontilles, Alicante, España.

Se trabaja con un material de 115 biopsias, de pacientes diagnosticados clínicamente de lepra. Todos ellos tienen valoración clínica, bacteriológica y alguno de ellos inmunológica (R. Mitsuda).

En la parte histológica se presenta valoración convencional de las lesiones desde el punto de vista histológico con las técnicas de HE Y Fite (búsqueda de bacilos) realizando el citado estudio sin conocer en un primer momento los datos clínicos. El trapajo evaluará todos los casos motivos del presente estudio con la consiguiente correlación clínico-patológica al contrastar los hallazgos histológicos y los datos clínicos. A posteriori se realizará una selecció: de los casos más significativos procurando recoger ejemplos de la totalidad del espectro de la lepra. El número pensado para tal selección oscila alrededor de 30 casos. De estos se realizará estudio inmunohistoquímico intentando valorar la expresión del macrófago en la lepra, con especial hincapié en la vertiente tuberculoide del espectro así como en los casos etiquetados como dimorfos, mediante anticuerpos mono y policlonales.

Relación de Anticuerpos primarios a emplear: Protaina S-100, CDIa, CD-68, HLA-DR (Mb3), Factor XIIIa.

Mutsuhiro Furuta₁, Kentaro Hatano₁, Takanobu Matsuki₁, Yoshiko Okano₁, Koichi Nakaya₂, Takeshi Ikeda₂, Masahiro Fujino₂, Masanao Makino₁.

¹⁾National Sanatorium Oku-komyo-en. Okayama. Japan ²⁾National Kyoto-minami Hospital, Kyoto. Japan

In the 1975 issue of the International Journal of Leprosy ( Volume 43. Number 2 ). we reported "Amyloidosis in Leprosy" Recently, in Oku-komyo-en National Sanatorium, we could not perform autopsys for all cases. So it is not clear as before how often amyloidosis occur. But it dose not mean that amyloidosis has ever faded away. We had a prominent case of amyloidosis recently, and examined the tissue not only using HE stain and amyloid stain but also using the polarized microscope of the non-stain materials. And some eminent cases of the past are examined again in same manner. As a result, without using amyloid stain, we found the existence of the amyloid degeneration by non stain materials. Over more as the degenerated lesion of the connective fibers connected to the amyloid deposition also shows polarization, we got the impression that is quite differ from amyloid stain observation.

It has been said that the secondary amyloidosis is related to AA amyloid. We think that amyloidosis spreads by the pathologic change mainly of the small blood vessels. In other words, the existence of the wound infection of the leprosy and other cases of so called secondary amyloidosis has the important correlation with the emergence of amyloidosis.

THE POLARIZED SUBSTANCES SEEN IN THE TISSUE OF LEPROSY RENDERING THE CHRACTER OF APOPTOSIS;

Kentaro Hatano, Takanobu Matsuki. Tomohiko Saito, Masanao Makino. Mutsuhiro Furuta

We would like to report the result of the pathological findings of the leprosy tissue, which seem to imply the correlation to apoptosis.

We have been observing in the tissue of a leprosy patient the existence of microscopic fine particles that have the character of polarization. Having obtained fifteen skin biopsies of the leprosy patients for diagnostic purpose, whose treatment was just about to start, or just after the onset of the treatment. Our observation was done using a polarized microscope and stain such as TUNEL, Fas. Bax. and Bel-2. We also observed above tissue by using electron microscope. These biopsies were all taken from the margin of the skin lesion conjugating with the healthy skin.

As we try to find what this microscopic fine particles are that has the polarizing character, we observed the substance which has the positive reaction to the TUNEL, Fas, and Bax. Also in the investigation using the electron microscope, we found the electron dense materials which looked like apoptotic body and also a concentrated nucleus.

These results were equally seen in all the biopsies regardless of patient's age. sex. classification, and the lesion, thus enhancing the suspect of apoptosis which affects as the common mechanism in the pathology of leprosy.

HISTOPATHOLOGICAL AND TRANSMISSIONAL ELECTRON MICROSCOPICAL OBSERVATION ON THE LEPROTIC LESIONS IN SCROTUM WITH DEEP INFILTRATION

Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China

In this article, a case of borderline lepromatous leprosy with histoid leproma was reported, who had also deeply Infiltrated lesions in scrotum. After MDT therapy for one and half a year, most lesions disappeared, hut that in scrotum with deep Infitration very slowly.

Histopatholoical observation revealed the scattered, degenerative foamy cells and the residual leprosy bacilli In smooth muscle cells in addition to the foamy cell infiltrates in subcutis of the lesions.

On transmission electron microscopy .vacuoles with various sizes, grouped or scattered leprosy bacilli of granular and solid type were seen. The latter had electronic density with peripheral transparent halo, indicating that they still had vital activity.

The authors emphasise that the treatment of this kind of leprosy patients had to be strengthened and it is important to pay further attention to the residual bacilli in leprosy control.

EPIDEMIOLOGICAL AND SOCIO-CULTURAL IMPACT OF THE SOCIAL MARKETING PROGRAMME FOR LEPROSY IN SRI LANKA

Penny Grewal¹, Nimal Kasturiaratchi², Padmini Gunawardene⁴, Dayamal Dewapura₁, Sunil Settinayake⁴, Lakshmi Somatunga⁴, Mitchell Weiss⁴, Vinya Ariyaratne

¹Novartis Foundation for Sustainable Development, Switzerland, ²University of Peredeniya, Sri Lanka, ¹Swiss Tropical Institute, Switzerland, ⁴Anti-Leprosy Campaign, Sri Lanka, , 'University Sri Jaywardenepura, Sri Lanka

In 1990 a social marketing programme for leprosy was launched in Sri Lanka to detect and treat hidden cases. Social marketing aims to influence the voluntary behaviour or target audiences (e.g. encourage persons affected by leprosy to seek treatment) in order to improve their personal welfare (e.g. cure of leprosy without deformities) and that of their society (e.g. reduce the pool of infection). This involved creating awareness of the signs of leprosy, dispelling prejudices, improving access to treatment and strengthening the ability of the health services to deal with the new case load.

A study was carried out among 1,800 non-affected persons including school teachers and midwives in 1997, three years after discontinuation of the social advertising campaign in order to assess its residual impact on knowledge, socio-cultural attitudes and practice. Using the Explanatory Model Interview Catalogue framework, respondents were shown photographs of representative signs of leprosy and given information about symptoms to provide a focus for questions about possible diagnosis, cause, prognosis with treatment, social attitudes and sources of information. Narrative data was collected for a third of the sample.

The findings reveal the long term impact of an intensive campaign and the sustainability of changes in societal attitudes which have been extremely positive, particularly among midwives and school teachers. Minority ethnic groups, such as Muslims, however appear to have been relatively untouched by the campaign. This paper will focus on areas with significant improvements in knowledge, attitude and behaviour (e.g. recognition and medical recourse, prognosis) as well as findings indicating effects that fell short of expectations.

Leprosy has been eliminated from Sri Lanka and this paper will also discuss the epidemiological impact of the campaign.

LINGERING PROBLEMS OF POOR COMMUNITY PERCEPTION, DISCRIMINATION AND SOCIAL STIGMA AGAINST LEPROSY-A STUDY OF YOUTHS IN SOUTH-EASTERN NIGERIA.

M.M.Meremikwu, C.O.Odigwe, E.N.U.Ezedinachi, D.G.Nkanga and A.N.Meremikwu University of Calabar, Calabar, Nigeria.

It has been suggested that increasing demonstration of the curability of leprosy would lead to a positive change in social attitude to leprosy patients and a gradual reduction in the age-long social stigma against the disease. To assess the level of community perception and social stigmatization of leprosy against the background of the successful implementation of the WHO MDT Programme in Nigeria, using a semi-structured, validated questionnaire, we studied 657 youth (10-25 yrs; mean = 17.1 ± 6.6) who were students of five secondary schools in South-Eastern Nigeria. There were 344 (52.4%) male and 313 (47.6%) female. Most ascribed the cause of leprosy to worms (15.0%). virus (28.6%), evil spirits (15.8%) and a curse (6.0%), while a few (26.3%) suggested a bacterial agent. Frequency of responses on the modes of transmission were 33.8%, 18.1%, 15.8%, 13.5% and 9.8% for sharing food, breathing, act of witches, sharing a seat, and hand-shake respectively. The hospital (37.6%) Church (36.8%) and traditional healers (6.8%) were suggested as preferred treatment places; while 18.1% said there was no cure. Most would not share classroom seat (85.6%), bus seat (75.0%) or toilet seat (82.0%) with a person affected by leprosy; 82.0% would not even shake hands with them. The reasons for discrimination were fear of being affected by (67.6%). social stigma (40.0%), traditional belief (32.2%) and religious belief (18.3%). There is a great need for health education in this community to improve the epidemiologic knowledge of the disease, its curability and to reduce the level of social stigma against it.

Many leprosy patients tell about the fear they have for actions taken by the community towards them. Different studies show that due to this patients try to hide their disease and subsequently stop taking their treatment. To see if this fear for community actions is based on real events. 300 community members were interviewed about actions taken by the community towards leprosy patient during the past 20 years. This resulted in 192 patient-stones in total.

The majority (94.8%) of the patients described had visible signs like patches (10%)or wounds and/or deformities (84.8%).

Of these patients 2.6% experienced only eating restrictions. 43.8% had to sit separately, were not allowed to enter people's homes or to touch other people. 29.2% was not allowed to enter a teashop. not allowed to use a public well, not allowed in social functions, problems to get medical care or had problems in their work and 12.5 % of the patients were send out of their village. These negative community actions have not changed during the past 20 years. Even last year 13% of the patients was exiled from the village.

Also it was found that once the community started taking actions towards a patient, this action continues forever.

What however has changed is that nowadays 34.3% of the patients receive positive support compared to only 16% of the patients 20 years ago. Main reason for community actions arc: fear of infection by germs and transmission of the curse of God.

It can be concluded that the social stigma on leprosy is still present and that the statement "Once seen as a leper, always a leper" is still true. As actions by the community are taken towards patients with visible signs, it can be concluded that the prevention of wounds and deformities is of high priority in patient education. Patients should be counselled on how to deal with community actions.

A community programme should be developed in which cause and treatment of leprosy is explained. As knowledge alone is not enough to change the negative behavior towards leprosy patients, a more participatory approach should be developed.

THE SOCIOECONOMIC ASPECTS OF THE POPULATION AFFECTED BY LEPROSY IN SOROCABA. BRAZIL

The population studied comprised 1288 patients of one Health Unit, including cured ones. Their profile was mostly males (56%) economically active age from 15-59 years old (59%) and 39% above 60 years old. Some coming from neighboring towns (21%) where treatment is available. The number of patients treated in 1996 was 629 whereas the epidemiological registry of active cases was about 450 which means that cured patients still Come for medical assistance.

A sample was drawn to be studied in relation to non-leprosy affected households. The results indicated that patients were poorer than the general population as a whole being concentrated in classes C. D and E. Also, the characteristics of the head-of-household were similar as far as age, sex and home ow nership (the majority ow ned it).

However, the households were different as far as work situation and schooling. That is. more retired persons in the leprosy affected households than their neighbors, and less than 4 years of school in leprosy affected households, whereas the neighbors had up to 8 years of formal education.

The results are discussed in relation to other publications about socioeconomic situation of leprosy patients in Brazil and suggestions for economic rehabilitation are proposed.

Healthy villages can support patients with disabilities with or without infective disease. In our rural community of Hampshire New Forest, we have a practice population of 3500 patients, some have chronic disabilities. We appointed a healthy village coordinator' who received referrals from the primary health care team. The co-ordinator identified and collated community resources including facilities in the local schools, village and church halls and linked the individual needs with the community resource. Research data showed that the referred individuals had improved well being, with reduced prescribing of medication and reduced referrals to hospitals. Their quality of living had improved.

A healthy village concept supports WHO Health for All, and Healthy City projects. The model is based on the rural health work formerly carried out by Dr Stanley Browne in the former Belgian Congo, and in China by the late Ma Haida. A world without leprosy needs to integrate people with chronic disabilities in their communities. A 'healthy village project' can provide the structure to support health and social care needs for our patients in the next millennium.

ACTIVITIES FOR ENLIGHTENMENT ON HANSEN DISEASE IN JAPAN Akitoshi Murakami and Masao Yuhu, National Hansen Institution Kikuchi-Keihuen, Kumamoto, Japan

The day April 1, 1996 was the greatest breakthrough in Japan for all ex-Hansen patients who had been segregated in Hansen institutions. On this day, Leprosy Protection Law was abolished, and we staff of the institution shared pleasure with the ex-patients. They have lost many significant things by segregation for more than 40 years after the treatment was established, including bonds of hometown, family and community of their own. There were two reasons for happening of such a sad affair in Japan. One is that Leprosy Protection Law was not abolished; instead it was revised to enact in 1953 under strong suggestion by a couple of Hansen specialist physicians at that time. The other is that Japanese leprosy association ignored Roman Declaration by the 6th international leprosy congress in 1957 that isolation against Hansen disease should be abandoned.

In kikuchi-Keihuen, we started activities for enlightenment in 1992 to the general public that had misunderstood that Hansen disease was an awful disease. As a result, many people had right understanding of the disease, which in turn made it possible for ex-patients to regain bonds of local communities and hometown and family. In addition, abolishment of Leprosy Protection Law in 1996 has promoted this event. In Japan, many of married exe-patients do not have their own children because of duty of a contraceptive operation. Therefore, they particularly enjoy heartwarming exchanges with school children.

Our recent experiences show that activities for enlightenment on Hansen disease is very effective to eliminate prejudice and discrimination. We also appeal that we should never repeat historical fault in other diseases such as AIDS.

ASSESSMENT OF THE FACTORS BEHIND HIGH DEFAULT RATES AMONG LEPROSY PATIENTS IN NEPAL, (analysis ongoing)

In the six districts of the Eastern leprosy Control Project in Nepal approx. 40% of the registered leprosy patients are non compliant to their treatment. This study was conducted to find the main reasons why some of the registered patients do not finish their treatment. Patients were called 'defaulters' when they had missed 12 consecutive months of treatment. Patients were released from treatment. 'RFT's', when they had finished 24 doses of MDT within 36 months 36 defaulters and 47 RFT's could be traced and interviewed. From all patients in depth interviews were taken at their homes. Topics for discussion were diseases related issues, helpsecking behavior, treatment experience, social impact of the disease, and family support Reasons for defaulting found were severe side effects. lack of knowledge about the disease, denial of the disease, feeling of being cured, no hope for cure, quality of care at Hp's, long duration of treatment Reasons for compliance and becoming RFT were fear of the disease and the impact of treatment. Most of the patients were hiding their disease for the communities. RFT's were more successful in this Most patients live isolated within the family. The term compliance appeared to be quite narrow, since it was defined as confirmity with 'Western' medicine People's decision to continue or not with the prescribed treatment is subject to mam different forces, c. g. spiritually, cultural concepts of disease, community pressure, experienced quality of care. To improve the compliance to Western medicine the patients do not have to understand the theory underlying biomedicine. but they have to accept it. In this case other motivational factors must be present, like trust in the received care, receiving enough caring and concern. Patient education should include information about the cause of their disease and its relation to its treatment, the duration of treatment, its side effects, and the learning of coping skills. Health workers should be trained in the social aspects of leprosy, and should be better trained in communicating with patients Also community health education should be conducted with communities and their leaders about causes of leprosy and its curability.

FOCUS GROUP WORKSHOPS ON LEPROSY AND ITS IMPACT AMONG RURAL COMMUNITIES IN NORTHERN INDIA - A PRELIMINARY STUDY

Persons affected by leprosy (PALs) often suffer from many social disadvantages and even severe degree of social disruption. It is often seen that even with a medical cure and economic assistance. PALs were not easily accepted back in to their communities. This project aims to bring back community and PALS closer in their social network through a scheme of Focus Group Workshops.

Leprosy workers trained as facilitators conducted Focus Group Workshops in leprosy endemic areas among several community groups. A 6 monthly follow up data were collected, analysed and compared with documented baseline data.

Preliminary results indicated that focus group workshops give ample opportunity for interaction among villagers and has significantly raised their awareness. Knowledge and their ability to communicate with PALs . A significant number of participants shared with their families, friends and neighbours and disseminated the new information they had received. About one third of the participants wish to become facilitators.

It is suggested that community based focus group workshops will have a very significant role in preparing and equipping communities to take care of PALs through elimination to eradication.

Authors: Maria Beatriz P. Orsini, Gilmar S. Figueiredo, llma N. Porto, Maria Aparecida Alves Ferreira, Mônica N. V. Apipe, Ronise C. Lima.

The study presents lhe analysis of the determinants of MDT treatment abandonment by leprosy patients at the Citrolàndia Health Centre, located in a region which developed itself close to a sanatorium Treatment abandonment has been one of the main obstacles to the elimination of leprosy as a public health problem.

It is a qualitative research carried out through semi-structured interviews with patients who have abandoned treatment and others who are being treated regularly. Its main objective is to know the reasons for compliance or non-compliance to treatment.

Alter a reviewing the records it was observed that 30% of the 179 pacients in the active registry had abandoned treatment.

These patients were contacted through mail or visits to their households and then interviewed.

Patients claim they have abandoned treatment due specially to their disbelief in a cure, the occurence of reactions and neuritis during treatment and the side effects of the drugs.

The authors have come to the conclusion that the social representations of the disease and its evolution is greatly influenced by leprosy historic and cultural determinants in the region as well as by the difficulty of the service in carrying out educational measures of impact and actions of vigilance to health.

LESSONS FOR LEPROSY PROGRAMMES F ROM SOCIAL MARKETING AND SOCIAL ADVERTISING : USING THEORETICAL FRAMEWORKS TO IMPROVE THE EFFECTIVENESS OF CAMPAIGNS

¹Novartis Foundation for Sustainable Development, Switzerland, ²Anti-Leprosy Campaign, Ministry of Health, Sri Lanka

In view of the inevitable sealing back of resources for leprosy in the post elimination era, it is crucial that the community understands more about leprosy, its signs, symptoms and treatment prospects. This will help create a supportive social environment which encourages persons with suspicious lesions to seek diagnosis and timely treatment. Health care providers will also have to be motivated to learn more about leprosy in order to detect and treat or refer new cases.

The behaviour change required with regard to leprosy is a "high involvement" decision. Such decisions are typically made through a series of stages namely precontemplation, contemplation, action and maintenance (Transtheoretical model; Prochaska and DiClemente, 1983). Stage specific strategies are required to move the target audience to action and maintenance. At the precontemplation stage, for example, the target group does not see the proposed behaviour as relevant to their own needs often due to a lack of awareness or different values. This stage requires strategies based on cognitive models to create an interest in and awareness of leprosy as well as change of values. After precontemplation, behaviour is driven primarily by perceived benefits, perceived costs, perceived social influences and perceived behavioural control. Once the initial action has been taken, behavioural models become more important than cognitive models.

This paper shows how the transtheoretical model has been adapted for leprosy in Sri Lanka and the stage specific methods used (e.g. highly visible mass media campaign at precontemplation / contemplation; entertainment educational methods like TV and radio dramas at contemplation, interactive sessions to trigger action, ensuring quality care to motivate compliance). The paper also discusses the experience acquired from its practical application (e.g. difficulties in ensuring that improved recognition is accompanied by stigma reduction) and the advantages and limitations of the theoretical framework.

A STUDY OF KNOWLEDGE, ATTITUDE AND PRACTICES (KAP) AMONG LEPROSY PATIENTS IN A LEPROSY CONTROL UNIT.

This study is aimed to assess the existing level of knowledge about leprosy, attitude towards society and day to day practices needed among the leprosy patients. One Leprosy Control Unit is selected for the study. A pretested questionnaire was administered to 336 leprosy patients in random method. Overall level of knowledge about leprosy is found to be low. However, there are significant differences in knowledge, attitude and practice (KAP) among rural-urban, male-female, educated-uneducated, lower-higher socio economic status group of patients. There are lot of misconceptions in knowledge regarding cause, transmission, treatment and infectivity. Negative attitude towards society which reflects negative attitude of society towards leprosy patients is mainly found among those who are deformed. So far as practices are concerned - 62% of patients are attending the clinic regularly, 35% of the patients with anaesthetic hands & feet are practising self care at home and 25% are using MCR shoes. Level of knowledge about leprosy among the deformed is much lower than those without deformity. Since overall KAP levels were low I conclude that regular Health Education to the patients and community awareness programme should be stressed. Health Education has been incorporated as an integral component of leprosy control programme since long time but unfortunately it has been almost totally neglected so far.

In Brazil, Like others counties in latin America catholic church since the 70' years has been involved in social transformation as we can see in the work of "Pastoral da saúde".

The authors relate a ezperience held in vale do Jequitinhonha-MG, Brazil in the last seven years in which health's profissionais share experience with people born the Jequitinhonhas valley and volunteer of health's pastoral.

The authors discuss the importance of aspectes like religious aind cultuial dimensions of life in rural areas with 180.00 citizens in 16 towns in mortheast of Minas Gerais state

The Phenomenon and its relation with " exclusion locus" and neighbourhood. Eduardo R. de Abreu

In a Field Study established since 1984 and repeated in 1989 and 1998 the author pretend to describe the cultural changes and transformation of the valves relative to leprosy patients In two towns not for from Sanatório Santa Izabel, a colory Hospital with aproximately 850 patients.

This paper describe relation ship between citizen from these theree communityes in the last fifteen years.

THE LEPROSY PATIENTS ATTITUDE TOWARDS THEIR CHRONIC AND RECURRING ULCERS: - A STUDY REPORT

Acworth Leprosy Hospital Society for Research, Rehabilitation and Education in Leprosy, Wadala, Mumbai-400 031, India.

A study was launched to understand what the leprosy patients think about reasons behind their chronic and recurring ulcers and their attitude towards these deformities. Ninety such leprosy patients attending leprosy centre and residing in leprosy colonies were interviewed. Out of them 41 were males and 49 were females in age group of 30 to 45 years. The most of then illitrate (26%) or having primary education (65%) and the profession as begging (23%) and unemployed (40%). 95% of them were suffering from plantar ulcers.

The ressons for recurring ulcers ware givan by them as due to loss of sensation (40%), injuries from stones, nails and glasses. (31%), blister formation due to "chapples" or corns (21%), the bites of rats (7%). 37% of them agreed that because of ulcers, their life was disturbed and they are ashemed to move freely in Che Society (69%). All of them know the medical treatment of ulcers and care of hands and feet. But becuase of severe apthy and frustration they neglected that part and managing only with bandages and oinments. They accepted these wounds are going to be their life component. It is suggested that 50% of them who are earning their livehood can be persuaded through their immediate family members and relatives to take care of their ulcers with sucessful results. Studies on those lines are needed.

Persons with leprosy are routinely perceived by many as communicable, unhealthy, unworthy, sinful and unable to be contributing members of society. These erroneous stereotypes can easily become a self-fulfilling prophecy, denying those of us impacted by this rare illness the simple opportunity to succeed.

Historically, as ignorance about leprosy escalated, so did funds allocated to isolate and label millions of persons affected by this bacillus. This can best be illustrated on a bell shaped curve.

Conversely, as more and more individuals were placed in segregated settings, the less they were involved in exercising basic civil rights and the more likely they were to be denied opportunities to make choices on how and where to live. This can be illustrated by an inverted bell shaped curve.

As funding now decreases in response to the prospect of "elimination", the Culture of Leprosy is in dire need of a supportive emotional environment. Opportunities for choice, dignity and respect continue to remain flat. Unless this support becomes international policy, persons diagnosed with leprosy in the future will likely live in fear of being "discovered". The pendulum will swing back to the side of exclusion, decapitating all efforts to live like other persons, without disabilities.

International Association for Integration, Dignity and Economic Advancement (IDEA), P. O. Box 133 Oak Hill, WV 25901 USA

Despite tremendous medical advances, "leprosy" remains the metaphor for the worst that can befall a human being. What are the reasons for this and what are the steps that must be taken to transform the traditional image of despair into a positive image of hope and triumph?

In looking for answers to these questions, it is important to look at the image of leprosy which is presented to the community. When we show the miraculous effects of MDT, do we only show cleared skin lesions or do we show someone who has been given back their future? Do we send a dual message to the public when we say people are cured but then continue to call them "patients".

Positive images of complete human beings are not just for people interested in social issues. They are essential to the effective treatment and control of leprosy and to the elimination of the disease, which includes the elimination of social exclusion, prejudice and discrimination. If society is to change its image of leprosy, it must see individuals with names and personalities who are living full and productive lives, and happened to once have a curable disease called leprosy.

Institute for Health Policy Studies, School of Medicine, University of California at San Francisco. USA

This first comprehensive study of leprosy in the United States provides a case example of a low endemic country. The research assesses the situation of patients who are primarily from immigrant, ethnic and minority groups, and identifies factors influencing recognition of symptoms, availability and access to care, compliance to treatment, and long-term follow-up care. The research also focuses on the variation in services available to these patients, including the Public Health Service Hospital, Government funded regional out-patients centers, and private clinics and physicians, in addition to how training, knowledge and experience of health care providers in a low endemic country influences diagnosis, referral, treatment and rehabilitation. Changes currently taking place in U.S. health care and the impact of health, welfare and immigration reform upon this vulnerable patient population are documented. One objective of the study is to assess culturally sensitive research methods to determine those most appropriate for conducting research on leprosy patients in situations similar to the United States. This study therefore provides a model for studying leprosy in low endemic countries. The research findings and recommendations will be useful for other countries with declining patient populations.

Arega Kassa Zelelew
Ethiopian National Leprosy Disabled Association
P.O.Box 24530. Addis Ababa. Ethiopia

According to WHO, the term "Disabled Person" means any person unable to ensure by himself, wholly or partly, the necessities of a normal individual and/or social life, as a result of a deficiency, either congenital or not, in his/her physical or mental capabilities.

Disability may be the result of biological factors affecting the individual before birth or the result of natural or manmade causes of damage. Among these factors leprosy is one of the leading cause of disability in the world. The disability caused by leprosy affects the individual's social life more than his physical capacity, because of stigma. I will consider the following points in order to understand the facts.

2. The problems faced by those disabled by leprosy as compared to those disabled by other causes.

In conclusion, The Ethiopian National Leprosy Disabled Association (ENLDA), which was established with the objective of solving the complicated problems facing its members as stated above, has used all available opportunities to spread such knowledge in order to change attitudes in society towards leprosy disabled persons.

The education of the public by leprosy workers is challenging and must be kept up. Lastly I want to stress again that the leprosy disabled person wishes to enjoy dignity and recognition in society.

IDEA, Regional Office for Africa, #48, Toyin Street Opp. Water Parks, Ikeja, Lagos, Nigeria

This paper is about people, about an urgent human situation, and about human response to that situation. In the next two years, WHO will declare HD "eliminated". In the meantime, as IDEA slowly but surely becomes established all over the world, IDEA Africa, though still in the process of setting up her Regional Office, has already gotten down to serious business, building up a veritable network across the continent, sponsoring and encouraging direct PAL participation in important international events, creating some pilot projects and making their enabling presence felt here and there. Nigeria leads in this effort and the pioneer members of IDEA Africa are pursuing the programs and targets they had set for themselves with a sense of commitment and with all seriousness.

The main objectives of this paper are to: 1) take a cursory look at the HD situation presently in Africa, from the point of view of African PALs and other IDEA Africa Members, and put the finding side by side with the implications of the imminent WHO elimination target; 2) express the opinion of PALs on elimination by the year 2000; 3) estimate how many people need IDEA intervention in Africa: 4) examine effect of some rehabilitation strategies and methods used by some older organizations who have been in the business of rehabilitating PALs long before IDEA was born.

(This investigation was sponsored by members of IDEA Africa, with logistial support from the TLMI, GLRA and the Federal Government of Nigeria.)

A Psycho-social study was conducted on 150 Leprosy affected families and their children and 200 members of the general public to assess the social acceptance of children of leprosy affected people. Special focus was given on education, occupation, and marriages. The results show that the children of leprosy affected families are well accepted into schools/colleges, also they do not face much discrimination by the general public in getting employment or at the place of work.

However, in the marriage context social stigmatisation of leprosy affected families is still significant. In addition many leprosy affected families expressed rejection without being able to cite specific experiences. The study shows that there is lack of awareness of leprosy among the general public especially among socio-economic disadvantaged people. Designated schools for families of leprosy patients tend to demotivate the leprosy affected families from attempting to integrate their children into general schools. This calls for counselling of leprosy affected families There is also a need for intensive health education to members of the general public with special focus on those of low socio-economic status and those who hold to orthodox or conservative traditions which tend to potentiate the rejection of leprosy affected people.

SOCIAL STIGMA STATUS OF PALS IN THE PROJECT AREA COMMUNITY- PRELIMINARY FINDINGS-

The present scenario of Leprosy with decline of prevalence and deformity among new patients and higher percentage of MDT. Coverage with priority for Community awareness, the social changes that has taken place in the community towards the leprosy patients has taken an important preposition.

So a study has been conducted at The Leprosy Mission Hospital, Dayapuram, Manamadurai to find out the General Stigma attached to Leprosy patients especially with deformity together with their knowledge on disease and control programme benefits.

The study population includes patients currently under treatment and OPD Programme, their households, immediate neighbourhood and a community sample, a Community Leader and a Village functionary. Structured questionnaire was designed separately for each category of respondents and was conversed by trained Leprosy workers.

Preliminary analysis suggests that there is a decrease in the level of social stigma. It also reveals the need for continued awareness Programme. The full analysis of the data is being done.

There are measures to eliminate Leprosy and other economic upliftment measures like providing sarees/ dhoties, bed sheets, Bank loans and other financial assistance. This study is designed to measure the status of Social Stigma.

Nimal Kasturiararchi¹, Mitchell Weiss², Penny Grewal³, Padmini Gunawardene⁴, Dayamal Dewapura⁴, Sunil Settinayake⁴, Lakshmi Somatunga⁴,Vinya Ariyaratne⁵

¹University of Peredeniya, Sri Lanka, ²Swiss Tropical Institute, Switzerland, ⁴Novartis Foundation lor Sustainable Development, Switzerland, ⁴Anti-Leprosy Campaign, Sri Lanka, ⁵University Sri Jaywardenepura, Sri Lanka

Leprosy is a stigmatised disease in many societies with serious implications for the management of leprosy programmes. With the wide scale use of MDT in leprosy endemic countries, people have seen positive prognostic features which have led to a significant reduction in fear of the disease and stigma. This collective illness experience is lacking in low endemic countries where stigma may operate differently.

To ascertain how stigma affects help seeking behaviour and the overall illness experience in Sri Lanka, 160 patients were selected at random from three categories of patients on treatment: those detected without deformities.

with numbness and with grade 2 deformities. Semi-structured interviews were carried out to obtain narrative accounts of illness experience including patterns of distress, personal experience with stigma, names for the disease, help seeking behaviour and experience with treatment.

The study revealed how patients suffered from their own stigmatising ideas about this illness, rather than social castigation. Their suffering arose from concern about their diagnoses characterised by their internalisation of the cultural syndrome, stress of having their diagnoses known to others resulting in possible social isolation. The distress due to the local term used to denote leprosy is very significant. In addition, financial concerns due to the physical effects of leprosy such numbness or deformities were mentioned as well as symptoms pointing to transient psychological conditions.

The findings indicate that these individually internalised experiences need more attention than the social attitudes towards this disease. To assure quality of care, health care providers who treat these patients must be trained in counselling techniques, psychiatric referral and disability care so that they arc aware of the psychological impact of culturally internalised stigma, even in the absence of overt social somatization.

Elimination will remain a dream in the hearts and minds of persons affected by HD if integration is not realized, respect and dignity are not restored, and equal rights and privileges are not enjoyed. It is time to consider ourselves equal partners in the delivery of basic information and knowledge.

Our testimonies and success stories are the best educational tools. We can encourage others to seek early treatment, teach prevention of disabilities, assit in early diagnosis and referral, and be a support group. Our physical disabilities can be memoriès of the past. HD can be just one chapter in our lives.

In the Philippines, we have developed a program whereby facts about HD, testimonies, experiences and success stories are presented in musical and narrative form. Values, culture and lifestyle are portrayed, dramatized and spoken in local dialects. Target audiences are college and university students; areas/ communities with high HD prevalence rates; areas/ cummunities with strong social rejection; and companies/ institutions which don't accepted persons affected by HD in the workforce.

We can make a big difference in the hearts and minds of the public. This is a challenge ... a mission ... that needs the involvement of each individual affected by HD.

WHETHER RFT STRATEGY IN MDT LEADS TO MORE AMPUTATIONS IN LEPROSY PATIENTS -A 20 YEAR STUDY

Dr. V. Durai, & Dr. P.K. Oommen Central Leprosy Teaching & Research Institute. Chengalpattu

The introduction of fixed duration of treatment envisages RFT after 6 doses in 9 months and 24 doses in 36 months for PB cases and MB cases respectively. This strategy has resulted in loss of regular contacts between medical team and the residual cases with insensitive hands and feet. This was in contrast to the mono drug treatment period, where patients had regular contacts with medical team. The residual problems such as management of ulcer, care of anesthetic feet & hand requires the attention of medical team even after completion of MDT for prevention of deformity.

In this study, patients admitted in Central Leprosy Teaching and Research Institute from 1976 to 1995 was used for analysis. A total number of 293 amputations, below-knec level, symes and midfoot amputations were done. The amputations performed before 1986 considered as mono era patients and after that considered as MDT era. The criterion for selection of patients for amputations and the surgical team philosophy on management over the last two decades has remained unchanged.

Various factors that lead to amputations were discussed in detail. This study reveals that RFT strategy in MDT has not resulted in decreasing the risk of mutilating surgeries. It is suggested that a working system of POD and also to have follow up of all the high risk patients with insensitive hands & feet, atleast once in a month.

With so much uncertainy about the future of Hansen's Disease centers throughout the world, the experience of St. Giles, the last HD Hospital in England, and its five remaining residents is an important example of how progress can lead to a feeling of abandonment.

In the mid-eighties, St. Giles ceased to be a hospital and was taken over by a housing association. Over time, we were joined by 25 individuals, most of whom have mental disabilities. I sympathize with them, as they have to be housed somewhere due to similar closure of their own centers, but I question whether this population was the best suited to join us at St. Giles. In addition, our care has decreased from 24-hour, 7-day-a-week specialized medical care to one part-time nurse. The atmosphere is nothing like it was when we all had the same problems and understood each other. In many ways, I feel more isolated and alone than ever.

Hansen's Disease centers have been homes to thousands. As our numbers decrease, decisions about mixed-use for these centers cannot be made simply on financial grounds. Psychological, medical and social factors must be taken into consideration and discussed with those whose lives will be impacted by the decisions. It is essential that abandoned buildings don't result in abandoned lives, no matter how small our numbers may be.

President for International Advocacy, International Association for Integration, Dignity & Economic Advancement (IDEA), 1541 Kalakaua Ave., #802 Honolulu, Hawaii, 96826 USA

Twenty years ago I was denied service in a restaurant because I had Hansen's Disease. Fifteen years ago I was arrested for attempting to have a voice in decisions concerning my future. Ten years ago I was appointed to the Hawaii Board of Health. Two years ago I spoke at the dedication of a housing complex for senior citizens and persons with disabilities. Last year I spoke at the United Nations.

The process that led to these changes provides practical solutions for eliminating society's fear and resulting prejudice against people with HD.

When injustices accumulate over a long period of time, the human spirit can no longer accept such conditions, and three things occur: 1) Individuals realize that they have to assert themselves and speak out publicly in order to be seen as people, not a disease; 2) They realize that one cannot fight discrimination alone so network with others who have had HD; and 3) Reach out to caring people in the community to become partners in overcoming restrictive policies, archaic attitudes and discriminatory actions.

Ultimately, this process shows the community that those of us with HD are many things, but there is one thing we are not - we are not "lepers".

While documenting the history of leprosy around the world, many dramatic and inspiring accounts have been written or told. Too often, however, the stories come from religious leaders, doctors or social workers and forget to include the words of the people who actually were affected by the disease and had to overcome an ignorant society to live productive lives.

If you visit the original (and now abandoned) Kalawao settlement on the Kalaupapa peninsula, you will hear detailed descriptions about Father Damien, Mother Marianne, Robert Louis Stevenson, even the wife of a pharmacist who kept a diary, but you won't hear a single memory of the thousands of people from Hawaii who were taken from their families and sent there with the disease. We will never know who these people were. Even their gravestones, most of them washed away or crumbled to bits, are gone.

Fortunately, such an incomplete history will not be repeated at modern-day Kalaupapa where people who had the disease have been encouraged to share their stories in books, newspaper articles and video interviews. As a result, these remarkable individuals will be remembered not simply as "patients," but as human beings with full lives. With these stories, a much more accurate account of life in Kalaupapa -- its tribulations and its triumphs -- has emerged.

These first-hand memories are not only necessary to tell the true history of leprosy and how it affected people, but to hearten others who have been recently diagnosed and fear their lives are over.

As a reporter for The Maui News, I have written more than 50 articles about Kalaupapa's people, focusing on life after the disease. I would like to share this message so others around the world will do the same.

Nimal Kasturiaratchi¹, Mitchell Weiss²,Penny Grewal³, Padmini Gunawardene⁴,Dayamal Dewapura³, Sunil Settiiuyake⁴, Lakshmi Somarunga⁴, Vinya Ariyaratne⁵

¹University of Peredeniya, Sri Lanka, ²Swiss Tropical Institute, Switzerland, *Novarris Foundation for Sustainable Development, Switzerland, ⁴Anti-Leprosy Campaign, Sri Lanka, ⁵University Sri Jaywardenepura, Sri Lanka

Although, Leprosy is considered a stigmatising disease the exact nature of stigma is difficult to be studied. Leprosy workers consider stigma as given and attempts to repeal it by educating patients and general public to view it as an "ordinary" illness. This exercise becomes futile when the complex nature of stigma is nor understood fully and when its subtle ways of manifesting are not recognised.

This paper presents how stigma manifests itself when three methodologies were adopted to determine it. The methods referred to are: ethnography, empirical questionnaire and analyses of qualitative narrative statements made by respondents made as answers to quantitative questions.

These studies, conducted in Sri Lanka, suggests that ethnograhic studies reveal the overall cultural themes of stigma which can be best utilised in health education programmes. The quantitative (empirical) studies on the other hand enabled the understanding of the comparative perspectives of stigma among different types of respondents including the sufferers themselves. The analyses of narratives indicated the subtle mechanisms of internalisation of stigma indicating how psychiatric, social and cultural manifestations could occur.

Social marketing, patients care, and involvement of health care providers within the antileprosy programmes warrant different types of information. The Sri Lankan experience may assist leprosy workers in other countries to select an appropriate methodology to study stigma depending on the needs.

Usually people affected by leprosy spend most of their lifetime with their family and in their communities. However, there has been a tendency -especially in areas where there is a lot of stigma attached to leprosy - to 'draw out' leprosy sufferers from their communities into leprosy institutions. Initially, this assistance provides great benefit. However, on a longer term basis, such institutions can result in both the loss of the natural community support and the creation of high expectations on the side of the leprosy-affected clients, for social and economic security. Thus the clients can become very dependent. In the past help has often been provided from a specialist to a 'leprosy patient' - rather top down. Now is the time to recognise people affected by leprosy as equal partners. It is time to discover communities as partners in our efforts to facilitate help for our clients. As we move towards the eradication of leprosy, it is time to develop sound strategies for rehabilitation, based on such partnerships.

We have to start to go to the homes of our clients, to meet their families and communities in order to be able to understand their situation and to help them to live an independent life with dignity. In addition, it is our responsibility to motivate, equip and enable communities to assist their people affected by leprosy. Treatment of leprosy has been integrated into the general health system. We must now work through an integrated approach in facilitating rehabilitation. Community-based rehabilitation approaches have the great potential to work in real partnership with people with disabilities, including those affected by leprosy and their communities.

Vo Tri Toan, Kirsten Løvdal Bjune and Gunnar Bjune Centre for International Health. University of Bergen. N-5021 Bergen, Norway

The Central Highland has Vietnam's highest prevalence of leprosy. The health infra structure is weak, population scattered and consists of more than 50% minority populations with more than ten different languages and cultures. The National Leprosy Eradication Programme is implementing the Special Area Programme for Elimination of Leprosy (SAPEL) and Leprosy Elimination Campaign (LEC) strategies to reach the highland population.

Gia Rai and Banah are the two largest ethnic minorities in Gia Lai Province. Remoteness of the villages makes health and educational services practically non-accessible. Traditionally they practised slash and bum agriculture and supplement their meagre resources by hunting and gathering in the surrounding forest hills. The villages have to move every three to four years when the soil is exhausted. A fixed pattern of movement brings the village back to its first location at fifty years cycles. However, environmental deterioration during the war. immigration of fanners from the lowlands and increase in the indigenous population have made this life style non-sustainable. Socio-economic conditions in leprosy villages are appalling. The Government of Vietnam attempts to improve the conditions through a special programme for Elimination of Starvation and Alleviation of Poverty Programme (ESAP).

For at least 100 years Gia Rai and Banah have segregated leprosy families in special villages where most of the adults have major leprosy deformities and disabilities and have to rely upon their children and neighbouring villages for food supplies. The segregation pattern is unique in the sense that the patients have usually lived for a long time well integrated in their village of birth until all families with leprosy in the village split off and establish a new village much the same way as villages which have grown too large split into two. There are no obvious psychological hostility towards the leprosy village, and communication between this and the mother village seems to be free. The traditional organisation of the leprosy village is the same as in the culture as such (matriarchal extended families) with one significant difference; their settlement is permanent and thus more fit for sustainable development.

We will present an explorative medical anthropological study done with the aim of developing the 37 leprosy villages widely dispersed in the province to nuclei for improved living conditions and sustainable development for the ethnic minorities as a whole. Data were provided by the local health services and provincial authorities and supplemented with participatory observations in a few representative leprosy villages.

Yihuang County Station for Skin Diseases Control. Yihuang County, JiangXi Province. China

One year after being enrolled at the JiangXi MedicaI College in 1972, be unfortunately was diagnosed as leprosy. Because of the long establiched stigma in the society towards leprosy, be discontinued his study and was accepted in a leprosy village for isolated treatment.

Since then, he did not give him seIf up as hopeless but put up a tenacious fight against the illness. and served patients warnheartedly inside and outside the village with his know ledge. His selkless service has benefited the health of a great number of people including saving an youth's life from freezing river His untiring efforts and contributions to leprosy control and general health care for more than 20 years made him trusted by related authorities. He has succeeded in physical and social rehabilitation both

Leprosy is a unique social disease. A social disease needs a social cure. Any patient affected by any disease other than leprosy ceases to be a patient once he is cured of the disease. But in the case of leprosy it is not to be so. Even alter cure one has to carry the tag of Social stigma. This situation warrants the need for ushering in a Social Cure for leprosy patients.

Social cure of leprosy is acceptance of a person cured of leprosy by the contemporary society and allowing him to function as a normal individual socially, without discrimination, let or hindrance, on all walks of life. Capsule is a set of community action programme envisaged to prepare a congenial atmosphere to bring about a Social Cure for leprosy patients.

No programme, however good that be, can bring lasting changes in the beliefs and attitudes of the people unless that doesn't become the peoples programme. The following Special groups are formed and sustained in the community.

♦ Community Action Groups
♦ Advocacy Groups
♦ Friends of Leprosy affected Groups
♦ Participating the patients directly in disability limiting exercises

The above given special programmes initiated will help accelerate the reintegration of the leprosy cured persons into the society which ultimately is the Social Cure for leprosy.

A small survey was earned out in northern Bangladesh to assess and compare the level of knowledge, attitudes and practice towards leprosy and TB among two areas that differed widely in the amount of health education received about these diseases

The results indicate that without a health education programme, levels of knowledge about the cause and treatability of the diseases are poor. Only 16% of respondents in the 'uninformed' area mentioned 'skin patch' in a question about what they knew about leprosy, and 44% mentioned 'cough' as a symptom of TB. In the area that had received health education, 90% mentioned respectively 'skin patch' and 'cough' 78% of the respondents would not buy goods from a shopkeeper known to have leprosy, 76% if he had TB in the unreached area, but in the community who had received health education the proportions were reversed with three quarters agreeing to purchase from a diseased shopkeeper.

There are low levels of knowledge about leprosy and TB, and unfavourable attitudes in a community that has not received health education. However, knowledge levels were much higher and attitudes more positive in an area that had received a health education programme.

The authors present fhotos. Interviews, friends and relatives testimony of a brave man who fhought since childhood until his death against prejudice in favour of people affected by leprosy, promoting dignity for all.

ECONOMIC SELF SUFFICIENCY AND SOCIAL INTEGRATION OF DISPLACED LEPROSY AFFECTED PERSONS THROUGH MICRO ENTERPRISES.

Persons directed by leprosy in addition to the need to adjust to physical disability may find themselves segregated and displaced in the community. Thus it is important to emphasise the process of normalisation by providing them the opportunities to enhance their economic and social status

A Domiciliary Rehabilitation Scheme launched by the Gentian Leprosy Relief Association Fund in 1974 has experimented the promotion of micro enterprises by providing the persons, interest free loans.

A study covering 50 beneficiaries revealed that 83% of them have attained enhanced income and self sufficiency through the different enterprises which they could start out of the loans extended by the scheme. The study also revealed that 66% of the respondents have found that their purchasing power has increased by 30% and they can lead an independent life.

• This study revealed that by developing a sound strategy of loans to promote micro enterprises for self employment and monitor the scheme through counselling and followup by trained and comitted staff the social integration of displaced leprosy affected persons can be done on a wide scale.

FACTORS THAT AFFECT LEPROSY PATIENT'S DECISION TO DISCLOSE HIS ILLNESS TO OTHERS

Edgardo M. Gonzaga, M.D, Troy Aguedo Gepte IV. M.P., Socorro P. Lupisan, M.D. Febicita M. MedaRa. M.D.

Department of Epydemiology and Biostatistics, Research Institute For Tropical Medicine, Alabang, Muntintapa City, Philippines.

A study was conducted among leprosy patients seen at the Leprosy Section of the Research lnstitute For Tropical Medicine to determine the factors that affect leprosy patient's decision to disclose his ... to others (based on Triandi's Theory).

Qualitative methods such as Key Informant lnterview anf Focus Group Discussion (FGD) were utilized in the construction of the questionnaires. One of the authors served as the key informant based on his experience with leprosy. The lnterview was informal Based on the outcome of the interview, a field guide consisting of open eded questions was prepared for the intended FGD. The FGD was done to effect opinions and answers to questions regarding the topic. A group of eight (8) leprory patients were gathered together as one rooms at the unit.

Questionnaires were designed and scaled based on the outcome of the FGD and were pre- tested. Scaling utilized adjectival responses with corresponding discrete numerical, equivalents. All fifty (50) respondents were instructed to choose a number from one to five of which 1 would indicate a responses closest to the selection on the left sido , 5 would indicate response closest to that on the right side, A selection of 3 indicate a neutral response.

Data were entered using the EPI- INFO software. STATA software was used in the analysis. To maximize realibilty and validity of items in each subscale, item analysis was performed for all items in the questionaire using the following methods: 1) descriptive analysis; 2) inter- Item analysis; 3) item total analysis; 4) Internal consistency coefficient (Croabach's alpha); and factor analysis. Methods 1 to 4 were essential in deteting or retatning items in each subscale. Method 5 was utilized to confirm decision.

Eighteen (18) items were found to be valid for scaling, of which two each pertains to social factors, affect, valnes, motivating factors and habit, while 8 items belong to facilitating factors. More items would have to be developed and pre- tested for scaling to satify the requirement of at least 5 items per factor using the Triandi Model. Questionnaire construction, as shown in some modules would involve a series of activities and pre- testing before a final draft is assessed as suitable for data collectioan.

Objective: To assess the quality of life (QOL) of leprosy patients, in relation to their impairment grade (EHF score) and to compare them with other dermatology patients.

Subjects: 60 leprosy patients with varying degrees of impairment, who attended ALERT Hospital, were included. 24 patients attending the acne clinic were included for comparison.

Instrument: The WHOQOL-BREF questionnaire was developed by WHO to assess quality of life. It has been validated in many different cultural settings, and for different disease states. The 26 questions are divided into four domains (physical health, psychological health, social relationships and environment). This instrument therefore addresses the measurement of -handicap* according to the International classification of Impairments, Disabilities and Handicaps (WHO. 1980).

Results: There was a highly significant decrease in QOL in all domains for leprosy patients, compared with acne patients. There was a strong inverse correlation between EHF score and QOL in leprosy patients, for each domain. Female leprosy patients had significantly lower scores than male patients in two domains, psychological health and social relationships.

Conclusion: Leprosy patients have a low QOL when compared with acne patients and this is directly related to their EHF score. The poster describes the use of the WHOQOL-BREF questionnaire.

The aim of this study is to investigate the degree of depression in leprosy patients.

This study was done with the leprosy patients (25 male. 25 female) and non leprosy persons (25 male. 25 female). Both groups had equal social characteristics.

Porteus or Alexander IQ test annd Beck and Hamilton depression scale was used for analysis.

In 38 leprosy patients (76.0%) have depression in moderate and severe degree. This ratio was 34.0% (n=17) in control group: 80.0% (n=20) in female leprosy cases; and 36.0% (n=9) in control females.

These results indicate that depression may create more problems for leprosy patients.

Depression may result of the medical and social problems of leprosy patients and worsen to solve of their problems.

LEPROSY PATIENTS AS CHILD OR ADULT WOMAN -THEIR INTERRELATIONSHIP WITH FAMILY COUNTER PART

S. Joshi, P. Kathe and S.S. Naik Acworth Leprosy Hospital Society for Research, Rehabilitation and Education in Leprosy, Wadala, Mumbai-400 031, India.

Seventy five children and 96 adult leprosy patients attending leprosy clinic in Mumbai were interviewed with their family members especially

children of leprosy patients and income generating parents of child leprosy patients. It was observed that after initial disturbance at the time of diagnosis, the healthy family members had shown acceptance and. positive behaviour towards leprosy patients in due course of time (75%), probably due to rapid clinical regression due to MDT and proper health education in Society. However the healthy parents showed some reservation (40%) but children at large shoved positive attitude in acceptance of disease.

Seventy women leprosy patients registered during last five years were interviewed for their status and acceptance in families and compared with old leprosy women patients residing in leprosy colonies. It was observed that there was a dast ict change in positive acceptance of family members towards women leprosy patients in recent period due to early detection and effective MDT treatment.

A study was undertaken on ex-leprosy patients living in three colonies in and around Vizianagaram town, to explore their attitude to begging and willingness to be rehabilitated.

Open Ended Interview Schedule was administered by our professionally trained social worker.

STUDY OF PSYCHO SOCIAL ASPECTS OF DEFORMED AND NON DEFORMED HANSENS PATIENTS - CROSS SECTIONAL COMPARATIVE STUDY

Available 30 deformed Hansens patients were taken from hospital and 30. Grade I deformed Hansens patients matched for the age & sex were chosen randomly from the list of the control area patients of Philadelphia Leprosy Hospital. Salur. A pre tested structured interview schedule was administered by the investigator . Results have been analysed using statistical methods for significance.

Analysis of the results demonstrated a significant difference among deformed and non deformed Hansens patients in the following area.

This study demonstrates how deformity effects the psycho social aspects of Hansens patients.

Maryann Richard, Samjhana Gurung, and Ruth Pariyar Counselling Department, Green Pastures Hospital, Pokhara, Nepal

Counselling Services at Green Pastures Hospital (GPU), Pokhara, Nepal began in October 1993. A Nepali nurse and I, an Expatriate Counselling Psychologist, have worked together to understand and respond to the counselling needs of the GPH in-patients. Our goal was to help reduce the negative effects of leprosy stigmatization through assessment of those in need and men follow-up individual counselling. We began to see referrals from the doctors and our own selection focusing on those who were somewhat confused, not interacting much with others, anxious, depressed and on rare occasions psychotic. A Psychosocial Assessment form was designed to address the person's Psychological and Socio-Economic needs. Using this form as a starting point we assessed each in-patient at GPH (and some selected out-patients) and then chose which persons needed individual counselling. Typically, we met with each person needing counselling for 30 - 45 minutes weekly. Those with depression or psychosis would be met almost daily, but little real counselling is done until they are stabilized on medication. Assessments and counselling follow-up have helped us to focus our efforts on those needing psychosocial help. We then in conjunction with other departments at GPH meet in a rehabilitation team to discuss with the person their concerns and needs looking at strategies for meeting the person's needs. Patients feel listened to and understood. They also feel more able to meet the difficulties they face in their home environments after counselling. As there are no basic listening courses available in Nepal, we began to teach Psychosocial Listening Courses to nurses in N.G.O.s so that (hey would be better equipped to wholistically care for persons affected with leprosy.

Counselling services at Green Pastures Hospital (GPH), Pokhara, Nepal began in October 1993. A young Nepali nurse took up the half-time post and I, a Counselling Psychologist, joined her as her teacher and supervisor in January 1994. Our goal was to help reduce the negative effects of leprosy stigmatization on persons affected with leprosy through a psychosocial assessment of those in need and then follow-up individual counselling. We began to see referrals from GPH doctors and our own selection focusing on those who were somewhat confused, not interacting much with others, anxious, depressed and on rare occasions psychotic. From the above assessments it seemed to be clear that for some people stigmatization, whether initiated by self-rejection or rejection by others, was a common theme. We felt that the best way to talk about these feelings of rejection was through small support groups. Our groups run 5 x 2 hour sessions over 5 weeks. They composed of 5-6 individuals and divided into men's, women's and children's groups. In these groups people are encouraged to remember things from three phases in their lives: before contracting leprosy, after contracting leprosy up to the present, and life after leaving GPH. Themes which arise are stigmatization, depression, reconciliation, and dependency. Our discussions are supplemented by pictures used to further explain these themes. Using a Group Therapy method more people can be dealt with at one time, they learn from one another's successes and failures, and experience reduced levels of anxiety about their life after leaving GPH.

A POSITIVE OUTCOME IN COMMUNITY EYE HEALTH CARE SERVICE OP THE LEPROSY SUFFERES IN EASTERN INDIA IN THE LAST TWO DECADES :

For many years, social stigma has kept the Leprosy sufferers away from all the social opportunities including the existing health care facilities for the general mass. In Pre Dapsone and Dapsone Era (i.e. upto 1988) Eye Health Care Services and comprehensive Eye health care camps were organised only in the leprosorium for these patients. The materialisation of the concept of 'Release from treatment' following successful Multi Drug Therapy has revolutionised the community eye health care delivery outlook in Eastern India. In post MDT Era the Leprosy affected persons are enjoying all the services rendered for the general healthy people whether in the general hospital or in the mass Eye Operation camps. Even the general healthy cataract blind people of the neighbouring villages, staying side by side of the Leprosy sufferer & accepting the same nursing , are undergoing surgery in the comprehensive Eye Camps being held within the After Care Leprosy colony campus by active organisation and participation of the after care leprosy sufferers organisation. Tlhis is a great positive turn to our community Eye Health effort 'From darkness to light'

In this study, we have planned to give results of our scholarship projects. 53% of 545 students were male and 47% female. 72% of them were primary school students. 9 were university students.

Community based rehabilitation services has one important component of economic upliftment and social integration. Economic rehabilitation of PAL's who are physically, mentally or socially handicapped forms an integral part of any disability management program. A unique approach of identification of beneficiary from social history, status verification and need analysis has been adopted. The economic assistance was then made available, preferably in kind (for occupation) to the 188 PAL's. Their social status was closely monitored with follow-up of more than 5 years. The excellent results demonstrate that majority of the PAL's have been well settled and support their family. In some instances the family members have also benefited by the aid. It is a sustainable development from human angle. There is no stigma associated with PAL's can be judged by sheer participation of community in such function and involvement of community leaders and opinion makers. Various other plans have shown their eagerness to spare the funds and be partners in making social integration through economic rehabilitation possible for large number of deserving cases. In fact, the integration of this aspect in other plans is necessary and will become the cornerstone of integration of leprosy disabled with other disabled. The concept, management and benefits will be presented.

We realized that if we were able to rehabilitate leprosy patient socially in other words if we can create a new way of living and earning money for the treated patient we could prove the society and ourselves that leprosy could be really controlled in the near future.

For this reason we planned social projects for our patients. In this study we planned to give 106 projects, 60% of them were from rural area. 47% of the projects were animal projects. We helped them for house reconstruction also (n:23). We could find sponsor for 22%projects.

A SOCIAL INVESTIGATION OF CURED PERSONS AFFECTED BY LEPROSY IN COUNTIES ATTACHED TO SHANGHAI MUNICIPALITY

The goal of basic eradication of leprosy was reached in Shanghai in 1990 and there are 1 411 cured persons affected by leprosy in its county area at present A specially designed questionnaire was administered to 477 randomly selected subjects (male 344, female 133) with an average age of 61.8 years (52% of them >60 years) among the mentioned cures. Following points were observed in this study: 1) disability rate (WHO II & III grade) was as high as 59.75%, 2) 135 (28%) were illiterates, 277 (58%) primary level, 57 (12%) primary middle school level, 3) 43(9%) not married, 434 (91%) married, 4 (1%) divorced, 91 (19%) beneft of spouse. 468 (98%) have a harmonious family; 4) there was still discrimination against cures (100. 21%) and cures' family (91, 19%). 5) 348 (72.96% ) economically self-supported . but only 75 ( 15,7% ) with an annual income of more than 4 000 yuan and 92(19.3%) less than 2 000 yuan, and as many as 112 (23.5%) cures are still in need of financial support from others; 6) 467 (98%) wish to gel help from rehabilitation programme and 415 (87%) like to have home visit by medical workers. 7) 458(96%) are basically familiar with the symptoms of relapse and 472 (99%) will consult a doctor actively if relapse occurs.

The above findings indicated a big success achieved in leprosy control and a remarkable reduction of discrimination against persons affected by Ieprosy in Shanghai. But financial straits, daily life care and medical rehabilitation are serious problems to be solved for the remaining cures. A combined programme of leprosy rehabilitation and community based rehabilitation should be worked out and could be implemented smoothly.

Dong'an County Health and Epidemic Prevention Station. Dong'an. Hunan Province. China

The revised defense style questionnaire was administered to 8 outpatients with leprosy (male 7, female 1; average age 33 years) and to control subjects from the general population. The difference of mean score on immature defense style factors (t=5.311, p<0.01) and on rationalization factor (t=4 394, p<0,01) in patient's group was significantly higher than those in normal individuals. The patients had a greater tendency towards immature defense style with poor self-control consciousness and serious rationalization psychology. The author recognized that projection (t=7.563, p<0.01), passive aggression (t=9.790, p<0,01) and dependence (t=6.250, p<0,01) were main symptoms of immature defense style, and that in order to reduce the pressure from the community and to ease their psychological suffering they dealed with events they faced with concealment of disease and tried to cover their nervousness and uneasiness due to suffering from Leprosy. The author also indicated that passive phycological defense style was more frequently observed in new patients without previous antileprosy therapy.

KNOWLEDGE AND ATTITUDE OF PHC WORKERS IN IBADAN METROPOLIS TOWARDS LEPROSY AND ITS INTEGRATION INTO PHC SERVICES

Integration of leprosy services into Primary Health Care is a goal of the Nigerian Leprosy Control Programme that aims at making services cost-effective and accessible. Previous studies have shown that health workers do not differ from the general public in their aversive attitudes towards leprosy patients. This study was undertaken to document the knowledge and attitude of Local Government Area (LGA) health staff towards leprosy and integration into PHC in 5 LGAs that comprise Ibadan metropolis and to serve as a basis for planning training programmes. All available PHC staff working in the LGA clinics were interviewed using a self-administered questionnaire. Twenty questions, containing 135 knowledge items were used to produce a score about the cause, treatment, complications and management of leprosy. Sanitarians scored significantly higher (90 points) than Nurse/Mid wives (87) and Communty Health Extension Workers (82) (p< 0.0004). Though few had previous inservice training in leprosy (14%), those who had training scored higher (90) than those who did not (84) (p< 0.006). Two attitude scales measured attitudes towards patients and towards integration of services. Both were significantly higher for persons who had attended inservice training. The results point to the value of and need for more training.

SURVEY OF DISABILITY RATES IN 28.674 PERSONS AFFECTED BY LEPROSY IN JIANGSU PROVINCE PROF CHINA

Zhang Lianhua. Xie Zhizheng. Xie Zhizheng. He Yuhui et al Jiangsu Provincial Institute of Dermatology. P R of China

A survey of impairments ami disability was carried out in Jiangsu Province at the end of 1996 to provide data useful for planning a provincial rehabilitation programme. Findings showed that the disability rate (WHO grades 1-3) was 61.42% overall with very significant differences related to sex, leprosy classification, literacy and occupation. Experience gained during the survey showed that the disability rate influenced the patients' capability of work and activities of daily living. Impairment and disability sometimes commenced during or after treatment, but most frequently before start of treatment. The proportion of new cases who were detected within two years of observing the first signs of leprosy was in inverse proportion to the grade II disability rate among those patients. The authors emphasise the importance of early detection and treatment of leprosy and neuritis and of self-care training for those with nerve function impairment, Study findings illustrate the fact that the earlier that impairment prevention and rehabilitation measures are instituted the better. Involvement of the whole of society in programmes of leprosy rehabilitation is important and welcomed.

RELEVANCE TO FUTURE PLANNING OF LESSONS LEARNED DURING THE CHINA NATIONAL REHABILITATION PROJECT

Jean Watson, Zhamj Guocheng. Yan Liang Bin. Jiang Juan. Wei Xiaoyu. Angelika Piefer

A national. China Leprosy Rehabilitation Project, undertaken in 2 stages during the years 1990-1998. is described. This was a collaboration project between the Ministry of Health of P R of China. The Leprosy Mission International and other ILEP organisations. Numbers of cases involved totaled 13.000 in stage 1 from 1990-1993 and 27.959 in stage 2 from 1995-1998. The first project objective was to improve and complete the management and supervision systems in preparation for future national projects. Specific objectives related to preservation of nerve function, prevention and overcoming of secondary impairments and improvement of function. Management experience is described in areas such as:

Benefits of this project could usefully be extended to thousands of leprosy affected persons living outside the current project areas. The paper outlines some management lessons learned from project experiences and their relevance to forward planning of activities designed to minimise impairments and thus their effects on lives of leprosy-affected persons and their families and communities.

Wim H. van Brakel_. Alison M. Anderson, Michiel de Boer, Erik Scholten, Frauke C. Wörpel. Rohit Saiju, Hari B. BK, Sambha Sherpa. Shaha K. Sunwar. Juna Gurung.

PURPOSE: To describe the development of a scale to assess difficulty in activities of daily living experienced by people in rural areas of developing countries, such as Nepal.

METHOD: Staff experienced in working with leprosy affected people were consulted about activities of daily living they thought should be included in an assessment A 68-question survey questionnaire was made, sampling five domains of the Disability (D) classification of the International Classification of Impairments, Disabilities and Handicaps (ICIDH, WHO, 1980). Basic on a survey using this questionnaire, some questions were omitted and a few new ones were added. These were rearranged into a new questionnaire. This new questionnaire was translated and back-translated to check the understanding of the Wording. Criterion validity was checked by comparing the sum score of the scale with a sum score given by a panel of experienced staff in a sample of 37 patients. Intra and inter-interviewer reliability was assessed on 29 patients using weighted kappa statistics. Stability over a period of a week was evaluated in a simitar way. Considering the results of these studies, several questions showing weak reliability or stability were omitted.

RESULTS: Of the original 68 questions, 38 were included in second draft of the instrument Five questions were added to assess difficulty in relationships, one question about the use of assistive devices and two about occupation and employment The sum score of the scale against the expert score gave a Spearman correlation coefficient of 0.72. Intra* and inter-interviewer reliability testing gave kappa values of 0.77 (95%CI 0.73-0.81) and 0.61 (95%CI 0.56-0.67). respectively. The stability test resulted in a kappa of 0.76 (95%CI 0.70-0.82). Four questions that gave very poor results were omitted from the final draft of the instrument CONCLUSION: A questionnaire-based scale was developed to assess difficulty experienced in activities of daily living in persons affected by leprosy living in rural areas of a developing; country - the Green Pastures Activity Scale. The assessment, based on the Declassification of the ICIDH, performed well during validity and reliability testing. The GPAS consists of 34 activity questions, 5 relationship questions, and 3 questions on the use of assistive devices, occupation and employment It can be used be used in needs assessment for rehabilitation and for objective-oriented evaluation of the success of rehabilitation interventions, such as surgery, and physio and occupational therapy.

USE OF THE EYES, HANDS. FEET (EHF) SCORE AS AN IMPAIRMENT SEVERITY SCORE IN LEPROSY

PURPOSE: To discuss the concepts of 'classification' and 'severity grading' in relation to impairment in leprosy, and to describe the use of an impairment sum score, the Eyes, Hands, Feet (EHF) score, as an indicator of the severity and the evolution of impairment over time.

METHODS: The use of an impairment sum score, the EHF score, is illustrated using data on impairment at diagnosis and after a two-year interval from MB patients released from MDT in the Western Region of Nepal. The WHO 1988 'disability grading scale (0-2, for both eyes, hands and feet - six sites) was used as a measure of impairment. For the analysis the WHO grades for the six sites were summed to form an Eyes, Hands, Feet (EHF) score (minimum 0, maximum 12). The sensitivity to change over time of the EHF score was compared with that of the 'method of maximum grades'.

RESULTS: Using the 'method of maximum grades', 509/706 patients (72%) appeared not to have changed in impairment status versus only 399 (57%) with the EHF score. Improvement or deterioration of impairment status was missed in 113 patients (16%). In 216/706 patients (31%), the changes detected with the EHF score were bigger than those revealed by the method of maximum grades.

CONCLUSIONS: The six components of the WHO impairment grading may be added up to form a E(yes)H(ands)F(eet) sum score of impairment This score can be used to monitor changes in impairment status in individual or groups of patients. It should be recorded and reported at least at diagnosis and release from treatment Reporting could be done as the 'proportion of patients with improved EHF score', 'stable EHF score' and 'EHF score worse', and 'proportion of patients without impairment', 'proportion with WHO grade 1' and 'proportion with WHO grade 2' .

PURPOSE: To describe the results of a survey aimed at describing disability in people affected by leprosy.

METHOD: A survey was carried out using a questionnaire containing 74 questions on activities of daily living. Two hundred and sixty-nine persons affected by leprosy were interviewed.

RESULTS: The prevalence of different types of impairment in this sample ranged from 7.6% (foot drop) to 36% (weakness little finger abduction). The most commonly affected indoor activities were shaving (25%), cutting nails (22%) and tying a knot (18%). Among the outdoor activities, running. ploughing, threshing and milking a cow or buffalo were the most commonly affected (26-34%).

CONCLUSIONS: Disability as defined in the 'International Classification of Impairments, Disabilities and Handicaps' (ICIDH) has received little attention in the field of leprosy. This survey shows that 1) experiencing more severe difficulties with activities of daily life (ADL) is a common problem in persons with chronic impairments due to leprosy, and 2) the level of difficulty can be assessed and measured.

As disability is a main outcome of interest in rehabilitation, we recommend that efforts should be made to include an ADL assessment as a standard activity for monitoring and evaluation of rehabilitation, both for individuals and on programme level. Knowledge of the disability status of a person will be valuable in needs-assessment for rehabilitation interventions and in clinical decision making regarding surgical and other treatment

RAPID APPAISAL IN ASSESSMENT OF THE FACTORS RELATED TO LEPROSY REHABILITATION - A PRELIMINARY REPORT

Shu-min Chen, • Cun-lian, •• Bing la, • Rong-tao Zheng, • Lan Zhang • and Xue- dong Wang •• Shandong Provincial Institute of Dermatology. Jinan City. Shandong Province. China

To determine the knowledge and attitudes of key persons directly involved in leprosy rehabilitation at basic levels and to explore the possible factors having influence on leprosy rehabilitation, a sectional study, using rapid appraisal approach . i e an internew with interviewer, administered questionnaire. was conducted for 39 leprosy disabled patients. 35 rural doctors, 10 paramedical workers at township level and 37 village heads in which the disabled individuals due to leprosy live within 10 days.

Results: The willingness for leprosy disability rehabilitation was not associated with the demographic characteristcs of the disabled patients. The disabled, rural doctors and paramedical workers were lack of basic knowledge on leprosy and disability due to this disease. There still was some stigma reflecting in the relusal of some village heads (49%) to contact with the disabled people affected by leprosy. 41% of the disabled. 69% of rural doctors. 80% of paramedical workers and 81% of the heads of villages did not correctly recognized who would have the responsibility for leprosy rehabilitation.

The authors concluded and recommended 1) for very individulized needs end attitudes towards leprosy rehabilitation among leprosy disabled persons, the methodology to be used in leprosy rehabilitation programmes must be different from that utilized in current vertical leprosy control programme; 2) most leprosy disabled patients are cures of aged people (80% of them >50 years) with permanent peripheral never damage in varying degrees and needs of life-long care, a modle of community-based rehabilitation approach should be considered; 3) training of medical staff at basic levels, especially at village and township levels would be very crucial in the success of the rehabilitation project; and 4) for the purpose of creating a favorable social environment to develop and implement rehabilitation programme, motivation and involvement of the heads of villages in disability rehabilitation must be very important.

Manisha Saxena, and Vijay Kochar,
Faculty Member, RTCH, FPAI, 20-2-753,
Doodh Bowli Road, Hyderabad-500 064(A.P.) INDIA.

Some times identically disabled persons exhibit differential adaptation when faced with the functional demands of mobility, personal hygiene, household work etc. This reflects the relative success or failure of different patterns of coping. Hence this study intends to examine the coping mechanisms of the study cases and suggest interventions.

The experimental group in the study comprises of leprosy cases and the control group of non-leprosy disabled cases. Basing on both physical and functional ability the study cases were classified into four broad groups.

The population of the study is composed of 100 leprosy cases and 100 non-leprosy disabled cases. Direct personal interview method using structured schedule complemented with observations was used for data collections. Some case studies were also conducted. About 50 significant others and 40 health workers were informally interviewed to study their perceptions.

The study reveals the relative success and failure of different coping mechanism among both the leprosy and non-leprosy disabled cases. The suggested intervention to enhance coping mechanisms will be discussed in detail at the time of presentation of this paper.

A SOCIOLOGICAL STUDY OF REHABILITATION AMONG LEPROSY AND NON-LEPROSY DISABLED CASES

Rehabilitation must not only deal with physical restoration but also with the psycho-social and economic effects induced by the disease and disability. Hence in this study Rehabilitation wis studied from physical, social, psychological and economic perspectives. The study attempts to understand the interplay of various factors associated with leprosy and non-leprosy disabled cases which are shaping the rehabilitation process.

The experimental group in the study comprises of leprosy cases and the control group of non-leprosy disabled cases. The respondents were classified into four broad groups basing on the extent of rehabilitation

The sample of the study was composed of 100 leprosy cases and 100 non-leprosy disabled cases. Direct personal interview method using structured schedule complemented with observations was used for data collection.

Some case studies were also conducted. About 50 significant others and 40 health workers were informally interviewed to study their perceptions.

The study reveals the process of rehabilitation in the context and framework of disability. The conclusions of the study would help to formulate rehabilitation programme basing on the magnitude of the rehabilitation problem and will be discussed in detail at the time of presentation of this paper.

STAGES IN THE REHABILITATION OF THE LEPROSY HANDICAPPED (AS ORGANISED BY POONA DISTRICT LEPROSY COMMITTEE)

Leprosy Rehabilitation is a challenging process. Poona District Leprosy Committee has been working on this for last several years and has demonstrated the following stages in the Rehabilitation process.

i) Individual Rehabilitation: 177 patients
ii) Intensive Group Rehabilltation-CBR: 122 patients
iii)Intensive Group Rehabilitation-CBR:200 patients (eg.Powerloom)
iv) Industrial Socio-Economic Rehabilitation 400 patients - Advanced CBR
v) Co-operative society: 100 patients

All these stages are discussed in detail in the text of the paper and will be demonstrated by coloured transparencies and with the help of video clippings (VHS format of PAL/Secan/System) from the film "Mehta Cooperative Rehabilitation Model".

This has led to not only Rehabilitation of individual patient but of the entire family which has been brought back into the mainstream of 'Normal' society. The success of the programme is emphasised as it is working for last 18 years and could well serve as a model not only for other leprosy centres but also for those working in the field of other handicapped.

Concepts on Care After Cure (CAC) are not necessarily unique to leprosy and have been practiced in several chronic diseases. However CAC programme for leprosy are in some ways different and should adopt realistic strategies. taking into account both the physical and socio economic ravages of the disease. Since 1987. we have experimented with CAC programmes in our control areas. In this paper our experiences in the Chitoor District of Andhra Pradesh are shared as we prepare towards a world where leprosy and its potential damage are contained.

Spread over 512 sq. kms. the study area has a population of approx. 150.000 where leprosy control activities were carried out since 1979. A total of 3284 patients have been registered and treated for leprosy. Barring those who had died or left the area. 1382 peersons were followed up so far. Of these 280 had Grade 2 deformities due to leprosy and the others had varying degrees of general and leprosy related complaints.

The programme consisted of 3 clearly defined activities: health education to empower families and individuals to care for themselves; Institutional provision of curative / reconstructive services for management and prevention of disability and socio economic rehabi1itati on. Specific inputs that were required and their impact are presented and discussed.

A Chinese. National Leprosy Rehabilitation Project was undertaken between 1990 and by the Ministry of Health in collaboration with. The Leprosy Mission International and other ILEP organisations.. This involved pilot experiments in activities to prevent and overcome impairments and to serve as examples for further development of rehabilitation work in China and in Asia. More than 50% of the 299.000 accumulated leprosy cases alive at the end of 1996 had nerve function impairment affecting face, hands or feet.

This paper describes the two stages of the project, the second taking place from 1995-98 in support of 27.959 leprosy affected persons in 14 provinces. Project principles, objectives and activities are outlined together with the roles of the Ministry of Health and the National Centre for Leprosy Control in project organisation. The Ministry initiated disability prevention activities and delegated responsibility for implementation to the National Centre. The Centre organised surveys to identify needs, planned project activities and trained national and provincial leprosy staff. The Centre rehabilitation team, together with Leprosy Mission International experts, was responsible for ongoing technical project supervision. Sasakawa foundation supported provincial and national training programmes. Improvements made in stage two are described. Outcomes are summarised in this paper and detailed in other papers. The importance of continuation of disability prevention and leprosy rehabilitation activities in China is emphasised.

In the past two decades, institutionalised rehabilitation of leprosy patients in Ghana has been discouraged, and therefore leprosy patients have been treated and rehabilitated within or close to their communities. Only a few old and often severely disabled patients are permanently cared for in sheltered institutions.

Ghana has an extended family system which offers considerable social support to all non-self-sufficient people (children, elderly, sick and disabled people) within their communities.

For disabled people, including leprosy patients, this "natural welfare system" is supported by multi-sectorial teams which include health, social, and community development workers and educators, who provide a holistic rehabilitation programme at all levels.

Dr.P.K. Gopal, Mr. T. Jayaraj Devadas & Mr.G. R.Srinivasan
IDEA INDIA, 58, Gelvam Nagar, Colloctorate p. G.
Eroco-638 011 . INDIA.

As leprosy is eliminated as a Public Health Problem throughout much of the world, emphasis will increasingly need to be placed on the social aspects of the disease. Most countries faced with the problems of leprosy have focussed their efforts on medical and control aspects, but socio-economic issues have not received adequate attention.

Then at least some data are available on physical disability the data on social and economic disabilities of leprosy affected persons is not available.

As per the studies made in the field of rehabilitation, the Ieprosy affected persons have been divided into six categories for the purpose of socio-economic assistance.

The study describes the application of th methodology to select the eligible individuals for social and economic rehabilitation. The authors conducted a sample study for categorizing the Leprosy affected persons. A total number of 53,000 leprosy affected persons were assessed and eligible persons have been identified.

This methodology could be applied in any region for starting social and economic action for leprosy affected persons.

In present study, 126 leprosy cases with different type of claw hand deformity were selected from the rural area of Kheda District. These patients which were selected for study were under treatment, RFT & RFC. Different varities of splints like Adductor Band, Loops, Gutter Splints were given. Ink impression in graph book was taken for each patient. Regularity of splint application was followed & final follow up with ink impression was done after 3 months duration. Angle measurement was done for few patients. Result will be discussed in details, during presentation.

FIRST BRAZILIAN ELECTROMYOGRAPHY (EMG) NETWORK BETWEEN HANSEN'S DISEASE (HD) REHABILITATION CENTERS

"Lauro de Souza Lima", Research Institute, Bauru, SP, São Julião Hospital, Campo Grande, MS, Brazil

The Nerve Conduction Studies (NCS) are applied world-wide as the choice method to assess them, Peripheral Neuropathies. It's specially used in HD to evaluate the severity of nerve injury, to determine the characteristics of the lesion, to make the foresight of the outcome, and on these basis to elaborate the terapeutic decision. Nevertheless this method is not available to overall patients, other simple and useful methods are applied. There are not suficient doctors to make NCS, even in HD Rehabilitation Centers, where researches about treatment monitoring protocols must be developed. In order to improve the HD Rehabilitation Centers on this subject, we have looked for a system to be managed by a technician and supervised by a doctor at a distando.

There is already this system, and we have found out it in Sweden, in the Department of Clinic Neurophysiology, University Hospital Uppsala. The author shows the experience of the First Brazilian EMG network.

The Foundation for Medical Research, 84-A, R.G.Thadani Marg, Worli. Mumbai 400 018. India.

Systematic and concerted efforts in understanding the process of nerve damage in leprosy have been undertaken by a multidisciplinary team at The Foundation in the last two decades. The observations hive had important implications in the basic neurological sciences as well as in understanding of mechanisms of pathophysiology, immunology. and microbiology of the disease. Furthermore the studies have helped to devise tests for monitoring of chemotherapy and clinical relapses, understanding precipitation of debilitating reactions, immunological and regenerative potential of peripheral ntrves and highlighting the role of persister organisms in recurrence of leprosy.

SOCIO -ECONOMIC REHABILITATION OF PEOPLE WITH LEPROSY TOWARDS A WORLD Y LEPROSY BY THE YEAR 2000 AD AND BEYOND NITHOUT

In many diseases, rehabilitation Is an after-thought. When a patient is cured, then we think about qettinq him back to his home, work Community e.t.c.

In Leprosy rehabilitation is an interqral part of the programme of prevention as well of As treatment and of final restoration to national Social relationships.

Beinq a cripplinq and disablinq diease, leprosy is second to poliomylltis in developing countries.

Affected persons are disturbed and find it difficult to live in Communities like those not afflicted by the disease

Without effective rehabilitation. Leprosy Control is a failure because patients will not be willing to expose themselves for treatment unle ss they can see that others who have done so have been able to return to a meaningful existe nce.

Without effective rehabilitation measures, medical treatment may also be a failure because patients who are rendered free from mycobacterium Leprae can never be called cured if they are left with blindness and crippling deformities and disabilities as a sequel of the disease

To realise the dream of eliminatinq/eradicatinq leprosy by the year 2000 A.d. will be possible if and only if the problem of rehabilitation (Social/and economic) of leprosy persons is effectively addressed

MASTER PLAN FOR A SOCIO ECONOMIC REHABILITATION OF THE DISPLACED LEPROSY AFFECTED PERSONS IN INDIA -A PROPOSAL.

In a country like INDIA considering the size of the leprosy problem, the Socio economic rehabilitation is indeed a formidable challenge. Different voluntary organisation are involved in different aspects along with the services offered by the Government. It a necessary to workout an integrated Rehabilitation plan with a well co-ordinated networking arrangement with the existing programme of the Government as well as that of the voluntary agency.

It is estimated that 30% of the 800.000 leprosy affected persons who require attention are found to be displaced and out of this 25% of them are already availing help from the existing facilities of the Government and Voluntary organisations. This will work out to a total of 180,000 persons needing rehabilitation interventions.

As a methodology it is planned to provide loans, educational assistance. Aids and Appliances and Offer training, counselling motivation and help them to market the product after assessing their needs and aptitudes.

For implementing the programme the country can be divided in to 4 regions (East, West, North and South) and identify 20 nodal agencies in each region. These nodal agencies can be identified out of the active units of the Governments or Voluntary organisations existing in the region. The programme will be phased out for 5 years.

The budget for implementing the programme will come to around Rs. 3,040/- (US $80) per patient which is inclusive of organisational expenses.

• Dongguan City Hospital for Chronic Disease Control, Guangdong Province, China
# Guangdong Provincial Intitute of Dermatology, Guangzhou City, China

Donguan city had once been a high leprosy epidemic area. The total number of registered leprosy patientas was 3 990. Out of them , 3.650 were cured patients. For solving the living problems of those homeless cured patients , in 1965 the local goverment built a welfare facility with an area of 500 hectares including a building area of 30 000 square meters. Three hundred and thirty six (222 males and 114 females) live in this facility at present with an average age of 61 years. One hundred and ninety eight of them are disabled (more than WHO grade II) people. Through 30 years of construction, a social-ecnomic rehabilitation community of leprosy has built up with the support of the government In view of the market needs and the characteristics of the residents, up to now 44 chicken farms have been built up producing 500 000 chickens and 4 000 000 chicks annually. The production income increses year by year reaching I 135 000 Chinese yuan in 1996. Vocational training of the residents and inviting technical stalls for guidance have been carried out in order to raise production efficiency continuously. " Distribution according to work " system has been developed on the basis of ensuring the basic living expenses. The residents' income increased gradually and steadily. The residents' rights have been respected and quite a number of them already returned back to the society. One hundred and eighty residents have married. In addition, residents are provided with medical care and rehabilitation help providing them protective shoes and artificial limbs if needed. The authors pointed out that the mentioned example could be a way of cutting the goverment's financial burden and benifiting the society, the patients and their families.

Leprosy patients with grossly mutilated hands experience tremendous difficulties to maintain dental hygeine. In a study of 120 patients of different types of leprosy, 40% were found to have significant orodental changes (Sharma N.K et al, 1996). We believe that even patients with severe handicaps could be helped to prevent serious sequale by innovative adaptations like grip-aids.

The WHO theme of 1994 viz. "Oral Health for Healthy Life" stressed the need for "inexpensive and culturally acceptable" methods for offering dental care which synchronised with our observations on araldite ("M-Seal") grip-aids on tooth brushes. We provided grip-aids on tooth brushes and distributed tooth paste containing fluorides to 20 leprosy patients with hand deformities in order to restore and maintain oral health.

All patients were subjected for clinical examination for dental problems by a qualified dentist Initially 15 out of 20 patients had dental caries with partial resorption of the calcified structure of the tooth caused by dental plaque. Two patients had acute pulpitis caused by odontogenic infection and three patients had gingivitis. After a mean follow-up period of one year, it was observed that the grip-aid had prevented the formation of dental plaque and protected the tooth against development of caries in 16 (80%) patients. The grip-aid had also helped in increased frequency of brushing in all the patients. We believe that for restoration of dignity of deformed patients and establishing human relations in the society, this simple device may be helpful by improving the oral hygiene.

L'USAGE DE BOTTE DE UNNA ÉLASTIQUE DANS LE TRAITEMENT D'ULCÈRE PLANTER EN PACIENTS LEPREUX: MANAUS-AM-BRÉSIL.

Instituto de Dermatologia Tropical e Venereologia ''Alfredo da Matta"
Rua Codajas, 24 - Cachoeirinha
Manaus - Amazonas - Brasil - 69065-130

La perte de la sensibilité est usuellement le premier symptôme de déficit neural dans la lèpre, avec la diminution de la sensation de la température et douleur en arrivant avant, une perte de la sensation de sensibilité et pression. Aux pieds, la sensation de douleur protège pas seulement contre les objests pointaigus, mais aussi contre les effets d'excessive pression en les ares de la région planter, bien que, la perte de la sensibilité soit minimum, les pressions exercées dans le régions planters peuvent porter à la nécrose aseptiques du graisseux tissu en laissant cette are assez susceptible à traumatisme, l'ulcération et I'infection. En ces atteintes répétés sont avec beaucoup de fréquence, les majeures causes de mutilations observées en membres inférieures de pacients lépreux avec déficit neural.

En cet'étude prospectif, fait avec l'usage de la Botte de Unna Élastique, matériel à la base de bandage élastique, en contenant l'ozido de zinc que n'endurce pas, l'acacia, la glycérine, l'huile de castor, et le pretolato blanche, usuellement indiqué en ulcères veineux de la jambe et d'oedème lymphatique et cet étude là a été usagé au traitement de pacients lepreux avec l'ulcère planter et les resultads ont été animateurs.

S. Joshi, P. Kathe and S.S. Naik Acworth Leprosy Hospital Society for Research, Rehabilitation and Education In Leprosy, Wadala, Mumbai-400 031, India.

In view of World heading towards leprosy elimination the concept of Community Based Rehabilitation has replaced the Institutional rehabilitation for leprosy patients. The pilot study was undertaken to find out the feasibility of Community Based Rehabilitation In slum of Mumbai and rural area of Raigad district of Maharashtra State. After examination of 8135 persons in the slum of Mumbai 65 disabled persons (Rate 7.9/1000) were detected of which 11 were leprosy patients (Rate 1.3/1000). In rural area after examination of 4342 persons 28 disabled persons were detected (Rate 6.4/1000) of which 8 were leprosy patients (Rate 1.8/1000), It seems that the general disability rate and leprosy disability rate in slums of Mumbai and in Che rural area is practically the same.

It is further noticed that disability rate is higher in males, more unemployment in disabled in rural area, polio is major caused for disability and disability due to accident is more in urban area.

with the help of community leaders, the introduction of these disabled persons to the instintes having facilities of training, job placement and financial assistance to their business is initiated which is giving positive response. The details of same will be presented.

Guangdong HANDA Rehabilitation and Welfare Association (abbreviated as HANDA) was Established on August 19,1996.

HANDA received 1.400,000 RMB (about US$ 170.000)from 10 charity organizations and 53 individuals of the world in the past two years.

Martin Ndombe, Barthelemy Dunda
The leprosy Mission Congo Co-ordination Office. Kinshasa, Congo

Kivuvu Rehabilitation Center is located in Bas-Congo Province, Democratic Republic of Congo.

Previously used as "Leprosy Hospital", Kivuvu had no choice but to be transformed into a rehabilitation Center for almost 10 years, after Primary health care and Integration became national health policy in the country.

As a rehabilitation center, mostly Kivuvu takes care of severe ulcers, reactions and foot wear needs. Some projects, as mill, beans and onion fields, are managed in order to assist admitted patients.

20 patients were almost permanent in the center during the year 1996. among them 14 with severe ulcers needing strict bed rest, and 6 with less severe lesions staying around in the village. During that year, the average of stay period in the center was 3 months.

From different surveys done, it appears that most of the RFT patients (Released from treatment), would prefer to stay at the center rather than going back in their villages where they live abandoned by relatives and friends.

That raises the problem of leprosy stigma that is still high among the population, remaining a big obstacle for leprosy integration both in the public health system, and in the society. Good heath education, self-care group initiatives, and also health workers motivation remain the key for real integration.

OUTCOMES OF RECONSTRUCTIVE SURGERY IN LEPROSY - A FUNCTIONAL, SOCIO-ECONOMIC AND REHABILITATION PERSPECTIVE.

Sonepur district with a papulation of 500,000 had prevalance rate of 228/10,000 and deformity rate of 7%. In the past 3 years over 200 patients from this district have had reconstructive surgery for hands and feet following completion of MDT. Most patients are from a rural background and engaged in agriculture. A study was undertaken to asses the outcomes of deformity correction on the individual, family and society. The thrust was to asses the effects of deformity correction on function, cosmesis, work performance, earning level, personality, attitude, confidence and expectations. The impact on the family, relationships, social barriers and changes in acceptance was assessed. An effort was made through village discussions to determine the impact that deformity correction has had in making the disease socially acceptable. Most clients returned to their original occupation and to their own homes. Motivation was an important factor in the individual's final rehabilitation. Nearly all surgical failures (8%) had poor motivation and did not adhere to post operative programme. The factors influencing the outcome of surgical reconstruction along with the impact of deformity correction on the individual and the socio-economic asspects will be presented.

LONG-TERM FOLLOW UP OF JOINT STABILIZATION PROCEDURES IN THE TREATMENT OF DEFORMED FEET IN LEPROSY

Zai-ming Wang, Fu-tian Li and Li-wen Dong Shanghai Zunyi Hospital, Shanghai , China

Joint arthrodens has been proved very effective in correcting leprosy deformed feet and in treating leprosy sole ulcers as well, and consequently can prevent some patients from suffering due to amputation. Foot joint stabilization procedures were performed in 41 feet (24 of them with sole ulcers) of 36 patients. Triple arthrodesis was done in 12 feet, ankle arthrodesis in 27 and pantalar in 2 Satisfactory immediate results of the procedure were observed in 37 but the remaining 4 not in success. The former 97 feet were followed up for a period of 2-32 years. 35 (94 6%) among them more than 10 yean. It was found that the walking ability of all 17 feet improved, sole ulcers occurred m 15 feel less than 10 years and only one amputation was done 20 years after doing joint stabilization procedures were performed respectively. Correction of deformed feet in leprosy by joint stabilization procedures has helped the patient to retain and use his own limb with its advantages for more than 10 years in average at least. The time of use for the operated limbs will definitely be prolonged if the patients could persist in doing self ware.

Title : RECONSTRUCTIVE SURGERY OF DEFORMITIES IN HANSENS DISEASE IN THE CAMPS. AN SVALUATION AND LONG TERM FOLLOW UP.

Authors : Dr.K.S.Rao, Dr. M. K. Siddalinga Swamy, Dr. Betal, Dr. Patond. Central Institute of Orthopendics. Safdarjang Hospital, New Delhi-29.

Abstract : Deformities are quite common in Leprosy patients. Very few centres are available for reconstructive surgery which may be quite faraway from the place of residence of the patients. A novel method of reconstructive surgery on a camp basis at a near place to the p«tlents was undertaken. Chandrapur a district in Maharashtra was considered after a rapport with the district leprosy officer. He was advised to examine and collect the case of deformities at his district hospital. A team of surgeons from central leprosy teaching and research institute along with locaI orthopaedic surgeons a camp was helo during 1992, 1993 and 1994. All the patients were examined and correctable deformities like claw fingers. drop foot and Iagenthalmes were selected for surgery. The surgical camp was held on the days in an year. The patients were given preoperative and postoperative exercise wariness by the physiotherapist . A fetal of 70 case were operated in 3 yeras. After surgery the patients were sent home and called for regular follow up which was done by the local orthopaedic surgeons. The physiotherapist visited their houses to give and advise postoperative excercises. The expert team examined the operated cases when they went for the next year for surgery. 48 claw finger. 10 drop foot and 12 lagopthalmos corrections were carried cut in these years. Correction was satisfactory in 90% of patients. Complications were mainly due to non coperacive patients, who did not for followup regularly. Therefore it is ideal to conduct reconstructive sugery in leprosy patients in the camps with the cooperation of experts and local organisations. More over the patients stays in his house and the hardship of travelling and staying in leprosy hospitals in prevented.

LEPROSY AFFECTS FACIAL NERVES IN A SCATTERED WAY F ROM THE MAIN TRUNK TO ALL PERIPHERAL BRANCHES

1 Dept. Plast Reconstr Surg. 3 Dept. Anaesthesia Vienna-Univ. Clinic, Austria 2 Green Pasture Hosp. Pokhara, Nepal: 4: K.E.M Hospital, Bombay, India

A recent study reports that leprous facial neuropathy is located at the main trunk close to the first bifurcation and that the disease may indeed develop fusiform swellings (Plast Reconstr Surg-accepted 1998). These findings stay in contrast to Antia's study (1966) in which the disease is described to exclusively affect the nerves peripheral zygomatic branches, but also confirm two previous reports which had expressed valid doubts about the solely peripheral localization of the disease. Based on these observations, we assumed that Antia's and our findings might be rather complementary than contradictory, and hypothesized that leprosy affects the seventh cranial nerve in a scattered way. This would mean that the -presumed- undetected proximal involvement of Antia's eleven leprous facial nerves (1966) had not been recognized due to their incidentally inconspicuous aspect at the main trunk.

To clarify this hypothesis, we decided to repeat Antia's study: facial nerves of 10 leprosy patients missing sufficient motor improvement after completion of their WHO-medication were first exposed at the main trunk; after evaluation of their macroscopically aspect, the functional status was investigated with intraoperative electroneurodiagnostics; all 10 nerves showed a lesion at the the first bifurcation; subsequent lateral parotidectomy revealed further lesions more farther distally, with all peripheral branches to be irregularly involved in a scattered way. Epineuriotomy showed various degrees of fibrosis of the epi-and interfascicular epineurium. Histopathological probes from the epifascicular epineurium confirmed these findings.

We conclude that 1) leprosy affects facial nerves in a scattered way from the main trunk to all peripheral branches 2) intraoperative electroneurodiagnostics is an effective means to detect the site and most proximal involvement of leprous facial neuropathy.

Dr. D. Vijayakumar, Dr. Helen C. Roberts
Premananda Memorial Leprosy Hospital
259/A, A.P.C. Road, Calcutta 700 006, India

Lagophthalmos In Leprosy patients can be corrected by Temporalis Muscle Transfer using palmarls longus or fascia lata as a graft tendon. 28 of the patients underwent such procedure using Modified procedure of JOHNSON'S TECHNIQUE during the period between 1995 - 1997.

The post - operative evaluation of these patients will be presented with relation to gap corneal pathology, vision, cosmetic effect, watering etc The modified procedure gives good cosmetic appearance and good visual Rehabilitation.

Shyamala Anand. Sunil Anand. G Rajan Babu. C S Walter The Leprosy Mission. Kothara. Po Paratwada. Dt Amravati. Maharashtra - 444 805. India

Leprosy affected people like everyone else, develop cataracts due to various factors-age. diabetes, oral steroid therapy. ocular trauma, chronic ocular inflammation - to name a tew This study reviews our experience with intraocular lens (IOL) implantation in 126 eyes of 104 leprosy affected patients over 2 1/2 years. The purpose of this study is to analyse the visual outcome of the surgeries, to determine the etiology of cataracts in these patients, to determine the effect of pre-existent ocular disease if any. on the outcome of the surgeries, to determine whether the visual outcome of the surgery was affected by the type of leprosy, smear positivity or ongoing anti-leprosy treatment and to analyse the post-operative complications. The study concludes that IOL implantation offers the best form of visual rehabilitation for leprosy affected patients when they develop cataracts as it gives very good visual results. The surgery is associated with very few post-operative complications when cataracts are age related Cases with past history of iridocyclitis however were associated with more intra and post operative complications. Smear positivity, type of leprosy and anti-leprosy treatment have little effect on the visual outcome of the surgery.

ABSTRACT EYEBROWS RECONSTRUCTION BY TRANSPLANTATION OF MULTIPLE PUNCH SCALP GRAFTS

Aldemar Vilela de Castro, Monica Maakaroury João Afonso Moreira Neto and Maria de Lourdes V Rodrigues

Medical School of Ribeirão Preto/São Paulo University. Sanatorio Santa Izabel. Belo Horizonte. Brazil

Leprosy remaims a serious health problem in Brazil The social stigma attached to the disease is strong and visible deformities may prevent the patients' adequate rehabilitation Loss of eyebrows (madarosis) is a well recognised although pathognomonic sign of leprosy, it's very frequent, bilateral and permanent. In this study, the missing eyebrows were reconstucted by transplantation of multiple punch full thickness scalp grafts. The cosmetic results were observed on 17 patients, 8 months after each operation. Of the 34 reconstructed eyebrows 22(64.70%) looked good, 6(17.65%) looked acceptable and 6(17.65%) looked poor. The cosmetic appearence was considered satisfactory- in 14(82.35%) patients and unsatisfactory in 3(17.65%) patients The full thickness scalp grafts snowed a successful take to the recipient sites and the technique proved to be simple, safe, eficient and didn't lead to any important complication These advantages assure the possibility of eyebrows reconstruction in a large number of leprosy patients, helping their rehabilitation and reintegration in normal society

Title: SURGICAL CORRECTION Or LAGOPTHALMOS BY TEMPORALIS MUSCLE TRANSFER IN HANSENS DISEASE.

Authors : Dr M. K. Siddalinca Swamy, Dr. K.S. Rao Central Institute of Orthopaedics. Safdarjang Hospital. New Delhi-29. (India)

Abstract; Leprosy is known for the deformities it causes due to involvement of nerves. Temporal branch of facial nerve is commonly involved resulting in Lagopthalmos. If conservative treatment fails surgery has to be done to prevent eye complications like exposure Keratitis. Iridoyclities. During the period from 1987 to 1994 44 Lagopthalmos were corrected by temporalis muscle transfer using a free graft. Most of the cases belong to boderline tuberculoid leprosy. Duration of paralysis varied from a months to 20 years, age of the patient varied from 30-60 years. 32 were males and 10 were females. Two patients underwent bilateral correction. Follow up of the patients varied from 1 year to 4 years with an average of 2.5 years. Corrections were satisfactory in 42 cases and failed in two cases due to adhesions. There were complications in 3 patients namely, tight band, corneal injury, and conjunctivitis which were corrected. Spontaneous blinking was present in most of the patients and the eyes remained closed during sleep.

TWO METHODS FOR INTRINSIC REPLACEMENT OF THE LEPROSY HAND; A COMPARISON OF HAND FUNCTION

Roland Kazen, Catherine Benbow, Asrat Mengiste, Yesabnech Abate, Fikre Mekuria Chachu, Philippe Thevoz

Methods for intrinsic replacement (Ulnar paralysis) of the hand in leprosy have limitations as to applicability and effect on hand function. Intrinsic replacement procedures do not essentially improve the metacarpal arch. Some procedures even exaggerate the arch deformation. Correction of the metacarpal arch is seldom performed. Only one method corrects the metacarpal arch at the same time as stabilising the metacarpophalangeal joints.

The aim of this study is to compare the immediate impact on hand function of two methods for intrinsic replacement, the Superficialis Pulley Insertion (Zankolli) and the Intrinsic Re-activation (Palande). A phase of long term follow up will be added later on.

A test battery for hand function has been developed taking into account the effect of an improvement of the metacarpal arch, measuring impairment, disability and personal assessment of hand problems.

Patients with mobile clawhands, with or without an additional median paralysis, are alternatively chosen for one of the procedures. For pre- and post-operative assessments the new test battery is used, including a new assessment method for the metacarpal arch. Results are compared.

Dr.P.K.Oommen and Dr.V.Durai Central leprosy Teaching &Research Institute. Chengalpattu - 603 001. Tamil Nadu. India.

In Hansen's disease paralysis of the ulnar nerve resulting in claw deformity of fingers and Z-deformity of thumb on attempted pinch is the most common deformities seen. Though surgical correction of the fingers in done the thumb is very often neglected, even in a median involvement. In the latter an abductor opponens plasty is done to correct claw thumb but the ulnar paralysis of thumb due to paralysis of adductor and part F.P.B., is often ignored. We have used half-index sublimis transfer as adductor replacement routing the sublimis along the course of the adductor and attaching it at the adductor insertion, to correct the Z-deformity and produce an effective pinch and found the results satisfactory. Importance of the adductor, details of the operation and results in 25 patients who had half-index sublimis as adductor replacement is presented in this paper.

This is a study to determine whether Posterior Tibial Nerve Decompression (PTND) will prevent recurrence of plantar ulcer. It involves 7 centres in India with 246 feet (233 patients) having one or two scars of the healed plantar ulcers and sensory impairment on the plantar surface. Allocation of individual feet was done on random basis to PTND + foot care and foot care alone. Comparability of feet for the relevant factors in the 2 groups was ascertained. Total duration of follow-up was 3 years with six-monthly examinations. Patients were also to report as and when ulceration of foot occurred. Follow-up was completed by 31st January 1998. Interim analysis was done for the data available till August 1997. It reveals that coverages for 1st to 6th follow-up examinations were 94%, 92%, 87%, 86%. 79% and 78%. Variation in recurrence rates for plantar ulcerations for the different centres in the two groups were within acceptable limits. (Analysis of variance with Arc sine transformation and weighting, between centres F = 3.32, p = 0.08). Overall recurrence rates were 39.5% and 36.9% for PTND + foot care and for foot care alone, and were very similar (Mantel-Haenszel Summary x² = 0.06. p = 0.80, Mantel-Haenszel weighted relative risk = 0.94). Various factors related to patients were considered to understand the reasons for this no difference and none was found to be significant. Sensory status (improvement or worsening) was similar in both the groups at the end of 4th follow-up. Healing time for the recurrent ulcers was also similar in the two groups.

Thus, PTND did not prevent recurrence of plantar ulcers, under the conditions of this study. Final results from the study will be presented.

Chong-zu Qian, Jin-hua Chen, Jian-ge Oian, Ai-ru Yu, Jian-jun Yao and Yong-gang Jin Zhejiang Provincial Institute of Dermatology. Deqing Town, Wukang County Zhejiang Province, China

The authors pertormed flap repair on 45 leprosy patients (35 males and 10 females) with plantar ulcers from 1982 to 1995. The patients' age ranged from 24 to 66 years. Of them 4 were active cases (MB) and 41 cured persons affected by leprosy (MB 25 and PB 16) As regards of the sites of ulcer, there were 6 in heel. 8 in lateral plantar, 2 in medial plantar, 5 in the first metatarsal head, 12 in the 2nd - 5th metatarsal head. I in big toe. 2 in medial ankle. 3 in lateral ankle. 4 in lower third of leg and 2 with forefoot detect. Subdermal vascular network skin flap had been used in 5 cases, local pedicled flap in 8. muscular in 12, composite tissue flap in 6. free flap in one, island flap in 8 and reverse island flap in 5. Fourty flaps totally survived (but 2 with partial margin necrosis) and 5 failed to survive. The survival rate of flag was 90%. In the follow-up period of 112 years, all flap-survived cases were satisfied with the results functionaly and cosmetically. but blisters occurred in n cases in the early stage of weight-hearing. The authors suggested that various kinds of flaps could be used in repairing plantar ulcers of leprosy by experienced surgions. but the flaps used in this study could not solve the problem of insensitivity of the foot. Self care education and protective footwear should be carried out and provided.

HEEL ULCERS IN LEPROSY TREATED WITH A FASCIO-CUTANEOUS ISLAND FLAP F ROM THE INSTEP OF THE SOLE: 10 YEARS EXPERIENCE.

Feet with heel ulcers, with major soft tissue loss, and often complicated by osteitis of the calcaneum, have seldom been successfully restored with conventional transposition flaps. Attempts using tissue from outside the glabrous skin area have shown high failure rates. Below knee amputation has often been the final outcome in the past.

In 1991, ALERT (P.E. Gravem) published preliminary results of reconstruction with a transposed fascio-cutaneous island flap from the instep, performed on 23 leprosy patients. The observation time was up to two years. We now review all patients operated on with this technique from 1986 onwards, including the patients from the first study. The observation time is up to 10 years.

The results are very encouraging and we feel this procedure should be recommended as a standard method for heel reconstruction in most cases where there is major soft tissue loss. Surgeons with some experience in basic plastic surgical principles should be able to perform the operation safely. The operation should become part of the surgical menu in major referral centres for leprosy patients. However, the operation is a relatively complicated plastic surgical procedure, and the technical hazard should not be underestimated.

The method will be presented in detail together with short and long term follow up results of the patients.

Mark Macdonald, Richard Schwarz; Anandaban Leprosy Hospital P.O. Box 151 Kathmandu.

The anaesthetic foot in leprosy can lead to recurrent ulcer formation and neuropathic disintegration of the foot, resulting in marked deformity and disability. Corrective osteotomy/arthrodesis, attempts to restore a more functional anatomical position leading to decreased impairment.

We present a retrospective review of major corrective foot surgery, performed at Anandaban on 49 patients (55 procedures) over a 12 year period. The commonest procedure was ankle joint fusion (51%) followed by combined ankle and sub-talar fusion (24%). Union occurred in greater then 95% of patients. A positive outcome was found in 84% of those with recurrent ulcers with a low amputation and failure of fusion rate.(7%)

The role of corrective surgery as a salvage procedure in the deformed foot as an alternative to amputation is established.

Objective: To develop a reliable and valid hand assessment battery to evaluate the results of surgical correction in the hand affected by leprosy.

1. Impairment (muscle, sensory and range of motion testing)
2. Disability (qualitative and quantitative functional tests)
3. Subjective assessment of hand problems

Method: Standardized tests were selected for the assessment of impairment. Functional tests were developed to measure disability. A short questionnaire was designed to record the patient's opinions of the difficulties experienced in daily life. 13 normal people, 15 pre-op and 15 post-op were each assessed by two out of three randomly assigned assessors.

Close agreement between pairs of observers was achieved for impairment in 97.5%, for disability in 82.4% and for the subjective assessment in 77.5%. Validity

1. Spearman's Rank Correlation Coefficient (r_s) was 0.90 for the correlation between standardized scores of impairment and the non-standardized test results for disability, r_s = 0.79 for the correlation between impairment and subjective assessment.

2. Although the pre- and post-operative groups were different cohorts, the mean values of the impairment, disability and subjective assessment scores show improvement of 8% for impairment, 24% for disability and 55% for subjective assessment.

Conclusion: This hand assessment battery can be used to evaluate the results of surgical correction.

THERAPEUTIC SURGERY FOR LEPROSY PATIENTS PERFORMED IN MANAUS, STATE OF AMAZONAS, BRAZIL.

Pedro Aurelio Leite Cunha, Marcus Vinícius Monteiro Alves, Maria Anete Queiroz de Moraes, Elbio Correa Rola, José Yranir do Nascimento.

Instituto de Dermatologia Tropical e Venereologia "Alfredo da Matta"
Rua Codajás. 24 - Cachoeirinha
Manaus - Amazonas - Brasil - 69065-130

The high affinity of M. leprosy for peripheral nerves is the key to the association between leprosy and disability. Besides the invasion of nerves by M. leprosy, resulting in inflammation with the consequent possibility of nerve damage, the pathogenesis of nerve destruction is closely linked with leprosy reactions and most of nerve damage occurs during reaction.

This prospective study examines the outcome of therapeutic surgery, mainly nerve decompression, for leprosy patients suffering the effects of chronic neuritis. From January to December 1996, 138 leprosy patients were included in the study; all the patients except 12 of them, had taken prednisone 1 mg/kg/day. The pre operative selection of patients was by pain or thickness of the nerve with the presence of anesthesia of hands or feet combined with muscle weakness, and the failure to improve the patient clinical condition by steroids treatment alone.

Detailed voluntary muscle testing (VMT) and sensibility testing (ST) was done before and each 3 months after nerve decompression, during 1 year, on 126 cases of the total included. Based on patients information all of them except 5 showed lack of spontaneous pain and no one claimed to feel worse. All patients but 19 showed improvement in protective sensation; two patients showed to feel worse. All patients but 25 had informed muscle strengthening during recovery. These results when compared with those obtained from VMT and ST testing were similar.

In this essay the optimum time for nerve release, the more adequate surgical procedure and the patient progress have been discussed. The procedures were simple and quick, not required general anesthesia, hospitalization and there were no relevant complication. It has shown that neurolysis have had encouraging results.

PLASTIC AND RECONSTRUCTIVE SURGERY IN THE TREATMENT OF PLANTAR ULCERATION OF LEPROSY PRINCIPIE AND PRACTICE

Li-wen Dong •, Fu-tian Li •, Zai-ming Wang•, Juan Jiang #, Guo-cheng Zhang#, Ju-gen Zhang+ and Yong-liang Ye+

• Shanghai Zunyi Hospital, Shanhai, China.
# Institutte of Dermatology, CAMS and PUMC. Nanjing City
+ Wu County for Skin Diseases Control, Suzhou City

Since early 70's. the authors have employed microscopic surgical technique to reconstruct the plantar ulceration wilh 8 types of the flaps in 76 leprosy patients. Postoperatively, alt the flaps survived, and the long term curative effects were proved satisfactory through our follow-up. Because of the neurovascular malnutrition in some patients who suffered from complete drop feet resulting from the damage of common peroneal nerve and high part of the tibial nerve, the osseous healing rate by the routine procedure of joint fushion was low. To avoid this problem, the authors have designed and used free fibula grafl based on the fibular artery pedicle for ankle joint fushion. Postoperatirely. the osseous healing situation appeared sound.

This paper deals with our experience in various intraocular operations done in leprosy patients over a period of 15 years.

The intraocular operations done are
1. Cataract extraction with or without I.O.L.
2. Phaco Emulsification
3. Trabeculectomy
4. Combined extraction
5. Extraction with vitrectomy.

The aim of the presentation is to highlight the likely complications and precautions to be taken before and after surgery in these patients as they have less corneal sensations, weakness of the orbicularis oculi. They have very less symptoms for the post operative complications.

- Reduced nucin content in tear film
- Reduced corneal sensation
- Cannot feel the injury or foreign body
- Weakness of the orbicularis
- Rubbing with infected hands
- Minimal symptoms.

TOTAL INTRAVENOUS ANAESTHESIA (TIVA) FOR INTRAOPERATIVE ELECTRONEURODIAGNOSTICS (JOE) AND TIME CONSUMING NEUROLYSIS OF PERIPHERAL NERVES AFFECTED BY LEPROSY

1: Dept. Anaesthesia-B 2: Dept. Plast Reconstr Surg . Vienna-Univ. Clinic. Austria 3: Green Pasture Leprosy Hospital. Pokhara. Nepal

Intraoperative electroneurodiagnostics during surgery of leprous nerves require full relaxation of patients and extensive interventions lasting several hours. We report about the specifics of 19 general anaesthesias performed on leprous patients in the Green Pasture Leprosy Hospital, Pokhara-Nepal.

For intubation all patients were relaxed with small bolus of vecuronium 0.5-1 mg/kg. For surgery of leprous facial nerves 9 patients (I) were anaesthetised with continuous infusion of propofol alone (5-10 mg/kg/hr). 8 patients scheduled for tibial nerve surgery and I patient for surgery of both nerves received at first continuous infusion of ketamine (1-2 mg/kg/hr) followed by propofol after performing IOE (II). Intraoperative pain treatment was performed with fentanyl (0.05-0.1 mg). For ventilation a positive-pressure respirator (East Healthcare, Oxford) in a half-open system was used. Oxygene was administered only during induction and at the end of anaesthesia. ECG. oxygene-saturation (criticare) and blood pressure were continuously monitored. We registered the time between end of infusion and the moment when patients were able for verbal reaction (waking time) and the occurence of vomiting and confusion during the following 24 hours.

Both TIVA-regimes produced adequate anaesthesia tor the operating procedures, they did not require more than 0.5 mg of fentanyl and the waking time was similar. The analgetic properties of ketamine was sufficient for the extended skin incision in tibial surgery.

Transfer of post-tibial muscle tendon for correcting footdrop has been extensively used in leprosy patients usually with satistactory results. However, the pre- and post-surgical care will distinctively influence its results. Twenty-one feet in 21 male patients with footdrop including 3 with plantar ulcers received above mentioned surgical procedure. At the same time, the authors provided them with nursing care of best quality. Before the operation, they were asked to learn how to do the functional exercise of posterior tibial muscle by themselves, and after the operation they exercised gradually and practiced their gait until had the gait corrected. Patients were followed up tor 3 months when the plaster had been removed. The results should that: 1) three plantar ulcers all healed without reoccurrence; 2) nineteen patients had a correct gait; 3) two patients still had a mild steppage gait due to old age and insufficient exercise; 4) angle of every fool in an active dorsiflexion was less than 85 • and in an active plantar flexion reached 100-110 • .The authors suggested that Ibotdrop patients complicated with plantar ulcers could be given the treatment of transfer of post-tibial muscle tendon if they could be well managed.

ABSTRACT EXTRACAPSULAR CATARACT EXTRACTION AND INTRAOCULAR LENS IMPLANTATION IN LEPROSY PATIENTS VISUAL OUTCOME AND COMPLICATIONS

Leprosy Department of Hospital Sao Geraldo. Sanatorio Santa Izabel. Belo Horizonte. Brazil

In Belo Honzonte, Brazil. 55 leprosy patients of all clinical types and grades (70 eyes) underwent extracapsular cataract extraction and intraocular lens implantation during a period of 4 years. The authors analysed the visual outcome and complications of these surgeries. The visual acuity unproved in 92.9% of the eyes and in 65.7% the acuity unproved by 4 lines or more on the Snellen chart. 39 eyes (55 7%) had at least one of the following postoperative complications, astigmatism 2 (3.0%). inflammation 13 (18 6%). synechiae 7 (10.1%), sphincter tears 19(27.2%). debris adherent to lens surface 11 (15.8%). dislocation of the IOL to anterior chamber 1 (1.5%). descentration of the lens 7 (10.1%), opacification of posterior capsule with loss of visual acuity 22 (315%) YAG capsulotomy was performed to restore the vision in 18 (25.7%) of these eyes. The postoperative complications were not too serious and could be controlled, most of them couldn't be associated to leprosy infiltration only

Dr. S. K. Tripathi, Dr. R. N. Mishra. Prof. Dr. A. K. Jha Amar Skin Institute, Makhania Kuan, Patna.

Trophic ulceration is the consequence of repeated trauma, deformity and bone damage in anaesthetised limb. In many cases it could be a constant source of agony and embarassment even after patient is cured. Punch grafting is very useful technique which promotes complete healing of the ulcer in most cases.

21 cases of non-healing trophic ulcers were selected after completion of regular MDT. Multiple 6 mm punches were grafted after debridement of the floor. Tight dressing applied. Dressings removed after 7 days.

More than 90% of grafts were taken-up in 17 cases (80.9%) after 7 days and healed subsequently. In 4 cases grafts were rejected leaving a healthy granulating base with partial healing of ulcer. These were regrafted and healed uneventfully. Stitching done at donor site in all cases.

Punch grafting is very useful, simple, inexpensive and least aggressive surgical procedure for non-healing trophic ulcers in leprosy.

The commenest cause of deformity of thumb in leprosy is median and ulnar paralysis. Surgical abductor-rotator replacement is done by transfering Extensor Indicis Proprious or Flexor Digitorum Superficial is or Palmaris Longus as motor. The often associated metacarpophalangeal instability is corrected by using the same motor used for abductor-rotator replacement with double insertion or by using a seperate tendon.

During the ten year period from 1979 to 1989, 111 patients with thumb deformity aged between 13 and 61 and paralysis of one year to twenty years duration underwent surgical correction at this centre and were followed up for periods ranging from 1 year to 15.5 years (mean 7.29 Years).

The results of abductor-rotator reconstruction by different procedures were evaluated using active abduction and rotation of the thumb and ability to perform pinch as parameters. They were compared and advantages and disadvantages of different procedures were discussed. The results of different procedures for metacarpophalangeal stabilisation were also analysed, compared and discussed.

THE RESTORATION OF PROTECTIVE SENSIBILITY IN THE HAND BY DIGITAL NERVE TRANSLOCATION

Istanbul Leprosy Hospital, Bakirkoy. 34747, and Istanbul Medical Faculty, Hand Surgery Department. Capa, 34390, Istanbul, Turkey

All techniques used for correction of traumatic paralysis give the same result in leprosy paralysis. But the leprotic hand also involves loss of sensation. Therefore, it is of great importance to reconstruct the motor nerve function of the hand together with protective sensitivity.

In this study loss of motor function and sensibility are regarded as components of a complex event. During restoration of motor function, translocation of functional digital nerves which innervate relatively less important areas of sensibility to nonfunctional digital nerves are performed in order to restore at least a protective sensibility in these otherwise anesthetic regions.

20 cases were operated between 1985 and 1994 (18 male, 2 female). The patients age ranged from 13 to 42 years. Our first case was a leprosy patient. Four cases emergency. 11 delayed cases of traumatic nerve legions, 5 leprosy patients. 12 cases had N. ulnaris, 6 cases N. medianus, 1 case N. medianus+N. ulnaris. I case N. medianus+ N. radialis lesions.

Postoperative follow-up ranged from 28 months to 119 months. The return of functional sensation was evaluated by FSR described by Tenny and Lewis, and BMRC classical sensation improvement rating. Subjective results were evaluated by use of 100 point scala of classic 6 questions prepared by Lewis.

FSR result were 10% very good, 40% fair, 10% poor. BMRC sensational improvement was 10% S3+, 30% S3, 40% S2, 10% SI; and subjective evaluation results were 10% very good, 60% good, 20% fair. 10% poor.

Digital nerve translocation can be chosen in selected cases, in addition to the motor function reconstruction procedures for its easy application, dependability and sufficient results.

FLEXOR APONEUROTIC RELEASE FOR RESISTANT ADAPTIVE SHORTENING OF LONG FLEXORS IN CLAW HANDS IN LEPROSY.

Adaptive shortening of long flexors (ASLF) occurs in long standing neglected claw deformity of hands in Leprosy. The inability to completely extend the proximal interphalangeal joint initiates shortening of the long digit flexors, mostly of the flexor digitorum superficialis. ASLF is classifed as mild, moderate and severe when PIP angles are present with wrist in 30º extension, neutral and 30º flexion respectively. Gentle passive stretching along with serial digital casting and night splinting is routinely instituted for all ASLF and on full correction splintage is discarded for two weeks prior to tendon transfer. Flexor aponeurotic release (FAR) is considered for
1) resistant ASLF despite adequate physical therapy for 6 weeks
2) persisting swelling of PIP joints
3) pain during gentle stretching
4) reduction of grip power during therapy and
5) recurrence of ASLF after discarding splintage. FAR consists of excising a 3-4 cms wide flap of deep fascia along with inter-muscular septum and fibrous bands of flexor origin in upper forearm. In 12 patients ASLF was corrected by FAR peroperatively and tendon transfer was done 4 weeks later. The procedure of FAR for resistant ASLF, its indications, clinical results and its advantages will be presented.

Dr. Helen G. Roberts
Premananda Memorial Leprosy Hospital
259/A A.P.C. Road, Calcutta 700 006, India

36 Eyes of 28 Leprosy patients underwent Cataract surgery at Premananda Memorial Leprosy Hospital in year 1997. About 40 percent of these eyes were implanted with intra ocular lenses. 92 percent of these patients had Multi-bacillary leprosy. 27 percent of these patients were smear positive at the time of surgery. 75 percent of these eyes were blind i.e. visiou < 1/60 and 25 percent of the eyes were severe visually Impaired i.e. vision <6/60. 90 percent of the eyes were restored to vision >6/18. Success Rate and the Sight Restoration Rate In these patients will be presented.

In conclusion, quality vision can be given to PAL's following Cataract surgery with Intra ocular lens implantation.

Paralysis of the anterolateral group of muscle of the leg resulting in Foot drop is one of the major factors contributing to the lower limb morbidity in the patients of Hansen's disease.

The Foot drop compells the patient to walk with a 'high stepping gait' subjecting the forefoot and the lateral border to high pressures resulting in trophic ulcerations. In established cases, reconstructive surgery is the only definitive means to correct the drop foot and entails the use of Tibialis Posterior muscle and rerouting it on the anterior aspect of the ankle to function as a dorsiftexor.

This study was done at Dr. Bandorawalla Leprosy Hospital, Pune 48. Fiftytwo patients were studied. Cases were predominently males and ranged from 18 to 45 years. Apart from details of surgical technique, emphasis has been laid on the importance of Biomechanical factors and Podiatric factors which must be looked into in obtaining an evenly weight bearing foot and providing a good ground clearance. Details of pre operative and post operative physiotherapy and role of footwear modifications in the functioning of the operated foot is also stressed.

The understanding of tissue deficit in the specialised skin of the sole of the foot is necessary for management of chronic plantar ulcers in leprosy feet. Author has devised the neurovascular subcutaneous island pedicle flap for forefoot ulcer, the distally based transposition flap for metatarsal head ulcers, the inferiorly based flap (with or without muscular component) for heel ulcers to provide for issue deficit. The techniques, follow-up and long term results will be presented for a series of cases.

INTRAOPERATIVE ELECTRONEURODIAGNOSTICS IN PERIPHERAL NERVES AFFECTED BY LEPROSY: TECHNIQUES, IMPLEMENTATION AND LIMITATIONS

E. Turkof¹, B. Richard², M. EI-Dahrawi, R. Ciovica¹, S. Kamal³, S.Tambwekar⁴

1: Dept. Plast. Reconstruc. Surg. Univ.Clinicoc Vienna, Austria: 2: Green-Pasture Leprosy Hospital. Pokhara, Nepal; 3. Kasr-El-Aini Univ. Hospital, Cairo. Egypt 4: K.E.M. Univ. Hospital. Bombay. India

Leprous nerves are affected in various ways according to the type of disease, duration of disease and the characteristics of the nerves. If surgery is to be performed in leprous neuropathy, it is crucial to release all affected segments to ensure effective interventions. Conventional nerve conduction velocity studies (NCV) are commonly performed preoperatively to verify the clinics and to determine the site of lesion. However, these routine techniques are limited in two ways: the proximal extend of lesion cannot be detected and a second affected site in case of scattered lesions (median nerves, tibial nerves) would not be identified.

Furthermore, measurements would be impaired if the common stimulation site is affected as well, which frequently is the case (distal upper arm/ulnar nerve, cubital region/median nerve, fibular head/peroneal nerve, popliteal region/tibial nerve). In contrast, with intraoperative electroneurodiagnostics nerves are stimulated at the most proximal possible and unaffected site of the nerve, the roots. Ibis enables a precise localization of the disease's proximal extend.

Since five years, intraoperative electroneurodiagnostics have been performed on leprous nerves during several international pilot studies (Bombay-India/ 1992+1994; Cairo-Egypt/1995; Pokhara-Nepal/1996+1997). In limb nerves, spinal root were electrically stimulated with surface electrodes, in facial nerves their exit at the pontal region were stimulated with needle electrodes over the temporal region. Efferent nerve compound action potentials were registered from the nerve's surface with bipolar wire electrodes moved proximally and distally along the exposed segments. Patient were fully relaxed to avoid volume conduction.

We report about our experience from over 2000 intraoperative recordings with various techniques, the implementation of the different methods, the interpretations of results and the limitation of the techniques.

MICROSURGICAL INTERFASCICULAR NEUROLYSIS OF THE MAIN TRUNK AND ALL AFFECTED PERIPHERAL BRANCHES OF LEPROUS FACIAL NERVES CAN AVOID TRANSFER PROCEDURES

E. Turkof¹, B. Richard², E. Knolle³, B. Katri², R. Ciovica¹, S. Tambwekar⁴

1: Dept Plast Reconstr. Surg. 3:Dept Anaesthesia-B, Vienna-Univ Clinic. Austria 2. Green Pasture Hosp.. Pokhara, Nepal 4: K.E M. Hospital. Bombay. India

Since 1966, musculofascial transfer procedures remain the only surgical treatment of leprous facial neuropathy. The goal of this study was to evaluate the possible benefit of invasive neurolysis in leprous facial neuropathy given the fact that the surgeon can reliably detect all affected nerve segments.

10 patients suffering from leprous facial neuropathy were enrolled in this international prospective pilot study. All patients were medically treated according to WHO recommendations and had undergone clinical and electrophysiological investigation prior to surgery. Interventions consisted of exposing facial nerves at the main trunk and to perform lateral parotidectomy. Subsequently, all affected nerve segments identified as such either by intraoperative electroneurodiagnostics and/or by their macroscopical and microscopical aspect were surgically treated by epineuriotomy and, if necessary, by microsurgical, interfascicular neurolysis.

Follow up was performed 10 months and 22 months after surgery. Despite the fact that patients represented a negative selection as far as duration and severity of the disease was concerned, clinical evaluation showed improvement of lagophtalmos and/or other functions of facial muscles in all but one patient.

We conclude that microsurgical interfascicular neurolysis, properly performed on all affected nerve segments, can be recommended in leprous facial neuropathy and can avoid transfer procedures.

METHODS OF TRAINING BASIC HEALTH WORKERS AND PATIENTS IN PREVENTION OF DISABILTY

P D Samson, Wong ML, Zhang Guocheng, J Jiang, J Watson, A Piefer, R Winslow, WCS Smith, Ministry of Health, Peoples Republic of China. The Leprosy Mission International. 08-06 Golden Mile Tower, 6001 Beach Road, Singapore 199589.

The prevention of disability project in the People's Republic of China is probably the largest project in the world addressing the problem of prevention of disabilities due to leprosy. Disabilities have been the major cause of social stigma in leprosy patients in China and prevent major hurdles in their rehabilitation.

We have implemented the Prevention of Disability (POD) programme of leprosy patients in 15 provinces in China which has involved the planning and implementation of training of both health workers and people affected by leprosy in self care. The methods of training used at National. Provincial and County levels have included lectures, group seminars, demonstrations and on the job training. Training to the health staff i.e. doctors, supervisors and basic health workers was the key to the programme's success. A total of 325 training courses were conducted and a total of 11.891 participants were present. 2.078 supervisors were also trained in this programme. The programme involved the process of transferring POD technology from experts to basic health workers to leprosy patients. However the follow-up supervision and re-inforcement of training has been a key to the success of the programme.

Evaluation of the achievements of the training programme was conducted by a independent team of national and international experts in 1998. Change in attitudes and behaviour of the patients to the problem was assessed. The response of patients to neuritis was good and patients followed the instructions careful, particularly if there was pain associated with the neuritis. Patients learned self care of eyes well, partly because eye problems are visible and closely linked to stigma. Self care of the hand was comparatively better than self care of the foot which may be related to function of the hand and visibility.

The evaluation of the effectiveness of training reflects on the importance of follow up supervision and reinforcement of training; and patients learning related to presence of pain and the visibility of the potential disability (deformity).

BASIC ACTIVITIES AND SKILLS DETERMINED IMPORTANT IN PREVENTING IMPAIRMENTS AND DISABILITY IN HD AND THEIR IMPACT ON TRAINING AND SUPERVISION IN BRAZIL IN 1997 AND 1998

Linda F. Lehman, Hannelore Vieth, Maria Beatriz P. Orsini, Maria Leide W. Oliveira

Health Foundation. Ministry of Health, Brasilia, D.F., Brazil American Leprosy Missions (ALM), Greenville. S.C., USA

Brazil has 27 states and over 5,000 municipalities. It continues to have over 36,000 new cases of HD diagnosed yearly. The coordinator of CNDS of the Ministry of Health in Brazil requested a collaborative National Prevention of Disability (POD) Project between the government and ALM in August of 1996. One outcome expected was to integrate essential POD activities into all HD control programs. Therefore is was necessary to identify essential activities and skills needed for preventing impairments and disability.

A consensus of basic activities and skills were developed by the National POD advisory committee combined with the results from four 1997 national supervisory training workshops. The combination represented disease control realities throughout Brazil.

Using these activities and skills, standardized training courses and systematic supervision were developed and implementation started in 1997. This presentation will also show the course content and objectives of two standardized training courses. One course developed for the trainer/supervisor and the other course for local health care workers. The skills learned in the courses are than followed up in systematic supervision activities. Supervision was felt to be the key component to maintaining and improving quality care as well as key to giving feedback for future training needs.

THE RESULTS OF 5 NATIONAL STANDARDIZED PREVENTION OF DISABILITY IN HANSEN'S DISEASE COURSES FOR THE TRAINER SUPERVISOR WHICH COVERED ALL 27 BRAZILIAN STATES IN 1997 AND 1998

Linda F. Lehman. Hannelore Vieth. Maria Beatriz P. Orsini, Maria Leide W. Oliveira

Health Foundation. Ministry of Health. Brasilia. D.F., Brazil American Leprosy Missions (ALM), Greenville, S.C., USA

The coordinator of CNDS of the Ministry of Health in Brazil requested a collaborative National Prevention of Disability (POD) Project between the government and ALM in August of 1996. One of the primary goals was to integrate essential POD activities into all Hansen's disease control programs. For this to be accomplished, two standardized training courses were developed in 1997, one for the trainer/supervisor and the other for local health care workers. This presentation will focus on the results of 5 national train the trainer/supervisor courses.

The objective of this course was to prepare 2 persons in each state to provide technical and administrative support to the state by facilitating standardized courses and implementing systematic supervision of essential POD activities within the state's HD control programs in integrated public health facilities.

The results of pre and post course testing, the results of individual participant final course evaluations, the course facilitator's evaluations, and the up to date status of follow-up training and supervision activities at the state level will be presented.

The presentation will also look at needs identified during and after the courses, factors which facilitated and impeded course implementation, and recommendations for future courses of this kind.

THE DEVELOPMENT AND IMPLEMENTATION OF NATIONAL STANDARDIZED PREVENTION OF DISABILITY TRAINING COURSES FOR ALL 27 BRAZILIAN STATES

Linda F Lehman, Hannelore Vieth, Maria Beatriz P. Orsini. Maria Leide W. Oliveira

Foundation. Ministry of Health. Brasilia. D.F., Brazil American Leprosy Missions (ALM). Greenville. S.C., USA

The coordinator of CNDS of the Ministry of Health in Brazil requested a collaborative National Prevention of Disability (POD) Project between the gov eminent and ALM in August of 1996, to start in 1997. This presentation will focus on the POD training courses currently being adopted in Brazil.

1. The recognition of the size of the HD problem in Brazil with 27 states and over 5.000 municipalities.
2. The recognition that POD is "an essential component of leprosy control programs" (WHO).
3. The identification and selection of a project coordinator.
4. The identification and selection of a national POD advisory committee.
5. The identification of POD needs in training and supervision.
6. The consensus of a working definition for POD and essential POD activities and tasks.
7. The elaboration of two types of courses, one for training trainers/supervisors and the other for training local health care workers.
8. The elaboration of educational material and training methods.
9. The establishment of a strategy which would enable each state to have its own capacits to train and supervise POD activities.
10.The development of evaluation criteria.
11.The identification of needed political and financial support required for a successful outcome.

V. Uma, John Stephen, S. Arunthathi, P. Krishnarnurthy, N.B.B. Reddy Damien Foundation India Trust, 27, Venugopal Avenue, Spurtank Road. Chetpet. Chennai - 600 031, India

In the context of the goal of elimination of leprosy as a public health problem by 2000 AD. and impending disbandment of vertical leprosy services in many areas, it becomes imperative to ensure that general health personnel are equipped with skills and knowledge to diagnose and manage leprosy. A distance learning programme has been developed by the DFIT in leprosy as an innovative educational strategy to cater to those health personnel who do not have the time and resources to undergo formal training in leprosy. The distance learning curriculum includes 10 modules of self directed, problem based learning materials. The requirements include participation in 2 contact sessions and the completion of 10 sets of assignments. Individualised feedback was given for the assignments. Contact sessions relied on task based, small group learning. Candidate performance was measured with objective structured clinical examinations. The distance education programme has been pilot tested on a total of 12 participants who were enrolled in 1997. Preliminary evaluation suggests that, with improvisations, distance education could become a highly effective and efficient educational intervention. The results of the final evaluation of one year experience with distance education will be presented at the conference.

S.A.R. Krishnan, Guido Groenen, Tesfaye Bulto P.O.Box 165, Addis Ababa, Ethiopia

The number of leprosy patients is decreasing world-wide. Specialized leprosy control projects, and even special services specifically aimed at leprosy patients (rehabilitation, vocational training, etc.) will become less and less cost efficient. At the same time, the number of leprosy patients that a single health worker will see, be it in a specialized leprosy programme or in an integrated general health care setting, risks becoming too low to maintain the necessary skills for diagnosis, treatment and prevention of disabilities.

How can we ensure the sustainability of the essential leprosy control functions in a situation of low endemicity?

Training of the general health staff at all levels would seem to be one of the key areas. However, specialist training of long duration (the kind of training still being given at the various leprosy training institutions) will not be acceptable, nor would it be appropriate. We have to devise new approaches to training in order to reach our target group. Some of the possibilities that are being examined:

It is the task of institutions like ALERT to develop these new training strategies together with the National Leprosy Control Programmes and the ILEP members.

T.Ethiraj, V.Uma, P Krishnamurthy Damien Foundation India Trust, 27 Venugopal Avenue, Spurtank Road, Chetpet, Chennai: 600 031, India

On the eve of entering the phase of horizontalisation of leprosy eradication programme, active case detection methods will have to be replaced by passive ones, the prime among them being voluntary reporting of leprosy cases. Proportion of voluntary cases among the new reflects to a large extent on the level of awareness about leprosy among the people. In this context, DFIT has made an effort in this direction. A workshop for training of trainers was conducted in order to tram the workers in health education at different projects.

The training methodology involved one day exposure to the participants to theoretical aspects through practical execises, and two days of field based training which included, situation analysis, problem identification, setting objectives, selection of suitable methodology, implementation and evaluation.

A core team of trainers was selected to train the workers in each project. Each worker developed an action plan for his subcentre.

Wonting to change the poor quality services that have been prevailing in the field of leprosy all over the country, we have developed a system which has been implemented experimentally over 70 paramedical workers and 20 supervisors of our own organization in different relevant courses. We found our system has successfully been producing able, confident and committed best ever staff. Careful candidate selection, providing task-oriented training and smooth absorption of newly graduated staft under close supervision, at least for the first few months, are vital for ensuring the quality services in the field. We found 4 months and 2 months basic courses for the PMWs and Supervisor respectively arc essential at present context.

Sudhakar Bandyopadhyay Gandhi Memorial Leprosy Foundation. Balarampur Control Unit: Purulia:723143 : india:

Folk is an attractive entertaining and educative media for mass communication with special relevance to rural people. Folk media could effectively be explored to disseminate messages, to increase people's awareness and possibilities for action, to solve difficult social issues. Action on stage have led to real life actions in many instances.

In Balarampur Unit of Gandhi Memorial Leprosy Foundation*Folk media mainly puppetry and street Play are being employed for Health communication.

A well-equipped team with locally prepared puppets, dresses, folding dias and music system perform the programmes. Stories for both the puppetry and street play are related to local incidents and scripts are prepared by the Leprosy workers.

An analysis of data collected for last 5 year (1992-96) produces encouraging outcome. Total 196 (Puppet-161 and Street Play-350) programmes were conducted in 151 villages with an average audience of 400. The effects include onspot reporting of 94 persons with suspicious lesions. Total 207 patients were reported and registered including cases referred by teachers, community leaders and family members being influenced by the programmes. It also helped prepare grounds to solve unfavourable social issues. It has also helped regularizing treatment compliance of patients.

The above findings suggest that folk media has potential contribution to creat mass-awareness in Leprosy and to change behavioral pattern as well.

A Management Tools Workshop was designed by Hep working committee for the project managers keeping the specific needs of Leprosy control programme German Leprosy Relief Association and Swiss Emmaus Leprosy Relief Work India conducted a senes of workshops during the two years 1996-97 covering about 40 NGOs in South India. A study was made to evaluate the effect of this training. Following are the findings:

♦ 86.4% reported that they are able to analyse the present situation of the project and accordingly they could prepare annual plan of action as well as a long term plan of action.
♦ 91.8% of the NGO's stated that now the vision about the mission is cleared. They could specify their priorities more precisely.
♦ 81.3% of the NGO's are now in a position to forecast a financial budget in a scientific manner different from the traditional manner.
♦ More than 73.9% of the NGO's could identify the areas where cost control is possible. Their annual financial outlay for 1998 is about 22 to 34% less than that of 1993 budget.
♦ 64.2% of the NGO's acknowledge that they have improved inter personal relationship with staff and between staff.
♦ 39.6% of the NGO's were in a position to identify excess staff who could be reduced without affecting the delivery of prevailing quality services.
♦ More than 74.1% of the NGO's informed that they are able to appreciate the significance of data available from their own ILEP 'B' forms (annual report)

The study revealed that Functional Management Tools will bring cost effectiveness and efficient management of Leprosy programmes.

Nimal Kasturiarachi¹, Penny Grewal² , Mitchell Weiss³, Padmini Gunawardene⁴, Dayamal Dewapura² , Sunil Settinayake⁴, Lakshmi Somatunga⁴ , Vinya Ariyaratne⁵

¹University of Peredeniya, Sri Lanka, ²Novartis Foundation for Sustainable Development, Switzerland, ¹Swiss Tropical Institute, Switzerland, ⁴Anti-Leprosy Campaign, Sri Lanka. ⁵University Sri Jaywardenepura, Sri Lanka

Misdiagnosis of leprosy among general health care providers, particularly ayurvedic practitioners, is common and has serious implications for the elimination of leprosy and the deformity load in the community.

A study was carried out in Sri Lanka among different types of health care providers, using photographs of representative signs of leprosy and a vignette describing the disease symptoms, in order to assess their diagnostic knowledge, treatment and referral patterns and sources of information.

The findings reveal that ayurvedic practitioners, particularly the non-graduates, tend to misdiagnosis leprosy. There are primarily two reasons for this: First, a lack of training in leprosy and/or inadequate clinical exposure for the few who were trained. Second, the existence of ayurvedic illness categories which resemble the symptomatology of early manifestations of leprosy which lead them to misdiagnose leprosy.

As health care providers with non-biomedical backgrounds outnumber those with a biomedical background in many Asian countries, it is important to include them in leprosy control activities. They are also easily accessible and charge relatively low consultation fees. Moreover, with the low incidence of leprosy, affected persons may not suspect are suffering from leprosy and would consult ayurvedic practitioners.

However, developing training programmes for such practitioners poses special challenges. One key issue is to incorporate biomedical knowledge into the ayurvedic ideological framework so that they entertain a differential diagnosis of leprosy. Another is to motivate them to refer persons suspected with leprosy for treatment as they lack a tradition of referrals. It is also crucial to develop innovative and cost effective methods of training to reach a significant number of ayurvedic practitioners.

Ahsan Ali, Jalal Uddin Ahmed, Derek Lobo, Nepisha Begum National Leprosy Control Programme, Dhaka, Bangladesh

Leprosy services were integrated into the general health services of Bangladesh in phases as of November 1993.

Prior to the establishment of MDT services at Government Health Centres, a 6-day training for doctors and a 1-day training for all the general health staff was given. The objectives of general health staff training were simple :

* to recognise early signs, suspect leprosy and refer the suspect case to the nearest health centre.
* to follow-up on treatment defaulters and motivate them.
* tp provide basic information on leprosy to the public.
* to support the leprosy services in the health centre.

Over 31,000 general health workers and 1,100 doctors from health centres and medical colleges were provided the training over a 5-year period from mid-1993 to date.

The details, outcome and impact of this massive training programme and its contribution to achieving the leprosy elimination goal in Bangladesh will be presented and discussed.

TRAINING NEED ASSESSSMENT IN THE SUPERVISION SKILL OF THE DISTRICT LEPROSY SUPERVISORS IN INDONESIA

The training need in supervision skill of the district leprosy supervisors (wasors) in Indonesia who supervise the health centre leprosy workers were assessed to ensure the achievement of the national ( and global) goal of elimination of leprosy / 2000. Thirty three among approximately 300 district wasors (11%) from 8 province representing arbitarary the eastern, central and western part of the country, were assessed by the provincial leprosy doctors or the leprosy supervisors. Data was obtained by interview and observation method using a check-list. The assessment study revealed that no special training course in supervision is needed provided constant guidance is given to the district supervisors. The guidance should include the importance of using a check-list during supervision (preferably providing a model check-list), improving ST and VMT techniques, the knowledge about the signs of severe reactions, identifying inadequacy in the performance of the health centre workers, improving it on the spot and recording the supervision which will serve as a report, feed back and material for the next visit.

THE PATIENT AS A COMMUNITY EDUCATOR IN THE CITY OF SÃO BERNARDO DO CAMPO, BRAZIL

Education is a fundamental component in the efforts towards Leprosy elimination. The distance between the health workers language and the patient's is often an obstacle to communication.

The paper presents a report of 10 years of health education performed by patients in Brazil. The impact of the efforts are discussed and suggestion for Leprosy education are proposed.

INCOME GENERATION PROJECT FOR PERSONS .AFFECTED BY LEPROSY AND DISABILITIES IN THE AREA OF SOROCABA. BRAZIL

The income generation project for persons affected by Leprosy and disabilities is being implemented in the area of Sorocaba, Brazil. The objectives are to equip persons affected by Leprosy and disabilities to develop economically table businesses so that they can contribute to the socioeconomic development of their families and communities restoring their dignity.

There are 791 persons affected by Leprosy in their economically active years (15-60 years of age) in the region, and 12.500 persons with disabilities. There arc good public services in health and education. But there are no socioeconomic rehabilitation programs available.

The training methodology was developed at the University of Georgia (USA) where the whole business administration curriculum is taught to low income students by using role play activities that simulate a business experience and procedures. The curriculum was translated to the local language and the games were adapted to the situation and a pilot training was conducted

The results of the pilot training are discussed and suggestions are made as to the use of hands-on approach to teach business administration to persons affected by leprosy and disabilities with little formal education. The project was des eloped with the partnership of the patients their participation is discussed

Training of Health Workers in Post-elimination era need conceptual reassessment. The curricula contents need be revised.

With the expected decline of prevalence in countries the needs of disabled persons have to be attended to. A part of this work would be within the ambit of the social welfare services. However the major responsibility will be with the health services to ensure care after cure as well as to interact with the Social Service Institutions for promotion of physical, economic and social well-being of the persons.

All Health Workers, would be required for early case detection, identification of persons at risk and for surveillance to detect relapses.

All these require purposeful training and orientation of the Staff as has been discussed in the paper.

A GESTIONNAIRE-BASED SURVEY IN ASSESSMENT OF KNOWLEDGE AND SKILLS IN EARLY DIAGNOSIS OF LEPROSY AMONG MEDICAL STAFF AT DIFFERENT LEVELS

Shu-min Chen, • Rong-tao Zheng , • Bing Li , • Lin Zhang • Cun-lian Han, •• and Xun-dong Wong ••

• Shandong Provincial Institute of Dermatology.
•• Ji Ning Leprosy Hospital, China

ln order to assess the knowledge and skills regarding early diagnosis of leprosy. 33 village doctors. 34 township doctors. 27 doctors in county hospitals from 3 counties. 22 physicians and surgeons as well as 13 dermatologists in two provincial hospitals were selected to complete self-administered questionnaires. Following were the results: correct answers of pathogen of leprosy were 82%, 94%, 81%, 86% and 100% respectively, of life-long medications were 91%, 88%, 89%, 72% and 83%, respectively; of MDT were 0%, 0%, 19%, 0% and 62% respectively; of infectivity of sole ulcers were 30%, 38%, 15%, 18% and 62% respectively; of early symptoms of leprosy (defined as numbness of extremities) were S2% 26%. 30% 3% and 77% respectively: of early signs of leprosy (defined as anesthetic skin lesion with or without peripheral never enlargement) were 0%, 3%, 33%,5% and 100% respectively; of how to do physical examination when a person was suspected of leprosy were 36%, 6%, 18%, 0% and 100% respectively; of having the knowledge in skin smear and biopsy when a person was suspected of leprosy, were 30%, 29%, 41%, 23% and 100% respectively. Many of the investigated subjects did not know where or whom to refer a suspect or a diagnosed leprosy patient for confirmation of diagnosis and treatment.

The authors recognized that majority of the medical staff at different levels in this group, except dermatologists, were lack of knowledge and skills in early diagnosis of leprosy, so that a relevant training programme in early diagnosis of leprosy should be conducted in a planned manner.

IN SERVICE TRAINING MODULE FOR SOCIAL ASSISTANTS AND THEORETICAL METHODS OF ASSESSMENT OF SUCH PRACTICES IN THE ATTENTION FOR HANSEN'S DISEASE PATIENTS

Otilia Simões J. Gonçalves, Heleida N. Metello, Wagner Nogueira. Angelina Lopes, Carmem Luisa M.P. Guisard, Ana Angela Alcantara C. Cardoso, Maria Sebastiana F. Bizetto, Raquel C. Jesus, Marcia H. Verri, Rute Pereira M. Coutinho

This paper relates the experience of the constrution of the theoretical and pratical module of in-service training for Social Assistants in the actions for social attention of Hansen's disease patients.

The authors present the phases and strategies for the development of this process at central level and the necessary interfaces with the regional realities that insue the theoretical identification and the operation of specific actions of the Social Assistants with the patients and the work of these professionals integrated with the other professionals of the team in health services.

In concludes with the presentation of the lines that design the practice of these professionals in the services offered to our clients, especially regarding Hansen's disease patients, through the definition of the atribuitions and actions left to them and therefore, the profile of the theoretical insertion of their routine practices.

'Info Kusta' is Indonesian for Information about Leprosy. The poster is in the form of a cartoon story. The pictures are clear, showing the early signs of leprosy.

One person is pointing at the patches on the back of his friend. The person with the patches is advised to go to the health centre for examination. At the time of examination, the patient mentions that the patches are not itchy and have no feeling. Leprosy is confirmed by the docter.

In the summary, the early signs are mentioned, and the necessity of going quickly to a health centre for examination, because if it is leprosy, it can be cured if treated while still in the early stage.

The aim of this presentation is to explain the clinical teaching approach as an effective method of training rural health workers to diagnose early tuberculosis and leprosy.

It deals with what to teach and how to teach it, in a realistic clinical situation. Trainees should be able to detect any patient with early signs of leprosy or tuberculosis.

LEPROSY AND TROPICAL SKIN DISEASES: DEVELOPMENT OP THE CURRICULUM FOR FINAL YEAR MEDICAL STUDENTS IN ETHIOPIA

ALERT, the All Africa Leprosy Tuberculosis and Rehabilitation Training Centre, has been providing a 3-week course in leprosy and dermatology for final year Medical Students in Ethiopia for many years.

Objective: To identify students needs, and to find out how far the courses at ALERT meet those needs.

Subject: 459 final year Medical Students participated in the training program between 1993 and 1997. They were asked to fill in a questionnaire about the course objectives, its contents, teaching methods and duration. They were interviewed in groups.

Results: Students expressed a clear desire for less leprosy and more tropical dermatology in the course. They also requested more task-based learning than classroom learning.

Conclusion: While the need for continuing training of all health workers in leprosy is recognised, this study shows a worrying decline of interest in leprosy on the part of this group of future doctors.

The All-Africa Leprosy. Tuberculosis and Rehabilitation Training Centre will offer the following courses in 1999.

- tropical dermatology (2 to 4 weeks)
- leprosy surgery (2 to 6 months)
- tropical eye care (2 to 12 weeks)
- physiotherapy for leprosy patients (1 to 3 months)

For the exact dates, please consult the 1999 Training Calendar, available from the ALERT delegates, or contact:

OCKIE KRUGER, FRIKKIE NAUDE, ERNEST RAMABOKELA THE LEPROSY MISSION SOUTHERN AFRICA

In countries with a low prevalence of Leprosy, you need to keep your awareness programmes on a high standard In South Africa we experimented on several ideas and found that one of the most effective ways of doing it is to produce a poster which can be used for Awareness, diagnosis, Health Education and at the same time provide essential information about Leprosy and where people can get help from

The different classification of the poster consists of Photos, a slogan and written information

It is already tested in South Africa and even led to self-diagnoses by patients It proves to be very effective in clinics, hospitals and other public places, like health centres, schools and shopping centres

Medical staff find it very usefull in keeping them aware of the disease but also for providing the necessary information for treatment

FIELD TEST OF THE CLARITY OF THE SELF-CARE BOOKLET FOR LEPROSRY PATIENTS PRODUCED AT NLTC, INDONESIA

The " Self-Care Booklet for Leprosy Patients " produced at the National Leprosy Training Centre, Indonesia, was field tested for its clarity to the patients Five areas of leprosy control programme prominant in the prevention of disability activities were selected for the study. The test was conducted by the leprosy doctors using a questionnaire accompanied by an instruction of how to fill it out. The questionnaire contains questions and instructions derived from the Booklet. The patients were asked to answer the questions and instructions before and after reading the Booklet in the sections compatible to the disability (ies) they are suffering from . The differences between the mean correct answers before and after reading the Booklet was compared The result showed that for the messages on insentive hand, foot, with or without ulcer and on lagophthalmus, the differences were significant (p < 0.05 to 0,01) For the messages on claw hands,claw toes and drop foot, the differences were insignificant ( p > 0.05 ) and these pans of the Booklet need improvement

DEVELOPMENT OF A CHECK-LIST BY TASK ANALYSIS TO ASSESS THE COMPETENCE OF THE DISTRICT LEPROSY WORKERS IN SUPERVISING THE HEALTH CNETRE JUNIOR LEPROSY WORKERS

A check list for assessing the competence of the district leprosy workers in supervision skill, who will supervise the heath centre leprosy workers, the spearheads of the elimination programme, has been developed by Task Analysis technique The Check List can be very useful for the programme managers, particularly those at the provincial level to identify the need for improving the district leprosy workers

HAND AND FOOT SENSORY STATUS OF OVER 250 HEALTH CARE WORKERS PARTICIPATING IN PREVENTION OF DISABILITY TRAINING COURSES IN BRAZIL F ROM 1993 TO 1998

National and state POD training courses, Brazil American Leprosy Missions, Greenville, S.C., USA

The practice of sensory testing during training courses is important to enable participants to develop both manual and interpretive skills. Participants have hands on experience testing each other as well as seeing what it is like to have their own hands and feet tested. Participants learn to understand what hands and feet of persons without pathology can feel. This enables them to suspect and/or identify mild sensory changes in early nerve impairment and identify severe sensory loss which would put a person at risk of injury during clinical practices with patients.

This poster demonstrates the response of over 250 health care workers hand and foot sensory status using the Semmes-Weinstein monofilaments. The monofilaments used were 0.05g, 0.2g, 2g, 4g, 10g, and 300g. All participants without pathology could feel the light touch of a pencil. Participants practiced imitating the pressure felt with the 2g monofilament with the pencil. All health care workers with known pathology were excluded from the analysis.

The importance of this poster is to demonstrate health care workers without known pathology were able to feel with their hands and feet. It raises the question if there are regional differences accounting for differences noted in sensation world wide.

As the number of leprosy patients decrease due to successful leprosy control, the need for specialised surgeons working full time on leprosy patients will also decrease. The motivation for financing and recruiting leprosy surgeons will diminish. Patients at risk of acquiring disabilities will still remain for some considerable time, and it would be unfair to withhold the potential benefits of surgery from those who could be helped by it. Preventative and Rehabilitative Surgery (PRS) is an essential part of any Prevention and Management of Disability programme. Even in an integrated setting, where leprosy control is part of the general public health activities, PRS should be available at the district or sub-regional level.

Leprosy surgery uses techniques from many specialities, especially from hand-, plastic-, and orthopaedic surgery. Any general surgeon with access to a standard operating theatre could perform basic PRS after a reasonable time of training in the principles of PRS.

The most efficient way to preserve the necessary skills and expertise seems to be to make sure that the representatives of the relevant surgical subspecialties are able to take care of specialised surgery on leprosy patients as part of their work. It is thus up to the specialised leprosy institutions that still have expert leprosy surgeons to start training those specialists. Once trained, they will be the resource people who will train the peripheral general surgeons in PRS in an integrated setting.

Hind Kusht Nivaran Sangh-Maharashtra Branch, ALHRRE, Wadala, Mumbai-400 031, India.

Leprosy teaching in non-allopathy medical colleges is practically negligible or not up to the mark in India. Medical graduates passing out from these medical colleges generally set up their private medical practice at the grass root level catering to the low socio economic group among which the possibility of detection of leprosy cases is comparatively more.

In Maharashtra State of India there are 37 Ayurvedic, 37 Homeopathic and 5 Unani Medical Colleges where approximately 4000 new admissions are taken every year. In 1992 an inter-action with these medical colleges by organising teaching sessions on leprosy to medical students was initiated. In order to ensure continuity in leprosy teaching, training of leprosy to teachers of the medical colleges was also undertaken. As such 39 medical colleges have been covered during the last 5 years and practically 1200 students received the benefit of leprosy teaching every year.

The follow up was maintained with these students by correspondence. It was found that graduated students who succeeded to obtain job as well as those who started their private practice detected 351 new leprosy cases during the last five years. This experiment Indicates that involvement of non-allopathy medical colleges is fruitful method for case detection in leprosy.

This poster illustrates the buildings, the graduates, the subject matter of their dissertations and their influence on the health provision of rural communities, especially in Africa.

It is estimated that 15-20% of leprosy patients prefer to take chemotherapy from practising dermatologists in Greater Bombay. Approximately 200 dermatologists are playing a significant role in the form of private health sector. It is observed that the criteria for identification, diagnosis, classification and treatment are arbitrary and deviant from WHO/NLEP strategies. Hence a project under SAPEL was undertaken with an objective to involve and orient dermatologists to improve the quality of the above aspects relating to leprosy elimination.

Workshops were held for 31 dermatologists in six batches on subjects such as current concepts in chemotherapy, skin smear taking, staining and laboratory aspects of leprosy. Simple reporting format was designed to collect information on the number of patients treated. Field workers visited the identified dermatologists to provide smear facilities, collect slides and provide reports. A questionnaire feedback after this effort showed

1	No. of dermatologists participating	31
2	No. of dermatologists trained in skin smear examination	8
3	No. of patients registered for MDT	463
4	No. of patients completed treatment*
	• PB-MDT- 6 doses	55
	• PB-MDT-> 6 doses	27
	• MB-MDT - 24 doses	52
	• MB-M0T-> 24 doses	50
5	Patients with reaction managed scientifically	597

• It is felt that many more sessions will be needed to orient them on the principles of fixed duration treatment.

The success of this Bombay experiment calls for coverage of several groups of dermatologists on the SAPEL model all over the country.

Conceived in 1987, this Foundation seeks solutions to care of the skin in the developing world..

Its principle mission is 'training' and for this purpose a Regional Dermatology Training Center was built in Tanzania for the countries of the Commonwealth Regional Health Secretariat of Central Eastern and Southern Africa. This center provides an integrated training programme over a period of two years ending in a University Diploma. It has been designated to become a Collaborating Center for dermatology, sexually transmitted diseases and leprosy. A second Center trained 250 nurses from Health Centers in Guatemala and there are new plans for the eight countries of Francophone West Africa.

Maria Aparecida Pinheiro Sanches, Otília Simões J. Gonçalves, Zenaide L. Lessa, Elza Berro, Maria de Lourdes B. Diniz

The project of creating a didatic instrument with the theme "Education in Health. Diagnosis and Educational Planning" derived from the experience in forming human resources for the Hanses Disease control program. This elaboration was subsided by the practice offered to professionals in developing educating actions in the "Health Education Courses and Hansen's Disease Program", since 1991. The creation of such na instrument resulted from a process of collective construction and reconstruction derived from the practices developed in the Pedagogical Workshops of Health Education and Local Planning. Participants have assessed, in step-by-step practice, its practical use, with a 95% approbation. The final product "Education in Health a Guide for Planing Educative Actions: Practice and Theory" reasulted in a theoretical, methodological and practical reference for Education in Health, with focus on the concepts of Education, Communication, Participation, Diagnosis and Participative Planning of actions and has been offered to the regional and local branches for the planning of educative actions.

HEALTH EDUCATION AND COUNSELLING: A KEY TO MULTIDRUG THERAPY COMPLIANCE IN LEPROSY.

The Urban Leprosy Centre of Lok Nayak Hospital, New Delhi was established in 1981 and every year about 350 to 400 new Leprosy cases are registered in the centre. 70% of the patients attending leprosy clinic are illitrate.

Counselling on 1500 Leprosy patient of both sexes attending the Urban Leprosy Centre of Lok Nayak

Hospital and associated Maulana Azad Medical College New Delhi were inducted for counselling as per stipulated proforma each patient was administrated 600 mg of Rifampicin once a month supervised, Dapsone 100 mg daily Clofazimine 50 mg daily along with Clofazimine in the doses of 300 mg once monthly in multibacillary (MB) Leprosy and Rifampicin 600 mg once a month and 100 mg of Dapsone in Paucibacillary (PB) Lprosy (W.H.O.).

Health education material used for educating and counselling were flash card, and posters on Leprosy.

These patients were advised to report for follow-up every month accordingly details of counselling and Health Education were formed in each patient, and were recorded on a proforma devised for the purpose.

The data was ultimately analysed and it was found M.D.T. Counselling forms the important prerequisite for good compliance. This procedure should, therefore form a part component of Multidrug therapy at all Leprosy Centres.

Management of leprosy and its consequences has always been a significant part of the programmes of the IFD.

Based on an analysis of 219 newly detected leprosy patients, the authors found that due to many very well-Know reasons these cases have been diagnosed on an average in 4 years after the onset of the clinical signs. During their first visit to the clinic only 116 (39.87%) of them were timely diagnosed as leprosy, 64(21,99%) as suspect and 111 (38.14%) missed to be made a correct diagnosis. Amongst the latter 111 cases. 73 were inidiagnosed as other diseases. wich as allergie dermatitis, neurofibromatosis, acne, pitynoasis vesicolor, pitynasis rosea, polyneuritis, rheumatism, nephritis etc. Skin diseases and nervous diseases were common conditions mimicking early leprosy The correct diagnosis rate during first visit to general hospital was 22,22% and that to leprosy professional clinic was 59.42%. The above mentioned data clearly indicated that health education about leprosy should be intensified for the community, medical students should be given more lessions in leprosy and practice teaching in leprosy clinic, and leprosy professionals working in county stations for skin diseases control should be given intensive/refreshed training because they frequently to have confirm diagnosis themselves for suspected casta.

Departments of Internal Medicine and *Social Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil

The objective of this presentation is to describe the creation, structuration and execution of an educational project directed at medical students for the teaching of leprosy through extracurricular activities. The League for the Combat of Leprosy has been active for 6 years at the Faculty of Medicine of Ribeirão Preto, USP. Supervised volunteer work is carried out in order to provide the students with a general overview, with activities in the Program of Leprosy Control in the municipality of Ribeirão Preto, São Paulo, Brazil.

The activities involve care for leprosy patients and their relatives as well as educational actions directed at the students, health professionals and the population in general. As an educational project linked to the University structure, the League has three basic objectives: patient care, teaching, and promotion of research, thus integrating the University with the other levels of health and community services. The members of the League are stimulated to learn about leprosy both as a biological disease and as a social disease and public health problem within the community context at the socioeconomic level Learning involves practical work such as supervised assistance, activities aiming at the prevention of morbidity and disability, and educational and health-promoting actions executed at a District Unit for primary health care. This type of work may contribute to medical training, helping the dissemination of knowledge, and expanding the services provided by the University to the academic-scientific medium and to the community. A first evaluation indicates that this project is feasible ami stimulates education in the area of leprosy, having become a reference model for the execution of the Program of Leprosy Control in the Ribeirão Preto region.

José Terencio, Vicente Gimeno, José R. Gómez, María Quintana y Pedro Torres.
Sanatorio de Fontilles. Alicante. España.

Fundado en 1907 por el jesuita P. Ferris en Alicante una de las zonas más endémicas de España ha desarrollado en sus 83 anos una triple labor Asistencial (tratando más de 3.000 enfermos) de Investigación y Formación.

En este aspecto ha realizado 74 Cursos de Leprologia, 34 para Médicos y 40 para Auxiliares Sanitarios, Misioneros y Trabajadores Sociales, habiendo formado 2.800 personas.

Los Cursos son anuales teóricos y prácticas de Bacteriología y Anatomía Patológica, Fisioterapia y Cirugía.

El Profesorado,a parte del personal del Hospital colaboran Profesores de Dermatología de España y prestigiosos Leprólogos mundiales.

Entre los asistentes hay una importante participación internacional de países Latino-americanos.

En los últimos años también se han impartido Cursos en Costa Rica, Nicaragua y Argentina.

THE DIFFERENCES BETWEEN HEALTH WORKERS » AND PATENTS' INTERPRETATIONS OF SOME TERMS USED IN LEFROSY CONTROL: IMPLICATIONS FOR HEALTH EDUCATION

The purpose of this study was to determine the differences between health workers' and Leprosy patients' interpretations of some terms frequently used in patients' education. Forty one health workers and Eighty six leprosy patients selected from two leprosy referral hospitals were interviewed. Majority of the health workers were unanimous in their interpretations of the terms. Chi - square tests revealed significant differences between the health workers' and patients' interpretations of all terms, except one (P 0.05 ). As a result health workers need to take into consideration patients' own interpretations of terms used during health education.

Drop-out	- 21(5.0%)	A - 15	B - 6
Completed Follow-up	- 455	A - 375	B - 80
Cure Rates		A - 360 (96%)	B - 78 (97.5%)
Relapse		A - 15 (4.0%)	B - 2 (2.5%)

Li Huan-Ying	Beijing Tropical Medicine Research Institute
Yuan Lian-Chao	"	"	"	"	"
Hu Lu-Fang	Sichuan Provincial Institute of Dermatology
Niny Yong	"	"	"	"	"
Huang Wen-Biao	Yunnan Provincial Institute of Dermatology
Zhou Yu-Xiang	"	"	"	"	"
Ye Fu-Chang	Guizhou Provincial Institute of Dermatology
Li Jin-l.an	"	"	"	"	"

Li Huan-Ying	Beijing Tropical Medicine Research Institute
Weng Xiao-Man	"	"	"	"	"
Li Fu-Tian	Shanghai Zun-Yi Leprosy Hospital
Ran Shun-Peng	Wenshan Prefectural Institute of Dermatology, Yunnan Province

International Journal of Leprosy and other Mycobacterial Diseases