Regarding relapse after long-term follow up of multibacillary patients treated by WHO multidrug regimen
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To the Editor:
The article "Relapse After Long-Term Follow Up of Multibacillary Patients Treated by WHO Multidrug Regimen," published in the INTERNATIONAL JOURNAL OF LEPROSY 63 (1995) 195-201, was a strong bomb to all leprosy researchers. The relapse rate reported by Dr. Jamet, et al. was so high that it astonished everyone.
I agree to treating some multibacillary (MB) patients with high bacterial indexes (Bis) with a longer duration of MDT. In my work since 1983, all MB patients were treated with MDT until smear negative. To date, there is only one MB patient treated with dapsone (DDS) monotherapy before MDT who relapsed at the end of the third year after 5 years of regular MDT. The mouse foot pad test demonstrated viable organisms. In the neighboring province, however, all of the MB patients were treated with MDT for only 2 years since 1985-1986, and there were two cases who relapsed (private communication). These two cases also had been treated for various durations with DDS monotherapy before MDT. I believe that in my work and in the neighboring province there are many MB patients with a BI of > 4.0 before MDT, but the relapse rate was very low in the two areas.
So, the high relapse rate reported by Dr. Jamet, et al., I think, perhaps was caused by irregular MDT treatment. Relapses caused by irregular MDT have occurred in China. Some patients took the tablets into their mouths (facing the doctor) but did not swallow them and disgorged the tablets (behind the doctor's back) for fear of slight side effects caused by the drugs.
Of 35 cases in the article reported by Dr. Jamet, et al., there were 15 who had been treated for various durations with DDS monotherapy before MDT; 5 had been treated with DDS monotherapy followed by various durations of DDS plus rifampin. I do not know how many relapse cases had been given DDS monotherapy before MDT. I found that some relapse cases seemed to be correlated with DDS monotherapy before MDT. Perhaps DDS, as a bacteriostatic monotherapy, before MDT formed a bad living environment for Mycobacterium leprae, and changed more M. leprae to persisters. When the bactericide (MDT) was given, there was no effect on the many viable persisters, thus causing a late relapse.
A relapsed patient is an infectious source. When leprosy is suspected, it must be quickly confirmed by re-testing the skin smear and skin biopsy to look for solid M. leprae. In my experience, some relapse cases after DDS monotherapy may have no obvious new skin lesions, even during the late stage. The active and visible lesions mainly depend on the status of inflammation in the dermis, such as the number of inflammatory cells, the dilatation of the small blood vessels, and the degree of edema in the dermal layer. In a word, they depend on the cellmediated immunity of the patient. If a lepromatous patient with a BI of > 4.0 docs not react to the numerous M. leprae, there will be no obvious new skin lesions at all.
I think that if there is an increase in the BI not accompanied by new lesions, the patient must be quickly re-examined by the various methods available today to confirm whether or not she/he had a relapse.
- Jianping Shen, M.D.
Department of Leprosy Research
Institute of Dermatology
Chinese Academy of Medical Sciences
14 Jiangwangmiao Street Nanjiang 210042
People's Republic of China