Assessment of BCG protective efficacy by case-control studies
This department is for the publication of informal communications that are of interest because they are informative and stimulating, and for the discussion of controversial matters. The mandate of this JOURNAL is to disseminate information relating to leprosy in particular and also other mycobacterial diseases. Dissident comment or interpretation on published research is of course valid, but personality attacks on individuals would seem unnecessary. Political comments, valid or not, also are unwelcome. They might result in interference with the distribution of the JOURNAL and thus interfere with its prime purpose.
To the Editor:
Two case-control studies assessing the efficacy of BCG on the prevention of leprosy were recently published by the INTERNATIONAL JOURNAL OF LEPROSY (2, 4). Rodrigues, et al. (4) found that BCG had a protective efficacy of 81% in a population of adolescents and children in central Brazil. A study from India by Muliyil, et al. (2), although not showing an overall protection, suggested a shift toward paucibacillary cases in vaccinated persons, also an important finding because a decrease in multibacillary cases should, theoretically, decrease the transmission of the disease.
Although the results of these studies arc perfectly coherent with the findings of previous cohort and case-control studies and field trials (1), therefore giving consistency to the hypothesis that BCG has a prophylactic effect against leprosy, we would like to address a méthodologie issue that we believe is important.
In case-control studies used to assess the efficacy of a treatment or a preventive measure on a disease, cases and controls ideally must have had the same risk of developing the disease. The efficacy of the studied measure is shown or not by whether the odds of the disease differ significantly among those exposed and nonexposed to it.
In the Brazilian study, the controls were chosen among schoolchildren from the same areas as the cases. There was no information about the prevalence of leprosy in people living in the same household of the cases and controls, but it is predictable that the cases were more likely to have had a household contact than the controls and, therefore, were more exposed to the disease. It is well known that the risk of developing leprosy is higher in family clusters, although it is debatable whether this happens by genetic predisposition or because the transmission of the disease requires intimate and prolonged contact, or for both reasons (3). In Muliyil's study, where the cases and controls came from the same population, the risk of having a household contact was measured and was 11.7- and 2.7-fold higher in the case group for contacts of multibacillary and paucibacillary cases, respectively.
The question is: Were the control groups in both studies good controls? Although the results agreed with those of other, theoretically, stronger cohort studies and field trials, we believe that the choice of controls as it was made could have been misleading. In the study by Muliyil, et al, the presence of a case in the household was actually taken into consideration and adjusted for a multivariate analysis. Nevertheless, we believe that appropriate controls should have had the same exposure as the cases: household controls would be best, but in this situation the prevalence of previous BCG vaccine probably would not differ in cases and controls. Members from households of patients with leprosy other than the contacts of the cases would make an interesting control group, and we think that further case-control studies to assess BCG efficacy in leprosy should consider this alternative in their design.
- Sergio de Andrade Nishioka, M.D., M.Sc.
Isabela Maria Bernardes Goulart, M.D.
Centro de Ciéncias Biomédicas
Universidade Federal de Uberlândia
Av. Pará 1720
38400-902 Uberlândia, M.G., Brasil
REFERENCES
1. FINE, P. E. M., PONNIGHAUS, J. M., MAINE, N., CLARKSON, J. A. and Buss, L. Protective efficacy of BCG against leprosy in northern Malawi. Lancet 2(1986)499-502.
2. MULIYIL, J., NELSON, K. E. and DIAMOND, E. L. Effect of BCG on the risk of leprosy in an endemic area: a case control study. Int. J. Lepr. 59(1991)229-236.
3. NOORDEN, S. K. The epidemiology of leprosy. In: Leprosy. Hastings, R. C., ed. Edinburgh: Churchill Livingstone, 1985, pp. 15-30.
4. RODRIGUES, M. L. 0., SILVA, S. A., NETO, J. C. A., ANDRADE, A. L. S. S., MARTELLI, C. M. T. and ZICKER, F. Protective effect of intradermal BCGagainst leprosy: a case-control study in central Brazil. Int. J. Lepr. 60(1992):335-339.