The other question is regarding the feasibility of vaccine trials against leprosy and various ethical aspects. As has been mentioned incidence rates have been showing changes. Estimates based on "incidence" rates using one single resurvey are quite fallacious. The "new cases" from the first resurvey would be a mixture of missed prevalent cases and the real new cases. Our observations indicate that in South Indian situation, incidence of leprosy is perhaps coming down substantially. Whether this is a natural decline or on account of MDT or some other known or unknown factors is difficult to say. But the fact is leprosy incidence is going to be rather low in time to come. Diagnostic techniques for leprosy, particularly, the early forms are insensitive and this would lead to missing of prevalent cases. When these cases are counted as incidence cases there is a danger of underestimation of vaccine efficacy. Similarly, if we are looking at a situation of lower specificity for diagnosis during resurveys, this would also lead to underestimation of vaccine efficacy. It is almost certain that precipitation of clinical form of leprosy, to certain extent, does occur following an immunologically potent antileprosy vaccine. There are no methods as of now to identify separately each of these components of leprosy which would affect assessment of vaccine efficacy. Thus, one would have to consider very large sample sizes and very long duration for follow-up. The long duration of follow-up would also lead to losses of cohort to a substantial extent. It is therefore obvious that the routine forms of antileprosy vaccine trials conducted so far would be a very difficult proposition. The need for developing and validating surrogate measures of protection cannot be overemphasized.
The ethical issues of concern are whether BCG can be denied, if some experts think that BCG is "the vaccine" against leprosy? Of course, from the results from Indian study, it is quite obvious that BCG has limitations. The next question is could we think of using placebo arm. If we tell the volunteers that they would be given the placebo, how many of them would accept to join the study? Can the consent be real informed consent? With a growing enlightenment about human rights and awareness about ethical issues, prospective vaccine studies are going to be difficult. It has to be fully borne in mind by each of the investigators that the ultimate responsibility for the vaccine trial would solely rest on the organizers of these studies.
Table - 1
Leprosy Incidence and Protective Effect of BCG Vaccination by BCG Strain
