Chemoprophylaxis against leprosy: expectations and methodology of a trial

Because of the great efficacy of multidrug therapy (MDT), it had been hoped that the widespread use of MDT would bring about a rapid decrease of the i ncidence of leprosy. To the present, a decrease of incidence has not been o bserved, possibly because of the long incubation period of the disease, and because general implementation of MDT is still recent. Other reasons, such as environmental sources of infection or the role of healthy carriers in t ransmitting Mycobacterium leprae, cannot be excluded. Therefore, one must s eek alternative or supplementary strategies, such as chemoprophylaxis. Hous ehold contacts of leprosy patients are at greater risk of developing lepros y than is the general population. Therefore, a randomized, controlled trial of chemoprophylaxis, using a single 10 mg/kg dose of rifampicin, or a plac ebo, is planned in nine projects in India, among the household contacts of newly detected leprosy patients. Based upon assumptions of a protective eff icacy of the chemoprophylaxis of 50%, an annual incidence of 2 per 1000 con tacts, a desired power of the study of 90%, and a level of significance of 95%, 15,000 household contacts will be allocated randomly by household to e ach arm of the study, and followed for 5 years. Considered as household con tacts will be all persons living in the same household as an index case and sharing the same kitchen. Pregnant women and infants will be excluded. To be certain that transmission of the organisms from the index case cannot oc cur once the prophylaxis is administered, rifampicin will be administered 2 months after diagnosis of the index case. Diagnosis of leprosy will be cli nical, and confirmed independently. Although household contacts usually con stitute only a small proportion of the new patients detected in a control p rogramme, their high-risk status makes them particularly appropriate for a study of the potential effect of chemoprophylaxis. Following the trial, one could evaluate the usefulness and feasibility of using the same strategy i n other population-groups, based on the number of persons necessary to trea t to prevent one case.