Chemotherapy of leprosy for control programmes: Scientific basis and practical application

Abstract

In 1976 the WHO Expert Committee on Leprosy, emphasized the need to prevent the serious development of DDS resitance, and, in view of this recommended that all active cases of multibacillary leprosy (LL, BL and BB), whether previously untreated or relapsed, should be treated with two effective drugs. In 1977 ILEP (Heathrow Report) went much further in emphasizing the urgency of introducing multidrug regimens; WHO convened a Study Group in Geneva in 1981 to review the information since their 1976 Expert Committee Report on the problems related to chemotherapy of leprosy in the field. The Study Group confined their review to the most efficacious and immediately available antileprosy drugs with proven activity against M. leprae in the mouse footpad infection, other than DDS, as potential candidates for multidrug regimens. Three drugs met these criteria: rifampicin, clofazimine, ethionamide/prothionamide. Rifampicin was by far the most potent of the three drugs and from its very rapid bactericidal activity on M. leprae, clinical trials have shown that once-monthly doses of 600 mg were as effective as daily, without resulting in any of the known serious toxic manifestations associated with rifampicin given once weekly. Clofazimine, was fully potent at a dose of 100 mg thrice weekly rather than daily. Ethionamide/prothionamide (both thoamides) are bactericidal, potent drugs against M. leprae, but because of their short half-lives and slower rate of killing M. leprae than rifampicin, they have to be administered daily. Moreover, both drugs (prothionamide less than ethionamide), at 500 mg daily, can cause unacceptable gastric symptoms in some patients. None of these drugs develop cross-resistance with DDS or cross-resistance with themselves. The Study Group recommended two multidrug regimens for treatment in the field. The need for two regimens, for pauci- or multibacillary patients respectively is essential as the regimen for the paucibacillary patients has only to cope with the possibility of primary DDS resistance with very small numbers of resistant organisms, whereas the regimen for multibacillary patients will have to cope with large potentially DDS-resistant bacterial populations, requiring two additional drugs to prevent the emergence of resistance to either one. The absolutely vital component to both these regimens is dependent upon the potency of rifampicin and therefore to ensure its ingestion by the patient, every monthly dose must be supervised. Supervised administration of rifampicin entirely by the leprosy control staff, will also help to prevent this expensive drug getting into the black market. The recommended regimen for pancibacillary patients is to be continued for 6 months only, the regimen for the multibacillary patients requires a minimum of 2 years, where ever possible to smeer negativity, then it can be stopped.