Progress in treatment of Kala-azar

Abstract

Kala-azar or visceral leishmaniasis affects the poorest of the poor in the Indian sub-continent. It is almost always fatal if untreated. Till a decade ago pentavalent antimonials, used since the 1940s, continued to be in use in spite of having high toxicity and emergence of parasite resistance in India. In the last decade several new drugs have become available in the treatment of kala-azar, namely miltefosine, paromomycin and liposomal amphotericin B. Both miltefosine, the only oral drug, and paromomycin require prolonged therapy directly observed therapy for 4 and 3 weeks respectively which is difficult to organise in the remote regions. Also miltefosine is contra-indicated in pregnancy and in women of childbearing age unless they use contraception while paromomycin requires daily injections. Recent approaches have targeted development of shorter combination regimens lasting 7 to 10 days (miltefosine plus paromomycin; liposomal amphotericin B and miltefosine; liposomal amphotericin B and paromomycin) and a single-dose liposomal amphotericin B (10 mg/kg) with excellent efficacy and safety in clinical trials. These shorter regimens in addition to assuring good compliance will also protect individual drugs from developing resistance in the long term. Currently large scale public health studies of these regimens are underway in the Indian sub-continent to help introduce them at the primary health centre level.