A therapeutic strategy for treating visceral Leishmaniasis in regions with drug resistance

Abstract

Visceral leishmaniasis (VL) affects 500,000 people annually worldwide, and Bihar alone accounts for approximately 45 % of that burden. For the last 2 decades there has been a steady decline in response to pentavalent antimonial (Sbv), the drug that has been used for treating VL for 7 decades. Oral miltefosine has been chosen as an alternative drug for use in the kala-azar elimination program in India, Nepal, and Bangladesh. There are only 4 approved antileishmanial drugs: Sbv, miltefosine, paromomycin, and amphotericin B and its lipid formulations. Except for liposomal amphotericin B, all the other drugs have to be administered for 21–30 days and have frequent side effects, leading to noncompliance and early discontinuation of treatment. These factors, along with the intrinsic characteristics of the drugs (e.g., a long half-life in the case of miltefosine), are conducive to the development of drug resistance. Thus, alternative strategies must be developed to prolong the effective life span of these drugs, such as the use of single-dose liposomal amphotericin B, or directly observed therapy when longer-duration treatments are used. Finally, combination therapy with multiple drugs should be implemented as early as possible, because these are likely to shorten the duration of therapy, improve compliance, and decrease both toxicity and cost of treatment.