Drug susceptibility in Leishmania isolates following Miltefosine treatment in cases of Visceral Leishmaniasis and post Kala-Azar dermal Leishmaniasis

Abstract

Background: With widespread resistance to antimonials in Visceral Leishmaniasis (VL) in the Indian subcontinent, Miltefosine (MIL) has been introduced as the first line therapy. Surveillance of MIL susceptibility in natural populations of Leishmania donovani is vital to preserve it and support the VL elimination program. Methodology and Principal Findings: We measured in vitro susceptibility towards MIL and paromomycin (PMM) in L. donovani isolated from VL and PKDL, pre- and post-treatment cases, using an amastigote-macrophage model. MIL susceptibility of post-treatment isolates from cured VL cases (n = 13, mean IC 50±SD = 2.43±1.44 μM), was comparable (p>0.05) whereas that from relapses (n = 3, mean IC 50 = 4.72±1.99 μM) was significantly higher (p = 0.04) to that of the pre-treatment group (n = 6, mean IC 50 = 1.86±0.75 μM). In PKDL, post-treatment isolates (n = 3, mean IC 50 = 16.13±2.64 μM) exhibited significantly lower susceptibility (p = 0.03) than pre-treatment isolates (n = 5, mean IC 50 = 8.63±0.94 μM). Overall, PKDL isolates (n = 8, mean IC 50 = 11.45±4.19 μM) exhibited significantly higher tolerance (p