Susceptibility of clinical isolates of Leishrnania aethiopica to miltefosine, paromomycin, amphotericin B and sodium stibogluconate using amastigote-macrophage in vitro model

Cutaneous Leishmaniasis (CL) caused by Leishmania aethiopica is a public health and social problem with a sequel of severe and mutilating skin lesions. It is manifested in three forms: localized CL (LCL), mucosal CL (MCL) and diffuse CL (DCL). Unresponsiveness to sodium stibogluconate (Sb-V) is common in Ethiopian CL patients. Using the amastigote-macrophage in vitro model the susceptibility of 24 clinical isolates of L. aethiopica derived from untreated patients was investigated. Eight strains of LCL, 9 of MCL, and 7 of DCL patients together with a reference strain (MHOM/ET/82/117/82) were tested against four antileishmanial drugs: amphotericin B, miltefosine, Sb-V and paromomycin. In the same order of drugs, IC50 (mu g/ml +/- SD) values for the 24 strains tested were 0.16 +/- 0.18, 5.88 +/- 4.79, 10.23 +/- 8.12, and 13.63 +/- 18.74. The susceptibility threshold of isolates originating from the 3 categories of patients to all 4 drugs was not different (p > 0.05). Maximal efficacy was superior for miltefosine across all the strains. Further susceptibility test could validate miltefosine as a potential alternative drug in cases of sodium stibogluconate treatment failure in CL patients. (C) 2013 Elsevier Inc. All rights reserved.