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

Exp Parasitol. 2013 May;134(1):68-75. doi: 10.1016/j.exppara.2013.01.022. Epub 2013 Feb 19.

Abstract

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, IC(50) (μg/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / pharmacology
  • Animals
  • Antimony Sodium Gluconate / pharmacology
  • Antiprotozoal Agents / pharmacology*
  • Cells, Cultured
  • Ethiopia
  • Humans
  • Inhibitory Concentration 50
  • Leishmania / classification
  • Leishmania / drug effects*
  • Leishmaniasis, Cutaneous / drug therapy
  • Leishmaniasis, Cutaneous / parasitology*
  • Macrophages, Peritoneal / parasitology*
  • Mice
  • Parasitic Sensitivity Tests / methods
  • Paromomycin / pharmacology
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / pharmacology

Substances

  • Antiprotozoal Agents
  • Phosphorylcholine
  • miltefosine
  • Paromomycin
  • Amphotericin B
  • Antimony Sodium Gluconate