Leishmania resistant to sodium stibogluconate: drug-associated macrophage-dependent killing.
A total of 17 Leishmania isolates, 6 of them isolated from antimony-resistant patients, were collected in the Sudan and tested for their sensitivity to sodium stibogluconate (Pentostam) as promastigotes. Six of those isolates were tested as amastigotes infecting a murine macrophage cell line. The results indicated that the conventional promastigote screening assay did not correlate with the clinical picture, whereas the amastigote/macrophage system produced results that pertained to the in vivo responses to the drug. A laboratory-generated resistant strain of L. major was adapted to grow at a high concentration of Pentostam (1000 micrograms/ml) as promastigotes but was quite sensitive to the drug at much lower concentrations in the amastigote/(macrophage system (20 micrograms/ml), thus suggesting that Pentostam's inhibitory action is mediated through the macrophage rather than through a direct toxic effect exerted on the parasite.
Ibrahim
M E
ME
Center for Medical Parasitology, University of Copenhagen, Denmark.
Hag-Ali
M
M
el-Hassan
A M
AM
Theander
T G
TG
Kharazmi
A
A
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000494:pharmacology*; D002460:Cell Line; D004351:Drug Resistance; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects*; D018320:Leishmania major / Q000187:drug effects*; D007896:Leishmaniasis / Q000469:parasitology; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology; D007898:Leishmaniasis, Visceral / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D013397:Sudan
D000967:Antimony Sodium Gluconate