The sensitivity of Leishmania species to aminosidine

Abstract

The aminoglycoside, aminosidine exhibited ED50S of between 1 and 5 microM against the amastigotes of Leishmania major and Leishmania tropica in mouse peritoneal macrophages whereas other strains causing New World cutaneous leishmaniasis such as Leishmania braziliensis were more refractory. Aminosidine was also active against all but one of the Leishmania donovani strains tested and when combined with sodium stibogluconate, the drug showed marked potentiation against the amastigotes of L. donovani in vitro and an additive effect in experimentally infected BALB/c mice.

Drug Resistance in Leishmaniasis

“…One explanation for this phenomenon is the intrinsic difference in species sensitivity to these drugs. In general, studies using the amastigote-macrophage model, L. donovani and L. brasiliensis were found to be three-to fivefold more sensitive to sodium stibogluconate than L. major, L. tropica, and L. mexicana (5,13,111). This was also shown in earlier studies by Berman et al, using another amastigotemacrophage model, which also demonstrated a wide variation in the sensitivity of isolates from cutaneous leishmaniasis cases to pentavalent antimonials (15).…”

Therapeutic switching in leishmania chemotherapy: a distinct approach towards unsatisfied treatment needs

“…Paromomycin is poorly absorbed after oral dosing and is still marketed as an oral treatment for amoebiasis and giardiasis and to decrease bacterial load in the gut in hepatic coma (Humatin; Parke-Davis, Morris Plains, NJ, USA). The antileishmanial properties of paromomycin were recognised by Kellina (1961) and were confirmed by Neal et al (1968;1995). Two 'proof of concept' studies, by the Kenya Fig.…”

“…The most important study is done by Sundar and Olliaro (2007), which led to the licensing of paromomycin for VL in India. Neal et al (1995) showed paromomycin and SSG to be synergistic in vitro and additive in a mouse model of VL. In a study of interactions between anti-leishmanial drugs, Seifert and Croft (2006) reported miltefosine and paromomycin to be additive in vitro and synergistic in the mouse VL model.…”

“…In vitro studies have shown that paromomycin can effectively kill both promastigotes and amastigotes (Neal and Croft 1984;Gebre-Hiwot et al 1992;Neal et al 1995). The 50% effective dose (ED 50 ) of paromomycin against L. donovani amastigotes ranges from 10 to 50 lM.…”

“…Data from mouse VL models and naturally infected dogs demonstrated that paromomycin is effective in vivo against L. donovani/L. infantum (Neal et al 1995;Buffet et al 1996;Gangneux et al 1997;Poli et al 1997;Vexenat et al 1998;Williams et al 1998).…”