A direct comparison of sodium stibogluconate treatment in two animal models of human visceral leishmaniasis, mouse and hamster

Abstract

The effect of sodium stibogluconate therapy, in the free or liposomal form, on the spleen, liver and bone marrow parasite burdens of L. donovani infected mice (BALB/c and B10) and hamsters was studied. Animals were infected i.v. (tail vein in mice, jugular vein in hamsters) and treated on either days 7 and 8 postinfection (acute model) or on days 31 and 32 postinfection or later (chronic model) with free (44.4 mg Sb (v)/kg/day) or liposomal (7.1 mg Sb (v)/kg/day) drug. Six days after the second drug dose animals were killed and parasite burdens assessed. Comparison of the parasite burdens in untreated L. donovani infected mice (B10 and BALB/c) and hamsters showed that higher burdens were obtained in hamsters in all 3 infection sites when the data were expressed as Leishman-Donovan units. However, if the data were expressed as the number of parasites/1000 host cell nuclei, liver burdens were similar in the two species although the parasite burdens remained higher in the spleen and bone marrow of hamsters. In the acute model, both free and liposomal drug treatment significantly reduced liver and spleen parasite burdens in BALB/c mice compared with controls, the liposomal form being significantly more suppressive at a sixth of the free drug dose. The two treatments had little effect on murine bone marrow burdens. In the hamster, the relative efficacies of the free and liposomal forms of the drug in the liver were similar to that in the mouse but in the spleen and bone marrow both treatments markedly reduced parasite numbers. The parasites in the hamster were therefore much more susceptible to drug treatment and this species-dependent effect was most marked in the bone marrow. In mice suffering from the chronic infection the effectiveness of free and liposomal stibogluconate decreased with the length of infection. A similar effect was also demonstrated in hamsters.