THERAPEUTIC EFFECT OF REFERENCE ANTILEISHMANIAL AGENTS IN MURINE VISCERAL LEISHMANIASIS DUE TO LEISHMANIA-INFANTUM

A sensitive, culture-based, microtitration technique has recently been developed for determining parasite burdens in organs recovered from B alb/c mice infected with Leishmania infantum. In the present study, th is technique was used to examine the efficacy of three, first-line, an tileishmanial agents in reducing parasite burdens and eradicating para sites from target organs in mice. Treatment with meglumine antimoniate (50 mg Sb-v/kg.day) significantly reduced the parasite burdens in the livers and lungs (by about 10-fold and >100-fold, respectively) but n ot those in the spleens. Although use of a higher dose of meglumine an timoniate (200 mg Sb-v/kg.day) resulted in an even more dramatic reduc tion in the parasite burdens in the livers, it had no significant effe ct on the burdens in the spleens. Treatment with amphotericin B (0.8 m g/kg every other day) resulted in significant reductions in the parasi te burdens in the livers, spleens and lungs of infected mice. Although low doses of aminosidine (20 mg/kg.day) had no effect, high doses (20 0 mg/kg.day) resulted in undetectable parasite burdens in the livers, for at least 100 days post-treatment, and marked reductions in burdens in the spleens. These results are consistent with previous data from studies using animal models of visceral leishmaniasis. Thanks to the s ensitivity of the technique, culture microtitration revealed that none of the drug schedules achieved the elimination of all parasites in al l target organs. The murine model used mimics some important features of HIV/Leishmania infantum co-infections in humans.