GENETIC-CONTROL OF DRUG-INDUCED RECOVERY FROM MURINE VISCERAL LEISHMANIASIS

The influence of host genetic background on the response of Leishmania donovani-infected mice to chemotherapy was studied using the H-2d and H-2b haplotypes on a BALB or a B10 genetic background. Animals were treated with free or liposomal sodium stibogluconate and parasite burdens in the liver, spleen and bone marrow were assessed. In all the mouse strains and their congenic derivatives examined, the liver responded best to therapy regardless of drug formulation, whilst the spleen and the bone marrow respectively were increasingly less responsive to chemotherapy. Treatment with free drug was more effective in congenic mice carrying the H-2b haplotype than in those carrying the H-2d haplotype and in mice carrying the same H-2 haplotype, animals from a BALB background were better responders than those from a B10 genetic background. Liposomal drug was more effective than free drug treatment in all four mouse strains and produced a similar significant suppression (>99%, P<0.001) in liver parasite burdens to that obtained using a six times greater free drug dose. This liposomal drug dose was more effective than free drug in reducing bone marrow parasite burdens in all four mouse strains and equally (BALB/c mice) or more effective (P<0.01, BALB/B, B10 and B10.D2 strains) in reducing spleen parasite numbers. Liposomal drug, particularly in the B10 genetic background, effectively negated the H-2 dependent influences apparent using free sodium stibogluconate. These results are discussed in relation to the genetic factors which are known to control the course of L. donovani infection in mice.