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 t reated with free or liposomal sodium stibogluconate and parasite burde ns in the liver, spleen and bone marrow were assessed. In all the mous e 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 che motherapy. Treatment with free drug was more effective in congenic mic e carrying the H-2b haplotype than in those carrying the H-2d haplotyp e and in mice carrying the same H-2 haplotype, animals from a BALB bac kground were better responders than those from a B10 genetic backgroun d. Liposomal drug was more effective than free drug treatment in all f our mouse strains and produced a similar significant suppression (>99% , P<0.001) in liver parasite burdens to that obtained using a six time s greater free drug dose. This liposomal drug dose was more effective than free drug in reducing bone marrow parasite burdens in all four mo use strains and equally (BALB/c mice) or more effective (P<0.01, BALB/ B, B10 and B10.D2 strains) in reducing spleen parasite numbers. Liposo mal drug, particularly in the B10 genetic background, effectively nega ted the H-2 dependent influences apparent using free sodium stibogluco nate. These results are discussed in relation to the genetic factors w hich are known to control the course of L. donovani infection in mice.