Studies on the Chemotherapy of Rodent Malaria and Drug Resistance

摘要

New ways were developed for evaluating the level and mode of action of antimalarial drugs against normal and drug resistant strains of rodent malaria parasites (RMP), particularly in the exoerythrocytic stages. The mechanisms by which malaria parasites become resistant to drugs were also studied. A complete evaluation of eleven WRAIR compounds was made and a further eight are still being investigated. Cyclical changes in respiratory physiology in normal and drug resistant RMP were revealed, leading to a hypothesis that chloroquine resistance in P.berghei is associated with utilisation of oxidative respiration. These findings and the recovery of gametocyte production after 20 years in the Keyberg strain underline the remarkable liability of these parasites Naphthoquinones and primaquine were shown to damage RMP mitochondria as evidenced by ultrastructural and cytochemical studies. A new type of potentiation between naphthoquinones and sulphonamides or folate reductase inhibitors is reported. (Author)