A rabbit--in vitro system to evaluate drug action against Plasmodium falciparum

A rabbit-in vitro model system is described which can determine the activity of anti-malarial drugs against erythrocytic stages of Plasmodium falciparum. Serum samples, collected from rabbits at various times after drug administration, wee incubated with synchronized ring form parasites using the microtest system. The extent to which the presence of drugs in the serum inhibited parasite growth was usually determined after 32 to 40 hours of incubation. Anti-malarial activity was observed in sera obtained from rabbits which received chloroquine, mefloquine, pyrimethamine and cycloguanil, but not in those which received 4-4' diacetyldiaminodiphenylsulphone (DADDS). The effects against the drug-sensitive strain were more marked than against the drug-resistant one. The serum activity persisted for a longer period of time after administration of mefloquine, pyrimethamine, pamoate, and cycloguanil pamoate than after administration of chloroquine, a drug with a shorter biological half-life. The results indicate that this model may be a useful system for identifying potential agents against drug-resistant falciparum malaria, particularly compounds which are converted in vitro to their active metabolites or which exert a prolonged suppressive activity after drug administration.