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Effects of Chloroquine, Quinine, and Cycloguanil upon the Maturation of Asexual Erythrocytic Forms of Two Strains of Plasmodium Falciparum in Vitro^*

Maturation of trophozoites of Plasmodium falciparum into schizonts was observed during studies in which defibrinated parasitized blood was placed in vials containing glucose and incubated without agitation for 24 hours. Chloroquine or quinine added to this system in vitro inhibited maturation at successively earlier stages of development as parasites were exposed to increasing amounts of these two drugs. In contrast, the most striking morphologic effect detected after the addition of the dihydrotriazine metabolite of chlorguanide (DHT) reflected formation of abnormal-appearing schizonts, with uninhibited maturation of parasites to the preschizont stage.

Studies of the effects of chloroquine, of quinine, and of DHT upon maturation of asexual parasites in vitro were performed with two strains of P. falciparum that had been studied in vivo: a chloroquine-sensitive strain from Uganda and a chloroquine-resistant strain from Malaya. Chloroquine, quinine, and DHT inhibited the maturation of trophozoites of the Ugandan strain to a greater extent than the maturation of trophozoites of the Malayan strain. The system employed to assess the effects of drugs in vitro may prove to be of practical value in a number of ways, including the differentiation of drug-sensitive from drug-resistant strains of P. falciparum and the preliminary appraisal of blood schizonticidal effects of prospective antimalarial agents.

^* These studies were supported by the Medical Research and Development Command, Department of the Army, under Contract DA-49-193-MD-2413 with The University of Chicago. This paper is contribution number 314 from the Army Malaria Research Program.

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