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Antimalarial Drug Trials on a Multiresistant Strain of Plasmodium Falciparum

Geoffrey M. Jeffery^*, William E. Collins AND Jimmie C. Skinner

Weekly doses of amodiaquine (0.3 g) and pyrimethamine (0.05 g) failed to suppress mosquito-induced infections with a Thailand strain of Plasmodium falciparum. In one of the two cases receiving 0.1 gram of pyrimethamine weekly, suppression was successful.

In therapeutic trials, normally curative dosages of amodiaquine, chloroquine, pyrimethamine, and proguanil failed to eliminate the asexual parasites of this strain, although in all cases there was evident variable modification of the parasitemias and clinical attack. Quinine temporarily eliminated the asexual parasites when used at 0.972 gram daily for 3 days. The single case treated with 1.944 grams of quinine daily for 3 days was cleared of the infection.

The administration of proguanil or pyrimethamine appeared to be sporontocidal for this strain, even though the asexual parasites were resistant to normally curative amounts. There was, however, evidence of a reduced effect. Primaquine was rapidly sporontocidal eliminating infectivity to mosquitoes within 1 and 2 days and gametocytes within 6 or 7 days. No significant sporontocidal activity could be noted for quinine or amodiaquine.

The observations confirm and extend the reports of resistance of this strain of P. falciparum to normally suppressive or curative amounts of amodiaquine, chloroquine, pyrimethamine, and proguanil.

^* Present address: Laboratory of Parasite Chemotherapy, NIAID, National Institutes of Health, Bethesda 14, Maryland.

Present address: Laboratory of Parasite Chemotherapy, NIAID, National Institutes of Health, P. O. Box 195, Chamblee, Georgia.

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