Evaluation of the sensitivity in vitro of Plasmodium falciparum and in vivo of Plasmodium chabaudi Malaria to various drugs and their combinations.

K1 strain of Plasmdoium falciparum is resistant in vitro to chloroquine, pyrimethamine and sulfadoxine. Response of this strain to combinations of antimalarial drugs in the in vitro hypoxanthine incorporation test was coupled with that of a line of strain NF54 relatively sensitive to chloroquine and fully sensitive to other antimalarials. Pyrimethamine and sulfadoxine showed potentiative synergism against NF54 and less marked against K1. Erythromycin and chloroquine showed potentiation, but less marked against NF54. Quinine and clindamycin had an additive effect against NF54 but potentiated against K1. Combinations of chloroquine with quinine or amodiaquine or of amodiaquine with clindamycin or erythromycin showed mild antagonistic or additive effects. In vivo studies in mice, using the 4-day suppressive test, the AS(3CQ) clone of Plasmodium chabaudi was resistant to pyrimethamine and chloroquine but sensitive to sulfadoxine. Similar combinations as above were carried out and their responses were compared between the resistant and sensitive strains. For both strains, the combinations of chloroquine-erythromycin, pyrimethamine-sulfadoxine, quinine-clindamycin showed potentiation; antagonistic effects were observed in chloroquine-amodiaquine combinations whereas when amodiaquine combined with erythromycin the effect was additive. Amodiaquine-clindamycin and chloroquine-quinine combinations have an antagonistic effect against the sensitive strain but additive against the resistant strain.