II. Responses of Sporozoite-Induced and Trophozoite-Induced Infections to Standard Antimalarial Drugs

Abstract

Quinine, quinacrine, chloroquine, amodiaquine, chlorguanide, and pyrimethamine, administered at fractions of their maximum tolerated doses, regularly cured established infections with trophozoites of the M strain of Plasmodium cynomolgi. Chloroquine and pyrimethamine were similarly effective against such infections with the B and Ro strains. On the other hand, none of these agents, administered at maximum tolerated doses, effected cure of established infections with sporozoites of the M strain or prevented infections when delivered from time of sporozoite challenge to the end of the incubation period. Chloroquine and pyrimethamine were equally ineffective against established infections or challenges with sporozoites of the B and Ro strains. In contrast, pamaquine, pentaquine, isopentaquine, and primaquine, administered in well tolerated doses, either alone or in combination with quinine, effected cure of established infections with sporozoites of the M strain and, delivered alone, provided full protection against infections with sporozoites. Primaquine, administered in combination with chloroquine, was similarly curative of established infections with sporozoites of the M, B, and Ro strains. Administered alone, it was fully protective against infections with the B and Ro strains. These responses to standard drugs, replicas of those obtained in infections with the New Guinea Chesson strain of Plasmodium vivax in human volunteers, provided the underpinning for use of infections with various strains of P. cynomolgi in the rhesus monkey in the search for more effective prophylactic, radical curative, and suppressive antimalarial drugs.