Gametocytocidal and sporontocidal effects of antimalarial drugs on malaria parasites. I. Effect of single and multiple doses of primaquine on Plasmodium cynomolgi

A study was undertaken to determine the gametocytocidal and sporontocidal activity of primaquine against blood-induced Plasmodium cynomolgi infections in seven rhesus monkeys (Macaca mulatta). Infected animals were treated orally with single (1.95 mg/kg primaquine base) or multiple doses of primaquine (0.65 mg/kg/day × 5 primaquine base). The effect of the drug on the sporogonic stages of the parasite was observed in Anopheles maculatus mosquitoes fed at appropriate intervals before and after treatment began. Mosquitoes were also fed on control untreated monkeys on a parallel feeding schedule. The results indicated that primaquine given in the above doses exerted a marked sporontocidal activity within 4 hr after initial medication whereas its gametocytocidal effect first became obvious 2–3 days later. Single doses of primaquine were less effective as compared to multiple doses in the sense that full mosquito infectivity was restored as early as 3 days after single dosage treatment. Primaquine (as base) given in much smaller amounts (0.08 mg/kg/day × 5 or 0.24 mg/kg × 1) acted exclusively as a sporontocidal agent. The sporontocidal action of primaquine was very rapid. Its gametocytocidal effect was less apparent.