Studies on the Antimalarial Effects of RC-12 and WR 14,997 on the Development of Plasmodium Cynomolgi in Mosquitoes and Rhesus Monkeys

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  • Primate Malaria Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, P. O. Box 80190, Chamblee, Georgia 30341

The antimalarial activity of RC-12 (1,2 dimethoxy-4-(bis-diethyl-aminoethyl)-amino-5-bromobenzene) and WR 14,997 (1-aminocyclopentane-carboxylic acid) against gametocytes and sporogony of Plasmodium cynomolgi was studied using Macaca mulatta monkeys and Anopheles maculatus mosquitoes. The effect of the drugs on the mosquito stages of the parasite was assessed both after treatment by gavage of infected monkeys and direct administration in sugar solutions to plasmodial-infected mosquitoes. Single- or multiple-dose treatments of RC-12 (25 mg/kg a day) were equally effective against gametocytes and sporogony of the parasite. Mosquito infection was interrupted within 8 to 24 hours following initial treatment. Feeding of RC-12 directly to infected mosquitoes resulted in no discernible effects on oocyst development and/or sporozoite formation in the mosquito. The salivary glands of drug-treated mosquitoes displayed marked morpho-pathological alterations as a result of drug ingestion. Repeated daily doses of WR 14,997 (60 mg/kg or 100 mg/kg) had no significant gametocytocidal, sporontocidal, or causal prophylactic activity against P. cynomolgi infections after being administered to the monkey host. In contrast, WR 14,997 exhibited a marked sporontocidal action against the parasite when the drug was administered with the mosquito diet. These results failed to support the assumption that there is a correlation in drug response between the sporogonic cycle of the malaria parasite in the invertebrate host and the tissue stages of the same parasite in the vertebrate host, when the drug was fed directly to the mosquito. However, there appears to be a direct relationship between the effect of the drug on the gametocytes and tissue stages when the drug is administered to the vertebrate host prior to mosquito feeding.