The causal prophylactic activity of the novel hydroxynaphthoquinone, S66C80, was assessed against the exo-erythrocytic (EE) stages of Plasmodium berghei cultured in the human hepatoma cell line, HepG2. 566C80 was found to be highly active as an inhibitor of EE development and was more active than the established causal prophylactic pyrimethamine. A 566C80 concentration of 1·85 × 10−9 M, added 3 h after sporozoite invasion, reduced the numbers of EE forms visible at 48 h by 50%, while the equivalent concentration of pyrimethamine was 1·95 × 10−8 M.

The activity of atovaquone against Plasmodium berghei ANKA during sporogonic development has been examined. Anopheles stephensi mosquitoes were fed on gametocyte infected mice which had been treated 8 h previously with atovaquone or diluent alone. Mosquito midguts were examined for oocysts, and salivary gland infections were estimated using an ELISA for the circumsporozoite protein (CSP). The number of oocysts per midgut fell by at least 97% when mosquitoes were fed on mice dosed with 0·1–10 mg atovaquone/kg body weight. This was paralleled by a decrease in the prevalence of oocyst-infected mosquitoes from 70–90% in controls to 40% or 10% respectively. No oocysts were observed at a dose of 100 mg/kg. CSP ELISA results indicated that mosquitoes fed on atovaquone failed to produce sporozoites. Mosquitoes which fed on gametocytaemic, atovaquone-treated mice (0·1–100 mg/kg) did not transmit malaria to naive mice. These results demonstrate that atovaquone has a highly potent inhibitory activity against the mosquito stages of P. berghei.