INHIBITORY ACTIVITY OF THE ANTIMALARIAL ATOVAQUONE (566C80) AGAINST OOKINETES, OOCYSTS, AND SPOROZOITES OF PLASMODIUM-BERGHEI

Ookinete formation from mature Plasmodium berghei gametocytes in vitro was partially inhibited by 0.05-0.1 mu M atovaquone and almost totall y blocked at a concentration of 0.25 mu M. Microgametocyte exflagellat ion was not affected by atovaquone at concentrations up to 300 mu M. O okinete formation was also inhibited in culture when addition of 0.20 mu M atovaquone was delayed by 4 hr, by which time DNA replication was likely to have been completed. Inhibition of ookinete formation by at ovaquone was not reversed by erotic acid. Plasmodium berghei-infected Anopheles stephensi mosquitoes were fed a second blood meal 4, 7, 14, and 20 days postinfection (p.i.) from mice that had been treated with atovaquone or control diluent 8 hr previously. Atovaquone blood feeds on day 4 reduced oocyst numbers on days 6-12, although sporozoite numb ers in the thorax and abdomen on day 20 were not significantly reduced Blood feeds on day 7 slowed oocyst growth, blood feeds on day 14 did not significantly reduce sporozoite numbers, and feeds to mosquitoes o n day 20 p.i. had no effect on transmission to naive mice. Sporozoite invasion of human hepatoma cells was unaffected by the presence of ato vaquone.