Prevention of sporogony of Plasmodium vivax in Anopheles dirus mosquitoes by transmission-blocking antimalarials

The sporontocidal activity of four dihydroacridine-diones (WR-233602, WR-243251, WR-250547, and WR-250548) and three fluoroquinolones (WR-279135, WR-279298, and WR-279288) was determined against naturally circulating isolates of Plasmodium vivax. Laboratory-reared Anopheles dirus mosquitoes were infected with P. vivax by feeding them on gametocytemic volunteers reporting to local malaria clinics in Kanchanaburi and Tak provinces, Thailand. Four days after the infectious feed, mosquitoes were re-fed on uninfected mice treated 90 minutes previously with a given drug at a dose of 100 mg base drug/kg mouse body weight. Sporontocidal activity was determined by assessing both oocyst and sporozoite development. None of the fluoroquinolones exhibited sporontocidal activity against P. vivax, whereas all 4 dihydroacridine-diones affected sporogonic development to some degree. WR-233602 affected oocyst development, but had no impact on sporozoite production, WR-250548 affected oocyst development and had a limited effect on sporozoite production, and WR-243251 and WR-250547 had a marked impact on all phases of sporogony. These data demonstrate that experimental dihydroacridine-diones are capable of interrupting the sporogonic development of P. vivax. These compounds may be useful in preventing malaria transmission.