Parasitology

Research Article

Inhibitory action of the anti-malarial compound atovaquone (566C80) against Plasmodium berghei ANKA in the mosquito, Anopheles stephensi

R. E. Fowlera1, P. F. Billingsleya1, M. Pudneya2 and R. E. Sindena1*

a1 Molecular and Cellular Parasitology Research Group, Department of Biology, Imperial College of Science, Technology and Medicine, London SW7 2BB

a2 Department of Molecular Sciences, Wellcome Research Labs, Langley Court, Beckenham, Kent BR3 3BS

Abstract

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.

(Received June 30 1993)

(Revised September 01 1993)

(Accepted September 02 1993)

Footnotes

* Reprint requests to Professor R. E. Sinden, Molecular and Cellular Parasitology Research Group, Department of Biology, Imperial College of Science, Technology and Medicine, London SW7 2BB.

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