Prophylactic activity of atovaquone against Plasmodium falciparum in humans

Document Type

Journal Article

Publication Date

1-1-1999

Journal

American Journal of Tropical Medicine and Hygiene

Volume

60

Issue

5

DOI

10.4269/ajtmh.1999.60.831

Abstract

The prophylactic antimalarial activity of atovaquone was determined in a randomized, double-blind, placebo-controlled study of healthy volunteers who were challenged by the bite of Plasmodium falciparum-infected Anopheles stephensi. Subjects were randomly assigned to one of three groups: six received seven dally doses of 750 mg of atovaquone, starting the day before challenge; six received a single dose of 250 mg of atovaquone the day before challenge; and four received placebo. Polymerase chain reaction-and culture- confirmed parasitemia developed in all four placebo recipients, but in none of the drag recipients, indicating that either of the atovaquone regimens provides effective prophylaxis (P = 0.005). However, in low-dose recipients, the drug levels by day 6.5 were profoundly subtherapeutic, indicating that parasites were eliminated prior to the establishment of erythrocytic infection. Atovaquone thus protects non-immune subjects against mosquito- transmitted falciparum malaria, and has causal prophylactic activity.

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