Prophylactic activity of atovaquone against Plasmodium falciparum in humans.
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 daily 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 drug 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.
Shapiro
T A
TA
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Ranasinha
C D
CD
Kumar
N
N
Barditch-Crovo
P
P
D000293:Adolescent; D000328:Adult; D000818:Animals; D000852:Anopheles / Q000469:parasitology / Q000502:physiology; D000962:Antimalarials / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053626:Atovaquone; D004311:Double-Blind Method; D006801:Humans; D007299:Insect Bites and Stings; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008875:Middle Aged; D009285:Naphthoquinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018512:Parasitemia / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000379:methods
D000962:Antimalarials; D009285:Naphthoquinones; D053626:Atovaquone