Prophylactic activity of atovaquone against Plasmodium falciparum in humans.

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 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.

• Authors: T A Shapiro, C D Ranasinha, N Kumar, P Barditch-Crovo
• Journal: The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 60 Issue 5 Pg. 831-6 (May 1999) ISSN: 0002-9637 [Print] United States
• PMID: 10344660 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antimalarials
• Naphthoquinones
• Atovaquone

Topics

• Adolescent
• Adult
• Animals
• Anopheles (parasitology, physiology)
• Antimalarials (adverse effects, pharmacokinetics, therapeutic use)
• Atovaquone
• Double-Blind Method
• Humans
• Insect Bites and Stings
• Malaria, Falciparum (immunology, prevention & control)
• Middle Aged
• Naphthoquinones (adverse effects, pharmacokinetics, therapeutic use)
• Parasitemia (parasitology)
• Plasmodium falciparum (drug effects, genetics, isolation & purification)
• Polymerase Chain Reaction (methods)