Prophylactic activity of atovaquone against Plasmodium falciparum in humans.

Abstract

Abstract. The prophylactic antimalarial activity of atovaquone was determined in a randomized, double-blind, placebocontrolled 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 ϭ 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.

Antiparasitic Agent Atovaquone

“…Atovaquone was also effective as a single agent in prevention of falciparum malaria in a mosquito challenge study (115). In that randomized, double-blind, placebo-controlled study, subjects were infected with P. falciparum and given low-dose atovaquone (250 mg administered once 1 day prior to infection, six subjects), high-dose atovaquone (750 mg daily for 7 days beginning 1 day prior to infection, six subjects), or placebo (four subjects).…”

Atovaquone/proguanil for the treatment and prevention of malaria

“…This was further suggested in a small trial [6] of healthy volunteers who received atovaquone or placebo before being challenged by bites of P. falciparuminfected mosquitoes. Whereas all placebo recipients developed malaria, six subjects who received a single, 250-mg dose of atovaquone on the day before challenge were protected, even though the drug levels, by day 6.5, were profoundly sub-therapeutic, suggesting that parasites had been eliminated prior to the establishment of erythrocytic infection.…”

“…Prophylactic efficacy and safety have been assessed in three randomized, placebo-controlled trials in residents of endemic areas, as reported by Lell and colleagues, Shanks and coworkers, and Sukwa and colleagues [2][3][4]. An open-label trial with nonimmune subjects exposed to P. falciparum malaria was reported by van der Berg and colleagues [5], and a randomized, controlled trial of volunteers given atovaquone or placebo and challenged with P. falciparum-infected mosquitoes, was reported by Shapiro and colleagues [6].…”

Malaria Chemoprophylaxis for the International Traveler, Current Options and Future Possibilities

“…Atovaquone/proguanil is a once daily medication that is effective against both the erythrocytic and exoerythorcytic stages of malaria making this an acceptable choice not only for P. falciprum, but also P. vivax and P. ovale, both of which have hepatic life cycles. The efficacy of atovaquone as a causal prophylaxis was seen in a small volunteer challenge study in which it was shown that parasites were eliminated prior to the establishment of erythrocytic infection, thus supporting causal efficacy (Shapiro et al, 1999). Atovaquone/proquanal has demonstrated efficacy for malaria prophylaxis in areas with predominantly P. vivax (Soto et al, 2006).…”