Recently, it was reported that sera from healthy volunteers given atovaquone-proguanil (Malarone) inhibited parasite transmission and asexual blood stage development for up to 6 weeks after treatment (1). The lengthy persistence of drug activity was quite unexpected because earlier studies had shown that proguanil and atovaquone had elimination halflives of about 14 to 20 h (2–4, 10, 11) and 2 to 3 days,(5, 9–11), respectively. This drug combination acts synergistically against malaria parasites and avoids the rapid selection of atovaquoneresistant parasites whenever parasites are exposed to the action of atovaquone alone (7).

The present study was designed to quantitate the persistence of atovaquone in three Caucasian volunteers who had participated in a study to assess the effects of repeated subclinical infections on the development of immunity to Plasmodium falciparum (8). The three volunteers (mean weight, 84.8 21.9 kg) had been inoculated intravenously with about 30 parasitized erythrocytes of P. falciparum (3D7 strain) on three occasions at 35-day intervals, and on each occasion, treatment with atovaquone-proguanil (1,000 mg atovaquone-400 mg proguanil daily for 3 days) was started 8 days later. Blood samples were collected at 6, 20, and 35 days after the onset of treatment (Fig. 1). None of the volunteers developed symptoms of malaria.