Safety and efficacy of atovaquone and proguanil hydrochloride for the prophylaxis of Plasmodium falciparum malaria in South Africa

The objective of this study was to determine the safety and efficacy of ato vaquone and proguanil hydrochloride combination therapy for the prophylaxis of Plasmodium falciparum malaria in at-risk nonimmune subjects in South Af rica. This open-label trial was conducted at research sites in South Africa during the main malaria transmission season, February through July. The st udy volunteers were temporarily living in, or traveling to, a malaria-endem ic area. They received 1 tablet of 250 mg atovaquone and 100 mg proguanil h ydrochloride once daily for up to 10 weeks. Subjects were monitored using s equential clinical and laboratory assessments. Thick blood smears were stai ned and evaluated by a central laboratory. An immunochromatographic test fo r P falciparum was also used for on-site patient management. Prophylactic s uccess was summarized using a 95% confidence interval for the proportion of subjects who did not develop parasitemia or who withdrew due to a treatmen t-related adverse event. A total of 175 subjects (15% women) were enrolled in the trial. The mean duration of drug exposure was 8.9 weeks. The combina tion of atovaquone and proguanil hydrochloride was well tolerated. The most frequently reported adverse events considered possibly related to study tr eatment were headache (7%), abdominal pain (2%), increased cough (2%), and skin disorder (2%). No serious adverse events were reported, and no treatme nt-emergent effects were noted for any laboratory variables. One subject wh o was noncompliant with therapy developed parasitemia, and 3 subjects withd rew due to a treatment-related adverse event (2 subjects with headache and 1 with nausea and dizziness). The prophylaxis success rate was 97%. In this study, atovaquone and proguanil hydrochloride combination therapy had an e xcellent safety and efficacy profile for prophylaxis of P falciparum malari a in nonimmune subjects.