Causal prophylactic efficacy of atovaquone-proguanil (Malarone (TM)) in a human challenge model

Plasmodia infect the liver for about 7 days before subsequently infecting t he blood. Present prophylaxis against Plasmodium falciparum malaria employs agents that primarily kill blood stages and must be continued for 28 days after the last exposure. Atovaquone-proguanil (Malarone (TM)) is a new anti malarial agent that is licensed in 35 countries as treatment against blood- stage infection, but its components (atovaquone and proguanil) have separat ely been shown to be active also against liver stages. To determine whether atovaquone-proguanil is sufficiently active against liver stages to be dis continued 7 days after exposure, we challenged 16 volunteers with P. falcip arum via infected mosquitoes. Twelve volunteers received atovaquone-proguan il (1 tablet daily) on the day prior to challenge, on the day of challenge, and for the next 6 days; 4 volunteers received matching placebo. All place bo volunteers demonstrated parasitaemia and malarial symptoms beginning on days 11 - 12 after challenge. No atovaquone-proguanil volunteer acquired ma laria. Atovaquone-proguanil is the first licensed antimalarial agent that k ills P. falciparum in the liver and that may be discontinued 7 days after t he last exposure.