title: Causal prophylactic efficacy of atovaquone-proguanil (Malarone) in a human challenge model.
abstract: Plasmodia infect the liver for about 7 days before subsequently infecting the 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) is a new antimalarial agent that is licensed in 35 countries as treatment against blood-stage infection, but its components (atovaquone and proguanil) have separately been shown to be active also against liver stages. To determine whether atovaquone-proguanil is sufficiently active against liver stages to be discontinued 7 days after exposure, we challenged 16 volunteers with P. falciparum via infected mosquitoes. Twelve volunteers received atovaquone-proguanil (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 placebo volunteers demonstrated parasitaemia and malarial symptoms beginning on days 11-12 after challenge. No atovaquone-proguanil volunteer acquired malaria. Atovaquone-proguanil is the first licensed antimalarial agent that kills P. falciparum in the liver and that may be discontinued 7 days after the last exposure.
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. jonathan.berman@na.amedd.army.mil
authors.forename: J D
authors.initials: JD
authors.lastname: Berman
authors.forename: R
authors.initials: R
authors.lastname: Nielsen
authors.forename: J D
authors.initials: JD
authors.lastname: Chulay
authors.forename: M
authors.initials: M
authors.lastname: Dowler
authors.forename: K C
authors.initials: KC
authors.lastname: Kain
authors.forename: K E
authors.initials: KE
authors.lastname: Kester
authors.forename: J
authors.initials: J
authors.lastname: Williams
authors.forename: A C
authors.initials: AC
authors.lastname: Whelen
authors.forename: M J
authors.initials: MJ
authors.lastname: Shmuklarsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use*; D053626:Atovaquone; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008109:Liver Diseases, Parasitic / Q000188:drug therapy*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002727:Proguanil / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D009285:Naphthoquinones; C109496:atovaquone, proguanil drug combination; D002727:Proguanil; D053626:Atovaquone