title: Randomized, placebo-controlled trial of atovaquone/proguanil for the prevention of Plasmodium falciparum or Plasmodium vivax malaria among migrants to Papua, Indonesia.
abstract: The increasing prevalence of resistance to antimalarial drugs reduces options for malaria prophylaxis. Atovaquone/proguanil (Malarone; GlaxoSmithKline) has been >95% effective in preventing Plasmodium falciparum malaria in lifelong residents of areas of holoendemicity, but data from persons without clinical immunity or who are at risk for Plasmodium vivax malaria have not been described. We conducted a randomized, double-blinded study involving 297 people from areas of nonendemicity in Indonesia who migrated to Papua (where malaria is endemic) < or =26 months before the study period. Subjects received prophylaxis with 1 Malarone tablet (250 mg of atovaquone and 100 mg of proguanil hydrochloride; n=148) or placebo (n=149) per day for 20 weeks. Hematologic and clinical chemistry values did not change significantly. The protective efficacy of atovaquone/proguanil was 84% (95% confidence interval [CI], 44%-95%) for P. vivax malaria, 96% (95% CI, 72%-99%) for P. falciparum malaria, and 93% (95% CI, 77%-98%) overall. Atovaquone/proguanil was well tolerated, safe, and effective for the prevention of drug-resistant P. vivax and P. falciparum malaria in individuals without prior malaria exposure who migrated to Papua, Indonesia.
authors.affiliation: Naval Medical Research Unit 2, Jakarta, Indonesia.
authors.forename: Judith
authors.initials: J
authors.lastname: Ling
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Baird
authors.forename: David J
authors.initials: DJ
authors.lastname: Fryauff
authors.forename: Priyanto
authors.initials: P
authors.lastname: Sismadi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bangs
authors.forename: Mark
authors.initials: M
authors.lastname: Lacy
authors.forename: Mazie J
authors.initials: MJ
authors.lastname: Barcus
authors.forename: Robert
authors.initials: R
authors.lastname: Gramzinski
authors.forename: Jason D
authors.initials: JD
authors.lastname: Maguire
authors.forename: Marti
authors.initials: M
authors.lastname: Kumusumangsih
authors.forename: Gerri B
authors.initials: GB
authors.lastname: Miller
authors.forename: Trevor R
authors.initials: TR
authors.lastname: Jones
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Chulay
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053626:Atovaquone; D018890:Chemoprevention; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000517:prevention & control*; D016780:Malaria, Vivax / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010349:Patient Compliance; D010963:Plasmodium falciparum / Q000187:drug effects; D010966:Plasmodium vivax / Q000187:drug effects; D002727:Proguanil / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014171:Transients and Migrants; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D009285:Naphthoquinones; D002727:Proguanil; D053626:Atovaquone