title: Atovaquone and proguanil hydrochloride for prophylaxis of malaria.
abstract: BACKGROUND
  The spread of drug-resistant malaria and appreciation of side effects associated with existing antimalarial drugs emphasize the need for new drugs to prevent malaria. The combination of atovaquone and proguanil hydrochloride was previously shown to be safe and highly effective for treatment of malaria, including multi-drug-resistant Plasmodium falciparum.
  
  
  METHODS
  We reviewed results of clinical trials that evaluated either a fixed-dose combination of atovaquone and proguanil hydrochloride for malaria prophylaxis or atovaquone alone for causal prophylactic activity against P. falciparum.
  
  
  RESULTS
  In three placebo-controlled trials, 331 subjects received 250 mg atovaquone and 100 mg proguanil hydrochloride (or an equivalent dose based on body weight in children) once daily for 10 to 12 weeks. The overall efficacy for preventing parasitemia was 98%. Among 175 nonimmune volunteers taking the same dose of atovaquone/proguanil once daily for 10 weeks while temporarily residing in a malaria-endemic area, malaria developed in one patient who was noncompliant with therapy. Results of volunteer challenge studies indicate that both atovaquone and proguanil have causal prophylactic activity directed against the liver stages of P. falciparum. Adverse events occurred with similar or lower frequencies in subjects treated with atovaquone/proguanil compared to placebo. Less than 1% of patients discontinued from these studies due to a treatment-related adverse event.
  
  
  CONCLUSIONS
  A fixed-dose combination of atovaquone and proguanil hydrocloride is a promising new alternative for malaria prophylaxis.
authors.affiliation: US Army Medical Research Unit-Kenya, Nairobi, Kenya.
authors.forename: G D
authors.initials: GD
authors.lastname: Shanks
authors.forename: P G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: T Y
authors.initials: TY
authors.lastname: Sukwa
authors.forename: J D
authors.initials: JD
authors.lastname: van der Berg
authors.forename: T A
authors.initials: TA
authors.lastname: Shapiro
authors.forename: T R
authors.initials: TR
authors.lastname: Scott
authors.forename: J D
authors.initials: JD
authors.lastname: Chulay
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D053626:Atovaquone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods*; D004338:Drug Combinations; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000187:drug effects*; D002727:Proguanil / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014195:Travel; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C109496:atovaquone, proguanil drug combination; D002727:Proguanil; D053626:Atovaquone