Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team

Lancet. 2000 Dec 2;356(9245):1888-94. doi: 10.1016/s0140-6736(00)03260-8.


Background: Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers.

Methods: In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory.

Findings: 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015).

Interpretation: Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antimalarials / adverse effects
  • Antimalarials / therapeutic use*
  • Anxiety / chemically induced
  • Atovaquone
  • Chloroquine / adverse effects
  • Chloroquine / therapeutic use
  • Dizziness / chemically induced
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Malaria, Falciparum / prevention & control*
  • Male
  • Middle Aged
  • Naphthoquinones / adverse effects
  • Naphthoquinones / therapeutic use
  • Proguanil / adverse effects
  • Proguanil / therapeutic use
  • Travel*
  • Treatment Outcome


  • Antimalarials
  • Drug Combinations
  • Naphthoquinones
  • Chloroquine
  • Proguanil
  • Atovaquone