Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study

Background Chloroquine plus proguanil is widely used for malaria chemoproph ylaxis 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 residen ts of malaria-endemic countries, but little is known about non-immune trave llers. Methods in a double-blind equivalence trial, 1083 participants travelling t o a malaria-endemic area were randomly assigned to two treatment groups: at ovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroqu ine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by tele phone 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 test ed in a reference laboratory. Findings 7 days after travel, at least one adverse event was reported by 31 1 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-pro guanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse e vents 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 d iscontinued in the atovaquone-proguanil group than in the chloroquine-progu anil group (one [0.2%] vs ten [2%], p=0.015). Interpretation Overall the two preparations were similarly tolerated. Howev er, significantly fewer adverse gastrointestinal events were observed in th e atovaquone-proguanil group in than in the chloroquine-proguanil group.