Human Parasitic Diseases

Background: Malaria infects 10,000 to 30,000 international travellers each year. It can be prevented through anti-mosquito measures and drug prophylaxis. We did a systematic review to assess the effects of currently used antimalaria drugs, given as prophylaxis to non- immune adult and child travellers to regions with chloroquine-resistant Plasmodium falciparum malaria.

Methods: We included randomized and quasi-randomized controlled trials of any antimalaria drug regimen currently used by inter- national travellers, compared against any other currently used regimen. In August 2009 we searched MEDLINE, EMBASE, LILACS, BIOSIS, mRCT, and the Cochrane Register of Controlled Trials (CENTRAL), without time restrictions. We searched reference lists, conference proceedings and one specialist journal, and contacted researchers and drug companies. We summarized the characteristics of the eligible trials, assessed their quality using standard criteria, and extracted relevant outcomes data. Where appropriate, we combined the results of different trials.

Results: Eight trials (4240 participants) were included. One-quarter of trial participants were soldiers. Duration of exposure to malaria ranged from 15 days to 13 weeks. All trials reported common adverse events from antimalaria drugs. Atovaquone-proguanil users and doxycycline users had similar frequencies of reported adverse effects. Atovaquone-proguanil users had fewer reports of any adverse effect than mefloquine users (RR 0.72, 95% CI 0.6 to 0.85), also fewer gastrointestinal adverse effects (RR 0.54, 95% CI 0.42 to 0.7), and fewer neuropsychiatric adverse effects (RR 0.49, 95% CI 0.38 to 0.63). Chloroquine-proguanil users had more reports of any adverse effect than users of other drugs (RR 0.84, 95% CI 0.73 to 0.96), also more gastrointestinal adverse effects (RR 0.71, 95% CI 0.6 to 0.85). We found no evidence on primaquine in travellers.

Conclusions: There is limited evidence on which currently available drug is most effective in preventing malaria. Atovaquone-proguanil and doxycycline are the best tolerated regimens. Doxycycline monohydrate appears exceptionally useful due to its good safety profile, low cost and protective efficacy against many travel-related infections, besides malaria. Mefloquine is associated with adverse neuropsy- chiatric outcomes. Chloroquine-proguanil is associated with adverse gastrointestinal outcomes. There is no evidence to support the use of primaquine as prophylaxis in travellers.