Mefloquine for preventing malaria in non-immune adult travellers

Malaria is a serious infectious disease of the tropics, spread by mosquitoes. Doctors have recommended various antimalaria drugs for travellers to these areas to take regularly to prevent infection. The problem is balancing good protection against the disease with the adverse effects of the drug. Due to some malaria becoming resistant to common drugs, there are fewer options for effective prevention.

Mefloquine is effective in preventing infection when compared to other drugs in areas with high levels of drug resistance, but it has adverse effects, including influences on mood, sleep and mental state. There remains considerable debate about how often these events occur, with a wide range of estimates. It is not disputed that these are true effects, and constrain the acceptability and tolerability of mefloquine for travellers.

Authors' conclusions: 

Mefloquine prevents malaria, but has adverse effects that limit its acceptability . There is evidence from non-randomised studies that mefloquine has potentially harmful effects in tourists and business travellers, and its use needs to be carefully balanced against this. Trials of comparative effects of antimalarial prophylaxis should include episodes of malaria and withdrawal from prophylaxis as outcomes.

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Background: 

Mefloquine is commonly prescribed to prevent malaria in travellers, and has replaced other drugs because Plasmodium falciparum is commonly resistant to them. However, mefloquine may be associated with neuropsychiatric harmful effects.

Objectives: 

To assess the effects of mefloquine in adult travellers compared to other regimens in relation to episodes of malaria, withdrawal from prophylaxis, and adverse events.

Search strategy: 

We searched the Cochrane Infectious Diseases Group specialized trials register (September 2002), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2002), MEDLINE (1966 to September 2002), EMBASE (1980 to September 2002), LILACS (September 2002), Science Citation Index (1981 to September 2002), and bibliographies in retrieved papers and standard textbooks. We contacted researchers in the subject of malaria chemoprophylaxis, and pharmaceutical companies.

Selection criteria: 

Randomised trials comparing mefloquine with other standard prophylaxis or placebo in non-immune adult travellers, and in non-travelling volunteers. For adverse events, any published case reports were collected.

Data collection and analysis: 

We independently assessed trial quality and extracted data. Adverse events from observational studies were categorised by the study type. We also contacted study authors.

Main results: 

We included 10 trials involving 2750 non-immune adult participants. Five of these were field trials, and of these all were in mainly male soldiers. One trial comparing mefloquine with placebo showed mefloquine prevented malaria episodes in an area of drug resistance (Peto odds ratio 0.04, 95% confidence interval 0.02 to 0.08). Withdrawals in the mefloquine group were consistently higher in four placebo controlled trials (odds ratio 3.56, 95% confidence interval 1.67 to 7.60). In five trials comparing mefloquine with other chemoprophylaxis, no difference in tolerability was detected.

We found 516 published case reports of mefloquine adverse effects. 63 per cent of these published reports involved tourists and business travellers. There were four fatalities attributed to mefloquine.

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