title: WITHDRAWN: Mefloquine for preventing malaria in non-immune adult travellers.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  We independently assessed trial quality and extracted data. Adverse events from observational studies were categorised by the study type. We also contacted study authors.
  
  
  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.
  
  
  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.
authors.affiliation: Headquarters 5th Division, Medical Branch, Copthorne Barracks, Shrewsbury, Shropshire, UK SY3 8LZ. ashley.croft810@land.mod.uk
authors.forename: A M J
authors.initials: AM
authors.lastname: Croft
authors.forename: P
authors.initials: P
authors.lastname: Garner
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D008297:Male; D015767:Mefloquine / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D014195:Travel; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D015767:Mefloquine