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Mefloquine to prevent malaria: a systematic review of trials

BMJ 1997; 315 doi: https://doi.org/10.1136/bmj.315.7120.1412 (Published 29 November 1997) Cite this as: BMJ 1997;315:1412
  1. Ashley Croft, consultant in public health medicinea,
  2. Paul Garner, headb
  1. a Headquarters Defence Secondary Care Agency, Ministry of Defence, St Giles' Court, London WC2H 8LD
  2. b International Health Division, Liverpool School of Tropical Medicine, Liverpool L3 5QA
  1. Correspondence to: Major AMJ Croft
  • Accepted 7 October 1997

Abstract

Objective: To evaluate the research evidence on the efficacy and tolerability of mefloquine chemoprophylaxis.

Search strategy: Any potentially relevant trial from the Cochrane Infectious Disease Group's register of controlled trials; systematic searches of Medline, Embase, Lilacs and Science Citation Index; scanning citations; and consulting drug companies and key investigators. We considered studies in all languages.

Inclusion criteria: Trials carried out in non-immune adult travellers, and in non-travelling volunteers, where an attempt had been made to conduct a randomised comparison of mefloquine against placebo or against alternative standard prophylaxis.

Results: 37 potentially eligible trials of mefloquine prophylaxis were identified, and 10 met the inclusion criteria. These 10 trials comprised a total of 2750 non-immune adult participants randomised to mefloquine or to a control. One placebo controlled trial examined malaria incidence directly and showed mefloquine to be highly effective in preventing malaria in an area of drug resistance. However, four placebo controlled trials showed that mefloquine was not well tolerated, and withdrawals were consistently higher in mefloquine treatment arms than in placebo arms (odds ratio 3.49 (95% confidence interval 1.42 to 8.56)). Five field trials compared mefloquine with other chemoprophylaxis. Mefloquine was no worse tolerated than other chemoprophylaxis, although there was possibly a trend towards higher withdrawals in mefloquine arms (odds ratio 1.33 (0.75 to 2.36)).

Conclusion: One trial showed mefloquine to be effective in preventing malaria, but withdrawal rates, presumably from side effects, were high across most studies. This is likely to impair mefloquine's effectiveness in general travellers, and it may therefore not be useful for routine prophylaxis. Mefloquine may be useful in specific situations such as for groups travelling to regions with a high risk of chloroquine resistant malaria and only limited access to effective medical care.

Key messages

  • We conducted a systematic review of the effectiveness of mefloquine in malaria chemoprophylaxis and found 10 randomised controlled trials of the drug in non-immune adult participants

  • In placebo controlled trials rates of withdrawal were significantly higher from mefloquine treatment, suggesting that the effectiveness of chemoprophylaxis may be limited by low adherence

  • Five field trials of mefloquine prophylaxis were conducted in non-immune participants, but all were young, fit soldiers, so that the findings of these field trials may not be generalisable to the normal population of general travellers

  • National malaria prevention guidelines should be evidence based, and candidate antimalarial drugs should not be licensed for routine use in prophylaxis until field trials in general travellers of both sexes have confirmed the tolerability of the new regimen

Footnotes

  • Accepted 7 October 1997
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