Side effects of mefloquine prophylaxis for malaria: an independent randomized controlled trial.

A prospective randomized double-'blind' trial was undertaken during a military exercise in East Africa to determine whether there was a significant difference in the incidence of side effects experienced by soldiers taking mefloquine 250 mg weekly compared with those taking chloroquine 300 mg weekly and proguanil 200 mg daily as chemoprophylaxis for malaria. Subject to their informed voluntary consent, male soldiers who were not aviators were included in the study. Identical questionnaires were completed voluntarily at the end of 2 and 8 weeks. Symptoms were classified by nature into-'all', 'neuropsychological', 'enteric' and 'other', and by severity into 'severe' and 'very severe'. The proportions of respondents experiencing side effects were compared to seek statistically significant differences between the chemoprophylactic groups. Questionnaire 1 was completed after 2 weeks by 183 of 317 subjects (58%) randomly assigned mefloquine and by 176 of 307 subjects (57%) randomly assigned chloroquine-proguanil. The incidence of putative side effects was not significantly different between the groups (71/183 vs. 70/176), odds ratio 0.96 (95% confidence interval [CI] 0.63 to 1.47). Questionnaire 2 was completed after 8 weeks by 145 of 317 subjects (46%) randomly assigned mefloquine and by 142 of 307 subjects (46%) randomly assigned chloroquine-proguanil. The incidence of putative side effects was still not significantly different between the groups (95/145 vs. 103/142), odds ratio 0.72 (95% CI 0.43 to 1.19). None of the subjects developed a serious neuropsychological reaction. Among respondents, 12.8% and 38% admitted lack of full compliance at 2 and 8 weeks, respectively. Exclusion of these subjects during a secondary analysis did not affect the results. None of the subjects developed malaria in the 12 months following return to the UK. Subject to the limitations of a response rate that was smaller than desired and the fact that the study was conducted in fit male military personnel, these results support evidence which indicates that mefloquine is no more toxic than chloroquine-proguanil.

RCT Entities:   Population Interventions Outcomes