Ten RCTs (n=4,539) were included in the review. Sample sizes ranged from 108 to 1083 patients.
Study quality was generally high, with Jadad scores of 4 or 5 where reported.
Atovaquone-proguanil versus placebo (6 RCTs): the pooled RR of malaria was 0.041 (95% confidence interval, CI: 0.020, 0.082). There was no evidence of statistical heterogeneity. The protective efficacy was calculated to be 95.8% (95% CI: 91.5, 97.9). There were some discrepancies between the text and tables.
Atovaquone-proguanil versus alternative prophylaxis (3 RCTs): 2 studies used a comparator of chloroquine-proguanil, while the other used mefloquine. Only one RCT reported any malaria cases; all three were in the chloroquine-proguanil group. Pooling of the 2 studies using chloroquine-proguanil comparator groups revealed no significant difference between the groups in incidence of malaria (p=0.25).
Adverse events (4 RCTs): patients in the atovaquone-proguanil groups had fewer severe adverse effects (RR 0.61, 95% CI: 0.42, 0.90) and showed a trend towards fewer self-reported adverse events (RR 0.82, 95% CI: 0.67, 1.01). There was no significant difference between the atovaquone-proguanil and comparator groups in incidence of neuropsychiatric events or proportion of patients completing their course of medication. Significant heterogeneity was detected in the analyses of self-reported effects and neuropsychiatric effects.