A systematic review and meta-analysis of the effectiveness and safety of atovaquone-proguanil (Malarone) for chemoprophylaxis against malaria

Objectives: A systematic review and meta-analysis of the effectiveness of atovaquone-proguanil (Malarone) as a chemoprophylactic agent against malaria. Methods: The data sources searched for this study included Cochrane systematic reviews (on infectious diseases), MEDLINE and EMBASE, Web of Knowledge and Annals of Tropical Medicine. All unconfounded randomized controlled trials assessing the chemoprophylaxis against malaria with atovaquone-proguanil were included in the review. Data on study design, study sample, inclusion and exclusion criteria, allocation, blinding, primary and secondary study end points were all extracted by one reviewer and independently rechecked by the second reviewer. Results: In general, all 10 studies identified had excellent quality with total scores of >= 4 using the Jadad criteria. Ten controlled trials comprising 4539 participants were included for this review. A meta-analysis of six of the ten studies found chemoprophylaxis with atovaquone-proguanil, with a prophylaxis efficacy of 95.8% (95% CI = 91.5-97.9), to be superior to placebo. It was also considered safe and better tolerated with fewer treatment-related adverse events that could lead to premature discontinuation of prophylaxis than in controls. Comparison with alternative chemoprophylaxis also showed atovaquone-proguanil to be better tolerated with fewer treatment-related self-reported adverse events (RR = 0.8234; 95% CI = 0.673164-1.01) or severe adverse events (RR = 0.6140; 95% CI = 0.420055-0.8975). Atovaquone-proguanil is well tolerated with no difference in non-compliance with placebo (RR = 0.8804; 95% CI = 0.6964-1.113; I-2 = 31.4%). Conclusions: Evidence from this review shows that atovaquone-proguanil is highly efficacious as a prophylactic agent against malaria infection and is very well tolerated compared with other antimalarial agents.