CRD Summary: The authors concluded that atovaquone-proguanil (Malarone) is a highly effective agent for malaria prophylaxis, which is well tolerated compared with other antimalarials. This was a generally well-conducted review and, despite considerable clinical differences between the studies, the conclusions are likely to be reliable.

CRD Commentary: The review question and the inclusion criteria were clear. The authors searched a number of databases and other relevant sources without language restrictions, thereby reducing the risk that relevant studies were not included and that language or publication bias was present. An appropriate validity assessment was conducted and review methodology was rigorous at all stages. There was considerable clinical heterogeneity between the included studies, which was reflected in statistical heterogeneity in some instances. As this heterogeneity was not further investigated, it is not completely clear that meta-analysis was appropriate in all instances. However, this was a generally well-conducted review of high-quality RCTs and the conclusions are likely to be reliable.