Variation in the Prevalence of Submicroscopic Malaria Infections: Historical Transmission Intensity and Age as Key Determinants

Molecular detection of Plasmodium falciparum infection has revealed large numbers of individuals with low-density (yet transmissible) infections undetectable by microscopy. Here we present an updated systematic review of cross-sectional malaria surveys to explore the prevalence and drivers of these submicroscopic infections and define where they are likely to be relevant to malaria control efforts. Our results show that submicroscopic infections predominate in low transmission settings, but also reveal marked geographical variation in their prevalence, being highest in South American surveys and lowest in West African studies. Whilst current transmission levels partly explain these results, we find that historical transmission intensity also represents a crucial determinant of the size of the submicroscopic reservoir. Submicroscopic infection was more likely in adults than children, although we did not observe a statistically significant influence of seasonality. Our results suggest that the contribution of submicroscopic infections to transmission likely varies substantially across settings, potentially warranting different approaches to their targeting in the approach to elimination.