Opening Pandora’s Box: Distribution of Plasmodium gametocytes in bloodstream

Malaria, a vector borne disease caused by Plasmodium spp., remains a major global cause of morbidity and mortality. Optimization of the disease control strategies requires a thorough understanding of the fundamental processes underlying parasite transmission. Although the number of transmissible stages of Plasmodium (gametocyte) in human blood is frequently used as an indicator of human-to-mosquito transmission potential, this relationship is not always clear. Important efforts have been made to develop molecular tools to fine-tune gametocyte densities estimation and therefore improve the prediction of mosquito infection rates, but a significant level of uncertainty around this estimate remains. Here we show with both human and avian malaria system that the within-vertebrate host distribution of gametocytes could explain much of this uncertainty. By comparing gametocyte densities in bloodstream between different body parts, we found a difference by nearly 50% in humans and by more than 15% in birds. An estimation of gametocyte density from only one blood sample, as is usually the case, could therefore drastically over- or underestimated the infectivity of gametocyte carriers. This might have important consequences on the epidemiology of the disease since we show, using the avian malaria system, that this variation influences the transmission of the parasite to the mosquito vector. In the light of our results, we argue that it is essential to consider the heterogeneous distribution of gametocyte to improve human diagnosis, identify infectious reservoirs and to test new malaria control strategies.