Modelling the population dynamics of Plasmodium falciparum gametocytes in humans during malaria infection

Every year over two hundred million people are infected with the malaria parasite. Renewed efforts to eliminate malaria has highlighted the potential to interrupt transmission from humans to mosquitoes which is mediated through the gametocytes. Reliable prediction of transmission requires an improved understanding of in vivo kinetics of gametocytes. Here we study the population dynamics of Plasmodium falciparum gametocytes in human hosts by establishing a framework which incorporates improved measurements of parasitaemia in humans, a novel mathematical model of gametocyte dynamics, and model validation using a Bayesian hierarchical inference method. We found that the novel mathematical model provides an excellent fit to the available clinical data from 17 volunteers infected with P. falciparum, and reliably predicts observed gametocyte levels. We estimated the P. falciparums sexual commitment rate and gametocyte sequestration time in humans to be 0.54% (95% credible interval: 0.30-1.00) per life cycle and 8.39 (6.54-10.59) days respectively. Furthermore, we used the data-calibrated model to predict the effects of those gametocyte dynamics parameters on human-to-mosquito transmissibility, providing a method to link within-human host kinetics of malaria infection to epidemiological-scale infection and transmission patterns.