Modeling the dynamics of <i>Plasmodium falciparum</i> gametocytes in humans during malaria infection.

Abstract

Renewed efforts to eliminate malaria have highlighted the potential to interrupt human-to-mosquito transmission - a process mediated by gametocyte kinetics in human hosts. Here we study the in vivo dynamics of <i>Plasmodium falciparum</i> gametocytes by establishing a framework which incorporates improved measurements of parasitemia, a novel gametocyte dynamics model and model fitting using Bayesian hierarchical inference. We found that the model provides an excellent fit to the clinical data from 17 volunteers infected with <i>P. falciparum</i> (3D7 strain) and reliably predicts observed gametocytemia. We estimated the sexual commitment rate and gametocyte sequestration time to be 0.54% (95% credible interval: 0.30-1.00%) per asexual replication cycle and 8.39 (6.54-10.59) days respectively. We used the data-calibrated model to investigate human-to-mosquito transmissibility, providing a method to link within-human host infection kinetics to epidemiological-scale infection and transmission patterns.