Coupling models of within-human, human-to-mosquito, and within-mosquito malaria parasite dynamics to identify key drivers of malaria transmission

The transmission of malaria parasites from humans to mosquitoes is essential for the parasite's life cycle. However, human-to-mosquito transmission remains poorly characterized due to insufficient quantification of biological parameters and limited tools for systematic study. To fill this knowledge gap, a mathematical model was fitted to data from multiple mosquito feeding experiments to estimate poorly quantified biological parameters. Drawing on these quantitative results, we developed a multi-scale model of human-to-mosquito transmission to identify the dominant host factors determining a human's infectiousness to mosquitoes. Our primary findings are that, for individuals with asymptomatic infections, 1) the time from exposure to the onset of infectiousness is primarily driven by in-human parameters governing asexual parasite multiplication, sexual conversion, and gametocyte maturation; and 2) for those with established infection, infectiousness is predominantly influenced by the availability of male gametocytes in the human bloodstream, mosquito blood meal volume, and gamete fertilization efficiency within the mosquito midgut.