Aims: Plasmodium falciparum, the most virulent human malaria parasite, matures via asexual reproduction within the human host, but undergoes sexual reproduction within its vector host, the Anopheles mosquito. Consequently, the mosquito stage of the parasite life cycle provides an opportunity to create novel parasite genetic information in mosquitoes infected with multiple parasite populations, altering parasite diversity at the population level. We examine the role that vector biology plays in modulating parasite diversity.
Methods: We develop a two-part stochastic model that estimates the diversity as a consequence of different bottlenecks and expansion events occurring during the parasite life cycle in the mosquito and couples the diversity development within the mosquito to transmission to humans. For the underlying framework, we use a stochastic model of within-vector P. falciparum dynamics and simulate infections with multiple distinct parasite populations. We use the output of the within-vector portion of our model to inform transmission of the parasites to the human population.
Results: The model framework shows that bottlenecks entering the oocyst stage decrease diversity from the initial gametocyte population in a mosquito’s blood meal. However, diversity increases with the possibility for recombination and proliferation in the formation of sporozoites. Furthermore, when we begin with only two distinct parasite genotypes in the initial gametocyte population, the probability of transmitting more than two unique genotypes from mosquito to human is over 50% for a range of initial gametocyte densities.
Conclusions: Our model quantitatively maps parasite diversity through the life cycle of the parasite including bottlenecks within the mosquito and in transmission to the human host. Such a quantitative mapping of diversity generation within the vector has important implications for disease transmission and malaria control.