Modeling the genetic relatedness of Plasmodium falciparum parasites following meiotic recombination and cotransmission

Abstract

Unlike in most pathogens, multiple-strain (polygenomic) infections of P. falciparum are frequently composed of genetic siblings. These genetic siblings are the result of sexual reproduction and can coinfect the same host when cotransmitted by the same mosquito. The degree with which coinfecting strains are related varies among infections and populations. Because sexual recombination occurs within the mosquito, the relatedness of cotransmitted strains could depend on transmission dynamics, but little is actually known of the factors that influence the relatedness of cotransmitted strains. Part of the uncertainty stems from an incomplete understanding of how within-host and within-vector dynamics affect cotransmission. Cotransmission is difficult to examine experimentally but can be explored using a computational model. We developed a malaria transmission model that simulates sexual reproduction in order to understand what determines the relatedness of cotransmitted strains. This study highlights how the relatedness of cotransmitted strains depends on both within-host and within-vector dynamics including the complexity of infection. We also used our transmission model to analyze the genetic relatedness of polygenomic infections following a series of multiple transmission events and examined the effects of superinfection. Understanding the factors that influence the relatedness of cotransmitted strains could lead to a better understanding of the population-genetic correlates of transmission and therefore be important for public health.