Modeling Malaria Parasite Survival Strategies in the Human Host

Abstract

This work focuses on the application of mathematical and statistical modeling to understand malaria infection and the corresponding immune responses in the human host in areas of high malaria exposure.

In high malaria endemic areas, seasonal transmission occurs such that during the wet season, individuals are highly exposed to malaria infection but are not in the dry season. This work investigates how repeated exposures to malaria parasites contribute to parasite survival in the host during the dry season. By extending an existing mathematical model, exposure of individuals to P.falciparum infections over their lifetimes were simulated, with the models capturing the generation of partial immunity to these infections. Our model predicts that individuals with repeated exposure to malaria parasites acquire partial immunity with time and this partial immunity is not fully protective but elongates the duration of infection. Counterintuitively, the most protected individuals have the longest infections. Accordingly, I present the hypothesis that individuals with the most exposure and protection from malaria may be the ones responsible for carrying the parasites through the dry season.

During the blood stage of malaria infection, when a shizont ruptures and releases merozoites, they must find and invade red blood cells (RBCs). However, it is known that the merozoites have a higher preference for infecting some cells (i.e. reticulocytes) compared to others. This work presents a probabilistic model of the invasion strategy a merozoite uses to find the “best” cell given the trade-off between longer search times and the benefit gained by the parasite. I observed that, different strategies of the parasites yield different susceptibilities of those parasites to killing.

Overall, this work demonstrates the use of mathematical and statistical modeling concepts to analyse the strategies of malaria parasites survival which will help in contributing to the elimination of the malaria disease.