Exploring virulence and transmission using a within-host model of the malaria parasite Plasmodium falciparum

Lauren Childs

Havard University

Malaria, caused by the parasite Plasmodium falciparum, is a major world problem, killing nearly a million people each year, primarily African children. Acute infections in susceptible hosts are characterized by uncontrolled parasite growth, resulting in high parasitemia, while chronic infections are typically asymptomatic, exhibiting low parasitemia. In a process known as antigenic variation, the parasite is able to evade the immune system in both acute and chronic infections through the expression of a variety of red blood cell surface proteins from the PfEMP1 family. These PfEMP1 proteins facilitate adhesion of parasitized red blood cells to host cells throughout the body, causing many of malaria's symptoms, and extending the duration of infection which enhances transmission. Severe disease outcomes (virulence) are associated with expression of a particular subgroup of PfEMP1 proteins. Here, we extend a mathematical model of in vivo parasite infection dynamics involving antigenic variation introduced in Recker et al. [1] by incorporating commitment to the sexual pathway, necessary for transmission. We confirm previous findings that highly structured antigenic variation, with variants appearing sequentially, maximizes infection duration in naive hosts, while more robust antigenic variation, with several variants appearing together, maximizes infection duration in semi-immune hosts. However, these findings assume that antigenic variation is a static process. In line with recent experimental observations, we allow the antigenic variation strategy to vary during "stress" and find that the same strategy-highly structured variation except under stress-can produce longer infections in both naive and immune hosts, at least in the case where the stress is low parasitemia.

[1] Recker M, Buckee CO, Serazin A, Kyes S, Pinches R, et al. (2011) Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern. PLoS Pathog 7(3): e1001306. doi:10.1371/journal.ppat.1001306

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