title: How selection forces dictate the variant surface antigens used by malaria parasites.
abstract: Red blood cells infected by the malaria parasite Plasmodium falciparum express variant surface antigens (VSAs) that evade host immunity and allow the parasites to persist in the human population. There exist many different VSAs and the differential expression of these VSAs is associated with the virulence (damage to the host) of the parasites. The aim of this study is to unravel the differences in the effect key selection forces have on parasites expressing different VSAs such that we can better understand how VSAs enable the parasites to adapt to changes in their environment (like control measures) and how this may impact the virulence of the circulating parasites. To this end, we have built an individual-based model that captures the main selective forces on malaria parasites, namely parasite competition, host immunity, host death and mosquito abundance at both the within- and between-host levels. VSAs are defined by the net growth rates they infer to the parasites and the model keeps track of the expression of, and antibody build-up against, each VSA in all hosts. Our results show an ordered acquisition of VSA-specific antibodies with host age, which causes a dichotomy between the more virulent VSAs that reach high parasitaemias but are restricted to young relatively non-immune hosts, and less virulent VSAs that do not reach such high parasitaemias but can infect a wider range of hosts. The outcome of a change in the parasite's environment in terms of parasite virulence depends on the exact balance between the selection forces, which sets the limiting factor for parasite survival. Parasites will evolve towards expressing more virulent VSAs when the limiting factor for parasite survival is the within-host parasite growth and the parasites are able to minimize this limitation by expressing more virulent VSAs.
authors: Theoretical Epidemiology, University of Utrecht, Yalelaan 7, 3584 CL Utrecht, The Netherlands. maiteseverins@gmail.com
authors: Maite
authors: M
authors: Severins
authors: Don
authors: D
authors: Klinkenberg
authors: Hans
authors: H
authors: Heesterbeek
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics*; D009033:Culicidae / Q000469:parasitology; D006801:Humans; D057131:Immune Evasion; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000635:transmission; D018448:Models, Immunological; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D012641:Selection, Genetic; D014774:Virulence
chemical_list: D000953:Antigens, Protozoan