Theoretical Epidemiology, University of Utrecht, Yalelaan 7, 3584 CL Utrecht, The Netherlands.
J R Soc Interface. 2012 Feb 7;9(67):246-60. doi: 10.1098/rsif.2011.0239. Epub 2011 Jul 6.
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.
疟原虫感染的红细胞表达变异表面抗原（VSAs），逃避宿主免疫，使寄生虫在人群中持续存在。存在许多不同的 VSA，这些 VSA 的差异表达与寄生虫的毒力（对宿主的损害）有关。本研究的目的是揭示关键选择力对表达不同 VSA 的寄生虫的影响差异，以便更好地了解 VSA 如何使寄生虫适应其环境的变化（如控制措施），以及这可能如何影响循环寄生虫的毒力。为此，我们构建了一个基于个体的模型，该模型捕获了疟疾寄生虫的主要选择力，即寄生虫竞争、宿主免疫、宿主死亡和蚊媒丰度，包括在宿主内和宿主间水平。VSA 是由它们推断给寄生虫的净增长率来定义的，模型跟踪所有宿主中每种 VSA 的表达和针对它的抗体积累。我们的结果显示了宿主年龄与 VSA 特异性抗体的有序获得，这导致了具有更高毒力的 VSA 与到达高寄生虫血症但仅限于年轻的相对非免疫宿主之间的二分法，以及毒力较低的 VSA 不会达到如此高的寄生虫血症但可以感染更广泛的宿主。寄生虫环境变化对寄生虫毒力的影响取决于选择力之间的确切平衡，这为寄生虫的生存设定了限制因素。当寄生虫生存的限制因素是宿主内寄生虫的生长，并且寄生虫能够通过表达更具毒性的 VSA 来最小化这种限制时，寄生虫将进化为表达更具毒性的 VSA。
