E-Article Understanding and Predicting Strain-Specific Patterns of Pathogenesis in the Rodent Malaria Plasmodium chabaudi

abstract: Despite considerable success elucidating important im-munological and resource-based mechanisms that control the dy-namics of infection in some diseases, little is known about how differences in these mechanisms result in strain differences in patterns of pathogenesis. Using a combination of data and theory, we dis-entangle the role of ecological factors (e.g., resource abundance) in the dynamics of pathogenesis for the malaria species Plasmodium chabaudi in CD4! T cell–depleted mice. We build a series of nested models to systematically test a number of potential regulatory mech-anisms and determine the “best ” model using statistical techniques. The best-fit model is further tested using an independent data set from mixed-clone competition experiments. We find that parasites preferentially invade older red blood cells even when they are more fecund in younger reticulocytes and that inoculum size has a strong effect on burst size in reticulocytes. Importantly, the results sugges