Parasites, by definition, extract resources from their hosts. Host resource availability is thus expected to play an important role in regulating parasite population dynamics within-hosts. The within-host dynamics of infections of the mouse malaria parasite, Plasmodium chabaudi, have been the focus of much theoretical but limited empirical study. These efforts have focused on elucidating the relative importance of the availability of red blood cells, in which malaria parasites reproduce, and immunity in determining infection dynamics. Here we explore how the availability of a micronutrient para-aminobenzoic acid (pABA), which is required by malaria parasites but not their mammalian hosts, interacts with red blood cell availability and immune system activity to determine the dynamics of malaria infections. We experimentally manipulated the availability of pABA in the water of mice infected with a strain of P. chabaudi and tracked the densities of both parasites and red blood cells through time. We then used a novel modeling strategy to explore the mechanism by which pABA availability alters infection dynamics.
The availability of pABA determined the growth rate of infections and the magnitude and timing of peak parasite density. Surprisingly, pABA supply also had a significant impact on infection dynamics in the period after parasite densities had peaked, as well as the relationship between parasite density and pathology, as measured by anemia. Since the post-peak dynamics of malaria infections are thought to be determined by immune system activity, as is much of the anemia that occurs as a symptom of malaria infection, these data suggest that pABA availability may alter the antimalarial immune response. Preliminary analysis of a model fit to these data, however, indicates that pABA availability could impact either the magnitude of the immune response and/or the dynamics of red blood cell replenishment, via its impact on parasite reproduction. Importantly, this analysis shows that these two hypotheses cannot be distinguished using standard data streams. Our work demonstrates that (multiple) bottom-up and top-down forces interact to determine parasite population dynamics within-hosts. We need to quantify these forces if we are to understand both the dynamics of infections and their consequences for host health.