title: Causes of variation in malaria infection dynamics: insights from theory and data.
abstract: Parasite strategies for exploiting host resources are key determinants of disease severity (i.e., virulence) and infectiousness (i.e., transmission between hosts). By iterating the development of theory and empirical tests, we investigated whether variation in parasite traits across two genetically distinct clones of the rodent malaria parasite, Plasmodium chabaudi, explains differences in within-host infection dynamics and virulence. First, we experimentally tested key predictions of our earlier modeling work. As predicted, the more virulent genotype produced more progeny parasites per infected cell (burst size), but in contrast to predictions, invasion rates of red blood cells (RBCs) did not differ between the genotypes studied. Second, we further developed theory by confronting our earlier model with these new data, testing a new set of models that incorporate more biological realism, and developing novel theoretical tools for identifying differences between parasite genotypes. Overall, we found robust evidence that differences in burst sizes contribute to variation in dynamics and that differential interactions between parasites and host immune responses also play a role. In contrast to previous work, our model predicts that RBC age structure is not important for explaining dynamics. Integrating theory and empirical tests is a potentially powerful way of progressing understanding of disease biology.
authors.affiliation: Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mideo
authors.affiliation: Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.|Institute of Immunity and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Savill
authors.affiliation: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Chadwick
authors.affiliation: Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.affiliation: Center for Infectious Disease Dynamics, Departments of Biology and Entomology, Pennsylvania State University, University Park, Pennsylvania 16802; and Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Read
authors.affiliation: Departments of Biology and Mathematics and Statistics, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Troy
authors.initials: T
authors.lastname: Day
authors.affiliation: Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.|Institute of Immunity and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.|Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Reece
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D004912:Erythrocytes / Q000469:parasitology* / Q000502:physiology; D005260:Female; D005838:Genotype; D016013:Likelihood Functions; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D015233:Models, Statistical; D016788:Plasmodium chabaudi / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence
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