Integrating theory and experimentation in the study of malaria

dc.contributor.authorMideo, Nicoleen
dc.contributor.supervisorDay, Troyen
dc.date2009-08-20 06:41:14.198's University at Kingstonen
dc.descriptionThesis (Ph.D, Biology) -- Queen's University, 2009-08-20 06:41:14.198en
dc.description.abstractMalaria poses a serious threat to much of the developing world and an enormous effort is under way to design vaccines and other novel interventions. Nevertheless, we understand very little about the ecology and evolution of malaria parasites. For instance, while scientists have had considerable success identifying factors involved in regulating parasite growth within hosts, it is extremely hard to disentangle the relative influences of host immunity and other within-host factors on infection dynamics. Many mathematical models have been directed at understanding the dynamics of malaria infections, and these have provided valuable insights. However, these models have also been criticized, most notably for lacking any statistical analysis of the goodness of fit of model predictions to data. Here, we develop a new modeling approach that improves on previous work, and apply it to a novel data set from a simplified rodent malaria system. We find that resource availability and competition are important drivers of dynamics, and we identify a number of parasite traits that may underlie differences in virulence between parasite strains. These include the number of progeny parasites produced per infected cell (burst size) and the invasion rates of target cells. We test these predictions with further experiments and find broad support for the role of burst sizes in determining virulence, but the role of invasion rates is less certain. We also find evidence of potential plasticity in these parasite traits in response to within-host environmental factors. These within-host interactions between parasites and hosts have effects that will scale up to between-host processes; we discuss the growing body of theory that seeks to combine these levels (‘embedded models’). Using between-host and embedded models, we test the plausibility of various hypotheses to explain why there are so few transmissible malaria parasite forms, yet vast numbers of host-damaging asexual forms are produced. We show that a specific form of density-dependent transmission-blocking immunity and the occurrence of multiple infections can each generate selection for this pattern. Overall, this thesis contributes to a better under- standing of malaria parasites, while providing a framework for addressing unanswered questions in disease biology, and offering interesting paths for future empirical work.en
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dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectmathematical biologyen
dc.subjectinfectious diseaseen
dc.subjectdisease dynamicsen
dc.titleIntegrating theory and experimentation in the study of malariaen
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