Causes of Variation in Malaria Infection Dynamics: Insights from Theory and Data
Causes of Variation in Malaria Infection Dynamics: Insights from Theory and Data
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DOI：
10.1086/662670
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发表时间：
2011-12-01
影响因子：
2.9
通讯作者：
Reece, Sarah E.
中科院分区：
文献类型：
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作者：
Mideo, Nicole;Savill, Nicholas J.;Reece, Sarah E.
寄生虫利用宿主资源的策略是疾病严重程度的关键决定因素（即，毒力）和感染性（即，主机之间的传输）。通过迭代理论和实证检验的发展，我们研究了啮齿动物疟原虫夏氏疟原虫的两个遗传上不同的克隆的寄生虫性状的变化是否解释了宿主内感染动力学和毒力的差异。首先，我们通过实验测试了我们早期建模工作的关键预测。正如预测的那样，毒性更强的基因型产生更多的子代寄生虫/感染细胞（爆发大小），但与预测相反，红细胞（RBC）的侵入率在研究的基因型之间没有差异。其次，我们进一步发展理论，用这些新数据来对抗我们早期的模型，测试一组新的模型，这些模型包含更多的生物现实主义，并开发新的理论工具来识别寄生虫基因型之间的差异。总体而言，我们发现了强有力的证据表明，爆发大小的差异有助于动态变化，寄生虫和宿主免疫反应之间的差异相互作用也发挥了作用。与以前的工作相比，我们的模型预测，RBC年龄结构是不重要的解释动态。整合理论和经验测试是一种潜在的强大的方式来促进对疾病生物学的理解。
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.