Infection severity across scales in multi-strain immuno-epidemiological Dengue model structured by host antibody level
Infection severity across scales in multi-strain immuno-epidemiological Dengue model structured by host antibody level
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DOI：
10.1007/s00285-020-01480-3
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发表时间：
2020-05-01
影响因子：
1.9
通讯作者：
Browne, Cameron J.
中科院分区：
文献类型：
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作者：
Gulbudak, Hayriye;Browne, Cameron J.
不同登革热病毒血清型的感染与宿主免疫力有着错综复杂的联系。特别是，宿主中某些水平的交叉反应抗体实际上可能会增加感染的严重程度，导致登革出血热（DHF）。登革热的免疫学和流行病学动力学耦合需要多尺度建模方法。在这项工作中，我们制定了一个内宿主模型，机械地概括了登革热感染中抗体依赖性增强的特征。宿主内规模，然后连接到流行病学传播的媒介-宿主偏微分方程模型结构的宿主抗体水平。该偶联允许通过不同登革毒株的初次和二次感染来跟踪动态的群体范围的抗体水平，沿着初次感染后交叉保护性免疫的减弱。对主机内和主机间系统进行了分析。通过基本和入侵再生数作为免疫变量的函数，在流行病模型的稳定性结果制定。此外，我们开发了数值方法，以模拟多尺度模型，并评估参数对疾病传播和DHF患病率的影响。
Infection by distinct Dengue virus serotypes and host immunity are intricately linked. In particular, certain levels of cross-reactive antibodies in the host may actually enhance infection severity leading to Dengue hemorrhagic fever (DHF). The coupled immunological and epidemiological dynamics of Dengue calls for a multi-scale modeling approach. In this work, we formulate a within-host model which mechanistically recapitulates characteristics of antibody dependent enhancement in Dengue infection. The within-host scale is then linked to epidemiological spread by a vector-host partial differential equation model structured by host antibody level. The coupling allows for dynamic population-wide antibody levels to be tracked through primary and secondary infections by distinct Dengue strains, along with waning of cross-protective immunity after primary infection. Analysis of both the within-host and between-host systems are conducted. Stability results in the epidemic model are formulated via basic and invasion reproduction numbers as a function of immunological variables. Additionally, we develop numerical methods in order to simulate the multi-scale model and assess the influence of parameters on disease spread and DHF prevalence in the population.