Department for Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modelling, Imperial College, London W2 1PG, UK
Institut Pasteur de Bangui, Bangui, Central African Republic.
J R Soc Interface. 2014 Jul 6;11(96). doi: 10.1098/rsif.2014.0094.
Dengue, the most common mosquito-borne viral infection of humans, is endemic across much of the world, including much of tropical Asia and is increasing in its geographical range. Here, we present a mathematical model of dengue virus dynamics within infected individuals, detailing the interaction between virus and a simple immune response. We fit this model to measurements of plasma viral titre from cases of primary and secondary DENV 1 infection in Vietnam. We show that variation in model parameters governing the immune response is sufficient to create the observed variation in virus dynamics between individuals. Estimating model parameter values, we find parameter differences between primary and secondary cases consistent with the theory of antibody-dependent enhancement (namely enhanced rates of viral entry to target cells in secondary cases). Finally, we use our model to examine the potential impact of an antiviral drug on the within-host dynamics of dengue. We conclude that the impact of antiviral therapy on virus dynamics is likely to be limited if therapy is only started at the onset of symptoms, owing to the typically late stage of viral pathogenesis reached by the time symptoms are manifested and thus treatment is started.
登革热是最常见的由蚊子传播的人类病毒感染，在世界上许多地方都流行，包括亚洲大部分热带地区，并在地理范围上不断扩大。在这里，我们提出了一个登革病毒动力学的数学模型，详细描述了病毒与简单的免疫反应之间的相互作用。我们将该模型拟合到越南登革热 1 型初次和二次感染病例的血浆病毒载量测量值。我们表明，控制免疫反应的模型参数的变化足以在个体之间产生观察到的病毒动力学变化。通过估计模型参数值，我们发现控制免疫反应的模型参数在初次感染和二次感染之间存在差异，这与抗体依赖性增强的理论一致（即在二次感染中，病毒进入靶细胞的速度增强）。最后，我们使用我们的模型来研究抗病毒药物对登革热宿主内动力学的潜在影响。我们的结论是，如果仅在症状出现时开始治疗，抗病毒治疗对病毒动力学的影响可能是有限的，因为在出现症状和开始治疗时，病毒发病机制通常已经达到晚期。
