Cerón Gómez Miller, Yang Hyun Mo
Departmento de Matemáticas, Universidad de Nariño, Colombia.
Departamento de Matemática Aplicada, IMECC, UNICAMP, Praça Sérgio Buarque de Holanda, CEP, Campinas, SP, Brazil.
Math Med Biol. 2019 Dec 4;36(4):411-438. doi: 10.1093/imammb/dqy016.
We develop a mathematical model to describe the role of antibody-dependent enhancement (ADE) in heterologous secondary infections, assuming that antibodies specific to primary dengue virus (DENV) infection are being produced by immunological memory. The model has a virus-free equilibrium (VFE) and a unique virus-presence equilibrium (VPE). VFE is asymptotically stable when VPE is unstable; and unstable, otherwise. Additionally, there is an asymptotic attractor (not a fixed point) due to the fact that the model assumes unbounded increase in memory cells. In the analysis of the model, ADE must be accounted in the initial stage of infection (a window of time of few days), period of time elapsed from the heterologous infection until the immune system mounting an effective response against the secondary infection. We apply the results yielded by model to evaluate ADE phenomonon in heterologous DENV infection. We also associate the possible occurrence of severe dengue with huge viremia mediated by ADE phenomenon.
我们建立了一个数学模型来描述抗体依赖增强(ADE)在异源二次感染中的作用,假设针对初次登革病毒(DENV)感染的特异性抗体由免疫记忆产生。该模型具有无病毒平衡点(VFE)和唯一的病毒存在平衡点(VPE)。当VPE不稳定时,VFE是渐近稳定的;否则,VFE是不稳定的。此外,由于模型假设记忆细胞无界增加,所以存在一个渐近吸引子(不是固定点)。在模型分析中,必须在感染的初始阶段(几天的时间窗口)考虑ADE,即从异源感染到免疫系统对二次感染产生有效反应所经过的时间段。我们应用模型得出的结果来评估异源DENV感染中的ADE现象。我们还将严重登革热的可能发生与由ADE现象介导的巨大病毒血症联系起来。