A current challenge for disease modeling and public health is understanding pathogen dynamics across scales since their ecology and evolution ultimately operate on several coupled scales. This is particularly true for vector-borne diseases, where within-vector, within-host, and between vector–host populations all play crucial roles in diversity and distribution of the pathogen. Despite recent modeling efforts to determine the effect of within-host virus-immune response dynamics on between-host transmission, the role of within-vector viral dynamics on disease spread is overlooked. Here, we formulate an age-since-infection-structured epidemic model coupled to nonlinear ordinary differential equations describing within-host immune-virus dynamics and within-vector viral kinetics, with feedbacks across these scales. We first define the within-host viral-immune response and within-vector viral kinetics-dependent basic reproduction number [Formula: see text] Then we prove that whenever [Formula: see text] the disease-free equilibrium is locally asymptotically stable, and under certain biologically interpretable conditions, globally asymptotically stable. Otherwise, if [Formula: see text] it is unstable and the system has a unique positive endemic equilibrium. In the special case of constant vector to host inoculum size, we show the positive equilibrium is locally asymptotically stable and the disease is weakly uniformly persistent. Furthermore, numerical results suggest that within-vector-viral kinetics and dynamic inoculum size may play a substantial role in epidemics. Finally, we address how the model can be utilized to better predict the success of control strategies such as vaccination and drug treatment.

中文翻译：

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具有载体内病毒动力学的免疫-流行病学载体-宿主模型

疾病建模和公共卫生当前面临的挑战是了解跨尺度的病原体动态，因为它们的生态学和进化最终在几个耦合的尺度上运行。对于媒介传播的疾病尤其如此，其中媒介内、宿主内以及媒介-宿主种群之间都在病原体的多样性和分布中发挥着关键作用。尽管最近的建模工作旨在确定宿主内病毒免疫反应动力学对宿主间传播的影响，但忽略了载体内病毒动力学对疾病传播的作用。在这里，我们制定了一个自感染以来的年龄结构流行病模型，该模型与描述宿主内免疫病毒动力学和载体内病毒动力学的非线性常微分方程耦合，并在这些尺度上提供反馈。我们首先定义宿主内病毒免疫反应和载体内病毒动力学依赖的基本繁殖数[公式：见正文]然后我们证明，只要[公式：见正文]无病平衡是局部渐近稳定的，并且在某些生物学可解释的条件下，全局渐近稳定。否则，如果[公式：见正文]它是不稳定的，并且系统具有独特的地方性正平衡。在恒定向量到宿主接种物大小的特殊情况下，我们表明正平衡是局部渐近稳定的，并且疾病是弱均匀持续的。此外，数值结果表明，载体内病毒动力学和动态接种量可能在流行病中发挥重要作用。最后，