AN IMMUNO-EPIDEMIOLOGICAL VECTOR–HOST MODEL WITH WITHIN-VECTOR VIRAL KINETICS

Abstract

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.