An Immuno-Epidemiological Model of Foot-and-Mouth Disease (FMD) in the African Buffalo Population with Carrier Transmission.

In this paper, we present a novel immuno-epidemiological model, linking host-pathogen interactions at within-host and population scales for foot-and-mouth disease virus (FMDV) in its natural host, African buffalo. Endemic persistence of FMD in buffalo populations is facilitated by chronic infections in carrier hosts: Upon exposure to the virus, buffalo become acutely infected, followed by either viral clearance and recovery with immunity, or persistent infection for several months. In our model, we divide the infectious population based upon these two stages, acute and carrier infection, so that we can dynamically capture the immunological characteristics of both phases of the disease to better understand the carriers' role in disease transmission. We first define the epidemiological basic reproduction number, R 0 , depending on the viral-immune kinetics from acute and carrier infected hosts. Then, we show that R 0 is a threshold condition for the local stability of the disease free equilibrium and for the existence of the endemic equilibrium. We also analytically establish that the system always displays forward bifurcation with respect to between-host epidemic parameters. Later, by using a sensitivity analysis (SA) approach developed for multi-scale models, we assess the impact of the acute infection and carrier phase immunological parameters on R 0 . Interestingly, our numerical results show that the viral and immunological parameters from a carrier infected host and the susceptible individual recruitment rates play significant roles in disease persistence, which are consistent with experimental and field studies.