Within-host viral growth and immune response rates predict FMDV transmission dynamics for African Buffalo

Abstract

Infectious disease dynamics operate across biological scales: pathogens replicate within hosts, but transmit among hosts and populations. Functional changes in the pathogen-host interaction thus generate cascading effects from molecular to landscape scales. We investigated within-host dynamics and among-host transmission of three strains of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. We combined data on viral dynamics and host immune responses with mathematical models to ask (i) How do viral and immune dynamics vary among FMDV strains? (SAT1, 2, 3); (ii) Which viral and immune parameters determine viral fitness within hosts?; and (iii) How do within-host dynamics relate to virus transmission among hosts? Our data reveal contrasting within-host dynamics among viral strains. However, SAT2 elicited more rapid and effective immune responses than SAT1 and SAT3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates against FMDVs, but not by variation among individual hosts in viral growth rate. By contrast, our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo; and that adaptive immune activation rate determines the infectious period. Together, these parameters define the basic reproductive number of the virus, suggesting that viral invasion potential may be predictable from within-host dynamics. Future work should test the generality of these findings by including additional FMDV strains, and create a multi-scale model to link within-host and between-host dynamics explicitly.

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

“…In this section, we present our immuno-epidemiological model that captures the disease spread of foot- and-mouth disease among African buffalo on two scales (namely the immunological and epidemiological). We first discuss our within-host model, which is initially presented in Macdonald et al (2022), modeling the virus and immune dynamics of the FMDV infected buffalo during the acute phase. Next, we present the within-host model for carrier-infected buffalo and formulate an age-since-infection structured PDE epidemic model.…”

“…Here, we introduce the within-host viral immune kinetics model describing the acute infection stage of infected host (formulated first in our prior work Macdonald et al (2022)). The model considers the interactions between the innate immune response, I A ( τ ), the virus in the bloodstream, P ( τ ), and the adaptive immune response A ( τ ), where τ refers to the time since infection within a host (in days).…”

“…(Macdonald et al (2022)). If I A 0 > 0 or A 0 > 0, then the pathogen (within the host) eventually clears, i.e ., …”

“…Parameter and state variable descriptions of system (1) are given in Table 3 and Table 4. The acute infection model parameters are estimated in our prior work Macdonald et al (2022).…”

“…In prior works, deterministic models of FMD have been used for understanding the spread of FMD (Pech and McIlroy, 1990; Chowell et al, 2006), the ways of controlling the spread of FMD (Gashirai et al, 2020; Shikumwifa, 2022), and the persistence of FMDV among live-stock and reservoir populations (Hayer et al, 2018; McLachlan et al, 2019). With regard to analyzing FMD at the immunological scale, there have been some works (Howey et al, 2009, 2012; Macdonald et al, 2022) in which systems of ordinary differential equations (ODEs) were constructed to model the viral and immunological dynamics of FMDV. Howey et al (2009) constructed a within-host model to capture the viral dynamics of needle-infected pigs and found a trend in which the higher the initial dose the earlier the development of viral detection.…”