Foot-and-mouth disease infection dynamics in contact-exposed pigs are determined by the estimated exposure dose

Authors: MORENO-TORRES, KARLA - Oak Ridge Institute For Science And Education (ORISE); BRITO, BARBARA - Oak Ridge Institute For Science And Education (ORISE); BRANAN, MATTHEW - Animal And Plant Health Inspection Service (APHIS); Rodriguez, Luis; DELGADO, AMY - Animal And Plant Health Inspection Service (APHIS); STENFELDT, CAROLINA - University Of Minnesota; Arzt, Jonathan

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/2/2018
Publication Date: 7/20/2018
Citation: Moreno-Torres, K.I., Brito, B.P., Branan, M.A., Rodriguez, L.L., Delgado, A.H., Stenfeldt, C., Arzt, J. 2018. Foot-and-mouth disease infection dynamics in contact-exposed pigs are determined by the estimated exposure dose. Frontiers in Veterinary Science. 5:167. https://doi.org/10.3389/fvets.2018.00167.
DOI: https://doi.org/10.3389/fvets.2018.00167

Interpretive Summary: The purpose of doing mathematical modeling of diseases is to create models that will decrease and ultimately eliminate the need to use live animals in experiments. Many models have been created to recreate infection with foot-and-mouth disease (FMD), which is one of the most important livestock diseases on the planet. However no model has ever been created which can estimate the dose (quantity) of FMD virus which passes from one animal to another during natural infection. The current manuscript accomplishes this goal for the first time by simulating FMD virus (FMDV) infection between groups of pigs. The outcome demonstrates that pigs can be infected by extremely low quantities of virus and the effect in the infected pigs is determined by just how much virus the pigs receive. This work is important because it contributes to how the US agriculture industry should prepare for a potential outbreak of FMD.

Technical Abstract: The quantitative relationship between the exposure dose of foot-and-mouth disease virus (FMDV) and subsequent infection dynamics has been demonstrated through controlled inoculation studies in various species. However, similar quantitation of viral doses has not been achieved during contact exposure experiments due to the intrinsic difficulty of measuring the virus quantities exchanged between animals. In the current study, novel modeling techniques were utilized to investigate FMDV infection dynamics in groups of pigs that had been contact-exposed to FMDV-infected donors shedding varying levels of virus, as well as in pigs inoculated via the intra-oropharyngeal (IOP) route. Estimated virus exposure doses were modelled and were found to be statistically significantly associated with the dynamics of FMDV RNA detection in serum and oropharyngeal fluid (OPF), and with the time to onset of clinical disease. The minimum estimated shedding quantity in OPF that defined infectiousness of donor pigs was 6.55 log10 genome copy numbers (GCN)/ml (95% CI 6.11, 6.98), which delineated the transition from the latent to infectious phase of disease. This corresponded to a minimum estimated exposure dose of 5.07 log10 GCN/ml (95% CI 4.25, 5.89) in contact-exposed pigs. Thus, we demonstrated that a threshold quantity of FMDV detection in donor pigs was necessary in order to achieve transmission by direct contact. The outcomes from this investigation contribute to a better understanding of the variability of infection dynamics which may occur during the progression of FMD in naturally exposed pigs. Moreover, these modeling approaches for dose-quantitation may be retrospectively applied to contact-exposure experiments or field scenarios. Hence, robust information could be incorporated into models used to evaluate FMD spread and control.