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 modeled 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 which occurred during the incubation phase. This quantity 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 demonstrate that variability of infection dynamics which occurs during the progression of FMD in naturally exposed pigs can be partially attributed to variations in exposure dose. 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.
Highlights
Detection and rapid response to a highly contagious pathogen such as foot-and-mouth disease virus (FMDV) may determine the difference between a controllable outbreak and a widespread epidemic [1, 2]
The significance of the smooth term indicated that the exposure dose received by contact-exposed pigs was significantly explained by the quantitated shedding of FMDV RNA in oropharyngeal fluid (OPF) of donors (p < 0.001). It is well-established that the inoculated dose of FMDV [8, 20, 32, 33] or the duration of contact exposure [18] may affect the infection dynamics of FMD in pigs, including the duration of the incubation period
No previous work has determined the effective exposure doses in contact-exposed pigs or quantitatively defined the manner in which infection dynamics are affected by different exposure doses
Summary
Detection and rapid response to a highly contagious pathogen such as foot-and-mouth disease virus (FMDV) may determine the difference between a controllable outbreak and a widespread epidemic [1, 2]. Even though multiple routes (mechanisms) of virus entry are plausible during direct contact exposure, identification of the oropharyngeal tonsils as sites of primary and sustained viral replication in pigs suggests that transmission occurs mainly via the oral route [17]. This understanding of pathogenesis of FMDV in pigs allows for the design of experimental studies which better replicate natural exposure. Such controlled experimental studies provide a foundation for our understanding of disease transmission and allow modelers to estimate disease spread and evaluate control options in a population
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