Table_1_Foot-and-Mouth Disease Infection Dynamics in Contact-Exposed Pigs Are Determined by the Estimated Exposure Dose.DOCX

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.

口蹄疫病毒（foot-and-mouth disease virus, FMDV）的暴露剂量与后续感染动态之间的定量关联，已通过多种受试物种的受控接种研究得到验证。然而，由于难以精准测定动物间传播的病毒载量，接触暴露实验中尚未实现类似的病毒剂量定量分析。本研究采用新型建模技术，对两类猪群展开FMDV感染动态研究：一类为与不同病毒排毒水平的FMDV感染供体猪直接接触的猪群，另一类为经口咽内（intra-oropharyngeal, IOP）途径接种的猪群。研究通过建模估算病毒暴露剂量，结果显示，该剂量与血清及口咽分泌物（oropharyngeal fluid, OPF）中FMDV RNA的检出动态、临床症状发作时间均存在统计学显著性关联。供体猪具备感染性的口咽分泌物最低估算排毒量为6.55 log₁₀基因组拷贝数（genome copy numbers, GCN)/ml（95%置信区间：6.11~6.98），该阈值界定了潜伏期内疾病从潜伏阶段向感染阶段的转变。该排毒量对应接触暴露猪群的最低估算暴露剂量为5.07 log₁₀ GCN/ml（95%置信区间：4.25~5.89）。由此证实，供体猪需达到特定的FMDV检出阈值，方可通过直接接触实现病毒传播。本研究结果表明，自然暴露于FMDV的猪群在口蹄疫病程中出现的感染动态异质性，可部分归因于暴露剂量的差异。此外，本研究所用的剂量定量建模方法，可回溯性地应用于接触暴露实验或野外疫情场景。因此，本研究获得的可靠数据可被纳入用于评估口蹄疫传播与防控的模型之中。