Investigation of risk factors for introduction of highly pathogenic avian influenza H5N1 infection among commercial turkey operations in the United States, 2022: a case-control study.

Introduction: The 2022-2023 highly pathogenic avian influenza (HPAI) H5N1 outbreak in the United States (U.S.) is the largest and most costly animal health event in U.S. history. Approximately 70% of commercial farms affected during this outbreak have been turkey farms. Methods: We conducted a case-control study to identify potential risk factors for introduction of HPAI virus onto commercial meat turkey operations. Data were collected from 66 case farms and 59 control farms in 12 states. Univariate and multivariable analyses were conducted to compare management and biosecurity factors on case and control farms. Results: Factors associated with increased risk of infection included being in an existing control zone, having both brooders and growers, having toms, seeing wild waterfowl or shorebirds in the closest field, and using rendering for dead bird disposal. Protective factors included having a restroom facility, including portable, available to crews that visit the farm and workers having access and using a shower at least some of the time when entering a specified barn. Discussion: Study results provide a better understanding of risk factors for HPAI infection and can be used to inform prevention and control measures for HPAI on U.S. turkey farms.

Parameterization of the durations of phases of foot-and-mouth disease in pigs.

The global interconnectedness of the pig-production industry and the diversity of foot-and-mouth disease (FMD) viruses (FMDVs) currently circulating, makes modeling disease spread and control in FMD-free areas challenging. However, advances in experimental design and transmission studies create opportunities to strengthen our understanding and ability to model FMD transmission. In the current study, we estimated the duration of defined phases of FMDV infection in pigs by using data from a large collection of controlled in vivo experiments. Because the detection of low-levels of viral RNA does not correspond to infectiousness, an experimentally defined minimum threshold of FMDV RNA shedding in oropharyngeal fluids was used to estimate the onset of infectiousness in experiments in which transmission was not evaluated. Animal-level data were used in Accelerated Failure Time models to assess the effect of experimental design factors in the duration of defined phases of FMDV infection: latent, incubation, pre-clinical infectious, clinical infectious, and total infectious periods. The estimated means of the phases were latent: 25 h (95%CI 21, 29), incubation: 70 h (95%CI 64, 76), pre-clinical infectious: 36 h (95%CI 32, 41), clinical infectious: 265 h (95%CI 258, 272) and total infectious: 282 h (95%CI 273, 290). Virus strains and exposure methods had no significant influence on the duration of latency, incubation, or clinical infectious phases. By contrast, the estimated means of the duration of the pre-clinical infectious and total infectious phases were significantly influenced by virus strains, and the duration of the pre-clinical infectious phase was significantly influenced by exposure methods. This study provides disease parameters based on an estimated threshold of the onset of infectiousness and a probability distribution representing the end of infectiousness. Disease parameters that incorporate experimentally-based quantitative proxies to define phases of FMDV infection may improve planning and preparedness for FMD.

Mycoplasma ovis infection in domestic sheep (Ovis aries) in the United States: Prevalence, distribution, associated risk factors, and associated outcomes.

Mycoplasma ovis is a hemotropic bacterium reported to infect sheep, goats, and deer species. Infection in these species can result in anemia, jaundice, and ill-thrift. Although of worldwide distribution, only rare reports of this bacterium in the United States exist. The objectives of this retrospective study were to identify the prevalence and distribution of M. ovis, and identify associated demographic and management risk factors, and reproductive and production outcomes associated with infection on domestic sheep (Ovis aries) operations in the United States. As part of the United States Department of Agriculture (USDA), Animal Plant Health Inspection Service, Veterinary Services' National Animal Health Monitoring System (NAHMS) Sheep 2001 and 2011 studies, blood was collected and sera banked from 21,369 ewes in 2001 and 13,128 ewes in 2011. Participating premises were located in 22 states across the United States for each sample year. In 2015 the USDA, Agricultural Research Service, Animal Disease Research Unit received aliquots of these sera, and DNA was extracted and analyzed by PCR for the presence of M. ovis genomic DNA. Flock presence and mean within-flock prevalence of M. ovis were 73.3% and 23.2%, respectively. Model selection using Mallow's Cp Criterion was used to determine which variables significantly affected flock presence and within-flock prevalence. The final flock presence model included flock size, year of blood collection, region, and vaccine administration. The final within-flock prevalence model included year of blood collection, interaction between flock size and region, and interaction between reported abortions and grazing with sheep from other operations. Medium and large operations had a higher flock presence and within-flock prevalence. Flock presence was higher in operations that administered any vaccines. Operations that reported any abortions and grazed with sheep from other operations had a higher within-flock prevalence.

Parameterization of the Durations of Phases of Foot-And-Mouth Disease in Cattle.

The objective of the current study was to update parameterization of mathematical simulation models for foot-and-mouth disease (FMD) spread in cattle utilizing recent knowledge of FMD virus (FMDV) pathogenesis and infection dynamics to estimate the duration of distinct phases of FMD. Specifically, the durations of incubation, latent, and infectious periods were estimated for 3 serotypes (O, Asia1, and A) of FMDV, individually and collectively (pan-serotypic). Animal-level data were used in Accelerated Failure Time (AFT) models to estimate the duration of the defined phases of infection, while also investigating the influence of factors related to the experimental design (exposure methods) and virus serotype on disease progression. Substantial influences upon the estimated duration of distinct phases of FMD included the quantity of viral shedding used as a proxy for the onset of infectiousness, virus serotypes, and experimental exposure methods. The use of detection of any viral RNA in nasal secretions as a proxy of infectiousness lengthened the total infectious period compared to use of threshold-based detection. Additionally, the experimental system used to infect the animals also had significant effects on the duration of distinct phases of disease. Overall, the mean [95% Confidence Interval (CI)] durations of pan-serotype disease phases in cattle were estimated to be: incubation phase = 3.6 days (2.7-4.8), latent phase = 1.5 days (1.1-2.1), subclinical infectious phase = 2.2 days (1.5-3.5), clinical infectious phase = 8.5 days (6.2-11.6), and total infectious phase = 10.8 days (8.2-14.2). This study highlights the importance of identifying appropriate proxy measures to define the onset and duration of infectiousness in FMDV-infected cattle in the absence of actual transmission data. Additionally, it is demonstrated herein that factors associated with experimental design, such as virus exposure methods, may significantly affect disease progression in individual animals and should be considered when data is extrapolated from experimental studies. Given limitations in experimental data availability, pan-serotypic parameters which include all routes of exposure and a threshold-defined onset of infectiousness may be the most robust parameters for exploratory disease spread modeling approaches, when information on the specific virus of interest is not available.

Quantitative impacts of incubation phase transmission of foot-and-mouth disease virus.

The current investigation applied a Bayesian modeling approach to a unique experimental transmission study to estimate the occurrence of transmission of foot-and-mouth disease (FMD) during the incubation phase amongst group-housed pigs. The primary outcome was that transmission occurred approximately one day prior to development of visible signs of disease (posterior median 21 hours, 95% CI: 1.1-45.0). Updated disease state durations were incorporated into a simulation model to examine the importance of addressing preclinical transmission in the face of robust response measures. Simulation of FMD outbreaks in the US pig production sector demonstrated that including a preclinical infectious period of one day would result in a 40% increase in the median number of farms affected (166 additional farms and 664,912 pigs euthanized) compared to the scenario of no preclinical transmission, assuming suboptimal outbreak response. These findings emphasize the importance of considering transmission of FMD during the incubation phase in modeling and response planning.

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

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.