Activation-Induced Cytidine Deaminase Impacts the Primary Antibody Repertoire in Naive Mice.

Genetic and environmental cues shape the evolution of the B cell Ig repertoire. Activation-induced cytidine deaminase (AID) is essential to generating Ig diversity through isotype class switching and somatic mutations, which then directly influence clonal selection. Impaired B cell development in AID-knockout mice has made it difficult to study Ig diversification in an aging repertoire. Therefore, in this report, we used a novel inducible AID-knockout mouse model and discovered that deleting AID in adult mice caused spontaneous germinal center formation. Deep sequencing of the IgH repertoire revealed that Ab diversification begins early in life and evolves over time. Our data suggest that activated B cells form germinal centers at steady state and facilitate continuous diversification of the B cell repertoire. In support, we identified shared B cell lineages that were class switched and showed age-dependent rates of mutation. Our data provide novel context to the genesis of the B cell repertoire that may benefit the understanding of autoimmunity and the strength of an immune response to infection.

Investigation of the distance to slaughterhouses and weather parameters in the occurrence of porcine reproductive and respiratory syndrome outbreaks in U.S. swine breeding herds.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases affecting the swine industry. The main objective of this study was to assess whether sow farm distance to slaughterhouses and meteorological variables were associated with PRRS outbreaks. This case-control study paired 104 sow farms with or without a reported PRRS outbreak (N = 208) during the same period. Data on the distance to the closest slaughterhouse, swine density, presence of an air filtration system, or a neighboring farm, and weather conditions were collected, and a multivariable conditional logistic regression model was created to investigate the association between variables of interest and the occurrence of a PRRS outbreak. Swine density, presence of an air filtration system, presence of a neighboring farm, and PRRS herd-level status before the outbreak were associated with the occurrence of PRRS outbreaks. Farms in areas with higher swine density and nearby swine farms had increased odds of reporting an outbreak compared to farms in low swine density areas and farms having no neighbors. Under the conditions of this study, none of the meteorological variables or the distance to the closest slaughterhouse were associated with occurrence of PRRS outbreaks.

Enquête sur la distance aux abattoirs et les paramètres météorologiques dans l'apparition d'épidémies de syndrome reproducteur et respiratoire porcin dans les troupeaux reproducteurs de porcs aux États-Unis. Le syndrome reproducteur et respiratoire porcin (SRRP) est l'une des maladies les plus importantes sur le plan économique affectant l'industrie porcine. L'objectif principal de cette étude était d'évaluer si la distance entre les élevages de truies et les abattoirs et les variables météorologiques étaient associées aux épidémies de SRRP. Cette étude cas-témoin a apparié 104 élevages de truies avec ou sans éclosion de SRRP déclarée (N = 208) au cours de la même période. Des données sur la distance à l'abattoir le plus proche, la densité porcine, la présence d'un système de filtration d'air ou d'une ferme voisine et les conditions météorologiques ont été recueillies, et un modèle de régression logistique conditionnelle multivariable a été créé pour étudier l'association entre les variables d'intérêt et l'occurrence d'une épidémie de SRRP.La densité porcine, la présence d'un système de filtration de l'air, la présence d'une ferme voisine et le statut du troupeau relativement au SRRP avant l'épidémie ont été associés à l'apparition d'épidémies de SRRP. Les fermes situées dans des zones à forte densité porcine et d'autres fermes porcines à proximité avaient plus de chances de signaler une épidémie que les fermes situées dans des zones à faible densité porcine et les fermes sans voisins. Dans les conditions de cette étude, aucune des variables météorologiques ni la distance à l'abattoir le plus proche n'étaient associées à la survenue d'épidémies de SRRP.(Traduit par Dr Serge Messier).

Antiobesity Effect of a Small Molecule Repressor of RORγ.

The orphan nuclear receptor RORγ is a key regulator for T helper 17 (TH17) cell differentiation, which regulates metabolic and circadian rhythm genes in peripheral tissues. Previously, it was shown that the small molecule inverse agonist of RORγ SR1555 [1-(4-((4'-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-[1,1'-biphenyl]-4-yl)methyl)piperazin-1-yl) ethanone] suppressed TH17 differentiation and stimulated induced T regulatory (iTreg) cells. Here, we show that treatment of cultured pre-adipocyctes with SR1555 represses the expression of RORγ while leading to increased expression of FGF21 and adipoQ. Chronic administration of SR1555 to obese diabetic mice resulted in a modest reduction in food intake accompanied with significant reduction in fat mass, resulting in reduced body weight and improved insulin sensitivity. Analysis ex vivo of treated mice demonstrates that SR1555 induced expression of the thermogenic gene program in fat depots. Further studies in cultured cells showed that SR1555 inhibited activation of hormone-sensitive lipase and increased fatty acid oxidation. Combined, these results suggest that pharmacological repression of RORγ may represent a strategy for treatment of obesity by increasing thermogenesis and fatty acid oxidation, while inhibition of hormone-sensitive lipase activity results in a reduction of serum free fatty acids, leading to improved peripheral insulin sensitivity.

Antiproliferation activity of a small molecule repressor of liver receptor homolog 1.

The orphan nuclear receptor liver receptor homolog 1 (LRH-1; NR5A2) is a potent regulator of cholesterol metabolism and bile acid homeostasis. Recently, LRH-1 has been shown to play an important role in intestinal inflammation and in the progression of estrogen receptor positive and negative breast cancers and pancreatic cancer. Structural studies have revealed that LRH-1 can bind phospholipids and the dietary phospholipid dilauroylphosphatidylcholine activates LRH-1 activity in rodents. Here we characterize the activity of a novel synthetic nonphospholipid small molecule repressor of LRH-1, SR1848 (6-[4-(3-chlorophenyl)piperazin-1-yl]-3-cyclohexyl-1H-pyrimidine-2,4-dione). In cotransfection studies, SR1848 reduced LRH-1-dependent expression of a reporter gene and in cells that endogenously express LRH-1 dose dependently reduced the expression of cyclin-D1 and -E1, resulting in inhibition of cell proliferation. The cellular effects of SR1848 treatment are recapitulated after transfection of cells with small-interfering RNA targeting LRH-1. Immunocytochemistry analysis shows that SR1848 induces rapid translocation of nuclear LRH-1 to the cytoplasm. Combined, these results suggest that SR1848 is a functional repressor of LRH-1 that impacts expression of genes involved in proliferation in LRH-1-expressing cancers. Thus, SR1848 represents a novel chemical scaffold for the development of therapies targeting malignancies driven by LRH-1.

Porcine Deltacoronavirus Occurrence in the United States Breeding Herds since Its Emergence in 2014.

PDCoV, an enveloped RNA virus, causes atrophic enteritis in neonatal piglets, leading to diarrhea, malabsorption, dehydration, and death. The study aims to fill the gap in the current epidemiological information about PDCoV in the U.S. pig population after its emergence in 2014. Data from the Morrison Swine Health Monitoring Project (MSHMP) between January 2015 and December 2023 were analyzed, representing approximately 60% of the U.S. breeding herd. Participating herds report weekly PDCoV health status. In total, 244 PDCoV outbreaks occurred in 186 sites from 22 production systems across 16 states. Case counts peaked during winter, and incidence ranged from 0.44% in 2017 to 4.28% in 2023. For sites that experienced more than one PDCoV outbreak during the study period, the interval between outbreaks was a median of 2.11 years. The South and Midwest regions reported the majority of cases. In 2017, a shift in the spatial distribution of cases from the Midwest to the South was observed. The findings underscore the importance of continued monitoring and strengthened control measures to mitigate the impact of PDCoV in U.S. breeding herds.

Survival of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in the Environment.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases of swine, with losses due to poor reproductive performance and high piglet and growing pig mortality. Transmission of porcine reproductive and respiratory syndrome virus (PRRSV) may occur by both direct and indirect routes; the latter includes exposure to PRRSV-contaminated fomites, aerosols, and arthropod vectors. This review has collected available data on the ex-vivo environmental stability and persistence of PRRSV in an effort to highlight important sources of the virus and to determine the role of environmental conditions on the stability of the virus, especially temperature. The ex-vivo settings include fomites (solid, porous, and liquid fomites), insects, people, and pork meat, as well as the role of environmental conditions on the stability of the virus, especially temperature.

First assessment of weeks-to-negative processing fluids in breeding herds after a Senecavirus A outbreak.

Senecavirus A (SVA) causes vesicular disease in swine and has been responsible for a rampant increase in the yearly number of foreign animal disease investigations conducted in the United States. Diagnostic investigations for SVA are typically performed by sampling animals individually, which is labor-intensive and stressful. Developing an alternative aggregate sampling method would facilitate the detection of this virus at the population level. In a preliminary study, SVA was detected in processing fluids (PF) collected in a breeding herd before and after outbreak detection. The objective of this study was to estimate the average number of weeks PF remain SVA-positive after an SVA outbreak. Ten farrow-to-wean breeding herds volunteered to participate in this studyby longitudinally collecting PF samples after an SVA outbreak was detected and submitting samples for RT-rtPCR testing. The PF samples from the 10 farms were SVA-positive for an average of 11.8 weeks after the outbreak. Here, we show that testing of PF may be a cost-effective method to detect SVA and help halt its spread in SVA-endemic regions.

Active surveillance for influenza A virus among swine, midwestern United States, 2009-2011.

Veterinary diagnostic laboratories identify and characterize influenza A viruses primarily through passive surveillance. However, additional surveillance programs are needed. To meet this need, an active surveillance program was conducted at pig farms throughout the midwestern United States. From June 2009 through December 2011, nasal swab samples were collected monthly from among 540 groups of growing pigs and tested for influenza A virus by real-time reverse transcription PCR. Of 16,170 samples, 746 were positive for influenza A virus; of these, 18.0% were subtype H1N1, 16.0% H1N2, 7.6% H3N2, and 14.5% (H1N1)pdm09. An influenza (H3N2) and (H1N1)pdm09 virus were identified simultaneously in 8 groups. This active influenza A virus surveillance program provided quality data and increased the understanding of the current situation of circulating viruses in the midwestern US pig population.

Time Farms Stay Naïve for Porcine Reproductive and Respiratory Syndrome.

BACKGROUND: Hesitation on eliminating Porcine Reproductive and Respiratory Syndrome virus (PRRSV) from breeding herds exists since it is difficult to predict how long the herd will remain virus-free. We aimed to estimate the time that breeding herds remained virus-free (naïve) after PRRSV elimination was achieved. METHODS: Production systems voluntarily shared their breeding herds' health status weekly between July 2009 and October 2021. PRRSV incidence rate and the total number of days a breeding herd remained virus-free were estimated. RESULTS: A total of 221 (17%) herds reached the naïve status 273 times. The median time sites remained in this status was approximately two years. The overall PRRS incidence rate after sites achieved a naïve status was 23.43 PRRS outbreaks per 100 farm years. CONCLUSION: Estimates obtained here provide insights on how frequently and for how long sites remain naïve, which contribute to informing management practices for PRRS control.

Sow mortality in a pig production system in the midwestern USA: Reasons for removal and factors associated with increased mortality.

BACKGROUND: Sow mortality has become a growing concern in the pig production industry over the past decade. Therefore, we aimed to describe sow mortality and associated factors in a production system in the midwestern USA. METHODS: Mortality records from 2009 to 2018 for four farrow-to-wean farms were described. Environmental, farm- and individual-level factors associated with weekly mortality and individual risk of dying throughout a sow's lifetime were assessed. RESULTS: Deaths occurred at a median of 116 days from last service, or 26 days postpartum. The median parity upon death was two. Overall, the main reasons for death were locomotion (27%) and reproduction (24%). A higher weekly number of deaths was associated with spring (incidence rate ratio [IRR] 1.27, compared to winter). Sows had a higher mortality when they were exposed to at least one porcine reproductive and respiratory syndrome (PRRS) outbreak during their lifetime (IRR 1.55) and when housed in groups (pens) during gestation (IRR 1.32). Conversely, they had  a lower mortality when housed in filtered farms (IRR 0.76), accounting for an interaction term between parity at removal and PRRS outbreak exposure. LIMITATIONS: Issues with data completion and information accuracy were present, and prospective data collection throughout sows' lifetimes is still needed. CONCLUSION: Efforts to reduce infectious diseases within the herd and manage environmental stressors should help reduce mortality.

Unveiling invisible farm-to-farm PRRSV-2 transmission links and routes through transmission tree and network analysis.

The United States (U.S.) swine industry has struggled to control porcine reproductive and respiratory syndrome (PRRS) for decades, yet the causative virus, PRRSV-2, continues to circulate and rapidly diverges into new variants. In the swine industry, the farm is typically the epidemiological unit for monitoring, prevention, and control; breaking transmission among farms is a critical step in containing disease spread. Despite this, our understanding of farm transmission still is inadequate, precluding the development of tailored control strategies. Therefore, our objective was to infer farm-to-farm transmission links, estimate farm-level transmissibility as defined by reproduction numbers (R), and identify associated risk factors for transmission using PRRSV-2 open reading frame 5 (ORF5) gene sequences, animal movement records, and other data from farms in a swine-dense region of the U.S. from 2014 to 2017. Timed phylogenetic and transmission tree analyses were performed on three sets of sequences (n = 206) from 144 farms that represented the three largest genetic variants of the virus in the study area. The length of inferred pig-to-pig infection chains that corresponded to pairs of farms connected via direct animal movement was used as a threshold value for identifying other feasible transmission links between farms; these links were then transformed into farm-to-farm transmission networks and calculated farm-level R-values. The median farm-level R was one (IQR = 1-2), whereas the R value of 28% of farms was more than one. Exponential random graph models were then used to evaluate the influence of farm attributes and/or farm relationships on the occurrence of farm-to-farm transmission links. These models showed that, even though most transmission events cannot be directly explained by animal movement, movement was strongly associated with transmission. This study demonstrates how integrative techniques may improve disease traceability in a data-rich era by providing a clearer picture of regional disease transmission.

Disentangling transport movement patterns of trucks either transporting pigs or while empty within a swine production system before and during the COVID-19 epidemic.

Transport of pigs between sites occurs frequently as part of genetic improvement and age segregation. However, a lack of transport biosecurity could have catastrophic implications if not managed properly as disease spread would be imminent. However, there is a lack of a comprehensive study of vehicle movement trends within swine systems in the Midwest. In this study, we aimed to describe and characterize vehicle movement patterns within one large Midwest swine system representative of modern pig production to understand movement trends and proxies for biosecurity compliance and identify potential risky behaviors that may result in a higher risk for infectious disease spread. Geolocation tracking devices recorded vehicle movements of a subset of trucks and trailers from a production system every 5 min and every time tracks entered a landmark between January 2019 and December 2020, before and during the COVID-19 pandemic. We described 6,213 transport records from 12 vehicles controlled by the company. In total, 114 predefined landmarks were included during the study period, representing 5 categories of farms and truck wash facilities. The results showed that trucks completed the majority (76.4%, 2,111/2,762) of the recorded movements. The seasonal distribution of incoming movements was similar across years (P > 0.05), while the 2019 winter and summer seasons showed higher incoming movements to sow farms than any other season, year, or production type (P < 0.05). More than half of the in-movements recorded occurred within the triad of sow farms, wean-to-market stage, and truck wash facilities. Overall, time spent at each landmark was 9.08% higher in 2020 than in 2019, without seasonal highlights, but with a notably higher time spent at truck wash facilities than any other type of landmark. Network analyses showed high connectivity among farms with identifiable clusters in the network. Furthermore, we observed a decrease in connectivity in 2020 compared with 2019, as indicated by the majority of network parameter values. Further network analysis will be needed to understand its impact on disease spread and control. However, the description and quantification of movement trends reported in this study provide findings that might be the basis for targeting infectious disease surveillance and control.

Mapping the Dynamics of Contemporary PRRSV-2 Evolution and Its Emergence and Spreading Hotspots in the U.S. Using Phylogeography.

The repeated emergence of new genetic variants of PRRSV-2, the virus that causes porcine reproductive and respiratory syndrome (PRRS), reflects its rapid evolution and the failure of previous control efforts. Understanding spatiotemporal heterogeneity in variant emergence and spread is critical for future outbreak prevention. Here, we investigate how the pace of evolution varies across time and space, identify the origins of sub-lineage emergence, and map the patterns of the inter-regional spread of PRRSV-2 Lineage 1 (L1)-the current dominant lineage in the U.S. We performed comparative phylogeographic analyses on subsets of 19,395 viral ORF5 sequences collected across the U.S. and Canada between 1991 and 2021. The discrete trait analysis of multiple spatiotemporally stratified sampled sets (n = 500 each) was used to infer the ancestral geographic region and dispersion of each sub-lineage. The robustness of the results was compared to that of other modeling methods and subsampling strategies. Generally, the spatial spread and population dynamics varied across sub-lineages, time, and space. The Upper Midwest was a main spreading hotspot for multiple sub-lineages, e.g., L1C and L1F, though one of the most recent emergence events (L1A(2)) spread outwards from the east. An understanding of historical patterns of emergence and spread can be used to strategize disease control and the containment of emerging variants.

Assessing the role of sow parity on PRRSv detection by RT-qPCR through weekly processing fluids monitoring in breeding herds.

The use of processing fluids to monitor the breeding herd's porcine reproductive and respiratory syndrome (PRRS) status has gained industry acceptance. However, little is known about PRRS virus RT-qPCR detection dynamics in processing fluids and factors that may contribute to maintain PRRS virus in the herd after an outbreak. This study aimed to describe weekly RT-qPCR processing fluid results in breeding herds after an outbreak and to evaluate the proportion of RT-qPCR positive results among parity groups. Processing tissues of 15 first parity (P1), 15 second parity (P2), and 15 third parity or higher (P3+) litters (parity groups) were collected weekly for between 19 and 46 weeks in nine breeding herds. Processing fluids were aggregated, and RT-qPCR tested by parity group weekly. Additionally, a subset of 743 processing fluid samples of litters that formed 50 parity groups, as previously described, were RT-qPCR tested individually at the litter level. The agreement between RT-qPCR results of processing fluid samples of parity groups (15 litters) and results based on individual litter testing was assessed using overall percent of agreement, Kappa statistic, and McNemar test. The association between RT-qPCR results and the parity group was evaluated using a generalized estimating equations model, after accounting for the effects of sampling week, breeding herd PRRS control strategy (i.e., open to replacements v/s closed) and herd. An autoregressive correlation structure was used to account for the repeated samplings within a herd in time. The overall agreement was 98 %, and Kappa statistic 0.955 (McNemar p = 1.0). Sensitivity of parity group processing fluid samples was estimated at 100 % (95 % CI 89-100 %), while specificity was estimated at 94 % (95 % CI 71-100 %). Although P1 aggregated litters had on average a higher proportion of RT-qPCR positive results from outbreak week 25 onwards, the proportion was not significantly different to the one observed for P2 and P3+ aggregated litters (p > 0.13). Additionally, herds that interrupted gilt entry had lower odds of PRRS RT-qPCR positivity than herds that continued entering gilts (OR = 0.35, 95 % CI 0.16-0.78). PRRS virus persistence in processing fluids was not affected by the sow parity effect in most of the breeding herds studied. No evidence of disagreement between RT-qPCR results of an aggregated sample of 15 litters and those of individual litters was observed. This level of litter aggregation testing strategy may be of particular use at the last stages of an elimination program under low PRRS virus prevalence.

Porcine Reproductive and Respiratory Syndrome (PRRSV2) Viral Diversity within a Farrow-to-Wean Farm Cohort Study.

Describing PRRSV whole-genome viral diversity data over time within the host and within-farm is crucial for a better understanding of viral evolution and its implications. A cohort study was conducted at one naïve farrow-to-wean farm reporting a PRRSV outbreak. All piglets 3-5 days of age (DOA) born to mass-exposed sows through live virus inoculation with the recently introduced wild-type virus two weeks prior were sampled and followed up at 17-19 DOA. Samples from 127 piglets were individually tested for PRRSV by RT-PCR and 100 sequences were generated using Oxford Nanopore Technologies chemistry. Female piglets had significantly higher median Ct values than males (15.5 vs. 13.7, Kruskal-Wallis p < 0.001) at 3-5 DOA. A 52.8% mortality between sampling points was found, and the odds of dying by 17-19 DOA decreased with every one unit increase in Ct values at 3-5 DOA (OR = 0.76, 95% CI 0.61-0.94, p = 0.01). Although the within-pig percent nucleotide identity was overall high (99.7%) between 3-5 DOA and 17-19 DOA samples, ORFs 4 and 5a showed much lower identities (97.26% and 98.53%, respectively). When looking solely at ORF5, 62% of the sequences were identical to the 3-5 DOA consensus. Ten and eight regions showed increased nucleotide and amino acid genetic diversity, respectively, all found throughout ORFs 2a/2b, 4, 5a/5, 6, and 7.

Emergent Molecular Techniques Applied to the Detection of Porcine Viruses.

Molecular diagnostic tests have evolved very rapidly in the field of human health, especially with the arrival of the recent pandemic caused by the SARS-CoV-2 virus. However, the animal sector is constantly neglected, even though accurate detection by molecular tools could represent economic advantages by preventing the spread of viruses. In this regard, the swine industry is of great interest. The main viruses that affect the swine industry are described in this review, including African swine fever virus (ASFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV), and porcine circovirus (PCV), which have been effectively detected by different molecular tools in recent times. Here, we describe the rationale of molecular techniques such as multiplex PCR, isothermal methods (LAMP, NASBA, RPA, and PSR) and novel methods such as CRISPR-Cas and microfluidics platforms. Successful molecular diagnostic developments are presented by highlighting their most important findings. Finally, we describe the barriers that hinder the large-scale development of affordable, accessible, rapid, and easy-to-use molecular diagnostic tests. The evolution of diagnostic techniques is critical to prevent the spread of viruses and the development of viral reservoirs in the swine industry that impact the possible development of future pandemics and the world economy.

Prevalence and risk factors for H1N1 and H3N2 influenza A virus infections in Minnesota turkey premises.

Influenza virus infections can cause respiratory and systemic disease of variable severity and also result in economic losses for the turkey industry. Several subtypes of influenza can infect turkeys, causing diverse clinical signs. Influenza subtypes of swine origin have been diagnosed in turkey premises; however, it is not known how common these infections are nor the likely routes of transmission. We conducted a cross-sectional study to estimate the prevalence of influenza viruses and examine factors associated with infection on Minnesota turkey premises. Results from influenza diagnostic tests and turkey and pig premise location data were obtained from the Minnesota Poultry Testing Laboratory and the Minnesota Board of Animal Health, respectively, from January 2007 to September 2008. Diagnostic data from 356 premises were obtained, of which 17 premises tested positive for antibodies to influenza A virus by agar gel immunodiffusion assay and were confirmed as either H1N1 or H3N2 influenza viruses by hemagglutination and neuraminidase inhibition assays. Influenza infection status was associated with proximity to pig premises and flock size. The latter had a sparing effect on influenza status. This study suggests that H1N1 and H3N2 influenza virus infections of turkey premises in Minnesota are an uncommon event. The route of influenza virus transmission could not be determined; however, the findings suggest that airborne transmission should be considered in future studies.

Modelling and assessing additional transmission routes for porcine reproductive and respiratory syndrome virus: Vehicle movements and feed ingredients.

Accounting for multiple modes of livestock disease dissemination in epidemiological models remains a challenge. We developed and calibrated a mathematical model for transmission of porcine reproductive and respiratory syndrome virus (PRRSV), tailored to fit nine modes of between-farm transmission pathways including: farm-to-farm proximity (local transmission), contact network of batches of pigs transferred between farms (pig movements), re-break probabilities for farms with previous PRRSV outbreaks, with the addition of four different contact networks of transportation vehicles (vehicles to transport pigs to farms, pigs to markets, feed and crew) and the amount of animal by-products within feed ingredients (e.g., animal fat or meat and bone meal). The model was calibrated on weekly PRRSV outbreaks data. We assessed the role of each transmission pathway considering the dynamics of specific types of production (i.e., sow, nursery). Although our results estimated that the networks formed by transportation vehicles were more densely connected than the network of pigs transported between farms, pig movements and farm proximity were the main PRRSV transmission routes regardless of farm types. Among the four vehicle networks, vehicles transporting pigs to farms explained a large proportion of infections, sow = 20.9%; nursery = 15%; and finisher = 20.6%. The animal by-products showed a limited association with PRRSV outbreaks through descriptive analysis, and our model results showed that the contribution of animal fat contributed only 2.5% and meat and bone meal only .03% of the infected sow farms. Our work demonstrated the contribution of multiple routes of PRRSV dissemination, which has not been deeply explored before. It also provides strong evidence to support the need for cautious, measured PRRSV control strategies for transportation vehicles and further research for feed by-products modelling. Finally, this study provides valuable information and opportunities for the swine industry to focus effort on the most relevant modes of PRRSV between-farm transmission.

A discrete-time survival model for porcine epidemic diarrhoea virus.

Since the arrival of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, elimination and control programmes have had partial success. The dynamics of its spread are hard to quantify, though previous work has shown that local transmission and the transfer of pigs within production systems are most associated with the spread of PEDV. Our work relies on the history of PEDV infections in a region of the southeastern United States. This infection data is complemented by farm-level features and extensive industry data on the movement of both pigs and vehicles. We implement a discrete-time survival model and evaluate different approaches to modelling the local-transmission and network effects. We find strong evidence in that the local-transmission and pig-movement effects are associated with the spread of PEDV, even while controlling for seasonality, farm-level features and the possible spread of disease by vehicles. Our fully Bayesian model permits full uncertainty quantification of these effects. Our farm-level out-of-sample predictions have a receiver-operating characteristic area under the curve (AUC) of 0.779 and a precision-recall AUC of 0.097. The quantification of these effects in a comprehensive model allows stakeholders to make more informed decisions about disease prevention efforts.

Modeling between-farm transmission dynamics of porcine epidemic diarrhea virus: Characterizing the dominant transmission routes.

The role of transportation vehicles, pig movement between farms, proximity to infected premises, and feed deliveries has not been fully considered in the dissemination dynamics of porcine epidemic diarrhea virus (PEDV). This has limited efforts for disease prevention, control and elimination restricting the development of risk-based resource allocation to the most relevant modes of PEDV dissemination. Here, we modeled nine pathways of between-farm transmission represented by a contact network of pig movements between sites, farm-to-farm proximity (local transmission), four distinct contact networks of transportation vehicles (trucks that transport pigs from farm-to-farm and farm-to-markets, as well as trucks transporting feed and staff), the volume of animal by-products in feed diets (e.g., fat and meat-and-bone-meal) to reproduce PEDV transmission dynamics. The model was calibrated in space and time with weekly PEDV outbreaks. We investigated the model performance to identify outbreak locations and the contribution of each route in the dissemination of PEDV. The model estimated that 42.7% of the infections in sow farms were related to vehicles transporting feed, 34.5% of infected nurseries were associated with vehicles transporting pigs between farms, and for both farm types, local transmission or pig movements were the next most relevant transmission routes. On the other hand, finishers were most often (31.4%) infected via local transmission, followed by the vehicles transporting feed and pigs between farms. Feed ingredients did not significantly improve model calibration metrics, sensitivity, and specificity; therefore, it was considered to have a negligible contribution in the dissemination of PEDV. The proposed modeling framework provides an evaluation of PEDV transmission dynamics, ranking the most important routes of PEDV dissemination and granting the swine industry valuable information to focus efforts and resources on the most important transmission routes.