LSD1 controls a nuclear checkpoint in Wnt/ß-Catenin signaling to regulate muscle stem cell self-renewal.

The Wnt/ß-Catenin pathway plays a key role in cell fate determination during development and in adult tissue regeneration by stem cells. These processes involve profound gene expression and epigenome remodeling and linking Wnt/ß-Catenin signaling to chromatin modifications has been a challenge over the past decades. Functional studies of the lysine demethylase LSD1/KDM1A converge to indicate that this epigenetic regulator is a key regulator of cell fate, although the extracellular cues controlling LSD1 action remain largely unknown. Here we show that ß-Catenin is a substrate of LSD1. Demethylation by LSD1 prevents ß-Catenin degradation thereby maintaining its nuclear levels. Consistently, in absence of LSD1, ß-Catenin transcriptional activity is reduced in both MuSCs and ESCs. Moreover, inactivation of LSD1 in mouse muscle stem cells and embryonic stem cells shows that LSD1 promotes mitotic spindle orientation via ß-Catenin protein stabilization. Altogether, by inscribing LSD1 and ß-Catenin in the same molecular cascade linking extracellular factors to gene expression, our results provide a mechanistic explanation to the similarity of action of canonical Wnt/ß-Catenin signaling and LSD1 on stem cell fate.

Characterization of Influenza D Virus Reassortant Strain in Swine from Mixed Pig and Beef Farm, France.

Influenza D virus was isolated from pigs on a mixed pig and beef farm in France. Investigation suggested bull-to-pig transmission and spread among pigs. The swine influenza D virus recovered was a reassortant of D/660 and D/OK lineages. Reported mutations in the receptor binding site might be related to swine host adaptation.

Effect of vaccination route (intradermal vs. intramuscular) against porcine reproductive and respiratory syndrome using a modified live vaccine on systemic and mucosal immune response and virus transmission in pigs.

BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is a viral disease with worldwide distribution and an enormous economic impact. To control PRRS virus (PRRSV) infection, modified live vaccines (MLVs) are widely used in the field, mainly administered via an intramuscular (IM) route. Currently, some MLVs are authorized for intradermal (ID) administration, which has many practical and welfare advantages. The objectives of the study were to compare the immune responses (systemic in blood and mucosal in lungs) and vaccine efficacy in preventing challenge strain transmission after IM or needle-free ID immunization of piglets with an MLV against PRRSV-1 (MLV1). METHODS: Groups of sixteen 5-week-old specific pathogen-free piglets were vaccinated with Porcilis PRRS® (MSD) either by an IM (V+ IM) or ID route (V+ ID) using an IDAL®3G device or kept unvaccinated (V-). Four weeks after vaccination, in each group, 8 out of the 16 piglets were challenged intranasally with a PRRSV-1 field strain, and one day later, the inoculated pigs were mingled by direct contact with the remaining 8 sentinel noninoculated pigs to evaluate PRRSV transmission. Thus, after the challenge, each group (V+ IM, V+ ID or V-) included 8 inoculated and 8 contact piglets. During the postvaccination and postchallenge phases, PRRSV replication (RT-PCR), PRRSV-specific antibodies (ELISA IgG and IgA, virus neutralization tests) and cell-mediated immunity (ELISPOT Interferon gamma) were monitored in blood and bronchoalveolar lavages (BALs). RESULTS: Postvaccination, vaccine viremia was lower in V+ ID pigs than in V+ IM pigs, whereas the cell-mediated immune response was detected earlier in the V+ ID group at 2 weeks postvaccination. In the BAL fluid, a very low mucosal immune response (humoral and cellular) was detected. Postchallenge, the vaccine efficacy was similar in inoculated animals with partial control of PRRSV viremia in V+ ID and V+ IM animals. In vaccinated sentinel pigs, vaccination drastically reduced PRRSV transmission with similar estimated transmission rates and latency durations for the V+ IM and V+ ID groups. CONCLUSIONS: Our results show that the tested MLV1 induced a faster cell-mediated immune response after ID immunization two weeks after vaccination but was equally efficacious after IM or ID immunization towards a challenge four weeks later. Considering the practical and welfare benefits of ID vaccination, these data further support the use of this route for PRRS MLVs.

An outbreak of botulism on a pig farm due to the newly described Clostridium botulinum type C.

This study reports a botulism outbreak on a pig farm. Clostridium botulinum type C was detected using PCR. The gene encoding the toxin corresponds to a novel type C neurotoxin recently described in a human botulism outbreak, raising the question of its prevalence in pigs and the related risks to humans.

Virus persistence in pig herds led to successive reassortment events between swine and human influenza A viruses, resulting in the emergence of a novel triple-reassortant swine influenza virus.

This report describes the detection of a triple reassortant swine influenza A virus of H1avN2 subtype. It evolved from an avian-like swine H1avN1 that first acquired the N2 segment from a seasonal H3N2, then the M segment from a 2009 pandemic H1N1, in two reassortments estimated to have occurred 10 years apart. This study illustrates how recurrent influenza infections increase the co-infection risk and facilitate evolutionary jumps by successive gene exchanges. It recalls the importance of appropriate biosecurity measures inside holdings to limit virus persistence and interspecies transmissions, which both contribute to the emergence of new potentially zoonotic viruses.

Evidence of porcine epidemic diarrhea virus (PEDV) shedding in semen from infected specific pathogen-free boars.

In 2013, PED emerged for the first time in the United States (US). The porcine epidemic diarrhea virus (PEDV) spread quickly throughout North America. Infection with PEDV causes watery diarrhea and up to 100% mortality in piglets, particularly for highly pathogenic non-InDel strains circulating in the US. PEDV is mainly transmitted by the fecal-oral route. Transmission via the venereal route has been suspected but not previously investigated. The aim of the study was to determine if PEDV could be detected in semen from infected specific pathogen-free (SPF) boars inoculated with a PEDV US non-InDel strain suggesting venereal transmission may occur. Two boars orally inoculated with PEDV showed clinical signs and virus shedding in feces. Transient presence of the PEDV genome was detected by RT-qPCR in the seminal (5.06 × 102 to 2.44 × 103 genomic copies/mL) and sperm-rich fraction of semen (5.64 × 102 to 3.40 × 104 genomic copies/mL) and a longer duration of viral shedding was observed in the sperm-rich fraction. The evidence of PEDV shedding in semen raises new questions in term of disease spread within the pig population with the use of potentially contaminated semen.

From the epidemiology of hepatitis E virus (HEV) within the swine reservoir to public health risk mitigation strategies: a comprehensive review.

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans, an emerging zoonosis mainly transmitted via food in developed countries and for which domestic pigs are recognised as the main reservoir. It therefore appears important to understand the features and drivers of HEV infection dynamics on pig farms in order to implement HEV surveillance programmes and to assess and manage public health risks. The authors have reviewed the international scientific literature on the epidemiological characteristics of HEV in swine populations. Although prevalence estimates differed greatly from one study to another, all consistently reported high variability between farms, suggesting the existence of multifactorial conditions related to infection and within-farm transmission of the virus. Longitudinal studies and experimental trials have provided estimates of epidemiological parameters governing the transmission process (e.g. age at infection, transmission parameters, shedding period duration or lag time before the onset of an immune response). Farming practices, passive immunity and co-infection with immunosuppressive agents were identified as the main factors influencing HEV infection dynamics, but further investigations are needed to clarify the different HEV infection patterns observed in pig herds as well as HEV transmission between farms. Relevant surveillance programmes and control measures from farm to fork also have to be fostered to reduce the prevalence of contaminated pork products entering the food chain.

Control of endemic swine flu persistence in farrow-to-finish pig farms: a stochastic metapopulation modeling assessment.

Swine influenza viruses (swIAVs) are known to persist endemically in farrow-to-finish pig farms, leading to repeated swine flu outbreaks in successive batches of pigs at a similar age (mostly around 8 weeks of age). This persistence in European swine herds involves swIAVs from European lineages including H1avN1, H1huN2, H3N2, the 2009 H1N1 pandemic virus and their reassortants. The specific population dynamics of farrow-to-finish pig farms, the immune status of the animals at infection-time, the co-circulation of distinct subtypes leading to consecutive or concomitant infections have been evidenced as factors favouring swIAV persistence within herds. We developed a stochastic metapopulation model representing the co-circulation of two distinct swIAVs within a typical farrow-to-finish pig herd to evaluate the risk of reassortant viruses generation due to co-infection events. Control strategies related to herd management and/or vaccination schemes (batch-to-batch or mass vaccination of the sow herd and vaccination of growing pigs) were implemented to assess their relative efficacy regarding viral persistence. The overall probability of a co-infection event for France, possibly leading to reassortment, was evaluated to 16.8%. The export of consecutive piglets batches was identified as the most efficient measure facilitating swIAV infection fade-out. Although some vaccination schemes (batch-to-batch vaccination) had a beneficial effect in breeding sows by reducing the persistence of swIAVs within this subpopulation, none of vaccination strategies achieved swIAVs fade-out within the entire farrow-to-finish pig herd.

Dynamic changes in bronchoalveolar macrophages and cytokines during infection of pigs with a highly or low pathogenic genotype 1 PRRSV strain.

Porcine reproductive and respiratory syndrome virus (PRRSV) replicates primarily in pulmonary alveolar macrophages (PAMs) and the resulting lung damage is influenced by strain virulence. To better understand the pathogenesis of PRRSV infection, we performed a longitudinal study of the PAM population and lung cytokines in specific pathogen-free pigs infected either with the highly pathogenic Lena strain or with the low pathogenic Finistere strain in comparison to uninfected pigs. Bronchoalveolar lavage fluid (BALF) and blood were collected to follow viral, cellular and cytokine changes in lung with respect to clinical signs and systemic events. Compared to Finistere-infected pigs, Lena-infected pigs exhibited more severe clinical signs and 10- to 100-fold higher viral loads in BALF and blood. Similarly, they showed an earlier drop in BALF cell viability and phagocytic activity along with a decrease in the macrophage count. From 8 to 15 days post-infection (dpi), monocytes increased both in BALF and blood from Lena-infected pigs. BALF and blood showed contrasting cytokine patterns, with low increase of IFN-α and TNF-α levels and high increase for IL-1α and IL-8 in BALF after Lena-infection. In contrast, in the blood, the increase was marked for IFN-α and TNF-α but limited for IL-1ß and IL-8. Down-regulation of PAM functions combined with inflammatory cytokine and monocyte recruitment may promote lung pathogenesis and virus replication in PRRSV infections with the highly pathogenic Lena strain. In contrast, the low pathogenic Finistere strain showed prolonged viral replication in lung, possibly related to the weak IFN-γ response.

Apport de la modélisation à l'étude de la dynamique de transmission de virus dans des populations : application aux virus influenza de type A en élevage porcin.

Modelling in epidemiology can be used for parameter estimation, understanding infectious process or control strategies evaluation, and is based on a mathematical model representing the infectious process derived from the SIR model (susceptible-infectious-removed). This model is further adapted to the disease under study with additional health statuses to represent more precisely the characteristics of the infectious agent and to couple the infection dynamics with the population dynamics of the studied system. This adaptation is documented by descriptive and analytic epidemiological studies to obtain a model representing the infectious process in a realistic way. Risk assessment and/or evaluation of control strategies can be proposed by the model simulation. The use of a modelling approach to understand the determinisms of a viral infectious process within a structured animal population is further illustrated by the example of swine influenza A viruses persistence in pig farms. The model set up to this aim is used to better understand the mechanisms related to viruses persistence within the herd and identify potential control measures that could be applied in farm conditions.

High Proportion of Asymptomatic Infections in an Outbreak of Hepatitis E Associated With a Spit-Roasted Piglet, France, 2013.

BACKGROUND: On 11 December 2013, 3 clustered cases of hepatitis E were reported on a French coastal island. Individuals had taken part in a wedding meal that included a spit-roasted piglet. The piglet had been stuffed with a raw stuffing partly made from the liver. Investigations were carried out to identify the vehicle of contamination and evaluate the dispersion of the hepatitis E virus (HEV) in the environment. METHODS: A questionnaire was administered to 98 wedding participants who were asked to give a blood sample. Cases were identified by reverse transcription-polymerase chain reaction and serological tests. A retrospective cohort study was conducted among 38 blood-sampled participants after the exclusion of 14 participants with evidence of past HEV infection. Relative risks (RR) and 95% confidence intervals were calculated based on food consumed at the wedding meal using univariate and multivariable Poisson regressions. Phylogenetic analyses were performed to compare the clinical HEV strains. Strains were detected in the liquid manure sampled at the farm where the piglet was born and in the untreated island wastewater. RESULTS: Seventeen cases were identified, 70.6% were asymptomatic. Acute HEV infection was independently associated with piglet stuffing consumption (RR = 1.69 [1.04-2.73], P = .03). Of clinical strains from the index cases, veterinary and environmental HEV strains were identical. CONCLUSIONS: Our investigation attributed this large HEV outbreak to the consumption of an undercooked pig liver-based stuffing. After infection, the cases became a temporary reservoir for HEV, which was detected in the island's untreated wastewater.

Maternally-derived antibodies do not prevent transmission of swine influenza A virus between pigs.

A transmission experiment involving 5-week-old specific-pathogen-free (SPF) piglets, with (MDA(+)) or without maternally-derived antibodies (MDA(-)), was carried out to evaluate the impact of passive immunity on the transmission of a swine influenza A virus (swIAV). In each group (MDA(+)/MDA(-)), 2 seeders were placed with 4 piglets in direct contact and 5 in indirect contact (3 replicates per group). Serological kinetics (ELISA) and individual viral shedding (RT-PCR) were monitored for 28 days after infection. MDA waning was estimated using a nonlinear mixed-effects model and survival analysis. Differential transmission rates were estimated depending on the piglets' initial serological status and contact structure (direct contact with pen-mates or indirect airborne contact). The time to MDA waning was 71.3 [52.8-92.1] days on average. The airborne transmission rate was 1.41 [0.64-2.63] per day. The compared shedding pattern between groups showed that MDA(+) piglets had mainly a reduced susceptibility to infection compared to MDA(-) piglets. The resulting reproduction number estimated in MDA(+) piglets (5.8 [1.4-18.9]), although 3 times lower than in MDA(-) piglets (14.8 [6.4-27.1]), was significantly higher than 1. Such an efficient and extended spread of swIAV at the population scale in the presence of MDAs could contribute to swIAV persistence on farms, given the fact that the period when transmission is expected to be impacted by the presence of MDAs can last up to 10 weeks.

Porcine epidemic diarrhea: the return of an old disease.

In 2013, 40 years after the first case of porcine epidemic diarrhea (PED) in Europe, PED has emerged in USA that was free of that disease before. The coronavirus, etiological agent of the disease and called PEDV, spread quickly within all the country and in America leading to a significant impact on the pig production. Two types of viral strains have been identified: highly virulent "non-InDel" strains and "InDel" strains because of insertion/deletion in the S gene and associated with less severe clinical cases. PEDV infection causes watery diarrhea and a mortality of up to 100 % in piglets. This review sums up the current knowledge on the virus, its transmission and its worldwide molecular epidemiology, on the physiopathology of the disease and the control measures.

Hepatitis E virus chronic infection of swine co-infected with Porcine Reproductive and Respiratory Syndrome Virus.

In developed countries, most of hepatitis E human cases are of zoonotic origin. Swine is a major hepatitis E virus (HEV) reservoir and foodborne transmissions after pork product consumption have been described. The risk for HEV-containing pig livers at slaughter time is related to the age at infection and to the virus shedding duration. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a virus that impairs the immune response; it is highly prevalent in pig production areas and suspected to influence HEV infection dynamics. The impact of PRRSV on the features of HEV infections was studied through an experimental HEV/PRRSV co-infection of specific-pathogen-free (SPF) pigs. The follow-up of the co-infected animals showed that HEV shedding was delayed by a factor of 1.9 in co-infected pigs compared to HEV-only infected pigs and specific immune response was delayed by a factor of 1.6. HEV shedding was significantly increased with co-infection and dramatically extended (48.6 versus 9.7 days for HEV only). The long-term HEV shedding was significantly correlated with the delayed humoral response in co-infected pigs. Direct transmission rate was estimated to be 4.7 times higher in case of co-infection than in HEV only infected pigs (0.70 and 0.15 per day respectively). HEV infection susceptibility was increased by a factor of 3.3, showing the major impact of PRRSV infection on HEV dynamics. Finally, HEV/PRRSV co-infection - frequently observed in pig herds - may lead to chronic HEV infection which may dramatically increase the risk of pig livers containing HEV at slaughter time.

La pluralité de l'hépatite E : des formes cliniques aux souches animales.

The concept of zoonotic viral hepatitis E has emerged a few years ago in countries where sporadic cases of hepatitis E were not associated with travel in geographical areas where the virus is endemic (tropical or subtropical regions) . Improved diagnostic methods and the awareness of clinicians helped to better assess the impact of infection by hepatitis E virus (HEV) and identify new related syndromes. Similarly, the description of chronic forms of hepatitis E in immunocompromised patients raises the question of the treatment and prevention of this disease. Recent advances in the identification of animal reservoirs of HEV have confirmed that the strains circulating in domestic and wild pigs are genetically close to strains identified in indigenous cases. Characterization of HEV infection in swine herds has identified risk factors associated to the virus spreading. In addition, the identification of HEV in the food chain or products containing pork has shown that it is a food-borne zoonosis. The arrival of recent technologies to identify new agents helped expand the family of HEV related viruses and identify potential new animal reservoirs.

Dynamic of swine influenza virus infection in weaned piglets in five enzootically infected herds in Germany, a cohort study.

BACKGROUND: Within the last decades industrial swine herds in Europe grown significantly, creating an optimized reservoir for swine influenza A viruses (swIAV) to become enzootic, particularly in piglet producing herds among newborn, partly immunologically naïve piglets. To date, the only specific control measure to protect piglets from swIAV is the vaccination of sows, which provides passive immunity through maternally derived antibodies in colostrum of vaccinated sows. Interruption of infection chains through management practices have had limited success. This study focused on weaned piglets in five enzootically swIAV infected swine herds in North-West and North-East Germany and aimed to better understand swIAV infection patterns to improve piglet protection and reduce zoonotic risks. Participating farms fulfilled the following inclusion criteria: sow herd with ≥ 400 sows (actual size 600-1850 sows), piglets not vaccinated against influenza A virus and a history of recurrent respiratory problems associated with continuing influenza A virus infection. Influenza vaccination was performed in all sow herds, except for one, which discontinued vaccination during the study. RESULTS: First swIAV detections in weaned piglets occurred at 4 weeks of age in the nursery and continued to be detected in piglets up to 10 weeks of age showing enzootic swIAV infections in all herds over the entire nursery period. This included simultaneous circulation of two subtypes in a herd and co-infection with two subtypes in individual animals. Evidence for prolonged (at least 13 days) shedding was obtained in one piglet based on two consecutive swIAV positive samplings. Possible re-infection was suspected in twelve piglets based on three samplings, the second of which was swIAV negative in contrast to the first and third sampling which were swIAV positive. However, swIAV was not detected in nasal swabs from either suckling piglets or sows in the first week after farrowing. CONCLUSIONS: Predominantly, weaned piglets were infected. There was no evidence of transmission from sow to piglet based on swIAV negative nasal swabs from sows and suckling piglets. Prolonged virus shedding by individual piglets as well as the co-circulation of different swIAV subtypes in a group or even individuals emphasize the potential of swIAV to increase genetic (and potentially phenotypic) variation and the need to continue close monitoring. Understanding the dynamics of swIAV infections in enzootically infected herds has the overall goal of improving protection to reduce economic losses due to swIAV-related disease and consequently to advance animal health and well-being.

Bayesian estimation of the sensitivity and specificity of coprological and serological diagnostic tests for the detection of Ascaris suum infection on pig farms.

Coprological and serological diagnostic tests were compared to define the status of a pig farm with regard to Ascaris suum. On each of the 100 farms in France visited for the study, 10 blood samples were taken from pigs at the end of fattening (at least 22 weeks old) and 20 to 30 faecal samples were taken, depending on the category of animals present on the farm (10 sows, 10 piglets aged 10 to 12 weeks and 10 pigs at the end of fattening, aged at least 22 weeks). A SERASCA® ELISA test (Laboratory of Parasitology, Ghent University) was performed on each blood sample (cut-off 0.5) and a coprological analysis on each faecal sample. A Bayesian approach was used to estimate the sensitivity and specificity of the coprological and serological tests. A farm was considered positive if at least one A. suum egg was observed in the faecal samples. With regard to the serological test, various hypotheses were tested in order to define the number of seropositive animals required to consider a farm positive for A. suum. The coprological test has very good specificity in the search for A. suum, whether 20 or 30 samples are taken per farm. However, even with an increase in the number of samples, the sensitivity of this diagnostic approach is very low (less than 30%). On the other hand, the serological diagnostic method, which consists of taking blood samples from 10 animals at the end of fattening, has good sensitivity and seems better suited to defining the status of a farm with regard to A. suum, provided that a farm is considered seropositive only if two out of 10 samples are positive.

Direct contact and environmental contaminations are responsible for HEV transmission in pigs.

Hepatitis E virus (HEV) can cause enterically-transmitted hepatitis in humans. The zoonotic nature of Hepatitis E infections has been established in industrialized areas and domestic pigs are considered as the main reservoir. The dynamics of transmission in pig herds therefore needs to be understood to reduce the prevalence of viremic pigs at slaughter and prevent contaminated pig products from entering the food chain. An experimental trial was carried out to study the main characteristics of HEV transmission between orally inoculated pigs and naïve animals. A mathematical model was used to investigate three transmission routes, namely direct contact between pigs and two environmental components to represent within-and between-group oro-fecal transmission. A large inter-individual variability was observed in response to infection with an average latent period lasting 6.9 days (5.8; 7.9) in inoculated animals and an average infectious period of 9.7 days (8.2; 11.2). Our results show that direct transmission alone, with a partial reproduction number of 1.41 (0.21; 3.02), can be considered as a factor of persistence of infection within a population. However, the quantity of virus present in the environment was found to play an essential role in the transmission process strongly influencing the probability of infection with a within pen transmission rate estimated to 2 · 10(-6)g ge(-1)d(-1)(1 · 10(-7); 7 · 10(-6)). Between-pen environmental transmission occurred to a lesser extent (transmission rate: 7 · 10(-8)g ge(-1) d(-1)(5 · 10(-9); 3 · 10(-7)) but could further generate a within-group process. The combination of these transmission routes could explain the persistence and high prevalence of HEV in pig populations.

Dynamics of influenza A virus infections in permanently infected pig farms: evidence of recurrent infections, circulation of several swine influenza viruses and reassortment events.

Concomitant infections by different influenza A virus subtypes within pig farms increase the risk of new reassortant virus emergence. The aims of this study were to characterize the epidemiology of recurrent swine influenza virus infections and identify their main determinants. A follow-up study was carried out in 3 selected farms known to be affected by repeated influenza infections. Three batches of pigs were followed within each farm from birth to slaughter through a representative sample of 40 piglets per batch. Piglets were monitored individually on a monthly basis for serology and clinical parameters. When a flu outbreak occurred, daily virological and clinical investigations were carried out for two weeks. Influenza outbreaks, confirmed by influenza A virus detection, were reported at least once in each batch. These outbreaks occurred at a constant age within farms and were correlated with an increased frequency of sneezing and coughing fits. H1N1 and H1N2 viruses from European enzootic subtypes and reassortants between viruses from these lineages were consecutively and sometimes simultaneously identified depending on the batch, suggesting virus co-circulations at the farm, batch and sometimes individual levels. The estimated reproduction ratio R of influenza outbreaks ranged between 2.5 [1.9-2.9] and 6.9 [4.1-10.5] according to the age at infection-time and serological status of infected piglets. Duration of shedding was influenced by the age at infection time, the serological status of the dam and mingling practices. An impaired humoral response was identified in piglets infected at a time when they still presented maternally-derived antibodies.

Mathematical modeling at the livestock-wildlife interface: scoping review of drivers of disease transmission between species.

Modeling of infectious diseases at the livestock-wildlife interface is a unique subset of mathematical modeling with many innate challenges. To ascertain the characteristics of the models used in these scenarios, a scoping review of the scientific literature was conducted. Fifty-six studies qualified for inclusion. Only 14 diseases at this interface have benefited from the utility of mathematical modeling, despite a far greater number of shared diseases. The most represented species combinations were cattle and badgers (for bovine tuberculosis, 14), and pigs and wild boar [for African (8) and classical (3) swine fever, and foot-and-mouth and disease (1)]. Assessing control strategies was the overwhelming primary research objective (27), with most studies examining control strategies applied to wildlife hosts and the effect on domestic hosts (10) or both wild and domestic hosts (5). In spatially-explicit models, while livestock species can often be represented through explicit and identifiable location data (such as farm, herd, or pasture locations), wildlife locations are often inferred using habitat suitability as a proxy. Though there are innate assumptions that may not be fully accurate when using habitat suitability to represent wildlife presence, especially for wildlife the parsimony principle plays a large role in modeling diseases at this interface, where parameters are difficult to document or require a high level of data for inference. Explaining observed transmission dynamics was another common model objective, though the relative contribution of involved species to epizootic propagation was only ascertained in a few models. More direct evidence of disease spill-over, as can be obtained through genomic approaches based on pathogen sequences, could be a useful complement to further inform such modeling. As computational and programmatic capabilities advance, the resolution of the models and data used in these models will likely be able to increase as well, with a potential goal being the linking of modern complex ecological models with the depth of dynamics responsible for pathogen transmission. Controlling diseases at this interface is a critical step toward improving both livestock and wildlife health, and mechanistic models are becoming increasingly used to explore the strategies needed to confront these diseases.