Bovine Herpes Virus Type 1 (BoHV-1) seroprevalence, risk factor and Bovine Viral Diarrhoea (BVD) co-infection analysis from Ireland.

Surveillance of endemic pathogens is essential for disease control, providing an evidence base for policy and advice. Bovine Herpes Virus Type 1 (BoHV-1), the causative agent of Infectious Bovine Rhinotracheitis (IBR), has been found to have high seroprevalence within the Irish cattle population. The aim of the present study was to establish seroprevalence levels for culled cattle in Ireland aged < 30 months and to establish whether BVD exposure and other factors was associated with BoHV-1 exposure. We employed random effects logit models coupled with repeated bootstrap sampling to provide robust estimates. The final dataset contained results for 5273 animals tested over two study years, 2018 and 2020. The animal-level seroprevalence of BoHV-1 was 21.43% (1130/5273; 95%CI: 20.32-22.53%). Univariable analysis suggested that BoHV-1 seropositivity risk was associated with BVDV serodiagnosis status, age, sex, year sampled, herd type, herd-size, and metrics of movement into the herd. Final random-effects multivariable models suggested increased risk associated with increasing herd size of the last herd, movements made by animals during the previous year, and the year the animal was sampled. Despite BVDV status and sex being retained in the final model, repeated bootstrap sampling of the regression model to estimate biased-corrected 95%CI suggested that these associations were not robust. The overall apparent prevalence of BoHV-1 exposure for culled cattle in Ireland declined in 2020 relative to 2018 (from 23.32 to 17.61%). Herd-size and the movement of animals were found to be important factors associated with animal-level risk, but there was less statistical support for sex-based or BVDV status associations.

Relationship between ambient temperature at sampling and the interferon gamma test result for bovine tuberculosis in cattle.

Bovine tuberculosis (bTB) is a disease of significant economic and zoonotic importance, therefore, optimising tests for the identification of Mycobacterium bovis infected cattle is essential. The Interferon Gamma (IFN-γ) Release Assay (IGRA) can diagnose M. bovis infected cattle at an early stage, is easy to perform and can be used alongside skin tests for confirmatory purposes or to increase diagnostic sensitivity. It is known that IGRA performance is sensitive to environmental conditions under which samples are taken and transported. In this study, the association between the ambient temperature on the day of bleeding and the subsequent IGRA result for bTB was quantified using field samples from Northern Ireland (NI). Results of 106,434 IGRA results (2013-2018) were associated with temperature data extracted from weather stations near tested cattle herds. Model dependent variables were the levels of IFN-γ triggered by avian purified protein derivative (PPDa), M. bovis PPD (PPDb), their difference (PPD(b-a)) as well as the final binary outcome (positive or negative for M. bovis infection). IFN-γ levels after both PPDa and PPDb stimulation were lowest at the extremes of the temperature distribution for NI. The highest IGRA positive probability (above 6%) was found on days with moderate maximum temperatures (6-16 °C) or moderate minimum temperatures (4-7 °C). Adjustment for covariates did not lead to major changes in the model estimates. These data suggest that IGRA performance can be affected when samples are taken at high or low temperatures. Whilst it is difficult to exclude physiological factors, the data nonetheless supports the temperature control of samples from bleeding through to laboratory to help mitigate post-collection confounders.

Is moving from targeted culling to BCG-vaccination of badgers (Meles meles) associated with an unacceptable increased incidence of cattle herd tuberculosis in the Republic of Ireland? A practical non-inferiority wildlife intervention study in the Republic of Ireland (2011-2017).

Bovine tuberculosis (BTB) remains as a costly disease of cattle-herds in the Republic of Ireland (ROI). This persistence is partially attributable to the presence of M. bovis infection in a wildlife reservoir, the European badger (Meles meles). Thus, both area-wide and limited-area targeted-badger-culling have been part of the ROI-BTB control/eradication program to help reduce the future incidence of a cattle-herd BTB breakdown (i.e. a "new herd-level occurrence of BTB"). However, neither badger-culling practice can be sustained as a major component in the ongoing BTB eradication program in the ROI. Vaccination of badgers with Bacille Calmette-Guérin (BCG) has been proposed as an alternative to badger culling. Thus, in 2011, a five-year non-inferiority study was implemented in seven counties in the ROI. This study was designed to compare and contrast the cattle-herd-BTB-incidence in areas where intramuscular badger vaccination would be implemented versus the cattle-herd-BTB-incidence in the remaining area of the same county where targeted-badger-culling was maintained as the standard treatment response to probable badger-sourced BTB breakdowns. Our outcome of interest was a new cattle-herd-BTB-episode (breakdown) with a total of >2 standard skin-test (SICTT) reactors detected during the episode. Treatments (badger vaccination or targeted badger culling) were cluster allocated based on where the majority of the herd owner's land was located. To assess the impact of the two treatments, we compared the incidence-risk, of our defined outcome, for cattle herds in the area under vaccination to the outcome incidence-risk for cattle herds in the remainder of the same county after 4 and 5 years of having implemented badger vaccination. A random-effects logit model with adjustment for clustering by treatment, and statistical control of herd-type, herd-size and five-year prior-BTB-episode history was used for our analyses. Although not included in the logistic model, a relative badger density metric based on the annual number of badgers captured-per-sett-night of capturing effort was developed for each treatment area; this metric indicated that relative badger density was approximately 40 % higher in vaccination areas than in the targeted badger-culling areas during our study. Overall, our study results indicated that vaccination was not inferior to targeted badger-culling in four counties and badger vaccination was deemed to produce ambivalent results in one (County Cork North) of the seven study sites in the ROI. A post-study investigation, in County Galway, where vaccination was deemed inferior to target culling, revealed that widespread purchases of cattle from a nearby cattle mart, by herd owners in the vaccination-area, was associated with the increased herd and vaccination-area risk of BTB. No single "biasing hypothesis" was evident for the apparent vaccine inferiority in the second study site (County Monaghan) where vaccination was deemed inferior to targeted culling; hence no further investigations were conducted.

Variation in Mycobacterium bovis genetic richness suggests that inwards cattle movements are a more important source of infection in beef herds than in dairy herds.

BACKGROUND: We used genetic Multi-Locus VNTR Analysis (MLVA) data gathered from surveillance efforts to better understand the ongoing bovine tuberculosis (bTB) epidemic in Northern Irish cattle herds. We modelled the factors associated with Mycobacterium bovis MLVA genotype richness at three analytical scales; breakdown level, herd level, and patch level, and compared the results between dairy and non-dairy production types. RESULTS: In 83% of breakdowns and in 63% of herds, a single MLVA genotype was isolated. Five or more MLVA genotypes were found in less than 3 % of herds. Herd size and the total number of reactors were important explanatory variables, suggesting that increasing MLVA genotype richness was positively related to increases in the number of host animals. Despite their smaller relative size, however, the highest MLVA genotype richness values were observed in non-dairy herds. Increasing inwards cattle movements were important positive predictors of MLVA genotype richness, but mainly in non-dairy settings. CONCLUSIONS: The principal finding is that low MLVA genotype richness indicates that small-scale epidemics, e.g. wildlife, contiguous farms, and within-herd recrudescence, are important routes of M. bovis infection in cattle herds. We hypothesise that these mechanisms will maintain, but may not explicitly increase, MLVA genotype richness. The presence of elevated MLVA richness is relatively rare and likely indicates beef fattening enterprises, which purchase cattle from over long distances. Cattle movements were furthermore an important predictor of MLVA genotype richness in non-dairy herds, but not in dairy herds; this may represent reduced cattle purchasing levels in dairy enterprises, compared to beef. These observations allude to the relative contribution of different routes of bTB infection between production types; we posit that infection associated with local factors may be more evident in dairy herds than beef herds, however in beef herds, inwards movements offer additional opportunities for introducing M. bovis into the herd.

Corrigendum: Bovine Tuberculosis in Britain and Ireland - A Perfect Storm? the Confluence of Potential Ecological and Epidemiological Impediments to Controlling a Chronic Infectious Disease.

[This corrects the article DOI: 10.3389/fvets.2018.00109.].

Spatiotemporal analysis of prolonged and recurrent bovine tuberculosis breakdowns in Northern Irish cattle herds reveals a new infection hotspot.

Despite a state-led eradication programme, bovine tuberculosis (bTB) remains endemic in Northern Ireland (NI). Of particular concern are "chronic" prolonged and recurrent bTB breakdowns, which represent significant financial and administrative burdens. However, little is known regarding the spatiotemporal distribution of chronic breakdowns in NI. We therefore analysed both the spatial and spatiotemporal distributions of chronic bTB breakdowns between 2004 and 2014. Significantly positive values for Moran's Index of spatial autocorrelation were found, and Local Moran's I clustering was employed to assess for spatial associations in the number and prevalence of chronic bTB breakdowns across NI. Additional spatio-temporal analysis using SaTScan showed that the burden of chronic bTB infection tends to be found where bTB levels are already high. However, a novel hotspot was revealed wherein the prevalence of chronic breakdowns was higher than expected; this should be the subject of follow-up surveillance.

Bayesian latent class estimation of sensitivity and specificity parameters of diagnostic tests for bovine tuberculosis in chronically infected herds in Northern Ireland.

In the European Union, the recommended ante-mortem diagnostic methods for bovine tuberculosis (bTB) include the single intradermal cervical comparative tuberculin (SICCT) test and the interferon-gamma (IFN-γ) test as an ancillary test. The SICCT test has a moderate sensitivity (Se) and high specificity (Sp), while the IFN-γ test has good Se, but a lower Sp than the SICCT test. A retrospective Bayesian latent class analysis was conducted on 71,185 cattle from 806 herds chronically infected with bTB distributed across Northern Ireland (NI) to estimate the Se and Sp of the common ante-mortem tests and meat inspection. Analyses were also performed on data stratified by farming type and herd location to explore possible differences in test performance given the heterogeneity in the population. The mean estimates in chronically infected herds were: (1) 'standard' SICCT: Se 40.5-57.7%, Sp 96.3-99.7%; (2) 'severe' SICCT: Se 49.0%-60.6%, Sp 94.4-99.4%; (3) IFN-γ(bovine-avian) using a NI optical density (OD) cut-off difference of 0.05: IFN-γ(B-A)NI: Se 85.8-93.0%, Sp 75.6-96.2%; (4) IFN-γ(bovine-avian) using a standard 'commercial' OD cut-off difference of 0.1: IFN-γ(B-A)0.1: Se 83.1-92.1%, Sp 83.1-97.3%; and (5) meat inspection: Se 49.0-57.1% Se, Sp 99.1-100%. Se estimates were lower in cattle from dairy farms than from beef farms. There were no notable differences in estimates by location of herds. Certain population characteristics, such as production type, might influence the ability of bTB tests to disclose truly infected cases.

Spatial and risk factor analysis of bovine viral diarrhoea (BVD) virus after the first-year compulsory phase of BVD eradication programme in Northern Ireland.

Bovine viral diarrhoea virus (BVDV) causes bovine viral diarrhoea (BVD), which is a contagious pathogen that can have a significant economic impact on cattle industries. In Northern Ireland (NI), the compulsory phase of a BVD eradication programme was implemented in 2016. The aim of this retrospective population based study was to utilize herd-level data after the first year of the compulsory phase (March 2016-March 2017) to determine the spatial distribution and variation of BVDV, to identify clusters of infection, and to quantify some risk factors associated with BVD in NI. Global spatial clustering (autocorrelation) and local spatial hot-spot analyses were used to specify the clustering areas (hot- and cold-spot). A suite of multivariable logistic analyses was performed to estimate the associations of spatial and non-spatial factors (relating to herd characteristics) with the risk of being a BVDV positive herd. Final models were compared by evaluating the model fit and the ability to account for spatial autocorrelation in the study area. There were 17,186 herds included in the analysis. The herd-level prevalence of BVDV was 11.31%. Significant spatial clustering of BVDV positive herds was presented in the central region of NI. A mixed effects logistic model, with a spatial random effect term, was considered the best model. The final model showed that a positive BVDV status during the voluntary phase prior to the compulsory phase started (OR = 2.25; CI 95% = 1.85-2.73), larger herd size (OR = 6.19; CI 95% = 5.22-7.34 for herd size > 100 animals) and a larger number of positive nearest neighbours within 4 km radius (OR = 1.24; CI 95% = 1.05-1.47 for 8-9 neighbours and OR = 1.41; CI 95% = 1.20-1.65 for 10-12 neighbours) were significantly related to the risk of a herd being tested positive for BVDV. The clear spatial pattern from the local spatial clustering analyses could be used for targeted surveillance and control measures by focusing on the central region of NI.

Bovine Tuberculosis in Britain and Ireland - A Perfect Storm? the Confluence of Potential Ecological and Epidemiological Impediments to Controlling a Chronic Infectious Disease.

Successful eradication schemes for bovine tuberculosis (bTB) have been implemented in a number of European and other countries over the last 50 years. However, the islands of Britain and Ireland remain a significant aberration to this trend, with the recent exception of Scotland. Why have eradication schemes failed within these countries, while apparently similar programs have been successful elsewhere? While significant socio-economic and political factors have been discussed elsewhere as key determinants of disease eradication, here we review some of the potential ecological and epidemiological constraints that are present in these islands relative to other parts of Europe. We argue that the convergence of these potential factors may interact additively to diminish the potential of the present control programs to achieve eradication. Issues identified include heterogeneity of diagnostic testing approaches, the presence of an abundant wildlife reservoir of infection and the challenge of sustainably managing this risk effectively; the nature, size, density and network structure of cattle farming; potential effects of Mycobacterium bovis strain heterogeneity on disease transmission dynamics; possible impacts of concurrent endemic infections on the disclosure of truly infected animals; climatological differences and change coupled with environmental contamination. We further argue that control and eradication of this complex disease may benefit from an ecosystem level approach to management. We hope that this perspective can stimulate a new conversation about the many factors potentially impacting bTB eradication schemes in Britain and Ireland and possibly stimulate new research in the areas identified.

Modelling the variation in skin-test tuberculin reactions, post-mortem lesion counts and case pathology in tuberculosis-exposed cattle: Effects of animal characteristics, histories and co-infection.

Correctly identifying bovine tuberculosis (bTB) in cattle remains a significant problem in endemic countries. We hypothesized that animal characteristics (sex, age, breed), histories (herd effects, testing, movement) and potential exposure to other pathogens (co-infection; BVDV, liver fluke and Mycobacterium avium reactors) could significantly impact the immune responsiveness detected at skin testing and the variation in post-mortem pathology (confirmation) in bTB-exposed cattle. Three model suites were developed using a retrospective observational data set of 5,698 cattle culled during herd breakdowns in Northern Ireland. A linear regression model suggested that antemortem tuberculin reaction size (difference in purified protein derivative avium [PPDa] and bovine [PPDb] reactions) was significantly positively associated with post-mortem maximum lesion size and the number of lesions found. This indicated that reaction size could be considered a predictor of both the extent (number of lesions/tissues) and the pathological progression of infection (maximum lesion size). Tuberculin reaction size was related to age class, and younger animals (<2.85 years) displayed larger reaction sizes than older animals. Tuberculin reaction size was also associated with breed and animal movement and increased with the time between the penultimate and disclosing tests. A negative binomial random-effects model indicated a significant increase in lesion counts for animals with M. avium reactions (PPDb-PPDa < 0) relative to non-reactors (PPDb-PPDa = 0). Lesion counts were significantly increased in animals with previous positive severe interpretation skin-test results. Animals with increased movement histories, young animals and non-dairy breed animals also had significantly increased lesion counts. Animals from herds that had BVDV-positive cattle had significantly lower lesion counts than animals from herds without evidence of BVDV infection. Restricting the data set to only animals with a bTB visible lesion at slaughter (n = 2471), an ordinal regression model indicated that liver fluke-infected animals disclosed smaller lesions, relative to liver fluke-negative animals, and larger lesions were disclosed in animals with increased movement histories.

Assessment of concurrent infection with bovine viral diarrhoea virus (BVDV) and Mycobacterium bovis: A herd-level risk factor analysis from Northern Ireland.

Bovine viral diarrhoea virus (BVDV) is a significant pathogen of cattle, leading to severe economic and animal-welfare impacts. Furthermore, the pathogen has been associated with impacting the progression or spread of other pathogens (e.g. Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB)). During this study we investigated (i) risk factors for BVDV at a herd-level and (ii) whether there was any association between BVDV and herd-level bTB risk. The data for this study were gathered from a voluntary BVDV control programme in Northern Ireland (2013-2015) based on the identification of virus positive animals through tissue tag testing of calves. We assigned a herd-level BVDV status to 2827 participating herds, where a herd was assumed "infected" if one or more animals tested positive for BVDV. Two model suites were developed. Firstly, we assessed risk factors for BVDV herd status using multivariable logit random-effects modelling, aggregating to the calendar year level (2013-2015; n=4828; model 1). Secondly, we aggregated data across the three years of the study to give an overall status for the whole study period (n=2827; logistic model 2). Risk factors included year, herd-type, herd size, number of births, inward trade moves, calf mortality, and region. Furthermore, the herd-level bovine tuberculosis status (based on the single intradermal comparative cervical tuberculin (SICCT) test outcomes, or confirmation at post-mortem), or the size of bTB breakdowns (number of SICCT test positive animals), of herds was also investigated to assess whether there was an association (co-infection) with herd BVDV status. The final models suggested that BVDV herd status was positively associated with increased levels of calf mortality, herd size, number of births, the number of BVDV tests undertaken and the number of animals introduced to the herd. There was a significant univariable positive association between BVDV status, and SICCT breakdown risk, breakdown size and confirmed bTB status in model 2. However, there was no evidence of significant associations between bTB status (using SICTT status, confirmed status or herd breakdown size) and BVDV status in final multivariable models when controlling for other significant confounders. These results provide information for action for the future control and eradication of BVDV in Northern Ireland, though these data provide little support for the hypothesised association between BVDV and bTB status at herd-level. Further animal-level analyses are necessary to investigate whether there is support for a BVD-bTB co-infection association, including the impact of co-infection on the severity of infection.

Spatial and temporal analyses of metrics of tuberculosis infection in badgers (Meles meles) from the Republic of Ireland: Trends in apparent prevalence.

Badgers are a wildlife host of Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), and an important contributor to the epidemiology of bTB in cattle in Ireland and Britain. Repeated culling of badgers in high prevalence cattle bTB areas has been used in the Republic of Ireland as one tool to reduce intra- and interspecific transmission of M. bovis. We assessed factors that influenced infection prevalence of culled badgers from 2009 to 2012 (n=4948) where spatial, temporal and intrinsic factor data were available using multivariable modelling. Prevalence appeared higher in western areas than eastern areas of Ireland and badgers were more likely to be test-positive if caught at a sett (burrow system) which was close to other infected setts (spatial clustering of infection). There was a significant positive association between badger test-status and cattle prevalence of M. bovis infection at a spatial scale of 1km around setts. Badgers were more likely to be deemed test positive if they were male (OR: 1.9) or a parous female (OR: 1.7), compared to a female who had never conceived. Our results are consistent with different groups within badger populations having differential exposures and therefore infection risk (for example, parous vs. non-parous females). Furthermore, bTB clusters within the badger population, with greater risk to badgers in setts that are closest to other infected setts. The effective scale of the association of bTB risk between badger and cattle populations may be relatively large in Ireland. Our data indicate that the overall trend in prevalence of M. bovis infection in badgers has decreased in Ireland (P<0.001) while controlling for significant confounders over the study period, and follows a longer temporal trend from 2007 to 2013, where unadjusted apparent prevalence declined from 26% to 11% during 2007 to mid-2011, followed by a stable trend between 9 and 11% thereafter (n=10,267).

Horse impoundments under Control of Horses legislation in the Munster region of Ireland: factors affecting euthanasia.

Recently, considerable international attention has been paid to the problem of unwanted horses. In Ireland, stray horses, particularly in urban areas, are a further problem. The Control of Horses Act 1996 was enacted in response to an ongoing problem of uncontrolled horses in public places. As yet, no research work has been conducted focusing on stray horses in Ireland. This paper describes horses impounded under the Act in the Munster region of Ireland during 2005-2012 and the factors influencing decisions regarding their disposal. A logistic regression model was developed to investigate factors influencing the probability that a horse was euthanised during impoundment. In total, 3625 seizure events were recorded, most towards the end of the study period. Predictors for euthanasia during 2010-2012 included seizure location, sex, age, colour, body condition score and year. This study highlights the problem of stray horses in Ireland, particularly in urban areas. There is a need for rigorous enforcement of newly enacted horse identification legislation, allowing a fully integrated traceability system. More is required to manage the long-established societal problems of stray horses in urban settings, with a uniform approach by all Local Authorities being long overdue.