BACKGROUND:Bovine tuberculosis (bTB) has substantial impacts on the Irish cattle industry. Between 2016 and 2024, its burden increased in Irish cattle. As an initial step towards understanding drivers of this increase, we explore long-term trends in measures of bTB burden and cattle demographics in Ireland. METHODS:Using data from 2008 to 2024, we describe changes in cattle management and demographics over time, as well as measures of bTB burden at herd- and animal-level. A negative binomial regression model was implemented to explore the association between year and herd type and the count of bTB cases. RESULTS:Between 2008 and 2024, dairy herd numbers remained stable (∼12% of all herds), but expanded significantly in herd size (median increased from 119 to 172), with the proportion of national cattle in dairy herds increasing from 23% to 34%. The proportion of bTB cases from dairy farms doubled. In 2024, 51% of all individual bTB cases were from dairy herds compared to 26% in 2008. LIMITATIONS:There may be misclassification biases in the disclosure of bTB cases across years due to policy changes in response to emerging evidence. CONCLUSION:The burden of bTB has increased substantially since 2015, which has coincided with a large increase in median dairy herd size.

In the United Kingdom (UK) and the Republic of Ireland (ROI), European badgers (Meles meles) are recognised as a reservoir host of Mycobacterium bovis (M. bovis), which they can transmit to cattle. Badgers are also suspected to contribute to the maintenance of Mycobacterium bovis in other European countries, including Spain and France. Therefore, badger vaccination can be used as a tool for the prevention and control of M. bovis infection in cattle.We present individual-level immunological and bacteriological data collected between 2002 and 2020 from 374 individual captive badgers from the UK, ROI and Spain. The data were generated through standardised experimental protocols developed for badgers and optimised in the ROI (experimental challenge protocol) and at the Animal and Plant Health Agency (APHA, UK) (immunological protocols). The analysis aimed to measure antigen-specific T-cell responses and antibody responses in BCG vaccinated and non-vaccinated badgers before and after experimental infection (challenge) with live bacteria M. bovis.The data were generated from individual badgers repeatedly sampled between seven and 16 times every two-to-three weeks. The data are blood-based immunological assays and bacterial culture results of clinical samples. The dataset also includes husbandry information (sex, original social group, housing pen), physiological measurements (temperature and weight), vaccine details (type, formulation, route, dose and strain) and M. bovis challenge parameters (dose concentration).

Mycobacterium bovis causes bovine tuberculosis (bTB), a chronic infectious disease with significant veterinary, public health, and economic consequences. The interferon-gamma (IFN-γ) assay is increasingly used alongside the Single Intradermal Comparative Tuberculin Test (SICTT) in Ireland's national bTB eradication programme, but age-specific patterns associated with IFN-γ positivity or post-mortem visible lesion detection (VLD) have not been fully characterised. This retrospective cohort study includes 267,674 SICTT-negative cattle tested with IFN-γ between May 2019 and December 2023 in high-risk Irish herds. Mixed-effects logistic regression models quantify associations between age and (i) IFN-γ positivity and (ii) VLD at slaughter among IFN-γ-positive cattle. Models adjust for sex, herd type, prior inconclusive SICTTs, number of prior 'risky' SICTT tests, and herd-level breakdown size (% of animals positive). Overall, 9.6% of SICTT-negative cattle test positive to IFN-γ. Our findings show that IFN-γ positivity increases with age, peaks in cattle aged 4-6 years, plateaus until 8 years, and declines thereafter. Relative to beef breeding herds, dairy, mixed, and 'other' herd types are associated with higher IFN-γ positivity, as is a history of prior inconclusive SICTTs, and fewer prior 'risky' SICTT exposures. Among IFN-γ-positive cattle, 21.9% exhibit VLD at slaughter. VLD positivity shows a U-shaped relationship with age, highest in the youngest (0-2 years), reducing in cattle aged 2-4, then increasing linearly to oldest (>8 years) cattle. The VLD odds are approximately half in dairy herds compared with beef breeding herds and are elevated in herds in the largest quartile of breakdowns (>6.25% of animals positive). The interpretation of these results should consider that IFN-γ-positivity and VLD likely reflect different stages of bTB infection, with early immune responses detected ante-mortem and visible lesions at post-mortem representing later stage disease; the absence of visible lesions therefore does not exclude M. bovis infection. It appears that age-specific IFN-γ positivity and VLD in high-risk herds are likely shaped by production systems, prior risky SICTT exposures, and herd-level outbreak dynamics rather than simple cumulative risk. The IFN-γ testing helps to identify infected cattle missed by SICTT, particularly in the early infection or large herd breakdowns and serves to support targeted, risk-based deployment to optimize Ireland's bTB eradication programme.

Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis-infected animals and detect 2592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 115 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.

Increasing reports of zoonotic avian influenza virus (AIV) spillovers to mammals signal critical shift in their ecology and raise substantial public health concerns. The highly pathogenic avian influenza H5N1 clade 2.3.4.4b has driven this expansion, with genetic adaptations enhancing replication in mammalian hosts. Adaptations have been identified in diverse carnivore species, including American mink ( Neogale vison ), red foxes ( Vulpes vulpes ), and otters ( Lutra lutra ). These carnivores often feed on, or share habitat with, wild birds, making them suitable species for monitoring AIV presence in mammals. Here we investigated exposure to influenza A viruses (IAVs), including H5 and H7 subtypes in three mesocarnivore species (red foxes, American mink, and European badgers) in Ireland. Using enzyme-linked immunosorbent assays, we detected a seroprevalence for IAVs of 24.6% (28/114) in foxes, 22.2% (2/9) in mink, and 1% (1/96) in badgers. Among red fox samples positive for antibodies against IAVs, 82.1% (23/28) were positive for antibodies against the H5 subtype. No antibodies against the H7 subtype were detected. We also examined the use of Nobuto filter paper as a reliable alternative to serum samples for IAVs antibody detection via ELISA and assessed the use of haemolysed serum samples. These findings, as well as those gathered from ongoing passive surveillance of wild birds, highlight that influenza A is circulating in wildlife in Ireland. If we are to better understand influenza A dynamics in Ireland, and globally, it is imperative that surveillance programmes are supported, and serosurveys provide one valuable tool for active surveillance.

The zoonotic bacterium, Mycobacterium bovis , causes bovine tuberculosis (bTB) and is closely related to Mycobacterium tuberculosis , the primary cause of human tuberculosis (hTB). Bovine TB remains recalcitrant to eradication in endemic countries where current diagnostics fail to identify all infected animals. While blood-based RNA biomarkers identified through machine learning have shown accurate discrimination of hTB-positive and hTB-negative individuals, similar approaches have not been explored for bTB. Here, we use RNA-seq and machine learning to investigate the utility of peripheral blood mRNA as a host-response biomarker for bTB using data from Ireland, the UK and the US. We identify a 30-gene signature and a 273-gene elastic net classifier that differentiate bTB-positive from bTB-negative cattle, achieving area under the curve (AUC) values of 0.986/0.900 for the former and 0.968/0.938 for the latter in training and testing, respectively. These two classifiers produced high sensitivity and specificity values (≥ 0.853 for both metrics) in the testing set. Additionally, we show that they robustly distinguish bTB+ animals from those infected with other bacterial or viral pathogens (AUC ≥ 0.819). These RNA-based classifiers accurately diagnose bTB and differentiate bTB from other diseases, representing a promising tool for augmenting current diagnostics to advance bTB eradication efforts in endemic regions. ### Competing Interest Statement The authors have declared no competing interest. Taighde Éireann - Research Ireland, 18/CRT/6214 Science Foundation Ireland, https://ror.org/0271asj38, SFI/08/IN.1/B2038, SFI/15/IA/3154 Department of Agriculture Food and the Marine, https://ror.org/008gjgb19, 17/RD/US-ROI/52, 2023RP902 European Commission, https://ror.org/00k4n6c32, CA22112 Fulbright Program, https://ror.org/014geb094

As a zoonotic disease, with a global impact on animal health, welfare and trade, bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, has been subject to strict control measures in many countries to reduce the impact of the disease on cattle and their handlers. However, eradication efforts have been constrained in some countries for several reasons, including limitations in diagnostic test sensitivity. As a result, a proportion of M. bovis-infected cattle are being misdiagnosed, which then become reservoirs of infection contributing to further spread of disease. A significant amount of research effort has focused on understanding the immune responses to M. bovis infection in cattle and on investigating how these can be leveraged to improve diagnostic performance. More recently, and predominantly in human and murine models of Mycobacterium tuberculosis infection, there has been a growing recognition that chemical modifications to DNA and proteins (referred collectively to as epigenetic mechanisms), which spatially govern gene activity across host chromosomes, can directly regulate the immune responses. However, knowledge of epigenetic changes in response to M. bovis infection in cattle is still in its infancy. Epigenetic "marks" (e.g., DNA methylation and histone modifications) are dynamic, and alterations induced by the infecting pathogen lead to a complex biochemical interplay that can ultimately determine the infection outcome. Drawing on the extensive wealth of epigenetic findings from studies on M. tuberculosis infection, this review explores the evidence for epigenetic control of the immune response to M. bovis and bTB disease by methylation and acetylation of host chromosomes. Understanding the extent and nature of epigenetic control may reveal how M. bovis coevolution with the bovine host shapes both immune outcomes and diagnostic test sensitivity.

The dynamics of Mycobacterium bovis infection in cattle can influence the proportion of infected animals that are diagnosed by ante-mortem tests in routine bovine tuberculosis (bTB) surveillance and monitoring programmes. Although the current diagnostic tests based on cell-mediated or serological responses are imperfect, they are effective in diagnosing the majority of infected animals. However, the lack of perfect sensitivity and specificity also leads to failure to diagnose all infected animals leading to persistence of infection in herds. The terms residual, subclinical, latent and anergy have been used interchangeably to denote the presence of continued undiagnosed M. bovis infection within cattle herds, which ultimately hinders the eradication of bTB and imposes substantial financial burdens on farming communities and national economies. Epidemiological data suggests the existence of M. bovis-infected, but often undetected, cattle within herds that contribute to eradication failure. This has similarities with human tuberculosis, caused by Mycobacterium tuberculosis, where latent infection is defined as the persistence of viable but quiescent bacilli for extended periods in patients without clinical symptoms but with a detectable immune response to M. tuberculosis antigens. If a similar infection state exists in cattle infected with M. bovis, the persistence of such animals in disease-managed herds is unlikely to be common given that those found to have positive immune responses to M. bovis antigens are routinely culled to minimise future risk of transmission. Apart from contributing to the burden of herd infection, such residual infection without detection may also ‘seed’ recipient herds following animal movements, and potentially play an important role in the overall epidemiology of bTB as the prevalence of disease decreases and the attendant altered predictive value of the diagnostic tests result in a greater proportion of infected animals remaining undetected. This review examines how the different stages of M. bovis infection in cattle may contribute to the failure to diagnose infected animals using conventional testing methodologies and the attendant risk this poses in creating prolonged or recurrent herd breakdowns.

The European badger, Meles meles, is an important wildlife host for Mycobacterium bovis and contributes to the epidemiology of bovine tuberculosis (bTB) in cattle in several countries. The control of zoonotic diseases, such as bTB, is a central component of global One-Health strategies. Such strategies are complicated by human-wildlife conflicts, particularly where wildlife reservoirs are legally protected. The contrasting objectives of disease management and wildlife conservation, therefore, can require significant investment in research to support evidence-based policies. In Britain and Ireland, for example, badgers are a legally protected species but are also subject to lethal control and vaccination for disease management. In this paper, we review recent (2012-2022) advances in research on this wildlife host on the island of Ireland, which is used to underpin national policies and identify research gaps. In recent years, significant advances in estimating key parameters related to badger management and population dynamics have been made, including estimating population abundance at varying scales (local, landscape, and national). Advances in tracking technology, integrated with mark-recapture and modelling tools, have provided significant insights into the movement ecology of badgers and their interactions with cattle. The adaptation of genetic technologies has improved our understanding of the transmission dynamics of M. bovis among different hosts. As a disease management strategy, the culling of badgers to control bTB has reduced badger densities significantly, although this is not considered a sustainable sole long-term solution to the problem of spillback infection. The recent development of vaccination strategies presents an additional approach to control the disease in wild populations. These types of interventions will require significant applied research to ensure they are sustainable and to maximise benefits. It is also expected that focused research efforts will improve human-wildlife coexistence in the context of the broader One-Health strategy.

Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that poses a zoonotic threat to humans. Research has shown that bTB susceptibility is a heritable trait, and that the peripheral blood (PB) transcriptome is perturbed during bTB disease. Hitherto, no study has integrated PB transcriptomic, genomic and GWAS data to study bTB disease, and little is known about the genomic architecture underpinning the PB transcriptional response to M. bovis infection. Here, we perform transcriptome profiling of PB from 63 control and 60 confirmed M. bovis infected animals and detect 2,592 differently expressed genes that perturb multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis - and trans -expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation. We integrate our gene expression data with summary statistics from multiple GWAS data sets for bTB susceptibility and perform the first transcriptome-wide association study (TWAS) in the context of tuberculosis disease. From this TWAS, we identify 136 functionally relevant genes (including RGS10 , GBP4 , TREML2 , and RELT ) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals. ### Competing Interest Statement The authors have declared no competing interest.

Food Risk Assess EuropeVolume 2, Issue 1 0017E Technical reportOpen Access Can a regional approach be applied to achieve eradication of bovine tuberculosis in Ireland? TB Scientific Working Group, TB Scientific Working GroupSearch for more papers by this authorJohn Griffin, John GriffinSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author TB Scientific Working Group, TB Scientific Working GroupSearch for more papers by this authorJohn Griffin, John GriffinSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author First published: 12 February 2024 https://doi.org/10.2903/fr.efsa.2024.FR-0017AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Given the lack of progress in recent years, new approaches must be considered in relation to the eradication of bovine tuberculosis (TB, caused by Mycobacterium bovis) in Ireland. This study examines the potential effectiveness of a regional approach within a broader national eradication programme, as requested by the Department of Agriculture, Food and the Marine (DAFM). Drawing on international experiences, the Scientific Working Group (SWG) of the national TB Stakeholder Forum evaluated the potential value of a regional approach for bovine TB eradication, the criteria that should be used to select regions, and the measures required to achieve – and subsequently maintain – freedom from infection. Regionalisation is a key tool in disease control, delineating subpopulations with defined health statuses within geographic boundaries. Using this approach, disease control and surveillance can be differentiated based on risk, to prioritise resource allocation and protect lower risk areas. The SWG underscores the necessity of regionalisation within a comprehensive strategic framework, including careful consideration of external biosecurity measures and stakeholder engagement. Criteria to guide the selection of region(s) should consider factors relating to the potential inward movement of M. bovis into the region (inward cattle movement, geographical boundaries, trade flows, land fragmentation), factors that impact the effective control of all infection sources within the region (TB levels in cattle, regional administration, badger controls), and stakeholder commitment. All countries that have progressed towards or achieved bovine TB eradication have applied a regional approach within a national eradication programme. Many of the above-mentioned technical measures already form part of the national eradication programme in Ireland; the primary additional measure to achieve and maintain regional freedom from infection relates to cattle trading. This research contributes to ongoing discussion on control strategies for bovine TB, emphasizing the importance of tailored approaches informed by scientific evidence and stakeholder engagement. References 1World Organisation for Animal Health. Terrestrial Animal Health Code, chapter 4.4. Zoning and Compartmentalisation. https://www.woah.org/en/what-we-do/standards/codes-and-manuals/terrestrial-code-online-access/?id=169&L=1&htmfile=chapitre_zoning_compartment.htm. 2016. Google Scholar 2Zuckerman OM. Badgers, cattle and tuberculosis. Report to the Right Honourable Peter Walker, MP. London: 1980. Google Scholar 3Rossi G, Crispell J, Brough T, et al. Phylodynamic analysis of an emergent Mycobacterium bovis outbreak in an area with no previously known wildlife infections. J Appl Ecol 2022; 59: 210–22. https://doi.org/10.1111/1365-2664.14046 10.1111/1365-2664.14046 Web of Science®Google Scholar 4Bessell PR, Orton R, O'Hare A, et al. Developing a framework for risk-based surveillance of tuberculosis in cattle: a case study of its application in Scotland. Epidemiol Infect 2013; 141: 314. https://doi.org/10.1017/S0950268812000635 10.1017/S0950268812000635 CASPubMedWeb of Science®Google Scholar 5 EFSA, ECDC. The European Union One Health 2021 Zoonoses Report. EFSA Journal 2022; 20. https://doi.org/10.2903/j.efsa.2022.7666 10.2903/j.efsa.2022.7666 Google Scholar 6 Ministerio De Agricultura PYA. Programa Nacional De Erradicacion De Tuberculosis Bovina 2023. https://www.mapa.gob.es/es/ganaderia/temas/sanidad-animal-higiene-ganadera/programatb2023_tcm30-640045.pdf. 2023. Google Scholar 7Pozo P, Bezos J, Romero B, et al. Once bitten twice shy: Risk factors associated with bovine tuberculosis recurrence in Castilla y Leon, Spain. Res Vet Sci 2023; 159: 72–80. https://doi.org/10.1016/J.RVSC.2023.04.011 10.1016/j.rvsc.2023.04.011 CASPubMedWeb of Science®Google Scholar 8Livingstone PG, Hancox N, Nugent G, et al. Development of the New Zealand strategy for local eradication of tuberculosis from wildlife and livestock. N Z Vet J 2015; 63: 98–107. https://doi.org/10.1080/00480169.2015.1013581 10.1080/00480169.2015.1013581 PubMedWeb of Science®Google Scholar 9More SJ, Radunz B, Glanville RJ. Review: Lessons learned during the successful eradication of bovine tuberculosis from Australia. Vet Rec 2015; 177: 224–32. https://doi.org/10.1136/vr.103163 10.1136/vr.103163 CASPubMedWeb of Science®Google Scholar 10More SJ. Can bovine TB be eradicated from the Republic of Ireland? Could this be achieved by 2030? Ir Vet J 2019; 72. https://doi.org/10.1186/s13620-019-0140-x 10.1186/s13620-019-0140-x Web of Science®Google Scholar 11Watchorn RC. Bovine Tuberculosis Eradication Scheme 1954-1965. Dublin: 1965. Google Scholar 12Fielding HR, McKinley TJ, Delahay RJ, et al. Effects of trading networks on the risk of bovine tuberculosis incidents on cattle farms in Great Britain. R Soc Open Sci 2020; 7. https://doi.org/10.1098/rsos.191806 10.1098/rsos.191806 Web of Science®Google Scholar 13Berrian AM, O'Keeffe J, White PW, et al. Risk of bovine tuberculosis for cattle sold out from herds during 2005 in Ireland. Vet Rec 2012; 170: 620. https://doi.org/10.1136/vr.100674 10.1136/vr.100674 CASPubMedWeb of Science®Google Scholar 14Wolfe DM, Berke O, More SJ, et al. The risk of a positive test for bovine tuberculosis in cattle purchased from herds with and without a recent history of bovine tuberculosis in Ireland. Prev Vet Med 2009; 92: 99–105. https://doi.org/10.1016/j.prevetmed.2009.07.012 10.1016/j.prevetmed.2009.07.012 CASPubMedWeb of Science®Google Scholar 15McGrath G, Tratalos JA, More SJ. A visual representation of cattle movement in Ireland during 2016. Ir Vet J 2018; 71. https://doi.org/10.1186/s13620-018-0129-x 10.1186/s13620-018-0129-x Web of Science®Google Scholar 16Tratalos JA, Madden JM, McGrath G, et al. Spatial and network characteristics of Irish cattle movements. Prev Vet Med 2020; 183:105095. https://doi.org/10.1016/J.PREVETMED.2020.105095 10.1016/j.prevetmed.2020.105095 PubMedWeb of Science®Google Scholar 17Conlan AJK, McKinley TJ, Karolemeas K, et al. Estimating the Hidden Burden of Bovine Tuberculosis in Great Britain. PLoS Comput Biol 2012; 8. https://doi.org/10.1371/journal.pcbi.1002730 10.1371/journal.pcbi.1002730 Web of Science®Google Scholar 18Clegg TA, More SJ, Higgins IM, et al. Potential infection-control benefit for Ireland from pre-movement testing of cattle for tuberculosis. Prev Vet Med 2008; 84: 94–111. https://doi.org/10.1016/j.prevetmed.2007.11.004 10.1016/j.prevetmed.2007.11.004 CASPubMedWeb of Science®Google Scholar 19Clegg TA, Good M, More SJ. Future risk of bovine tuberculosis recurrence among higher risk herds in Ireland. Prev Vet Med 2015; 118: 71–9. https://doi.org/10.1016/j.prevetmed.2014.11.013 10.1016/j.prevetmed.2014.11.013 CASPubMedWeb of Science®Google Scholar 20Doyle LP, Courcier EA, Gordon AW, et al. Bovine tuberculosis in Northern Ireland: quantification of the population disease-level effect from cattle leaving herds detected as a source of infection. Epidemiol Infect 2017; 145: 3505–15. https://doi.org/10.1017/S0950268817002424 10.1017/S0950268817002424 CASPubMedWeb of Science®Google Scholar 21White PW, Martin SW, De Jong MCM, et al. The importance of 'neighbourhood' in the persistence of bovine tuberculosis in Irish cattle herds. Prev Vet Med 2013; 110: 346–55. https://doi.org/10.1016/j.prevetmed.2013.02.012 10.1016/j.prevetmed.2013.02.012 PubMedWeb of Science®Google Scholar 22Byrne AW, Barrett D, Breslin P, et al. Bovine tuberculosis (Mycobacterium bovis) outbreak duration in cattle herds in Ireland: A retrospective observational study. Pathogens 2020; 9: 1–17. https://doi.org/10.3390/PATHOGENS9100815 10.3390/pathogens9100815 Web of Science®Google Scholar 23Tratalos JA, Fielding HR, Madden JM, et al. Can Ingoing Contact Chains and other cattle movement network metrics help predict herd-level bovine tuberculosis in Irish cattle herds? Prev Vet Med 2023; 211. https://doi.org/10.1016/j.prevetmed.2022.105816 10.1016/j.prevetmed.2022.105816 Web of Science®Google Scholar 24Biemans F, Tratalos J, Arnoux S, et al. Modelling transmission of Mycobacterium avium subspecies paratuberculosis between Irish dairy cattle herds. Vet Res 2022; 53: 1–16. https://doi.org/10.1186/S13567-022-01066-5 10.1186/s13567-022-01066-5 PubMedWeb of Science®Google Scholar 25Milne G, Graham J, McGrath J, et al. Investigating Farm Fragmentation as a Risk Factor for Bovine Tuberculosis in Cattle Herds: A Matched Case-Control Study from Northern Ireland. Pathogens 2022; 11. https://doi.org/10.3390/PATHOGENS11030299 10.3390/PATHOGENS11030299 PubMedWeb of Science®Google Scholar 26Byrne AW, Barrett D, Breslin P, et al. Bovine tuberculosis (Mycobacterium bovis) outbreak duration in cattle herds in Ireland: A retrospective observational study. Pathogens 2020; 9: 1–17. https://doi.org/10.3390/pathogens9100815 10.3390/pathogens9100815 Web of Science®Google Scholar 27Mill AC, Rushton SP, Shirley MDF, et al. Farm-scale risk factors for bovine tuberculosis incidence in cattle herds during the Randomized Badger Culling Trial. Epidemiol Infect 2012; 140: 219–30. https://doi.org/10.1017/S0950268811000434 10.1017/S0950268811000434 CASPubMedWeb of Science®Google Scholar 28Vial F, Johnston WT, Donnelly CA. Local cattle and badger populations affect the risk of confirmed tuberculosis in British cattle herds. PLoS One 2011; 6. https://doi.org/10.1371/JOURNAL.PONE.0018058 10.1371/JOURNAL.PONE.0018058 Google Scholar 29Johnston WT, Gettinby G, Cox DR, et al. Herd-level risk factors associated with tuberculosis breakdowns among cattle herds in England before the 2001 foot-and-mouth disease epidemic. Biol Lett 2005; 1: 53–6. https://doi.org/10.1098/RSBL.2004.0249 10.1098/rsbl.2004.0249 CASPubMedWeb of Science®Google Scholar 30Broughan JM, Maye D, Carmody P, et al. Farm characteristics and farmer perceptions associated with bovine tuberculosis incidents in areas of emerging endemic spread. Prev Vet Med 2016; 129: 88–98. https://doi.org/10.1016/J.PREVETMED.2016.05.007 10.1016/j.prevetmed.2016.05.007 CASPubMedWeb of Science®Google Scholar 31Gaughran A, MacWhite T, Mullen E, et al. Dispersal patterns in a medium-density Irish badger population: Implications for understanding the dynamics of tuberculosis transmission. Ecol Evol 2019; 9: 13142–52. https://doi.org/10.1002/ECE3.5753 10.1002/ece3.5753 PubMedWeb of Science®Google Scholar 32 TB Forum Scientific Working Group. What is the proportional contribution of cattle-to-cattle, badger-to-cattle, and deer-to-cattle transmission to bovine TB in Ireland? 2021. Google Scholar 33 TB Forum Scientific Working Group. What is the scope for existing (including recently developed) diagnostic methods to detect infected cattle which are not currently detected by the existing programme? 2021. Google Scholar 34 Government of Ireland. Presumed risk of national extinction of badgers in Ireland. Dublin: 2017. Google Scholar 35Aznar I, Frankena K, More SJ, et al. Quantification of Mycobacterium bovis transmission in a badger vaccine field trial. Prev Vet Med 2018; 149: 29–37. https://doi.org/10.1016/j.prevetmed.2017.10.010 10.1016/j.prevetmed.2017.10.010 CASPubMedWeb of Science®Google Scholar 36Gormley E, Ní Bhuachalla D, Murphy D, et al. Oral Vaccination of Free-Living Badgers (Meles meles) with Bacille Calmette Guérin (BCG) Vaccine Confers Protection against Tuberculosis. PLoS One 2017; 12. https://doi.org/10.1371/journal.pone.0168851 10.1371/journal.pone.0168851 Web of Science®Google Scholar 37Gormley E, Ní Bhuachalla D, Fitzsimons T, et al. Protective immunity against tuberculosis in a free-living badger population vaccinated orally with Mycobacterium bovis Bacille Calmette–Guérin. Transbound Emerg Dis 2021; 69: e10–9. https://doi.org/10.1111/tbed.14254 10.1111/tbed.14254 PubMedWeb of Science®Google Scholar 38Martin SW, O'Keeffe J, Byrne AW, et al. 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). Prev Vet Med 2020; 179. https://doi.org/10.1016/j.prevetmed.2020.105004 10.1016/j.prevetmed.2020.105004 Web of Science®Google Scholar 39Abdou M, Frankena K, O'Keeffe J, et al. Effect of culling and vaccination on bovine tuberculosis infection in a European badger (Meles meles) population by spatial simulation modelling. Prev Vet Med 2016; 125: 19–30. https://doi.org/10.1016/J.PREVETMED.2015.12.012 10.1016/j.prevetmed.2015.12.012 PubMedWeb of Science®Google Scholar 40Bouchez-Zacria M, Ruette S, Richomme C, et al. Analysis of a multi-type resurgence of Mycobacterium bovis in cattle and badgers in Southwest France, 2007-2019. Vet Res 2023; 54: 41. https://doi.org/10.1186/s13567-023-01168-8 10.1186/s13567-023-01168-8 CASPubMedWeb of Science®Google Scholar 41Barbier E, Boschiroli ML, Gueneau E, et al. First molecular detection of Mycobacterium bovis in environmental samples from a French region with endemic bovine tuberculosis. J Appl Microbiol 2016; 120: 1193–207. https://doi.org/10.1111/jam.13090 10.1111/jam.13090 CASPubMedWeb of Science®Google Scholar 42Allen AR, Ford T, Skuce RA. Does Mycobacterium tuberculosis var. bovis Survival in the Environment Confound Bovine Tuberculosis Control and Eradication? A Literature Review. Vet Med Int. 2021;2021. https://doi.org/10.1155/2021/8812898 10.1155/2021/8812898 Google Scholar 43Campbell EL, Byrne AW, Menzies FD, et al. Interspecific visitation of cattle and badgers to fomites: A transmission risk for bovine tuberculosis? Ecol Evol 2019; 9: 8479–89. https://doi.org/10.1002/ECE3.5282 10.1002/ece3.5282 PubMedWeb of Science®Google Scholar 44Campbell EL, Menzies FD, Byrne AW, et al. Grazing cattle exposure to neighbouring herds and badgers in relation to bovine tuberculosis risk. Res Vet Sci 2020; 133: 297–303. https://doi.org/10.1016/j.rvsc.2020.09.032 10.1016/j.rvsc.2020.09.032 PubMedWeb of Science®Google Scholar 45Akhmetova A, Guerrero J, McAdam P, et al. Genomic epidemiology of Mycobacterium bovis infection in sympatric badger and cattle populations in Northern Ireland. Microb Genom 2023; 9. https://doi.org/10.1099/MGEN.0.001023 10.1099/MGEN.0.001023 Web of Science®Google Scholar 46Crawshaw TR, Chanter JI, McGoldrick A, et al. A proof of concept study to assess the potential of PCR testing to detect natural Mycobacterium bovis infection in South American camelids. Ir Vet J 2014; 67. https://doi.org/10.1186/2046-0481-67-5 10.1186/2046-0481-67-5 Web of Science®Google Scholar 47Bermingham ML, More SJ, Good M, et al. Genetics of tuberculosis in Irish Holstein-Friesian dairy herds. J Dairy Sci 2009; 92: 3447–56. https://doi.org/10.3168/JDS.2008-1848 10.3168/jds.2008-1848 CASPubMedWeb of Science®Google Scholar 48Bermingham ML, More SJ, Good M, et al. Genetic associations between Johne's disease and susceptibility to Mycobacterium bovis and Mycobacterium avium subsp. avium in Irish Holstein Friesian dairy cows. Advances in Animal Biosciences 2010; 1: 302. https://doi.org/10.1017/S2040470010004450 10.1017/S2040470010004450 Google Scholar 49Bermingham ML, More SJ, Good M, et al. Genetic correlations between measures of Mycobacterium bovis infection and economically important traits in Irish Holstein-Friesian dairy cows. J Dairy Sci 2010; 93: 5413–22. https://doi.org/10.3168/JDS.2009-2925 10.3168/jds.2009-2925 CASPubMedWeb of Science®Google Scholar 50Boland F, Kelly GE, Good M, et al. Bovine tuberculosis and milk production in infected dairy herds in Ireland. Prev Vet Med 2010; 93: 153–61. https://doi.org/10.1016/j.prevetmed.2009.09.021 10.1016/j.prevetmed.2009.09.021 CASPubMedWeb of Science®Google Scholar 51Berry DP, Bermingham ML, Good M, et al. Genetics of animal health and disease in cattle. Ir Vet J 2011; 64: 1–10. https://doi.org/10.1186/2046-0481-64-5/FIGURES/2 10.1186/2046-0481-64-5 PubMedWeb of Science®Google Scholar 52Boland F, Kelly GE, Good M, et al. Bovine tuberculosis and udder health in Irish dairy herds. Vet J 2012; 192: 71–4. https://doi.org/10.1016/J.TVJL.2011.04.004 10.1016/j.tvjl.2011.04.004 CASPubMedWeb of Science®Google Scholar 53Ring SC, Purfield DC, Good M, et al. Variance components for bovine tuberculosis infection and multi-breed genome-wide association analysis using imputed whole genome sequence data. PLoS One 2019; 14. https://doi.org/10.1371/journal.pone.0212067 10.1371/journal.pone.0212067 Web of Science®Google Scholar 54Richardson IW, Bradley DG, Higgins IM, et al. Variance components for susceptibility to Mycobacterium bovis infection in dairy and beef cattle. Genetics Selection Evolution 2014; 46: 1–11. https://doi.org/10.1186/S12711-014-0077-1/TABLES/4 10.1186/s12711-014-0077-1 Web of Science®Google Scholar 55Banos G, Winters M, Mrode R, et al. Genetic evaluation for bovine tuberculosis resistance in dairy cattle. J Dairy Sci 2017; 100: 1272–81. https://doi.org/10.3168/JDS.2016-11897 10.3168/jds.2016-11897 CASPubMedWeb of Science®Google Scholar 56Bermingham ML, Bishop SC, Woolliams JA, et al. Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis. Heredity (Edinb) 2014; 112: 543–51. https://doi.org/10.1038/HDY.2013.137 10.1038/hdy.2013.137 CASPubMedWeb of Science®Google Scholar 57Mazorra-Carrillo JL, Alcaraz-López OA, López-Rincón G, et al. Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype. Front Vet Sci 2021; 8:734087. https://doi.org/10.3389/FVETS.2021.734087/BIBTEX 10.3389/fvets.2021.734087 PubMedWeb of Science®Google Scholar 58Gao Y, Wu H, Wang Y, et al. Single Cas9 nickase induced generation of NRAMP1 knockin cattle with reduced off-target effects. Genome Biol 2017; 18: 1–15. https://doi.org/10.1186/S13059-016-1144-4/FIGURES/7 10.1186/s13059-016-1144-4 PubMedWeb of Science®Google Scholar 59Raphaka K, Sánchez-Molano E, Tsairidou S, et al. Impact of genetic selection for increased cattle resistance to bovine tuberculosis on disease transmission dynamics. Front Vet Sci 2018; 5: 237. https://doi.org/10.3389/FVETS.2018.00237/FULL 10.3389/fvets.2018.00237 PubMedWeb of Science®Google Scholar 60Tsairidou S, Woolliams JA, Allen AR, et al. Genomic Prediction for Tuberculosis Resistance in Dairy Cattle. PLoS One 2014; 9:e96728. https://doi.org/10.1371/JOURNAL.PONE.0096728 10.1371/journal.pone.0096728 PubMedWeb of Science®Google Scholar 61 DAFM. Bovine TB Stakeholder Forum. Consultation Papers Informing Bovine TB Stakeholder Forum. Dublin: 2018. Google Scholar 62 DAFM. National Farmed Animal Health Strategy 2017 - 2022. 2017. Google Scholar 63 DAFM. Position paper for TB Forum in relation to disease control policy options to eradicate bovine TB by 2030. Dublin: 2019. Google Scholar 64Sheehy SJ, Christiansen KH. Cost/benefit analysis of Irish Bovine Tuberculosis Eradication Schemes. Dublin: 1991. Google Scholar 65O'Connor J. An assessment of the perceptions of stakeholders to bovine tuberculosis eradication in Ireland and the role of collaborative governance (Doctoral dissertation). University College Dublin. 2020. Google Scholar 66Ciaravino G, Ibarra P, Casal E, et al. Farmer and veterinarian attitudes towards the bovine tuberculosis eradication programme in Spain: What is going on in the field? Front Vet Sci 2017; 4:284304. https://doi.org/10.3389/FVETS.2017.00202/BIBTEX 10.3389/fvets.2017.00202 Web of Science®Google Scholar 67Cowie CE, Gortázar C, White PCL, et al. Stakeholder opinions on the practicality of management interventions to control bovine tuberculosis. Vet J 2015; 204: 179–85. https://doi.org/10.1016/J.TVJL.2015.02.022 10.1016/j.tvjl.2015.02.022 PubMedWeb of Science®Google Scholar 68Dorn ML, Mertig AG. Bovine Tuberculosis in Michigan: Stakeholder Attitudes and Implications for Eradication Efforts | Request PDF. Wildl Soc Bull 2005; 33: 539–52.https://www.researchgate.net/publication/261826353_Bovine_Tuberculosis_in_Michigan_Stakeholder_Attitudes_and_Implications_for_Eradication_Efforts (accessed 21 Jun 2023). 10.2193/0091-7648(2005)33[539:BTIMSA]2.0.CO;2 Web of Science®Google Scholar 69 Animal Health Australia. Emergency Animal Disease Response Agreement. https://animalhealthaustralia.com.au/eadra/. 2023. Google Scholar 70Griffin JM, Williams DH, Kelly GE, et al. The impact of badger removal on the control of tuberculosis in cattle herds in Ireland. Prev Vet Med 2005; 67: 237–66. https://doi.org/10.1016/j.prevetmed.2004.10.009 10.1016/j.prevetmed.2004.10.009 CASPubMedWeb of Science®Google Scholar 71Byrne AW, White PW, McGrath G, et al. Risk of tuberculosis cattle herd breakdowns in Ireland: Effects of badger culling effort, density and historic large-scale interventions. Vet Res 2014; 45. https://doi.org/10.1186/s13567-014-0109-4 10.1186/s13567-014-0109-4 PubMedWeb of Science®Google Scholar 72Wright DM, Reid N, Montgomery WI, et al. Herd-level bovine tuberculosis risk factors: Assessing the role of low-level badger population disturbance. Sci Rep 2015; 5. https://doi.org/10.1038/srep13062 10.1038/srep13062 Web of Science®Google Scholar 73Smith GC, Barber A, Breslin P, et al. Simulating partial vaccine protection: BCG in badgers. Prev Vet Med 2022; 204. https://doi.org/10.1016/j.prevetmed.2022.105635 10.1016/j.prevetmed.2022.105635 Web of Science®Google Scholar 74Byrne AW, Acevedo P, Green S, et al. Estimating badger social-group abundance in the Republic of Ireland using cross-validated species distribution modelling. Ecol Indic 2014; 43: 94–102. https://doi.org/10.1016/j.ecolind.2014.02.024 10.1016/j.ecolind.2014.02.024 Web of Science®Google Scholar 75Murphy D, Gormley E, Costello E, et al. The prevalence and distribution of Mycobacterium bovis infection in European badgers (Meles meles) as determined by enhanced post mortem examination and bacteriological culture. Res Vet Sci 2010; 88: 1–5. https://doi.org/10.1016/j.rvsc.2009.05.020 10.1016/j.rvsc.2009.05.020 CASPubMedWeb of Science®Google Scholar 76Murphy D, Gormley E, Collins DM, et al. Tuberculosis in cattle herds are sentinels for Mycobacterium bovis infection in European badgers (Meles meles): The Irish Greenfield Study. Vet Microbiol 2011; 151: 120–5. https://doi.org/10.1016/j.vetmic.2011.02.034 10.1016/j.vetmic.2011.02.034 CASPubMedWeb of Science®Google Scholar Volume2, Issue1January 20240017E ReferencesRelatedInformation

In Ireland, the interferon-gamma (IFN-γ) assay is routinely used as an ancillary test interpreted in parallel with the single intradermal comparative tuberculin test (SICTT) to maximize the detection of bovine tuberculosis (bTB) infected animals. Up until 2018, a positive test result was recorded in the IFN-γ ELISA assay following whole blood stimulation with purified protein derivative (PPD)-bovine (B), PPD-avian (A) and nil sample (N), using the interpretation criteria, B-N > 50 optical density units (OD), B > 100 and B-A > 0. Following a review of available data, the threshold of the B-A component changed to B-A > 80. As predicting the impact of changing the cut-off thresholds for the IFN-γ test de novo is challenging, the aims of this study were to follow animals that initially tested negative using the new IFN-γ assay interpretation criteria and investigate their future risk of disclosure with bTB, with a focus on animals that otherwise would have been removed when using the older interpretation criteria (0 < B-A ≤ 80). Enrolled animals (n = 28,669 cattle from 527 herds) were followed up for two years (2019-2021), or to point of bTB detection or death. At the end of follow-up, 1151 (4.0%) of enrolled animals were bTB cases. The majority of these cases were diagnosed using SICTT (80.5%). The cumulative number of positive animals that would have been removed if the old cut-off (0 < B-A ≤ 80) was used amounted to 1680 cattle (5.9% of the enrolled cohort). Of these, 127 (7.5%) were diagnosed with bTB during follow-up. In contrast, 1024 of the 1151 cattle which subsequently tested positive during the study period following a negative IFN-y test would not have been identified with the old or new IFN-y cut-off criteria. Survival analysis showed that animals that would have been removed under the old interpretation criteria were at increased risk of a positive diagnosis with bTB during follow-up compared to other test negative animals. A newly developed risk prediction model (using a Cox proportional hazard model) showed that age, animal number of SICTT tests, number of inconclusive SICTT tests, B-A (IFN-y assay), B-N (IFN-y assay), animals from store herds and the percentage of the rest of the herd that were positive during the breakdown were statistically significantly associated with bTB detection. However, inclusion of the IFN-γ OD variables did not show added value in terms of prediction performance of the model.

Abstract Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), represents a significant problem for the agriculture industry as well as posing a risk for human health. Current diagnostic tests for bTB target the cell-mediated immune (CMI) response to infection with M. bovis, primarily through screening of animals with the tuberculin skin test. Epigenetic modifications have been shown to alter the course of the immune response and differentially methylated regions (DMRs) might also influence the outcome of the skin test in cattle. Whole Genome Bisulphite Sequencing (WGBS) was used to profile DNA methylation levels from peripheral blood of a group of cattle identified as test positive for M. bovis (positive for the single intradermal comparative tuberculin test (SICTT) and/or the interferon-γ release assay compared to a test negative control group [n = 8/group, total of 16 WGBS libraries]. Although global methylation profiles were similar for both groups across the genome, 223 DMRs and 159 Differentially Promoter Methylated Genes (DPMGs) were identified between groups with an excess of hypermethylated sites in SICTT positive cattle (threshold > 15% differential methylation). Genes located within these DMRs included the Interleukin 1 receptor (IL1R1) and MHC related genes (BOLA and BOLA-DQB). KEGG pathway analysis identified enrichment of genes involved in Calcium and MAPK signalling, as well as metabolism pathways. Analysis of DMRs in a subset of SICTT negative cattle that were IFN-γ positive showed differential methylation of genes including Interleukin 10 Receptor, alpha (IL10RA), Interleukin 17 F (IL17F) and host defence peptides (DEFB and BDEF109). This study has identified a number of immune gene loci at which differential methylation is associated with SICTT test results and the degree of methylation could influence effective host immune responses.

The Single Intradermal Comparative Tuberculin Test (SICTT) and the interferon-gamma (IFN-γ) assay are the approved diagnostic tests for bovine tuberculosis (bTB) in Ireland. The aim of this pilot study was to explore if there was any added diagnostic benefit from applying the Enferplex bTB test (an antibody test) in severe bTB herd breakdowns after the removal of cattle that had tested positive to the SICTT and the IFN-γ test. In addition to the normal bTB testing and management protocols, the animals in these herds that tested negative to SICTT and the IFN-γ test were followed forward for a period of two years. All animals were tested by Enferplex at enrolment. The time to subsequent bTB detection (diagnosed with SICTT/IFN-γ tests or detection of visible lesions at routine slaughter) for animals that tested positive or negative to the Enferplex bTB test at the start of the study was compared using Kaplan–Meier survival curves and Cox based survival models. Of the 484 enrolled animals (from 11 herds), 171 (35.3%) and 151 (31.1%) initially tested positive in the Enferplex assay under the high sensitivity and high specificity interpretation settings respectively. The results of the survival analysis showed that there was no difference in the survival time to a positive diagnosis with bTB during the follow-up period between animals initially classified as positive and negative by the Enferplex test. Further research is warranted to explore the potential benefit of using the Enferplex test in other scenarios.

Food Risk Assess EuropeVolume 1, Issue 2 0009E Technical reportOpen Access What is the proportional contribution of cattle-to-cattle, badger-to-cattle, and deer-to-cattle TB transmission to bovine TB in Ireland? John Griffin, John GriffinSearch for more papers by this authorInma Aznar, Inma AznarSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorCatherine McAloon, Catherine McAloonSearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author John Griffin, John GriffinSearch for more papers by this authorInma Aznar, Inma AznarSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorCatherine McAloon, Catherine McAloonSearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author First published: 26 September 2023 https://doi.org/10.2903/fr.efsa.2023.FR-0009AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract: Tuberculosis (TB) caused by the Mycobacterium tuberculosis complex (MTBC), including M. bovis, affects humans and multiple animal species. Cattle are significant hosts, and their interaction with other species, such as badgers and deer, is crucial for TB transmission dynamics. This opinion explores the proportional contributions of various transmission pathways to TB in cattle in Ireland: cattle-to-cattle, badger-to-cattle, and deer-to-cattle. It was carried out by the Scientific Working Group of the TB Forum following a request from the Department of Agriculture, Food and the Marine. While cattle-to-cattle transmission remains dominant, badgers play a significant epidemiological role, especially given their close interaction with cattle. Deer, primarily in County Wicklow, have also shown potential for TB transmission to cattle. Environmental factors, host density, and inter-species interaction further complicate transmission dynamics. Achieving TB eradication requires a holistic approach, addressing every transmission source. Advanced genomic and epidemiological tools, alongside traditional methods, can provide deeper insights into the transmission dynamics. The TB Eradication Programme should address, at both national and local levels, all relevant sources of transmission of TB to cattle. Current relevant sources include all cattle sources that substantially contribute to herd infection, and all wildlife that are maintenance hosts, and particularly those with spillback of infection to cattle. This situation may change over time and should be kept under review. References 1Good M, Bakker D, Duignan A, et al. The history of in vivo tuberculin testing in bovines: Tuberculosis, a "One Health" issue. Frontiers in Veterinary Science. 2018; 5. https://doi.org/10.3389/fvets.2018.00059 10.3389/fvets.2018.00059 Web of Science®Google Scholar 2Broughan JM, Judge J, Ely E, et al. Review article a review of risk factors for bovine tuberculosis infection in cattle in the UK and Ireland. Epidemiology and Infection 2016; 144: 2899-926. https://doi.org/10.1017/S095026881600131X 10.1017/S095026881600131X CASPubMedWeb of Science®Google Scholar 3More SJ. Can bovine TB be eradicated from the Republic of Ireland? Could this be achieved by 2030? Irish Veterinary Journal. 2019; 72. https://doi.org/10.1186/s13620-019-0140-x 10.1186/s13620-019-0140-x PubMedWeb of Science®Google Scholar 4More SJ, Good M. Understanding and managing bTB risk: Perspectives from Ireland. Veterinary Microbiology. 2015; 176: 209-18. https://doi.org/10.1016/j.vetmic.2015.01.026 10.1016/j.vetmic.2015.01.026 PubMedWeb of Science®Google Scholar 5Francis J. Tuberculosis in Animals and Man: A Study in Comparative Pathology. London: Cassell and Co. Ltd 1958. Google Scholar 6Costello E, Doherty ML, Monaghan ML, et al. A study of cattle-to-cattle transmission of Mycobacterium bovis infection. Veterinary Journal 1998; 155: 245-50. https://doi.org/10.1016/S1090-0233(05)80019-X 10.1016/S1090-0233(05)80019-X CASPubMedWeb of Science®Google Scholar 7Neill SD, Hanna J, O'Brien JJ, et al. Transmission of tuberculosis from experimentally infected cattle to in-contact calves. The Veterinary record 1989; 124: 269-71. https://doi.org/10.1136/vr.124.11.269 10.1136/vr.124.11.269 CASPubMedWeb of Science®Google Scholar 8Neill SD, Hanna J, Mackie DP, et al. Isolation of Mycobacterium bovis from the respiratory tracts of skin test-negative cattle. The Veterinary record 1992; 131: 45-7. https://doi.org/10.1136/vr.131.3.45 10.1136/vr.131.3.45 CASPubMedWeb of Science®Google Scholar 9Menzies FD, Neill SD. Cattle-to-Cattle Transmission of Bovine Tuberculosis. Veterinary Journal. 2000; 160: 92-106. https://doi.org/10.1053/tvjl.2000.0482 10.1016/S1090-0233(00)90482-9 CASPubMedWeb of Science®Google Scholar 10Maddock ECG. Experiments on the infectivity for healthy calves of bovine tubercle bacilli discharged in dung upon pasture: Part I. From tubercular calves fed with emulsions of tubercle bacilli 1934-5. Part II. From tubercular cows passing tubercle bacilli in their dung 1935-6. Journal of Hygiene 1936; 36: 594- 601. https://doi.org/10.1017/S0022172400043953 10.1017/S0022172400043953 CASPubMedWeb of Science®Google Scholar 11Morris RS, Pfeiffer DU, Jackson R. The epidemiology of Mycobacterium bovis infections. Veterinary Microbiology 1994; 40: 153-77. https://doi.org/10.1016/0378-1135(94)90053-1 10.1016/0378-1135(94)90053-1 CASPubMedWeb of Science®Google Scholar 12Barbier E, Boschiroli ML, Gueneau E, et al. First molecular detection of Mycobacterium bovis in environmental samples from a French region with endemic bovine tuberculosis. Journal of Applied Microbiology 2016; 120: 1193-207. https://doi.org/10.1111/jam.13090 10.1111/jam.13090 CASPubMedWeb of Science®Google Scholar 13Allen AR, Ford T, Skuce RA. Does Mycobacterium tuberculosis var. bovis Survival in the Environment Confound Bovine Tuberculosis Control and Eradication? A Literature Review. Veterinary Medicine International. 2021; 2021. https://doi.org/10.1155/2021/8812898 10.1155/2021/8812898 PubMedWeb of Science®Google Scholar 14Corner LAL. The role of wild animal populations in the epidemiology of tuberculosis in domestic animals: How to assess the risk. In: Veterinary Microbiology. Vet Microbiol 2006. 303-12. https://doi.org/10.1016/j.vetmic.2005.11.015 10.1016/j.vetmic.2005.11.015 PubMedWeb of Science®Google Scholar 15Haydon DT, Cleaveland S, Taylor LH, et al. Identifying reservoirs of infection: A conceptual and practical challenge. Emerging Infectious Diseases. 2002; 8: 1468-73. https://doi.org/10.3201/eid0812.010317 10.3201/eid0812.010317 PubMedWeb of Science®Google Scholar 16O'Reilly LM, Daborn CJ. The epidemiology of Mycobacterium bovis infections in animals and man: A review. Tubercle and Lung Disease 1995; 76: 1-46. https://doi.org/10.1016/0962-8479(95)90591-X 10.1016/0962-8479(95)90591-X PubMedWeb of Science®Google Scholar 17Smith NH. The global distribution and phylogeography of Mycobacterium bovis clonal complexes. Infection, Genetics and Evolution 2012; 12: 857-65. https://doi.org/10.1016/j.meegid.2011.09.007 10.1016/j.meegid.2011.09.007 PubMedWeb of Science®Google Scholar 18Loiseau C, Menardo F, Aseffa A, et al. An African origin for Mycobacterium bovis. Evolution, Medicine and Public Health 2020; 2020: 49-59. https://doi.org/10.1093/EMPH/EOAA005 10.1093/emph/eoaa005 PubMedWeb of Science®Google Scholar 19Pritchard DG. A century of bovine tuberculosis 1888-1988: Conquest and controversy. Journal of Comparative Pathology 1988; 99: 357-99. https://doi.org/10.1016/0021-9975(88)90058-8 10.1016/0021-9975(88)90058-8 CASPubMedWeb of Science®Google Scholar 20Bölske G, Englund L, Wahlström H, et al. Bovine tuberculosis in Swedish deer farms: epidemiological investigations and tracing using restriction fragment analysis. The Veterinary record 1995; 136: 414-7. https://doi.org/10.1136/vr.136.16.414 10.1136/vr.136.16.414 CASPubMedWeb of Science®Google Scholar 21More SJ, Radunz B, Glanville RJ. Review: Lessons learned during the successful eradication of bovine tuberculosis fromAustralia. Veterinary Record. 2015; 177: 224-32. https://doi.org/10.1136/vr.103163 10.1136/vr.103163 CASPubMedWeb of Science®Google Scholar 22Miller RS, Sweeney SJ. Mycobacterium bovis (bovine tuberculosis) infection in North American wildlife: Current status and opportunities for mitigation of risks of further infection in wildlife populations. Epidemiology and Infection. 2013; 141: 1357-70. https://doi.org/10.1017/S0950268813000976 10.1017/S0950268813000976 CASPubMedWeb of Science®Google Scholar 23VerCauteren KC, Lavelle MJ, Campa H. Persistent spillback of bovine tuberculosis from white-tailed deer to cattle in Michigan, USA: Status, Strategies, and Needs. Frontiers in Veterinary Science. 2018; 5: 301. https://doi.org/10.3389/fvets.2018.00301 10.3389/fvets.2018.00301 PubMedWeb of Science®Google Scholar 24McGrath G, Tratalos JA, More SJ. A visual representation of cattle movement in Ireland during 2016. Irish Veterinary Journal. 2018; 71. https://doi.org/10.1186/s13620-018-0129-x 10.1186/s13620-018-0129-x Web of Science®Google Scholar 25Clegg TA, More SJ, Higgins IM, et al. Potential infection-control benefit for Ireland from pre-movement testing of cattle for tuberculosis. Preventive Veterinary Medicine 2008; 84: 94-111. https://doi.org/10.1016/j.prevetmed.2007.11.004 10.1016/j.prevetmed.2007.11.004 CASPubMedWeb of Science®Google Scholar 26Clegg TA, Good M, More SJ. Future risk of bovine tuberculosis recurrence among higher risk herds in Ireland. Preventive Veterinary Medicine 2015; 118: 71-9. https://doi.org/10.1016/j.prevetmed.2014.11.013 10.1016/j.prevetmed.2014.11.013 CASPubMedWeb of Science®Google Scholar 27Fielding HR, McKinley TJ, Silk MJ, et al. Contact chains of cattle farms in Great Britain. Royal Society Open Science 2019; 6. https://doi.org/10.1098/rsos.180719 10.1098/rsos.180719 Web of Science®Google Scholar 28Fielding HR, McKinley TJ, Delahay RJ, et al. Effects of trading networks on the risk of bovine tuberculosis incidents on cattle farms in Great Britain. Royal Society Open Science 2020; 7. https://doi.org/10.1098/rsos.191806 Google Scholar 29Rossi G, Crispell J, Brough T, et al. Phylodynamic analysis of an emergent Mycobacterium bovis outbreak in an area with no previously known wildlife infections. bioRxiv. 2020. https://doi.org/10.1101/2020.11.12.379297 10.1101/2020.11.12.379297 Google Scholar 30Hahesy T, Scanlon M, Carton OT, et al. Cattle manure and the spread of bovine tuberculosis. In: Selected Papers 1991. Tuberculosis Investigation Unit. Dublin: 1991. Google Scholar 31Hahesy T, Scanlon M, Carton OT, et al. Aerosol dispersal of cattle slurry on holdings restricted due to bovine tuberculosis. In: Selected Papers 1995. Tuberculosis Investigation Unit, University College Dublin. 1995. Google Scholar 32Karolemeas K, McKinley TJ, Clifton-Hadley RS, et al. Recurrence of bovine tuberculosis breakdowns in Great Britain: Risk factors and prediction. Preventive Veterinary Medicine 2011; 102: 22-9. https://doi.org/10.1016/j.prevetmed.2011.06.004 10.1016/j.prevetmed.2011.06.004 CASPubMedWeb of Science®Google Scholar 33Conlan AJK, McKinley TJ, Karolemeas K, et al. Estimating the Hidden Burden of Bovine Tuberculosis in Great Britain. PLoS Computational Biology 2012; 8. https://doi.org/10.1371/journal.pcbi.1002730 10.1371/journal.pcbi.1002730 Web of Science®Google Scholar 34Dawson KL, Stevenson MA, Sinclair JA, et al. Recurrent bovine tuberculosis in New Zealand cattle and deer herds, 2006-2010. Epidemiology and Infection 2014; 142: 2065-74. https://doi.org/10.1017/S0950268814000910 10.1017/S0950268814000910 CASPubMedWeb of Science®Google Scholar 35Mee JF, Geraghty T, O'Neill R, et al. Bioexclusion of diseases from dairy and beef farms: Risks of introducing infectious agents and risk reduction strategies. Veterinary Journal. 2012; 194: 143-50. https://doi.org/10.1016/j.tvjl.2012.07.001 10.1016/j.tvjl.2012.07.001 PubMedWeb of Science®Google Scholar 36Skuce RA, Allen AR, McDowell SWJ. Herd-level risk factors for bovine tuberculosis: A literature review. Veterinary Medicine International. 2012; 2012. https://doi.org/10.1155/2012/621210 10.1155/2012/621210 PubMedGoogle Scholar 37Noonan NL, Sheane WD, Harper WR, et al. Wildlife as a possible reservoir of bovine tuberculosis. . Irish Veterinary Journal 1975; 29. Google Scholar 38Murphy D, Gormley E, Costello E, et al. The prevalence and distribution of Mycobacterium bovis infection in European badgers (Meles meles) as determined by enhanced post mortem examination and bacteriological culture. Research in Veterinary Science 2010; 88: 1-5. https://doi.org/10.1016/j.rvsc.2009.05.020 10.1016/j.rvsc.2009.05.020 CASPubMedWeb of Science®Google Scholar 39Murphy D, Gormley E, Collins DM, et al. Tuberculosis in cattle herds are sentinels for Mycobacterium bovis infection in European badgers (Meles meles): The Irish Greenfield Study. Veterinary Microbiology 2011; 151: 120-5. https://doi.org/10.1016/j.vetmic.2011.02.034 10.1016/j.vetmic.2011.02.034 CASPubMedWeb of Science®Google Scholar 40Furphy C, Costello E, Murphy D, et al. DNA typing of mycobacterium bovis isolates from badgers (Meles meles) culled from areas in ireland with different levels of tuberculosis prevalence. Veterinary Medicine International Published Online First: 2012. https://doi.org/10.1155/2012/742478 10.1155/2012/742478 Google Scholar 41Griffin JM, Williams DH, Kelly GE, et al. The impact of badger removal on the control of tuberculosis in cattle herds in Ireland. Preventive Veterinary Medicine 2005; 67: 237-66. https://doi.org/10.1016/j.prevetmed.2004.10.009 10.1016/j.prevetmed.2004.10.009 CASPubMedWeb of Science®Google Scholar 42Costello E, O'Grady D, Flynn O, et al. Study of Restriction Fragment Length Polymorphism Analysis and Spoligotyping for Epidemiological Investigation of Mycobacterium bovis Infection. 1999. Google Scholar 43Olea-Popelka FJ, Flynn O, Costello E, et al. Spatial relationship between Mycobacterium bovis strains in cattle and badgers in four areas in Ireland. Preventive Veterinary Medicine 2005; 71: 57-70. https://doi.org/10.1016/j.prevetmed.2005.05.008 10.1016/j.prevetmed.2005.05.008 CASPubMedWeb of Science®Google Scholar 44Olea-Popelka FJ, Fitzgerald P, White P, et al. Targeted badger removal and the subsequent risk of bovine tuberculosis in cattle herds in county Laois, Ireland. Preventive Veterinary Medicine 2009; 88: 178-84. https://doi.org/10.1016/j.prevetmed.2008.09.008 10.1016/j.prevetmed.2008.09.008 CASPubMedWeb of Science®Google Scholar 45Kelly GE, More SJ. Spatial clustering of TB-infected cattle herds prior to and following proactive badger removal. Epidemiology and Infection 2011; 139: 1220-9. https://doi.org/10.1017/S0950268810002323 10.1017/S0950268810002323 CASPubMedWeb of Science®Google Scholar 46Skuce RA, Allen AR, Mcdowell SWJ, et al. Bovine Tuberculosis (TB): A Review Of Cattle-To-Cattle Transmission, Risk Factors And Susceptibility. 2011. http://www.dardni.gov.uk Google Scholar 47Biek R, O'Hare A, Wright D, et al. Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations. PLoS Pathogens 2012; 8. https://doi.org/10.1371/journal.ppat.1003008 10.1371/journal.ppat.1003008 Web of Science®Google Scholar 48Akhmetova A, Guerrero J, McAdam P, et al. Genomic epidemiology of Mycobacterium bovis infection in sympatric badger and cattle populations in Northern Ireland. Published Online First: 2021. https://doi.org/10.1101/2021.03.12.435101 10.1101/2021.03.12.435101 Google Scholar 49Skuce RA, Mallon TR, McCormick CM, et al. Mycobacterium bovis genotypes in Northern Ireland: Herd-level surveillance (2003 to 2008). Veterinary Record 2010; 167: 684-9. https://doi.org/10.1136/vr.c5108 10.1136/vr.c5108 CASPubMedWeb of Science®Google Scholar 50Trewby H. The genetic and spatial epidemiology of bovine tuberculosis in the UK: from molecular typing to bacterial whole genome sequencing. Published Online First: 2016.https://eleanor.lib.gla.ac.uk/record=b3152954 (accessed 12 May 2021). Google Scholar 51Milne MG, Graham J, Allen A, et al. 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. BMC Microbiology 2019; 19. https://doi.org/10.1186/s12866-019-1530-7 10.1186/s12866-019-1530-7 PubMedWeb of Science®Google Scholar 52Byrne AW, Paddy Sleeman D, O'Keeffe J, et al. The ecology of the European badger (Meles meles) in Ireland: A review. Biology and Environment. 2012; 112: 105-32. https://doi.org/10.3318/BIOE.2012.02 10.3318/BIOE.2012.02 Google Scholar 53Kelly DJ, Mullen E, Good M. Bovine Tuberculosis: The Emergence of a New Wildlife Maintenance Host in Ireland. Frontiers in Veterinary Science 2021; 8. https://doi.org/10.3389/fvets.2021.632525 10.3389/fvets.2021.632525 Web of Science®Google Scholar 54Byrne AW, White PW, McGrath G, et al. Risk of tuberculosis cattle herd breakdowns in Ireland: Effects of badger culling effort, density and historic large-scale interventions. Veterinary Research 2014; 45. https://doi.org/10.1186/s13567-014-0109-4 10.1186/s13567-014-0109-4 PubMedWeb of Science®Google Scholar 55Wright DM, Reid N, Montgomery WI, et al. Herd-level bovine tuberculosis risk factors: Assessing the role of low-level badger population disturbance. Scientific Reports 2015; 5. https://doi.org/10.1038/srep13062 10.1038/srep13062 Web of Science®Google Scholar 56Good M. The Tuberculin Test and its Role in the Strategic Management and Eradication of Tuberculosis in Cattle. 2011. Google Scholar 57More SJ. What is needed to eradicate bovine tuberculosis successfully: An Ireland perspective. Veterinary Journal. 2009; 180: 275-8. https://doi.org/10.1016/j.tvjl.2009.01.027 10.1016/j.tvjl.2009.01.027 PubMedWeb of Science®Google Scholar 58Godfray HCJ, Donnelly CA, Kao RR, et al. A restatement of the natural science evidence base relevant to the control of bovine tuberculosis in Great Britain. Proceedings of the Royal Society B: Biological Sciences. 2013; 280. https://doi.org/10.1098/rspb.2013.1634 10.1098/rspb.2013.1634 PubMedWeb of Science®Google Scholar 59Payne A, Boschiroli ML, Gueneau E, et al. Bovine tuberculosis in "Eurasian" badgers (Meles meles) in France. European Journal of Wildlife Research 2013; 59: 331-9. https://doi.org/10.1007/s10344-012-0678-3 10.1007/s10344-012-0678-3 Web of Science®Google Scholar 60Hardstaff JL, Marion G, Hutchings MR, et al. Evaluating the tuberculosis hazard posed to cattle from wildlife across Europe. Research in Veterinary Science 2014; 97: S86-93. https://doi.org/10.1016/j.rvsc.2013.12.002 10.1016/j.rvsc.2013.12.002 PubMedWeb of Science®Google Scholar 61Carden RF, Carlin CM, Marnell F, et al. Distribution and range expansion of deer in Ireland. Mammal Review. 2011; 41: 313-25. https://doi.org/10.1111/j.1365-2907.2010.00170.x 10.1111/j.1365-2907.2010.00170.x Web of Science®Google Scholar 62Doyle R, Clegg TA, McGrath G, et al. The bovine tuberculosis cluster in north County Sligo during 2014-16. Irish Veterinary Journal. 2018; 71. https://doi.org/10.1186/s13620-018-0135-z 10.1186/s13620-018-0135-z Web of Science®Google Scholar 63Griffin JM, Hahesya T, Lynch K, et al. The association of cattle husbandry practices, environmental factors and farmer characteristics with the occurrence of chronic bovine tuberculosis in dairy herds in the Republic of Ireland. 1993. Google Scholar 64Dodd K. Tuberculosis in free-living deer. The Veterinary record 1984; 115: 592-3. https://doi.org/10.1136/vr.115.23.592 10.1136/vr.115.23.592 CASPubMedWeb of Science®Google Scholar 65Nugent G, Gortazar C, Knowles G. The epidemiology of Mycobacterium bovis in wild deer and feral pigs and their roles in the establishment and spread of bovine tuberculosis in New Zealand wildlife. New Zealand Veterinary Journal 2015; 63: 54-67. https://doi.org/10.1080/00480169.2014.963792 10.1080/00480169.2014.963792 PubMedWeb of Science®Google Scholar 66Shury TK, Bergeson D. Lesion distribution and epidemiology of mycobacterium bovis in elk and white-tailed deer in South-Western Manitoba, Canada. Veterinary Medicine International 2011; 2011. https://doi.org/10.4061/2011/591980 10.4061/2011/591980 PubMedGoogle Scholar 67Crispell J, Cassidy S, Kenny K, et al. Mycobacterium bovis genomics reveals transmission of infection between cattle and deer in Ireland. Microbial Genomics 2020; 6: 1-8. https://doi.org/10.1099/mgen.0.000388 10.1099/mgen.0.000388 CASWeb of Science®Google Scholar 68Croucher NJ, Didelot X. The application of genomics to tracing bacterial pathogen transmission. Current Opinion in Microbiology. 2015; 23: 62-7. https://doi.org/10.1016/j.mib.2014.11.004 10.1016/j.mib.2014.11.004 PubMedWeb of Science®Google Scholar 69White PW, Martin SW, de Jong MCM, et al. The importance of "neighbourhood" in the persistence of bovine tuberculosis in Irish cattle herds. Preventive Veterinary Medicine 2013; 110: 346-5. https://doi.org/10.1016/j.prevetmed.2013.02.012 10.1016/j.prevetmed.2013.02.012 PubMedWeb of Science®Google Scholar 70Byrne AW, Kenny K, Fogarty U, et al. Spatial and temporal analyses of metrics of tuberculosis infection in badgers (Meles meles) from the Republic of Ireland: Trends in apparent prevalence. Preventive Veterinary Medicine 2015; 122: 345-54. https://doi.org/10.1016/j.prevetmed.2015.10.013 10.1016/j.prevetmed.2015.10.013 CASPubMedWeb of Science®Google Scholar 71Aznar I. Infection dynamics and effective control strategies of tuberculosis in badgers and cattle in Ireland. . 2018. 10.18174/430133 Google Scholar 72Donnelly CA, Nouvellet P. The contribution of badgers to confirmed tuberculosis in cattle in high-incidence areas in England. PLoS Currents 2013; 5. https://doi.org/10.1371/currents.outbreaks.097a904d3f3619db2fe78d24bc776098 10.1371/currents.outbreaks.097a904d3f3619db2fe78d24bc776098 Google Scholar 73 DAERA. Bovine tuberculosis in Northern Ireland. 2017 annual report. 2018. Google Scholar 74Denny GO, Wilesmith JW. Bovine tuberculosis in Northern Ireland: A case- control study of herd risk factors. Veterinary Record 1999; 144: 305-10. https://doi.org/10.1136/vr.144.12.305 10.1136/vr.144.12.305 CASPubMedWeb of Science®Google Scholar 75Crispell J, Benton CH, Balaz D, et al. Combining genomics and epidemiology to analyse bi-directional transmission of mycobacterium bovis in a multi-host system. eLife 2019; 8. https://doi.org/10.7554/eLife.45833 10.7554/eLife.45833 Web of Science®Google Scholar 76Thulke HH, Lange M, Tratalos JA, et al. Eradicating BVD, reviewing Irish programme data and model predictions to support prospective decision making. Preventive Veterinary Medicine 2018; 150: 151-61. https://doi.org/10.1016/j.prevetmed.2017.11.017 10.1016/j.prevetmed.2017.11.017 PubMedWeb of Science®Google Scholar 77Biemans F, ben Romdhane R, Gontier P, et al. Modelling transmission and control of Mycobacterium avium subspecies paratuberculosis within Irish dairy herds with compact spring calving. Preventive Veterinary Medicine 2021; 186:105228. https://doi.org/10.1016/j.prevetmed.2020.105228 10.1016/j.prevetmed.2020.105228 CASPubMedWeb of Science®Google Scholar 78Livingstone PG, Hancox N, Nugent G, et al. Development of the New Zealand strategy for local eradication of tuberculosis from wildlife and livestock. New Zealand Veterinary Journal. 2015; 63: 98-107. https://doi.org/10.1080/00480169.2015.1013581 10.1080/00480169.2015.1013581 PubMedWeb of Science®Google Scholar 79O'Brien DJ, Schmitt SM, Fitzgerald SD, et al. Management of bovine tuberculosis in Michigan wildlife: Current status and near term prospects. Veterinary Microbiology 2011; 151: 179-87. https://doi.org/10.1016/j.vetmic.2011.02.042 10.1016/j.vetmic.2011.02.042 PubMedWeb of Science®Google Scholar Volume1, Issue2September‐December 20230009E ReferencesRelatedInformation

Population Medicine considers the following types of articles:• Research Papers -reports of data from original research or secondary dataset analyses.• Review Papers -comprehensive, authoritative, reviews within the journal's scope.These include both systematic reviews and narrative reviews.• Short Reports -brief reports of data from original research.• Policy Case Studies -brief articles on policy development at a regional or national level.• Study Protocols -articles describing a research protocol of a study.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.

Population Medicine considers the following types of articles:• Research Papers -reports of data from original research or secondary dataset analyses.• Review Papers -comprehensive, authoritative, reviews within the journal's scope.These include both systematic reviews and narrative reviews.• Short Reports -brief reports of data from original research.• Policy Case Studies -brief articles on policy development at a regional or national level.• Study Protocols -articles describing a research protocol of a study.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.

Food Risk Assess EuropeVolume 1, Issue 2 0007E Technical reportOpen Access What topics should be prioritised for the provision of funding by DAFM using the ERAD TB research fund in the period 2022-2024? John Griffin, John GriffinSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author John Griffin, John GriffinSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author First published: 26 September 2023 https://doi.org/10.2903/fr.efsa.2023.FR-0007AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract This opinion covers areas of policy-oriented scientific research relating to bovine tuberculosis bTB) eradication in Ireland. It identifies areas for prioritised research by the Department of Agriculture, Food and the Marine for the period 2022-2024 based on stakeholder feedback. Key areas of emphasis include understanding different sources of Mycobacterium bovis infection, such as wildlife reservoirs and cattle movement, the role of whole genome sequencing (WGS) in epidemiology, the evaluation of badger vaccination, enhancement of diagnostic tests, and understanding stakeholder attitudes and compliance regarding control measures. A holistic approach, encompassing various research tools and methodologies, including whole genome sequencing, mathematical modelling, machine learning and the use of inward contact chains, are suggested to facilitate a comprehensive BTB understanding. Though a priority list is proposed, the importance of maintaining adaptability and funding high-merit projects outside the list is emphasised, to support the continued evolution and effectiveness of BTB control strategies in Ireland. References 1Rudan I, Gibson JL, Ameratunga S, et al. Setting priorities in global child health research investments: Guidelines for implementation of CHNRI method. Croatian Medical Journal 2008; 49: 720–33. doi:https://doi.org/10.3325/cmj.2008.49.720 10.3325/cmj.2008.49.720 PubMedWeb of Science®Google Scholar 2Rudan I, Yoshida S, Chan KY, et al. Setting health research priorities using the CHNRI method: VII. A review of the first 50 applications of the CHNRI method. Journal of Global Health 2017; 7. doi:https://doi.org/10.7189/jogh.07.011004 10.7189/jogh.07.011004 PubMedGoogle Scholar 3Rudan I. Setting health research priorities using the CHNRI method: IV. Key conceptual advances. Journal of Global Health 2016; 6. doi:https://doi.org/10.7189/jogh.06.010501 10.7189/jogh.06.010501 PubMedGoogle Scholar 4Irvine C, Armstrong A, Nagata JM, et al. Setting Global Research Priorities in Pediatric and Adolescent HIV Using the Child Health and Nutrition Research Initiative (CHNRI) Methodology. 2018. www.surveymonkey.com Google Scholar 5Campbell EL, Byrne AW, Menzies FD, et al. Interspecific visitation of cattle and badgers to fomites: A transmission risk for bovine tuberculosis? Ecology and Evolution 2019; 9: 8479–89. doi:https://doi.org/10.1002/ECE3.5282 10.1002/ece3.5282 PubMedWeb of Science®Google Scholar 6Allen AR, Ford T, Skuce RA. Does Mycobacterium tuberculosis var. bovis Survival in the Environment Confound Bovine Tuberculosis Control and Eradication? A Literature Review. Veterinary Medicine International. 2021;2021. doi:https://doi.org/10.1155/2021/8812898 10.1155/2021/8812898 PubMedWeb of Science®Google Scholar 7Crispell J, Cassidy S, Kenny K, et al. Mycobacterium bovis genomics reveals transmission of infection between cattle and deer in Ireland. Microbial Genomics 2020; 6: 1–8. doi:https://doi.org/10.1099/mgen.0.000388 10.1099/mgen.0.000388 CASWeb of Science®Google Scholar 8Gaughran A, MacWhite T, Mullen E, et al. Dispersal patterns in a medium- density Irish badger population: Implications for understanding the dynamics of tuberculosis transmission. Ecology and Evolution 2019; 9: 13142–52. doi:https://doi.org/10.1002/ECE3.5753 10.1002/ece3.5753 PubMedWeb of Science®Google Scholar 9Clegg TA, More SJ, Higgins IM, et al. Potential infection-control benefit for Ireland from pre-movement testing of cattle for tuberculosis. Preventive Veterinary Medicine 2008; 84: 94–111. doi:https://doi.org/10.1016/j.prevetmed.2007.11.004 10.1016/j.prevetmed.2007.11.004 CASPubMedWeb of Science®Google Scholar 10Adkin A, Brouwer A, Downs SH, et al. Assessing the impact of a cattle risk- based trading scheme on the movement of bovine tuberculosis infected animals in England and Wales. Preventive Veterinary Medicine 2016; 123: 23–31. doi:https://doi.org/10.1016/j.prevetmed.2015.11.021 10.1016/j.prevetmed.2015.11.021 CASPubMedWeb of Science®Google Scholar 11Adkin A, Brouwer A, Simons RRL, et al. Development of risk-based trading farm scoring system to assist with the control of bovine tuberculosis in cattle in England and Wales. Preventive Veterinary Medicine 2016; 123: 32–8. doi:https://doi.org/10.1016/j.prevetmed.2015.11.020 10.1016/j.prevetmed.2015.11.020 CASPubMedWeb of Science®Google Scholar 12Mccallan L, Mcnair J, Skuce R. A review of the potential role of cattle slurry in the spread of bovine tuberculosis. Agri-food and Biosciences Institute: Belfast, UK 2014. Google Scholar 13Good M, Clegg TA, Duignan A, et al. Impact of the national full herd depopulation policy on the recurrence of bovine tuberculosis in Irish herds, 2003 to 2005. Veterinary Record 2011; 169: 581. doi:https://doi.org/10.1136/vr.d4571 10.1136/vr.d4571 CASPubMedWeb of Science®Google Scholar 14Gormley E, Ní Bhuachalla D, Murphy D, et al. Oral Vaccination of Free-Living Badgers (Meles meles) with Bacille Calmette Guérin (BCG) Vaccine Confers Protection against Tuberculosis. PLoS One 2017; 12(1). doi:https://doi.org/10.1371/journal.pone.0168851 10.1371/journal.pone.0168851 Web of Science®Google Scholar 15Chambers MA, Aldwell F, Williams GA, et al. The effect of oral vaccination with Mycobacterium bovis BCG on the development of tuberculosis in captive European badgers (Meles meles). Frontiers in Cellular and Infection Microbiology 2017; 7. doi:https://doi.org/10.3389/fcimb.2017.00006 10.3389/fcimb.2017.00006 Google Scholar 16Balseiro A, Prieto JM, Álvarez V, et al. Protective Effect of Oral BCG and Inactivated Mycobacterium bovis Vaccines in European Badgers (Meles meles) Experimentally Infected With M. bovis. Frontiers in Veterinary Science 2020; 7. doi:https://doi.org/10.3389/fvets.2020.00041 10.3389/fvets.2020.00041 PubMedWeb of Science®Google Scholar 17Payne A, Ruette S, Jacquier M, et al. Estimation of Bait Uptake by Badgers, Using Non-invasive Methods, in the Perspective of Oral Vaccination Against Bovine Tuberculosis in a French Infected Area. Frontiers in Veterinary Science 2022; 9. doi:https://doi.org/10.3389/fvets.2022.787932 10.3389/fvets.2022.787932 PubMedWeb of Science®Google Scholar 18Middleton S, Steinbach S, Coad M, et al. A molecularly defined skin test reagent for the diagnosis of bovine tuberculosis compatible with vaccination against Johne's Disease. Scientific Reports 2021; 11: 2929. doi:https://doi.org/10.1038/s41598-021-82434-7 10.1038/s41598-021-82434-7 CASPubMedWeb of Science®Google Scholar 19Kelly DJ, Mullen E, Good M. Bovine Tuberculosis: The Emergence of a New Wildlife Maintenance Host in Ireland. Frontiers in Veterinary Science 2021; 8. doi:https://doi.org/10.3389/fvets.2021.632525 10.1017/dsj.2021.7 Web of Science®Google Scholar 20VerCauteren KC, Lavelle MJ, Campa H. Persistent spillback of bovine tuberculosis from white-tailed deer to cattle in Michigan, USA: Status, Strategies, and Needs. Frontiers in Veterinary Science. 2018; 5: 301. doi:https://doi.org/10.3389/fvets.2018.00301 10.3389/fvets.2018.00301 PubMedWeb of Science®Google Scholar 21More SJ. Can bovine TB be eradicated from the Republic of Ireland? Could this be achieved by 2030? Irish Veterinary Journal. 2019; 72. doi:https://doi.org/10.1186/s13620-019-0140-x 10.1186/s13620-019-0140-x PubMedWeb of Science®Google Scholar Volume1, Issue2September‐December 20230007E ReferencesRelatedInformation

Food Risk Assess EuropeVolume 1, Issue 2 0006E Technical reportOpen Access How can DAFM best make use of whole genome sequencing to improve the effectiveness of the TB eradication programme? John Griffin, John GriffinSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorMáire McElroy, Máire McElroySearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author John Griffin, John GriffinSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorMáire McElroy, Máire McElroySearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author First published: 26 September 2023 https://doi.org/10.2903/fr.efsa.2023.FR-0006AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Whole genome sequencing (WGS) is a technique used to determine the complete DNA sequence of an organism's genome. In the context of bacterial pathogens, such as the causative agent of bovine tuberculosis (Mycobacterium bovis), WGS offers insights into the nucleotide sequence variations that arise due to mutations during bacterial replication. By tracing these mutations, researchers can differentiate between bacterial strains and assess the historical divergence and relatedness of strains. The Irish Department of Agriculture, Food and the Marine (DAFM) sought an opinion from the TB Forum scientific working group on the utility of WGS in the bovine tuberculosis (bTB) eradication programme. Through various case studies in regions such as Cumbria and Woodchester Park, UK, WGS provided insights into the directionality of transmission between species, revealing complex interplays between cattle, badgers, and deer. For instance, in Cumbria, cattle-to-cattle transmission dominated initial phases of an outbreak before the bacteria established in the local badger population. In contrast, studies in other regions suggested varying roles for wildlife in the transmission and persistence of M. bovis. WGS will enhance the efficacy of the BTB Eradication Programme in Ireland, and can be harnessed to attribute infection sources, identify transmission pathways, and quantify transmission rates across species. A major project in Ireland, BTBGenIE, funded by DAFM and led by University College Dublin, is already integrating WGS with traditional eradication and surveillance activities. It is essential that M. bovis genome sequence data are shared with the national and international scientific community in a routine and contemporaneous manner, to maximise the opportunities for analysis and public good arising from WGS studies. This is especially relevant for Northern Ireland considering the movement of cattle between Northern Ireland and the Republic of Ireland. References 1Aranaz A, Bana EL, Mateos A, et al. Spacer Oligonucleotide Typing of Mycobacterium bovis Strains from Cattle and Other Animals: a Tool for Studying Epidemiology of Tuberculosis. Journal of Clinical Microbiology 1996; 34: 2734–40. 10.1128/jcm.34.11.2734-2740.1996 CASPubMedWeb of Science®Google Scholar 2Roring S, Scott AN, Hewinson RG, et al. Evaluation of variable number tandem repeat (VNTR) loci in molecular typing of Mycobacterium bovis isolates from Ireland. Veterinary Microbiology 2004; 101: 65–73. doi:https://doi.org/10.1016/J.VETMIC.2004.02.013 10.1016/j.vetmic.2004.02.013 CASPubMedWeb of Science®Google Scholar 3Allen AR, Dale J, McCormick C, et al. The phylogeny and population structure of Mycobacterium bovis in the British Isles. Infection, Genetics and Evolution 2013; 20: 8–15. doi:https://doi.org/10.1016/J.MEEGID.2013.08.003 10.1016/j.meegid.2013.08.003 CASPubMedWeb of Science®Google Scholar 4Evans JT, Smith EG, Banerjee A, et al. Cluster of human tuberculosis caused by Mycobacterium bovis: evidence for person-to-person transmission in the UK. Lancet 2007; 369: 1270–6. doi:https://doi.org/10.1016/S0140-6736(07)60598-4 10.1016/S0140-6736(07)60598-4 PubMedWeb of Science®Google Scholar 5Smith NH, Berg S, Dale J, et al. European 1: A globally important clonal complex of Mycobacterium bovis. Infection, Genetics and Evolution 2011; 11: 1340–51. doi:https://doi.org/10.1016/J.MEEGID.2011.04.027 10.1016/j.meegid.2011.04.027 PubMedWeb of Science®Google Scholar 6Smith NH, Dale J, Inwald J, et al. The population structure of Mycobacterium bovis in Great Britain: Clonal expansion. Proceedings of the National Academy of Sciences 2003; 100: 15271. doi:https://doi.org/10.1073/PNAS.2036554100 10.1073/pnas.2036554100 CASPubMedWeb of Science®Google Scholar 7Fleischmann RD, Adams MD, White O, et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 1995; 269: 496–512. doi:https://doi.org/10.1126/SCIENCE.7542800 10.1126/science.7542800 CASPubMedWeb of Science®Google Scholar 8Cole ST, Brosch R, Parkhill J, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998; 393: 537–44. doi:https://doi.org/10.1038/31159 10.1038/31159 CASPubMedWeb of Science®Google Scholar 9Garnier T, Eiglmeier K, Camus J-C, et al. The complete genome sequence of Mycobacterium bovis. www.defra.gov.ukanimalh Google Scholar 10Meehan CJ, Goig GA, Kohl TA, et al. Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nature Reviews Microbiology 2019; 17: 533–45. doi:https://doi.org/10.1038/S41579-019-0214-5 10.1038/s41579-019-0214-5 CASPubMedWeb of Science®Google Scholar 11Lorente-Leal V, Farrell D, Romero B, et al. Performance and Agreement Between WGS Variant Calling Pipelines Used for Bovine Tuberculosis Control: Toward International Standardization. Frontiers in Veterinary Science 2021; 8: 1540. doi:https://doi.org/10.3389/FVETS.2021.780018/BIBTEX 10.3389/fvets.2021.780018 Web of Science®Google Scholar 12Kohl TA, Harmsen D, Rothgänger J, et al. Harmonized Genome Wide Typing of Tubercle Bacilli Using a Web-Based Gene-By-Gene Nomenclature System. EBioMedicine 2018; 34: 131–8. doi:https://doi.org/10.1016/J.EBIOM.2018.07.030 10.1016/j.ebiom.2018.07.030 PubMedWeb of Science®Google Scholar 13Bouckaert R, Vaughan TG, Barido-Sottani J, et al. BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis. PLOS Computational Biology 2019; 15:e1006650. doi:https://doi.org/10.1371/JOURNAL.PCBI.1006650 10.1371/journal.pcbi.1006650 CASPubMedWeb of Science®Google Scholar 14Didelot X, Gardy J, Colijn C. Bayesian inference of infectious disease transmission from whole-genome sequence data. Molecular Biology and Evolution 2014; 31: 1869–79. doi:https://doi.org/10.1093/MOLBEV/MSU121 10.1093/molbev/msu121 CASPubMedWeb of Science®Google Scholar 15Didelot X, Kendall M, Xu Y, et al. Genomic Epidemiology Analysis of Infectious Disease Outbreaks Using TransPhylo. Current Protocols 2021; 1:e60. doi:https://doi.org/10.1002/CPZ1.60 10.1002/cpz1.60 PubMedGoogle Scholar 16Biek R, O'Hare A, Wright D, et al. Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations. PLoS Pathogens 2012; 8. doi:https://doi.org/10.1371/journal.ppat.1003008 10.1371/journal.ppat.1003008 Web of Science®Google Scholar 17Kao RR, Price-Carter M, Robbe-Austerman S. Use of genomics to track bovine tuberculosis transmission. Revue Scientifique et Technique 2016; 35: 241–58. doi:https://doi.org/10.20506/rst.35.1.2430 10.20506/rst.35.1.2430 CASGoogle Scholar 18van Tonder AJ, Thornton MJ, Conlan AJK, et al. Inferring Mycobacterium bovis transmission between cattle and badgers using isolates from the Randomised Badger Culling Trial. PLoS Pathogens 2021; 17. doi:https://doi.org/10.1371/JOURNAL.PPAT.1010075 10.1371/JOURNAL.PPAT.1010075 Web of Science®Google Scholar 19Crispell J, Benton CH, Balaz D, et al. Combining genomics and epidemiology to analyse bi-directional transmission of Mycobacterium bovis in a multi-host system. Elife 2019; 8. doi:https://doi.org/10.7554/eLife.45833 10.7554/eLife.45833 Web of Science®Google Scholar 20Rossi G, Crispell J, Brough T, et al. Phylodynamic analysis of an emergent Mycobacterium bovis outbreak in an area with no previously known wildlife infections. Journal of Applied Ecology 2022; 59: 210–22. doi:https://doi.org/10.1111/1365-2664.14046 10.1111/1365-2664.14046 Web of Science®Google Scholar 21Salvador LCM, O'Brien DJ, Cosgrove MK, et al. Disease management at the wildlife-livestock interface: Using whole-genome sequencing to study the role of elk in Mycobacterium bovis transmission in Michigan, USA. Molecular Ecology 2019; 28: 2192–205. doi:https://doi.org/10.1111/mec.15061 10.1111/mec.15061 CASPubMedWeb of Science®Google Scholar 22Crispell J, Cassidy S, Kenny K, et al. Mycobacterium bovis genomics reveals transmission of infection between cattle and deer in Ireland. Microbial Genomics 2020; 6: 1–8. doi:https://doi.org/10.1099/mgen.0.000388 10.1099/mgen.0.000388 CASWeb of Science®Google Scholar 23More SJ, Radunz B, Glanville RJ. Review: Lessons learned during the successful eradication of bovine tuberculosis from Australia. Veterinary Record. 2015; 177: 224–32. doi:https://doi.org/10.1136/vr.103163 10.1136/vr.103163 CASPubMedWeb of Science®Google Scholar 24Glaser L, Carstensen M, Shaw S, et al. Descriptive Epidemiology and Whole Genome Sequencing Analysis for an Outbreak of Bovine Tuberculosis in Beef Cattle and White-Tailed Deer in Northwestern Minnesota. PLoS ONE 2016; 11. doi:https://doi.org/10.1371/JOURNAL.PONE.0145735 10.1371/JOURNAL.PONE.0145735 Web of Science®Google Scholar 25Murphy D, Cummins J, Johnston D, et al. Various applications of whole genome sequencing for assisting the role of the Irish National Reference Laboratory for Bovine Tuberculosis. In: Proceedings Seventh Internationa Conference on Mycobacterium bovis, 7-10 June, Galway, Ireland. 2022. Google Scholar 26Orloski K, Robbe-Austerman S, Stuber T, et al. Whole genome sequencing of Mycobacterium bovis isolated from livestock in the United States, 1989-2018. Frontiers in Veterinary Science 2018; 5: 253. doi:https://doi.org/10.3389/FVETS.2018.00253/BIBTEX 10.3389/fvets.2018.00253 PubMedWeb of Science®Google Scholar 27Duffy SC, Srinivasan S, Schilling MA, et al. Reconsidering Mycobacterium bovis as a proxy for zoonotic tuberculosis: a molecular epidemiological surveillance study. The Lancet Microbe 2020; 1: e66–73. doi:https://doi.org/10.1016/S2666-5247(20)30038-0 10.1016/S2666-5247(20)30038-0 CASPubMedGoogle Scholar 28Gonzalo-Asensio J, Malaga W, Pawlik A, et al. Evolutionary history of tuberculosis shaped by conserved mutations in the PhoPR virulence regulator. Proceedings of the National Academy of Sciences 2014; 111: 11491–6. doi:https://doi.org/10.1073/PNAS.1406693111/-/DCSUPPLEMENTAL 10.1073/pnas.1406693111 CASPubMedWeb of Science®Google Scholar 29Mata E, Farrell D, Ma R, et al. Independent genomic polymorphisms in the PknH serine threonine kinase locus during evolution of the Mycobacterium tuberculosis Complex affect virulence and host preference. PLOS Pathogens 2020; 16:e1009061. doi:https://doi.org/10.1371/JOURNAL.PPAT.1009061 10.1371/journal.ppat.1009061 CASPubMedWeb of Science®Google Scholar Volume1, Issue2September‐December 20230006E ReferencesRelatedInformation

Food Risk Assess EuropeVolume 1, Issue 2 0008E Technical reportOpen Access What is the scope for existing (including recently developed) diagnostic methods to detect infected cattle which are not currently detected by the existing programme? John Griffin, John GriffinSearch for more papers by this authorInma Aznar, Inma AznarSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorCatherine McAloon, Catherine McAloonSearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author John Griffin, John GriffinSearch for more papers by this authorInma Aznar, Inma AznarSearch for more papers by this authorPhilip Breslin, Philip BreslinSearch for more papers by this authorMargaret Good, Margaret GoodSearch for more papers by this authorStephen Gordon, Stephen GordonSearch for more papers by this authorEamonn Gormley, Eamonn GormleySearch for more papers by this authorCatherine McAloon, Catherine McAloonSearch for more papers by this authorFraser Menzies, Fraser MenziesSearch for more papers by this authorSimon More, Simon MoreSearch for more papers by this authorSiobhán Ring, Siobhán RingSearch for more papers by this authorJimmy Wiseman, Jimmy WisemanSearch for more papers by this author First published: 26 September 2023 https://doi.org/10.2903/fr.efsa.2023.FR-0008AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract This document critically reviews the range of diagnostic methods currently employed in Ireland to detect animals infected with Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), that are not currently detected by the existing eradication programme. The review was carried out by the Scientific Working Group of the TB Forum following a request from the Department of Agriculture, Food and the Marine. Particular emphasis is placed on the Comparative Intradermal Tuberculin Test (CITT) and the Interferon-gamma (IFN-γ) assay, noting that different tests are used strategically, maximising the advantages and minimising the limitations of each test. The CITT is routinely used as a screening test, with its reliability closely linked to the tester's skill and experience. The IFN-γ assay is used as an ancillary test, noting that its specificity remains a concern. Antibody-based tests, such as ELISA, show promise in identifying BTB during its more advanced stages of infection. There is little evidence of 'a silver bullet' in the area of bTB diagnostics. For the foreseeable future, it is likely that the CITT, using tuberculin PPD, will remain the screening test of choice for cattle. It will be supplemented by the other currently approved tests and newly developed tests as ancillary tests. Experience from a number of countries has shown that eradication can be achieved in the absence of perfect diagnostic tests. For this to happen, the testing programme must be supplemented by a range of risk-based approaches to herd management and animal movement. Where relevant, eradication is only possible if cattle-based efforts are complemented by an effective programme to manage transmission from wildlife to cattle. References 1Duignan A, Kenny K, Bakker D, et al. Tuberculin PPD Potency Assays in Naturally Infected Tuberculous Cattle as a Quality Control Measure in the Irish Bovine Tuberculosis Eradication Programme. Frontiers in Veterinary Science 2019; 6: 328. https://doi.org/10.3389/fvets.2019.00328 10.3389/fvets.2019.00328 PubMedWeb of Science®Google Scholar 2Pollock JM, McNair J, Bassett H, et al. Specific delayed-type hypersensitivity responses to ESAT-6 identify tuberculosis-infected cattle. Journal of Clinical Microbiology 2003; 41: 1856–60. https://doi.org/10.1128/JCM.41.5.1856-1860.2003 10.1128/JCM.41.5.1856-1860.2003 CASPubMedWeb of Science®Google Scholar 3Gormley E, Doyle M, Duignan A, et al. Identification of risk factors associated with disclosure of false positive bovine tuberculosis reactors using the gamma- interferon (IFNγ) assay. 2013. http://www.veterinaryresearch.org/content/44/1/117 Google Scholar 4Cooney R, Kazda J, Quinn J, et al. Environmental mycobacteria in Ireland as a source of non-specific sensitisation to tuberculins. Irish Veterinary Journal 1997; 50: 370–3. Web of Science®Google Scholar 5O'Reilly L, MacClancy B. Estimation of the sensitivity, specificity and predictive value of the intradermal test. Irish Veterinary Journal 1978; 32: 127– 8. Google Scholar 6Good M, Duignan A, Bevi AF, et al. Would screening with a Single Intradermal bTB Test work in Ireland? VI International M bovis Conference, Cardiff, Wales Published Online First: June 2014. https://doi.org/10.13140/2.1.3670.4647 Google Scholar 7Good M, Bakker D, Duignan A, et al. The history of in vivo tuberculin testing in bovines: Tuberculosis, a "One Health" issue. Frontiers in Veterinary Science. 2018; 5. https://doi.org/10.3389/fvets.2018.00059 10.3389/fvets.2018.00059 Web of Science®Google Scholar 8Wood PR, Corner LA, Rothel JS, et al. Field comparison of the interferon- gamma assay and the intradermal tuberculin test for the diagnosis of bovine tuberculosis. Australian veterinary journal 1991; 68: 286–90. https://doi.org/10.1111/j.1751-0813.1991.tb03254.x 10.1111/j.1751-0813.1991.tb03254.x CASPubMedWeb of Science®Google Scholar 9Monaghan M, Quinn P, Kelly A, et al. A pilot trial to evaluate the g-interferon assay for the detection of Mycobacterium bovis infected cattle under Irish conditions. Irish Veterinary Journal 1997; 50: 229–32. Web of Science®Google Scholar 10Wood PR, Jones SL. BOVIGAM™: An in vitro cellular diagnostic test for bovine tuberculosis. In: Tuberculosis. Churchill Livingstone 2001. 147–55. https://doi.org/10.1054/tube.2000.0272 Google Scholar 11Gormley E, Doyle MB, Fitzsimons T, et al. Diagnosis of Mycobacterium bovis infection in cattle by use of the gamma-interferon (Bovigam®) assay. In: Veterinary Microbiology. Vet Microbiol 2006. 171–9. https://doi.org/10.1016/j.vetmic.2005.11.029 Google Scholar 12 EFSA. Scientific Opinion on the use of a gamma interferon test for the diagnosis of bovine tuberculosis. EFSA Journal 2012; 10. https://doi.org/10.2903/j.efsa.2012.2975 10.2903/j.efsa.2012.2975 Google Scholar 13Pollock JM, Neill SD. Mycobacterium bovis infection and tuberculosis in cattle. Veterinary Journal. 2002; 163: 115–27. https://doi.org/10.1053/tvjl.2001.0655 10.1053/tvjl.2001.0655 CASPubMedWeb of Science®Google Scholar 14Amadori M, Lyashchenko KP, Gennaro ML, et al. Use of recombinant proteins in antibody tests for bovine tuberculosis. Veterinary Microbiology 2002; 85: 379–89. https://doi.org/10.1016/S0378-1135(02)00005-6 10.1016/S0378-1135(02)00005-6 CASPubMedWeb of Science®Google Scholar 15Lyashchenko KP, Greenwald R, Esfandiari J, et al. Animal-side serologic assay for rapid detection of Mycobacterium bovis infection in multiple species of free-ranging wildlife. Veterinary Microbiology 2008; 132: 283–92. https://doi.org/10.1016/j.vetmic.2008.05.029 10.1016/j.vetmic.2008.05.029 CASPubMedWeb of Science®Google Scholar 16McNair J, Corbett DM, Girvin RM, et al. Characterization of the early antibody response in bovine tuberculosis: MPB83 is an early target with diagnostic potential. Scandinavian Journal of Immunology 2001; 53: 365–71. https://doi.org/10.1046/j.1365-3083.2001.00874.x 10.1046/j.1365-3083.2001.00874.x CASPubMedWeb of Science®Google Scholar 17Wiker HG. MPB70 and MPB83 - Major antigens of mycobacterium bovis. Scandinavian Journal of Immunology. 2009; 69: 492–9. https://doi.org/10.1111/j.1365-3083.2009.02256.x 10.1111/j.1365-3083.2009.02256.x CASPubMedWeb of Science®Google Scholar 18Schiller I, Oesch B, Vordermeier HM, et al. Bovine tuberculosis: A review of current and emerging diagnostic techniques in view of their relevance for disease control and eradication. Transboundary and Emerging Diseases. 2010; 57: 205–20. https://doi.org/10.1111/j.1865-1682.2010.01148.x 10.1111/j.1865-1682.2010.01148.x CASPubMedWeb of Science®Google Scholar 19Casal C, Díez-Guerrier A, Álvarez J, et al. Strategic use of serology for the diagnosis of bovine tuberculosis after intradermal skin testing. Veterinary Microbiology 2014; 170: 342–51. https://doi.org/10.1016/j.vetmic.2014.02.036 10.1016/j.vetmic.2014.02.036 PubMedWeb of Science®Google Scholar 20de la Rua-Domenech R, Goodchild AT, Vordermeier HM, et al. Ante mortem diagnosis of tuberculosis in cattle: A review of the tuberculin tests, γ-interferon assay and other ancillary diagnostic techniques. Research in Veterinary Science. 2006; 81: 190–210. https://doi.org/10.1016/j.rvsc.2005.11.005 10.1016/j.rvsc.2005.11.005 CASPubMedWeb of Science®Google Scholar 21Costello E, O'Reilly P, Yeardsley D, et al. A study of enzyme-linked immunosorbent assay for the diagnosis of tuberculosis in cattle. Irish Veterinary Journal 1997; 50: 35–8. Web of Science®Google Scholar 22Waters WR, Buddle BM, Vordermeier HM, et al. Development and evaluation of an enzyme-linked immunosorbent assay for use in the detection of bovine tuberculosis in cattle. Clinical and Vaccine Immunology 2011; 18: 1882–8. https://doi.org/10.1128/CVI.05343-11 10.1128/CVI.05343-11 CASPubMedWeb of Science®Google Scholar 23Trost B, Stuber T, Surujballi O, et al. Investigation of the cause of geographic disparities in IDEXX ELISA sensitivity in serum samples from Mycobacterium bovis-infected cattle. Scientific Reports 2016; 6: 1–11. https://doi.org/10.1038/srep22763 10.1038/srep22763 PubMedWeb of Science®Google Scholar 24Thomas J, Balseiro A, Gortázar C, et al. Diagnosis of tuberculosis in wildlife: a systematic review. Veterinary Research. 2021; 52. https://doi.org/10.1186/s13567-020-00881-y 10.1186/s13567-020-00881-y PubMedWeb of Science®Google Scholar 25Whelan C, Shuralev E, O'Keeffe G, et al. Multiplex immunoassay for serological diagnosis of Mycobacterium bovis infection in cattle. Clinical and Vaccine Immunology 2008; 15: 1834–8. https://doi.org/10.1128/CVI.00238-08 10.1128/CVI.00238-08 CASPubMedWeb of Science®Google Scholar 26Whelan C, Shuralev E, Kwok HF, et al. Use of a multiplex enzyme-linked immunosorbent assay to detect a subpopulation of mycobacterium bovis- infected animals deemed negative or inconclusive by the single intradermal comparative tuberculin skin test. Journal of Veterinary Diagnostic Investigation 2011; 23: 499–503. https://doi.org/10.1177/1040638711403410 10.1177/1040638711403410 PubMedWeb of Science®Google Scholar 27Clegg TA, Duignan A, Whelan C, et al. Using latent class analysis to estimate the test characteristics of the γ-interferon test, the single intradermal comparative tuberculin test and a multiplex immunoassay under Irish conditions. Veterinary Microbiology 2011; 151: 68–76. https://doi.org/10.1016/j.vetmic.2011.02.027 10.1016/j.vetmic.2011.02.027 PubMedWeb of Science®Google Scholar 28Buddle BM, Wilson T, Denis M, et al. Sensitivity, specificity, and confounding factors of novel serological tests used for the rapid diagnosis of bovine tuberculosis in farmed red deer (Cervus elaphus). Clinical and Vaccine Immunology 2010; 17: 626–30. https://doi.org/10.1128/CVI.00010-10 10.1128/CVI.00010-10 CASPubMedWeb of Science®Google Scholar 29Greenwald R, Lyashchenko O, Esfandiari J, et al. Highly accurate antibody assays for early and rapid detection of tuberculosis in african and asian elephants. Clinical and Vaccine Immunology 2009; 16: 605–12. https://doi.org/10.1128/CVI.00038-09 10.1128/CVI.00038-09 CASPubMedWeb of Science®Google Scholar 30Stewart LD, Tort N, Meakin P, et al. Development of a novel immunochromatographic lateral flow assay specific for Mycobacterium bovis cells and its application in combination with immunomagnetic separation to test badger faeces. BMC Veterinary Research 2017; 13: 1–12. https://doi.org/10.1186/s12917-017-1048-x 10.1186/s12917-017-1048-x PubMedWeb of Science®Google Scholar 31Alonso N, Griffa N, Moyano RD, et al. Development of a lateral flow immunochromatography test for the rapid detection of bovine tuberculosis. Journal of Immunological Methods 2021; 491:112941. https://doi.org/10.1016/j.jim.2020.112941 10.1016/j.jim.2020.112941 CASPubMedWeb of Science®Google Scholar 32Arnold ME, Courcier EA, Stringer LA, et al. A Bayesian analysis of a test and vaccinate or remove study to control bovine tuberculosis in badgers (Meles meles). PLoS ONE 2021; 16:e0246141. https://doi.org/10.1371/journal.pone.0246141 10.1371/journal.pone.0246141 CASPubMedWeb of Science®Google Scholar 33Ashford RT, Anderson P, Waring L, et al. Evaluation of the Dual Path Platform (DPP) VetTB assay for the detection of Mycobacterium bovis infection in badgers. Preventive Veterinary Medicine 2020; 180. https://doi.org/10.1016/j.prevetmed.2020.105005 10.1016/j.prevetmed.2020.105005 Web of Science®Google Scholar 34Courcier EA, Pascual-Linaza A v., Arnold ME, et al. Evaluating the application of the dual path platform VetTB test for badgers (Meles meles) in the test and vaccinate or remove (TVR) wildlife research intervention project in Northern Ireland. Research in Veterinary Science 2020; 130: 170–8. https://doi.org/10.1016/j.rvsc.2020.03.007 10.1016/j.rvsc.2020.03.007 CASPubMedWeb of Science®Google Scholar 35Griffin JFT, Cross JP, Chinn DN, et al. Diagnosis of tuberculosis due to mycobacterium bovis in New Zealand red deer (cervus elaphus) using a composite blood test and antibody assays. New Zealand Veterinary Journal 1994; 42: 173–9. https://doi.org/10.1080/00480169.1994.35815 10.1080/00480169.1994.35815 CASPubMedWeb of Science®Google Scholar 36Rhodes SG, Buddle BM, Hewinson RG, et al. Bovine tuberculosis: Immune responses in the peripheral blood and at the site of active disease. Immunology 2000; 99: 195–202. https://doi.org/10.1046/j.1365-2567.2000.00944.x 10.1046/j.1365-2567.2000.00944.x CASPubMedWeb of Science®Google Scholar 37Buddle BM, de Lisle GW, Pfeffer A, et al. Immunological responses and protection against Mycobacterium bovis in calves vaccinated with a low dose of BCG. Vaccine 1995; 13: 1123–30. https://doi.org/10.1016/0264-410X(94)00055-R 10.1016/0264-410X(94)00055-R CASPubMedWeb of Science®Google Scholar 38Michelet L, de Cruz K, Karoui C, et al. Second line molecular diagnosis for bovine tuberculosis to improve diagnostic schemes. PLoS ONE 2018; 13:e0207614. https://doi.org/10.1371/journal.pone.0207614 10.1371/journal.pone.0207614 PubMedWeb of Science®Google Scholar 39Lorente-Leal V, Liandris E, Castellanos E, et al. Validation of a real-time PCR for the detection of mycobacterium tuberculosis complex members in Bovine tissue samples. Frontiers in Veterinary Science 2019; 6: 61. https://doi.org/10.3389/fvets.2019.00061 10.3389/fvets.2019.00061 PubMedWeb of Science®Google Scholar 40Sánchez-Carvajal JM, Galán-Relaño Á, Ruedas-Torres I, et al. Real-Time PCR Validation for Mycobacterium tuberculosis Complex Detection Targeting IS6110 Directly From Bovine Lymph Nodes. Frontiers in Veterinary Science 2021; 8: 231. https://doi.org/10.3389/FVETS.2021.643111 10.3389/fvets.2021.643111 Web of Science®Google Scholar 41Swift BMC, Meade N, Barron ES, et al. The development and use of Actiphage® to detect viable mycobacteria from bovine tuberculosis and Johne's disease-infected animals. Microbial Biotechnology 2020; 13: 738–46. https://doi.org/10.1111/1751-7915.13518 10.1111/1751-7915.13518 CASPubMedWeb of Science®Google Scholar 42Monaghan ML, Doherty ML, Collins JD, et al. The tuberculin test. Veterinary Microbiology 1994; 40: 111–24. https://doi.org/10.1016/0378-1135(94)90050-7 10.1016/0378-1135(94)90050-7 CASPubMedWeb of Science®Google Scholar 43O'Hagan MJH, Ni H, Menzies FD, et al. Test characteristics of the tuberculin skin test and post-mortem examination for bovine tuberculosis diagnosis in cattle in Northern Ireland estimated by Bayesian latent class analysis with adjustments for covariates. Epidemiology and Infection 2019; 147: 1–8. 10.1017/S0950268819000888 Web of Science®Google Scholar 44Thrusfield M, Christley R, Brown H, et al. Veterinary Epidemiology: Fourth Edition. Wiley Blackwell 2017. https://doi.org/10.1002/9781118280249 Google Scholar 45Good M, Duignan A. An evaluation of the Irish Single Reactor Breakdown Protocol for 2005-2008 inclusive and its potential application as a monitor of tuberculin test performance. Veterinary Microbiology 2011; 151: 85–90. https://doi.org/10.1016/j.vetmic.2011.02.029 10.1016/j.vetmic.2011.02.029 CASPubMedWeb of Science®Google Scholar 46Costello E, Egan JWA, Quigley FC, et al. Performance of the single intradermal comparative tuberculin test in identifying cattle with tuberculous lesions in Irish herds. Veterinary Record 1997; 141: 222–4. https://doi.org/10.1136/vr.141.9.222 10.1136/vr.141.9.222 CASPubMedWeb of Science®Google Scholar 47Bezos J, Casal C, Romero B, et al. Current ante-mortem techniques for diagnosis of bovine tuberculosis. Research in Veterinary Science. 2014; 97: S44–52. https://doi.org/10.1016/j.rvsc.2014.04.002 10.1016/j.rvsc.2014.04.002 PubMedWeb of Science®Google Scholar 48Broughan JM, Judge J, Ely E, et al. Review article a review of risk factors for bovine tuberculosis infection in cattle in the UK and Ireland. Epidemiology and Infection 2016; 144: 2899–926. https://doi.org/10.1017/S095026881600131X 10.1017/S095026881600131X CASPubMedWeb of Science®Google Scholar 49O'Hagan MJH, Ni H, Menzies FD, et al. Test characteristics of the tuberculin skin test and post-mortem examination for bovine tuberculosis diagnosis in cattle in Northern Ireland estimated by Bayesian latent class analysis with adjustments for covariates. Epidemiology and Infection 2019; 147: 1–8. https://doi.org/10.1017/S0950268819000888 10.1017/S0950268819000888 Web of Science®Google Scholar 50Borsuk S, Newcombe J, Mendum TA, et al. Identification of proteins from tuberculin purified protein derivative (PPD) by LC-MS/MS. Tuberculosis 2009; 89: 423–30. https://doi.org/10.1016/J.TUBE.2009.07.003 10.1016/j.tube.2009.07.003 CASPubMedWeb of Science®Google Scholar 51Santema W, Overdijk M, Barends J, et al. Searching for proteins of Mycobacterium avium subspecies paratuberculosis with diagnostic potential by comparative qualitative proteomic analysis of mycobacterial tuberculins. Veterinary Microbiology 2009; 138: 191–6. https://doi.org/10.1016/J.VETMIC.2009.03.021 10.1016/j.vetmic.2009.03.021 CASPubMedWeb of Science®Google Scholar 52Nuñez-Garcia J, Downs SH, Parry JE, et al. Meta-analyses of the sensitivity and specificity of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis in the UK and Ireland. Preventive Veterinary Medicine 2018; 153: 94–107. https://doi.org/10.1016/j.prevetmed.2017.02.017 10.1016/j.prevetmed.2017.02.017 PubMedWeb of Science®Google Scholar 53Conlan AJK, McKinley TJ, Karolemeas K, et al. Estimating the Hidden Burden of Bovine Tuberculosis in Great Britain. PLoS Computational Biology 2012; 8. https://doi.org/10.1371/journal.pcbi.1002730 10.1371/journal.pcbi.1002730 Web of Science®Google Scholar 54O'Hagan MJH, Ni H, Menzies FD, et al. Test characteristics of the tuberculin skin test and post-mortem examination for bovine tuberculosis diagnosis in cattle in Northern Ireland estimated by Bayesian latent class analysis with adjustments for covariates. Epidemiology and Infection 2019; 147: 1–8. https://doi.org/10.1017/S0950268819000888 10.1017/S0950268819000888 Web of Science®Google Scholar 55Kleeberg H. The tuberculin test in cattle. Journal of the South African Veterinary Medical Association 1960; 31: 213–25. Google Scholar 56Lilenbaum W, Schettini JC, Souza GN, et al. Comparison between a γ-IFN assay and intradermal tuberculin test for the diagnosis of bovine tuberculosis in field trials in Brazil. Journal of Veterinary Medicine, Series B. 1999; 46: 353–8. https://doi.org/10.1111/j.1439-0450.1999.tb01240.x 10.1111/j.1439-0450.1999.tb01240.x CASGoogle Scholar 57Lilenbaum W, Ribeiro ER, Souza GN, et al. Evaluation of an ELISA-PPD for the diagnosis of bovine tuberculosis in field trials in Brazil. Research in Veterinary Science 1999; 66: 191–5. https://doi.org/10.1053/rvsc.1998.0229 10.1053/rvsc.1998.0229 CASPubMedWeb of Science®Google Scholar 58Karolemeas K, de la Rua-Domenech R, Cooper R, et al. Estimation of the relative sensitivity of the comparative tuberculin skin test in tuberculous cattle herds subjected to depopulation. PLoS ONE 2012; 7. https://doi.org/10.1371/journal.pone.0043217 10.1371/journal.pone.0043217 Web of Science®Google Scholar 59Goodchild A v., Downs SH, Upton P, et al. Specificity of the comparative skin test for bovine tuberculosis in Great Britain. Veterinary Record 2015; 177: 258. https://doi.org/10.1136/vr.102961 10.1136/vr.102961 CASPubMedWeb of Science®Google Scholar 60Christensen J, Gardner IA. Herd-level interpretation of test results for epidemiologic studies of animal diseases. Preventive Veterinary Medicine 2000; 45: 83–106. https://doi.org/10.1016/S0167-5877(00)00118-5 10.1016/S0167-5877(00)00118-5 CASPubMedWeb of Science®Google Scholar 61Martin SW, Shoukri M, Thorburn MA. Evaluating the health status of herds based on tests applied to individuals. Preventive Veterinary Medicine 1992; 14: 33–43. https://doi.org/10.1016/0167-5877(92)90082-Q 10.1016/0167-5877(92)90082-Q Web of Science®Google Scholar 62Lahuerta-Marin A, Milne MG, McNair J, et al. Bayesian latent class estimation of sensitivity and specificity parameters of diagnostic tests for bovine tuberculosis in chronically infected herds in Northern Ireland. Veterinary Journal 2018; 238: 15–21. https://doi.org/10.1016/j.tvjl.2018.04.019 10.1016/j.tvjl.2018.04.019 CASPubMedWeb of Science®Google Scholar 63 OIE. The register of diagnostic kits - OIE - World Organisation for Animal Health. https://www.oie.int/en/what-we-offer/veterinary-products/diagnostic-kits/the-register-of-diagnostic-kits/(accessed 8 Jul 2021). Google Scholar 64Buddle BM, Keen D, Thomson A, et al. Protection of cattle from bovine tuberculosis by vaccination with BCG by the respiratory or subcutaneous route, but not by vaccination with killed Mycobacterium vaccae. Research in Veterinary Science 1995; 59: 10–6. https://doi.org/10.1016/0034-5288(95)90023-3 10.1016/0034-5288(95)90023-3 CASPubMedWeb of Science®Google Scholar 65Coad M, Downs SH, Durr PA, et al. Blood-based assays to detect Mycobacterium bovis-infected cattle missed by tuberculin skin testing. Veterinary Record 2008; 162: 382–4. https://doi.org/10.1136/vr.162.12.382 10.1136/vr.162.12.382 CASPubMedWeb of Science®Google Scholar 66Gormley E, Doyle MB, McGill K, et al. The effect of the tuberculin test and the consequences of a delay in blood culture on the sensitivity of a gamma- interferon assay for the detection of Mycobacterium bovis infection in cattle. Veterinary Immunology and Immunopathology 2004; 102: 413–20. https://doi.org/10.1016/j.vetimm.2004.08.002 10.1016/j.vetimm.2004.08.002 CASPubMedWeb of Science®Google Scholar 67Clegg TA, Good M, Doyle M, et al. The performance of the interferon gamma assay when used as a diagnostic or quality assurance test in Mycobacterium bovis infected herds. Preventive Veterinary Medicine 2017; 140: 116–21. https://doi.org/10.1016/j.prevetmed.2017.03.007 10.1016/j.prevetmed.2017.03.007 CASPubMedWeb of Science®Google Scholar 68Schiller I, Vordermeier HM, Waters WR, et al. Comparison of tuberculin activity using the interferon-γ assay for the diagnosis of bovine tuberculosis. Veterinary Record 2010; 167: 322–6. https://doi.org/10.1136/vr.c3403 10.1136/vr.c3403 CASPubMedWeb of Science®Google Scholar 69Carneiro PAM, de Moura Sousa E, Viana RB, et al. Study on supplemental test to improve the detection of bovine tuberculosis in individual animals and herds. BMC Veterinary Research 2021; 17: 1–8. https://doi.org/10.1186/s12917-021-02839-4 10.1186/s12917-021-02839-4 PubMedWeb of Science®Google Scholar 70Pollock JM, Welsh MD, McNair J. Immune responses in bovine tuberculosis: Towards new strategies for the diagnosis and control of disease. In: Veterinary Immunology and Immunopathology. Vet Immunol Immunopathol 2005. 37–43. https://doi.org/10.1016/j.vetimm.2005.08.012 10.1016/j.vetimm.2005.08.012 Google Scholar 71Waters WR, Maggioli MF, McGill JL, et al. Relevance of bovine tuberculosis research to the understanding of human disease: Historical perspectives, approaches, and immunologic mechanisms. Veterinary Immunology and Immunopathology 2014; 159: 113–32. https://doi.org/10.1016/j.vetimm.2014.02.009 10.1016/j.vetimm.2014.02.009 CASPubMedWeb of Science®Google Scholar 72Welsh MD, Cunningham RT, Corbett DM, et al. Influence of pathological progression on the balance between cellular and humoral immune responses in bovine tuberculosis. Immunology 2005; 114: 101–11. https://doi.org/10.1111/j.1365-2567.2004.02003.x 10.1111/j.1365-2567.2004.02003.x CASPubMedWeb of Science®Google Scholar 73McCallan L, Brooks C, Couzens C, et al. Assessment of serological tests for diagnosis of bovine tuberculosis. Veterinary Record. 2017; 181: 90. https://doi.org/10.1136/vr.104272 10.1136/vr.104272 CASPubMedWeb of Science®Google Scholar 74Xu F, Tian L, Li Y, et al. High prevalence of extrapulmonary tuberculosis in dairy farms: Evidence for possible gastrointestinal transmission. PLoS ONE 2021; 16:e0249341. https://doi.org/10.1371/journal.pone.0249341 10.1371/journal.pone.0249341 CASPubMedWeb of Science®Google Scholar 75Abernethy DA, Upton P, Higgins IM, et al. Bovine tuberculosis trends in the UK and the Republic of Ireland, 1995–2010. Veterinary Record 2013; 172: 312–312. https://doi.org/10.1136/VR.100969 10.1136/vr.100969 CASPubMedWeb of Science®Google Scholar 76Willeberg PW, McAloon CG, Houtsma E, et al. The Herd-Level Sensitivity of Abattoir Surveillance for Bovine Tuberculosis: Simulating the Effects of Current and Potentially Modified Meat Inspection Procedures in Irish Cattle. Frontiers in Veterinary Science 2018; 0: 82. https://doi.org/10.3389/FVETS.2018.00082 10.3389/fvets.2018.00082 Google Scholar 77Stański K, Lycett S, Porphyre T, et al. Using machine learning improves predictions of herd-level bovine tuberculosis breakdowns in Great Britain. Scientific Reports | 2021; 11: 2208. https://doi.org/10.1038/s41598-021-81716-4 10.1038/s41598-021-81716-4 CASPubMedWeb of Science®Google Scholar 78Olea-Popelka FJ, Costello E, White P, et al. Risk factors for disclosure of additional tuberculous cattle in attested-clear herds that had one animal with a confirmed lesion of tuberculosis at slaughter during 2003 in Ireland. Preventive Veterinary Medicine 2008; 85: 81–91. https://doi.org/10.1016/j.prevetmed.2008.01.003 10.1016/j.prevetmed.2008.01.003 CASPubMedWeb of Science®Google Scholar 79Clegg TA, Good M, More SJ. Risk factors for cattle presenting with a confirmed bTB lesion at slaughter, from herds with no evidence of within-herd transmission. Preventive Veterinary Medicine 2016; 126: 111–20. https://doi.org/10.1016/j.prevetmed.2016.02.003 10.1016/j.prevetmed.2016.02.003 CASPubMedWeb of Science®Google Scholar 80Byrne AW, Barrett D, Breslin P, et al. Post-mortem surveillance of bovine tuberculosis in Ireland: herd-level variation in the probability of herds disclosed with lesions at routine slaughter to have skin test reactors at follow-up test. Veterinary Research Communications 2020; 44: 131–6. https://doi.org/10.1007/s11259-020-09777-w 10.1007/s11259-020-09777-w PubMedWeb of Science®Google Scholar 81Byrne AW, Barrett D, Breslin P, et al. Bovine tuberculosis (Mycobacterium bovis) outbreak duration in cattle herds in Ireland: A retrospective observational study. Pathogens 2020; 9: 1–17. https://doi.org/10.3390/pathogens9100815 10.3390/pathogens9100815 Web of Science®Google Scholar 82Byrne AW, Barrett D, Breslin P, et al. Future risk of bovine tuberculosis (Mycobacterium bovis) breakdown in cattle herds 2013–2018: A dominance analysis approach. Microorganisms 2021; 9. https://doi.org/10.3390/microorganisms9051004 10.3390/microorganisms9051004 PubMedGoogle Scholar 83Clegg TA, Good M, Duignan A, et al. Longer-term risk of Mycobacterium bovis in Irish cattle following an inconclusive diagnosis to the single intradermal comparative tuberculin test. Preventive Veterinary Medicine 2011; 100: 147–54. https://doi.org/10.1016/j.prevetmed.2011.02.015 10.1016/j.prevetmed.2011.02.015 CASPubMedWeb of Science®Google Scholar 84Clegg TA, Blake M, Healy R, et al. The impact of animal introductions during herd restrictions on future herd-level bovine tuberculosis risk. Preventive Veterinary Medicine 2013; 109: 246–57. https://doi.org/10.1016/j.prevetmed.2012.10.005 10.1016/j.prevetmed.2012.10.005 CASPubMedWeb of Science®Google Scholar 85Clegg TA, Good M, More SJ. Future risk of bovine tuberculosis recurrence among higher risk herds in Ireland. Preventive Veterinary Medicine 2015; 118: 71–9. https://doi.org/10.1016/j.prevetmed.2014.11.013 10.1016/j.prevetmed.2014.11.013 CASPubMedWeb of Science®Google Scholar 86Gallagher MJ, Higgins IM, Clegg TA, et al. Comparison of bovine tuberculosis recurrence in Irish herds between 1998 and 2008. Preventive Veterinary Medicine 2013; 111: 237–44. https://doi.org/10.1016/j.prevetmed.2013.05.004 10.1016/j.prevetmed.2013.05.004 CASPubMedWeb of Science®Google Scholar 87Good M, Clegg TA, Duignan A, et al. Impact of the national full herd depopulation policy on the recurrence of bovine tuberculosis in Irish herds, 2003 to 2005. Veterinary Record 2011; 169: 581. https://doi.org/10.1136/vr.d4571 10.1136/vr.d4571 CASPubMedWeb of Science®Google Scholar 88Olea-Popelka FJ, White PW, Collins JD, et al. Breakdown severity during a bovine tuberculosis episode as a predictor of future herd breakdowns in Ireland. Preventive Veterinary Medicine 2004; 63: 163–72. https://doi.org/10.1016/j.prevetmed.2004.03.001 10.1016/j.prevetmed.2004.03.001 CASPubMedWeb of Science®Google Scholar 89Wolfe DM, Berke O, More SJ, et al. The risk of a positive test for bovine tuberculosis in cattle purchased from herds with and without a recent history of bovine tuberculosis in Ireland. Preventive Veterinary Medicine 2009; 92: 99–105. https://doi.org/10.1016/j.prevetmed.2009.07.012 10.1016/j.prevetmed.2009.07.012 CASPubMedWeb of Science®Google Scholar 90Berrian AM, O'Keeffe J, White PW, et al. Risk of bovine tuberculosis for cattle sold out from herds during 2005 in Ireland. Veterinary Record 2012; 170: 620. https://doi.org/10.1136/vr.100674 10.1136/vr.100674 CASPubMedWeb of Science®Google Scholar 91Dawson KL, Stevenson MA, Sinclair JA, et al. Recurrent bovine tuberculosis in New Zealand cattle and deer herds, 2006-2010. Epidemiology and Infection 2014; 142: 2065–74. https://doi.org/10.1017/S0950268814000910 10.1017/S0950268814000910 CASPubMedWeb of Science®Google Scholar 92Rossi G, Crispell J, Brough T, et al. Phylodynamic analysis of an emergent Mycobacterium bovis outbreak in an area with no previously known wildlife infections. bioRxiv. 2020. https://doi.org/10.1101/2020.11.12.379297 10.1101/2020.11.12.379297 Google Scholar 93Gomez JE, McKinney JD. M. tuberculosis persistence, latency, and drug tolerance. In: Tuberculosis. Churchill Livingstone 2004. 29–44. https://doi.org/10.1016/j.tube.2003.08.003 Google Scholar 94Álvarez AH, Estrada-Chávez C, Flores-Valdez MA. Molecular findings and approaches spotlighting Mycobacterium bovis persistence in cattle. Veterinary Research. 2009; 40. https://doi.org/10.1051/vetres/2009005 10.1051/vetres/2009005 PubMedWeb of Science®Google Scholar 95Sabio y García J, Bigi MM, Klepp LI, et al. Does Mycobacterium bovis persist in cattle in a non-replicative latent state as Mycobacterium tuberculosis in human beings? Veterinary Microbiology. 2020; 247:108758. https://doi.org/10.1016/j.vetmic.2020.108758 10.1016/j.vetmic.2020.108758 CASPubMedWeb of Science®Google Scholar 96Coussens PM, Volkova V, Barletta RG, et al. A Defined Antigen Skin Test That Enables Implementation of BCG Vaccination for Control of Bovine Tuberculosis: Proof of Concept. Frontiers in Veterinary Science | www.frontiersin.org 2020; 1: 391. https://doi.org/10.3389/fvets.2020.00391 10.3389/fvets.2020.00391 Google Scholar 97Middleton S, Steinbach S, Coad M, et al. A molecularly defined skin test reagent for the diagnosis of bovine tuberculosis compatible with vaccination against Johne's Disease. Scientific Reports 2021; 11: 2929. https://doi.org/10.1038/s41598-021-82434-7 10.1038/s41598-021-82434-7 CASPubMedWeb of Science®Google Scholar 98Clegg TA, Duignan A, More SJ. The relative effectiveness of testers during field surveillance for bovine tuberculosis in unrestricted low-risk herds in Ireland. Preventive Veterinary Medicine 2015; 119: 85–9. https://doi.org/10.1016/j.prevetmed.2015.02.005 10.1016/j.prevetmed.2015.02.005 CASPubMedWeb of Science®Google Scholar 99 APHA. Quality assurance of tuberculin skin testing in Great Britain. Veterinary Practice. 2021.https://veterinary-practice.com/article/quality-assurance-of-tuberculin-skin-testing-in-great-britain (accessed 18 Jun 2021). Google Scholar 100Duignan A, Good M, More SJ. Quality control in the national bovine tuberculosis eradication programme in Ireland. 2012. www.vci.ie Google Scholar 101 EFSA. The European Union One Health 2019 Zoonoses Report. EFSA Journal 2021; 19. https://doi.org/10.2903/j.efsa.2021.6406 10.2903/j.efsa.2021.6406 Web of Science®Google Scholar 102Reviriego Gordejo FJ, Vermeersch JP. Towards eradication of bovine tuberculosis in the European Union. Veterinary Microbiology 2006; 112: 101–9. https://doi.org/10.1016/J.VETMIC.2005.11.034 10.1016/j.vetmic.2005.11.034 CASPubMedWeb of Science®Google Scholar 103More SJ, Radunz B, Glanville RJ. Review: Lessons learned during the successful eradication of bovine tuberculosis from Australia. Veterinary Record. 2015; 177: 224–32. https://doi.org/10.1136/vr.103163 10.1136/vr.103163 CASPubMedWeb of Science®Google Scholar 104Livingstone PG, Hancox N, Nugent G, et al. Development of the New Zealand strategy for local eradication of tuberculosis from wildlife and livestock. New Zealand Veterinary Journal. 2015; 63: 98–107. https://doi.org/10.1080/00480169.2015.1013581 10.1080/00480169.2015.1013581 PubMedWeb of Science®Google Scholar 105More SJ, Good M. Understanding and managing bTB risk: Perspectives from Ireland. Veterinary Microbiology. 2015; 176: 209–18. https://doi.org/10.1016/j.vetmic.2015.01.026 10.1016/j.vetmic.2015.01.026 PubMedWeb of Science®Google Scholar Volume1, Issue2September‐December 20230008E ReferencesRelatedInformation