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

Bovine tuberculosis (bTB) is one of the globes most common, multihost zoonoses and results in substantial socioeconomic costs for governments, farming industries, and tax payers. Despite decades of surveillance and research, surprisingly, little is known about the exact mechanisms of transmission. In particular, as a facultative intracellular pathogen, to what extent does survival of the causative agent, Mycobacterium tuberculosis var. bovis (M. bovis), in the environment constitute an epidemiological risk for livestock and wildlife? Due largely to the classical pathology of cattle cases, the received wisdom was that bTB was spread by direct inhalation and exchange of bioaerosols containing droplets laden with bacteria. Other members of the Mycobacterium tuberculosis complex (MTBC) exhibit differing host ranges, an apparent capacity to persist in environmental fomites, and they favour a range of different transmission routes. It is possible, therefore, that infection from environmental sources of M. bovis could be a disease transmission risk. Recent evidence from GPS-collared cattle and badgers in Britain and Ireland suggests that direct transmission by infectious droplets or aerosols may not be the main mechanism for interspecies transmission, raising the possibility of indirect transmission involving a contaminated, shared environment. The possibility that classical pulmonary TB can be simulated and recapitulated in laboratory animal models by ingestion of contaminated feed is a further intriguing indication of potential environmental risk. Livestock and wildlife are known to shed M. bovis onto pasture, soil, feedstuffs, water, and other fomites; field and laboratory studies have indicated that persistence is possible, but variable, under differing environmental conditions. Given the potential infection risk, it is timely to review the available evidence, experimental approaches, and methodologies that could be deployed to address this potential blind spot and control point. Although we focus on evidence from Western Europe, the concepts are widely applicable to other multihost bTB episystems.

The prevalence of bovine tuberculosis (BTB) in the UK remains a significant economic burden and problem for the agri-food industry. Much effort has been directed towards improving diagnostics, finding vaccine candidates and assessing the usefulness of badger culling. The contribution that host genotype makes to disease outcome has, until recently, been overlooked; yet, it is biologically untenable that genetic variation does not play a role. In this review, we highlight the evidence, past and present, for a role of host genetics in determining susceptibility to BTB in livestock. We then address some of the major issues surrounding the design of future studies tasked with finding the exact causative genetic variation underpinning the TB susceptibility phenotype. Finally, we discuss some of the potential future benefits, and problems, that a knowledge of the genetic component to BTB resistance/susceptibility may bring to the agricultural industries and the wider scientific community.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a significant problem for livestock industries in many countries worldwide including Northern Ireland, where a test and slaughter regime has utilised the Single Intradermal Comparative Cervical Tuberculin (SICCT) test since 1959. We investigated the variation in post-mortem confirmation based on bTB visible lesion (VL) presence during herd breakdowns using two model suites. We investigated animal-level characteristics, while controlling for herd-level factors and clustering. We were interested in potential impacts of concurrent infection, and therefore we assessed whether animals with evidence of liver fluke infection (Fasciola hepatica; post-mortem inspection), M. avium reactors (animals with negative M. bovis-avium (b-a) tuberculin reactions) or Bovine Viral Diarrhoea Virus (BVDV; RT-PCR tested) were associated with bTB confirmation. The dataset included 6242 animals removed during the 14 month study period (2013–2015). bTB-VL presence was significantly increased in animals with greater b-a reaction size at the disclosing SICCT test (e.g. b-a = 5-9 mm vs. b-a = 0 mm, adjusted Odds ratio (aOR): 14.57; p < 0.001). M. avium reactor animals (b-a < 0) were also significantly more likely to disclose VL than non-reactor animals (b-a = 0; aOR: 2.29; p = 0.023). Animals had a greater probability of exhibiting lesions with the increasing number of herds it had resided within (movement; log-herds: aOR: 2.27–2.42; p < 0.001), if it had an inconclusive penultimate test result (aOR: 2.84–3.89; p < 0.001), and with increasing time between tests (log-time; aOR: 1.23; p = 0.003). Animals were less likely to have VL if they were a dairy breed (aOR: 0.79; p = 0.015) or in an older age-class (e.g. age-quartile 2 vs. 4; aOR: 0.65; p < 0.001). Liver fluke or BVDV variables were not retained in either multivariable model as they were non-significantly associated with bTB-VL status (p > 0.1). Our results suggest that neither co-infection of liver fluke nor BVDV had a significant effect on the presence of VLs in this high-risk cohort. M. avium tuberculin reactors had a significantly increased risk of disclosing with a bTB lesion, which could be related to the impact of co-infection with M. avium subsp. paratuberculosis (MAP) affecting the performance of the SICCT however further research in this area is required. Movements, test history, breed and age were important factors influencing confirmation in high-risk animals.

Understanding how emergent pathogens successfully establish themselves and persist in previously unaffected populations is a crucial problem in disease ecology, with important implications for disease management. In multi-host pathogen systems this problem is particularly difficult, as the importance of each host species to transmission is often poorly characterised, and the disease epidemiology is complex. Opportunities to observe and analyse such emergent scenarios are few. Here, we exploit a unique dataset combining densely collected data on the epidemiological and evolutionary characteristics of an outbreak of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB) in a population of cattle and badgers in an area considered low risk for bTB, with no previous record of either persistent infection in cattle, or of any infection in wildlife. We analyse the outbreak dynamics using a combination of mathematical modelling, Bayesian evolutionary analyses and machine learning. Comparison to M. bovis whole-genome sequences from Northern Ireland confirmed this to be a pathogen single introduction from the latter region, with evolutionary analysis supporting an introduction directly into the local cattle population 6 years prior to its first discovery in badgers. Once introduced, the evidence supports M. bovis epidemiological dynamics passing through two phases, the first dominated by cattle-to-cattle transmission before becoming established in the local badger population. Synthesis and applications. The Mycobacterium bovis emergent outbreak that was the object of this study was of considerable concern because of the geographical distance from previously known high-risk areas. Initial decisions about the outbreak control were supported by the whole-genome sequencing data. The further analyses described here were used to estimate the time of introduction (and therefore the likely magnitude of any hidden outbreak) and the rates of cross-species transmission, and provided valuable confirmation that the extent and focus of the imposed controls were appropriate. Not only do these findings strengthen the call for genomic surveillance, but they also pave the path for future outbreaks control, providing insights for more rapid and decisive evidence-based decision-making. As the methods we used and developed are agnostic to the disease itself, they are also valuable for other slowly transmitting pathogens.

Bovine tuberculosis (bTB) is a costly, epidemiologically complex, multi-host, endemic disease. Lack of understanding of transmission dynamics may undermine eradication efforts. Pathogen whole-genome sequencing improves epidemiological inferences, providing a means to determine the relative importance of inter- and intra-species host transmission for disease persistence. We sequenced an exceptional data set of 619 Mycobacterium bovis isolates from badgers and cattle in a 100 km² bTB ‘hotspot’ in Northern Ireland. Historical molecular subtyping data permitted the targeting of an endemic pathogen lineage, whose long-term persistence provided a unique opportunity to study disease transmission dynamics in unparalleled detail. Additionally, to assess whether badger population genetic structure was associated with the spatial distribution of pathogen genetic diversity, we microsatellite genotyped hair samples from 769 badgers trapped in this area. Birth death models and TransPhylo analyses indicated that cattle were likely driving the local epidemic, with transmission from cattle to badgers being more common than badger to cattle. Furthermore, the presence of significant badger population genetic structure in the landscape was not associated with the spatial distribution of M. bovis genetic diversity, suggesting that badger-to-badger transmission is not playing a major role in transmission dynamics. Our data were consistent with badgers playing a smaller role in transmission of M. bovis infection in this study site, compared to cattle. We hypothesize, however, that this minor role may still be important for persistence. Comparison to other areas suggests that M. bovis transmission dynamics are likely to be context dependent, with the role of wildlife being difficult to generalize.