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

Publication history: Accepted - 3 May 2018; Published online - 5 June 2018Successful 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 socioeconomic 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.Authors' work is funded by the Department of Agriculture, Environment and Rural Affairs, Northern Ireland (DAERA-NI

Does Mycobacterium tuberculosis var. bovis survival in the environment confound bovine tuberculosis control and eradication? A literature review

Publication history: Accepted - 25 January 2021; Published online - 5 February 2021.Bovine tuberculosis (bTB) is one of the globe’s 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. &e 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 shedM. 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.This work was commissioned and funded by the Department of Agriculture, Environment and Rural Affairs for Northern Ireland (DAERA-NI) under Evidence and Innovation Project 18/03/01

Herd-level bovine tuberculosis risk factors:assessing the role of low-level badger population disturbance

Bovine TB (bTB) is endemic in Irish cattle and has eluded eradication despite considerable expenditure, amid debate over the relative roles of badgers and cattle in disease transmission. Using a comprehensive dataset from Northern Ireland (>10,000 km2; 29,513 cattle herds), we investigated interactions between host populations in one of the first large-scale risk factor analyses for new herd breakdowns to combine data on both species. Cattle risk factors (movements, international imports, bTB history, neighbours with bTB) were more strongly associated with herd risk than area-level measures of badger social group density, habitat suitability or persecution (sett disturbance). Highest risks were in areas of high badger social group density and high rates of persecution, potentially representing both responsive persecution of badgers in high cattle risk areas and effects of persecution on cattle bTB risk through badger social group disruption. Average badger persecution was associated with reduced cattle bTB risk (compared with high persecution areas), so persecution may contribute towards sustaining bTB hotspots; findings with important implications for existing and planned disease control programmes

A new phylodynamic model of Mycobacterium bovis transmission in a multi-host system uncovers the role of the unobserved reservoir

Multi-host pathogens are particularly difficult to control, especially when at least one of the hosts acts as a hidden reservoir. Deep sequencing of densely sampled pathogens has the potential to transform this understanding, but requires analytical approaches that jointly consider epidemiological and genetic data to best address this problem. While there has been considerable success in analyses of single species systems, the hidden reservoir problem is relatively under-studied. A well-known exemplar of this problem is bovine Tuberculosis, a disease found in British and Irish cattle caused by Mycobacterium bovis, where the Eurasian badger has long been believed to act as a reservoir but remains of poorly quantified importance except in very specific locations. As a result, the effort that should be directed at controlling disease in badgers is unclear. Here, we analyse densely collected epidemiological and genetic data from a cattle population but do not explicitly consider any data from badgers. We use a simulation modelling approach to show that, in our system, a model that exploits available cattle demographic and herd-to-herd movement data, but only considers the ability of a hidden reservoir to generate pathogen diversity, can be used to choose between different epidemiological scenarios. In our analysis, a model where the reservoir does not generate any diversity but contributes to new infections at a local farm scale are significantly preferred over models which generate diversity and/or spread disease at broader spatial scales. While we cannot directly attribute the role of the reservoir to badgers based on this analysis alone, the result supports the hypothesis that under current cattle control regimes, infected cattle alone cannot sustain M. bovis circulation. Given the observed close phylogenetic relationship for the bacteria taken from cattle and badgers sampled near to each other, the most parsimonious hypothesis is that the reservoir is the infected badger population. More broadly, our approach demonstrates that carefully constructed bespoke models can exploit the combination of genetic and epidemiological data to overcome issues of extreme data bias, and uncover important general characteristics of transmission in multi-host pathogen systems

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

Publication history: Accepted - 25 June 2019; Published online - July 2019Background We used genetic Multi-Locus VNTR Analysis (MLVA) data gathered from surveillance efforts to better understand the ongoing bovine tuberculosis (bTB) epidemic in Northern Irish cattle herds. We modelled the factors associated with Mycobacterium bovis MLVA genotype richness at three analytical scales; breakdown level, herd level, and patch level, and compared the results between dairy and non-dairy production types. Results In 83% of breakdowns and in 63% of herds, a single MLVA genotype was isolated. Five or more MLVA genotypes were found in less than 3 % of herds. Herd size and the total number of reactors were important explanatory variables, suggesting that increasing MLVA genotype richness was positively related to increases in the number of host animals. Despite their smaller relative size, however, the highest MLVA genotype richness values were observed in non-dairy herds. Increasing inwards cattle movements were important positive predictors of MLVA genotype richness, but mainly in non-dairy settings. Conclusions The principal finding is that low MLVA genotype richness indicates that small-scale epidemics, e.g. wildlife, contiguous farms, and within-herd recrudescence, are important routes of M. bovis infection in cattle herds. We hypothesise that these mechanisms will maintain, but may not explicitly increase, MLVA genotype richness. The presence of elevated MLVA richness is relatively rare and likely indicates beef fattening enterprises, which purchase cattle from over long distances. Cattle movements were furthermore an important predictor of MLVA genotype richness in non-dairy herds, but not in dairy herds; this may represent reduced cattle purchasing levels in dairy enterprises, compared to beef. These observations allude to the relative contribution of different routes of bTB infection between production types; we posit that infection associated with local factors may be more evident in dairy herds than beef herds, however in beef herds, inwards movements offer additional opportunities for introducing M. bovis into the herd

Genetic evidence further elucidates the history and extent of badger introductions from Great Britain into Ireland

The colonization of Ireland by mammals has been the subject of extensive study using genetic methods and forms a central problem in understanding the phylogeography of European mammals after the Last Glacial Maximum. Ireland exhibits a depauperate mammal fauna relative to Great Britain and continental Europe, and a range of natural and anthropogenic processes have given rise to its modern fauna. Previous Europe-wide surveys of the European badger (Meles meles) have found conflicting microsatellite and mitochondrial DNA evidence in Irish populations, suggesting Irish badgers have arisen from admixture between human imported British and Scandinavian animals. The extent and history of contact between British and Irish badger populations remains unclear. We use comprehensive genetic data from Great Britain and Ireland to demonstrate that badgers in Ireland's northeastern and southeastern counties are genetically similar to contemporary British populations. Simulation analyses suggest this admixed population arose in Ireland 600–700 (CI 100–2600) years before present most likely through introduction of British badgers by people. These findings add to our knowledge of the complex colonization history of Ireland by mammals and the central role of humans in facilitating it

Evidence for local and international spread of Mycobacterium avium subspecies paratuberculosis through whole genome sequencing of isolates from the island of Ireland

Publication history: Accepted - 1 April 2022; Published online - 5 April 2022We describe application of whole genome sequencing (WGS) to a collection of 197 Mycobacterium avium subsp paratuberculosis (MAP) isolates gathered from 122 cattle herds across 27 counties of the island of Ireland. We compare WGS to MAP diversity quantified using mycobacterial interspersed random unit – variable number tandem repeats (MIRU-VNTR). While MIRU-VNTR showed only two major types, WGS could split the 197 isolates into eight major groups. We also found six isolates corresponding to INMV 13, a novel MIRU-VNTR type for Ireland. Evidence for dispersal of MAP across Ireland via cattle movement could be discerned from the data, with mixed infections present in several herds. Furthermore, comparisons of MAP WGS data from Ireland to data from Great Britain and continental Europe revealed many instances of close genetic similarity and hence evidence for international transmission of infection. BEAST MASCOT structured coalescent analyses, with relaxed and strict molecular clocks, estimated the substitution rate to be 0.10–0.13 SNPs/site/year and disclosed greater transitions per lineage per year from Europe to Ireland, indicating transmission into Ireland. Our work therefore reveals new insight into the seeding of MAP infection across Ireland, highlighting how WGS can inform policy formulation to ultimately control MAP transmission at local, national and international scales.We acknowledge funding from the Department of Agriculture, Food and Marine awards 15/S/651 (‘NexusMAP’) and 2019R404 (’BTBGe- nIE’)

European badger (Meles meles) responses to low-intensity, selective culling: using mark recapture and relatedness data to assess social perturbation

Publication history: Accepted - 20 June 2022; Published online - 28 July 2022Culling the main wildlife host of bovine tuberculosis in Great Britain (GB) and Ireland, the European badger (Meles meles), has been employed in both territories to reduce infections in cattle. In GB, this has been controversial, with results suggesting that culling induces disturbance to badger social structure, facilitating wider disease dissemination. Previous analyses hypothesized that even very low-level, selective culling may cause similar deleterious effects by increasing ranging of individuals and greater mixing between social groups. To assess this hypothesis, a novel, prospective, landscape-scale ‘before-and-after’ Test and Vaccinate or Remove (TVR) study was implemented. Test-positive badgers were culled and test-negative badgers were Bacillus Calmette–Guérin (BCG) vaccinated and released. Mark–recapture metrics of badger ranging and genetic metrics of social group relatedness did not change significantly over the study period. However, selective culling was associated with a localized reduction in social group relatedness in culled groups. Ecological context is important; extrapolation across territories and other disease epidemiological systems (epi-systems) is likely to be challenging. However, we demonstrate that small-scale, selective removal of test-positive badgers was not associated with metrics of increased ranging but was associated with localized changes in social group relatedness. This adds to the evidence base on badger control options for policy makers.Department of Agriculture, Environment and Rural Affairs (DAERA) N

Relative abundance of Mycobacterium bovis molecular types in cattle:a simulation study of potential epidemiological drivers

Background: The patterns of relative species abundance are commonly studied in ecology and epidemiology to provide insights into underlying dynamical processes. Molecular types (MVLA-types) of Mycobacterium bovis, the causal agent of bovine tuberculosis, are now routinely recorded in culture-confirmed bovine tuberculosis cases in Northern Ireland. In this study, we use ecological approaches and simulation modelling to investigate the distribution of relative abundances of MVLA-types and its potential drivers. We explore four biologically plausible hypotheses regarding the processes driving molecular type relative abundances: sampling and speciation; structuring of the pathogen population; historical changes in population size; and transmission heterogeneity (superspreading). Results: Northern Irish herd-level MVLA-type surveillance shows a right-skewed distribution of MVLA-types, with a small number of types present at very high frequencies and the majority of types very rare. We demonstrate that this skew is too extreme to be accounted for by simple neutral ecological processes. Simulation results indicate that the process of MVLA-type speciation and the manner in which the MVLA-typing loci were chosen in Northern Ireland cannot account for the observed skew. Similarly, we find that pathogen population structure, assuming for example a reservoir of infection in a separate host, would drive the relative abundance distribution in the opposite direction to that observed, generating more even abundances of molecular types. However, we find that historical increases in bovine tuberculosis prevalence and/or transmission heterogeneity (superspreading) are both capable of generating the skewed MVLA-type distribution, consistent with findings of previous work examining the distribution of molecular types in human tuberculosis. Conclusion: Although the distribution of MVLA-type abundances does not fit classical neutral predictions, our simulations show that increases in pathogen population size and/or superspreading are consistent with the pattern observed, even in the absence of selective pressures acting on the system