The Irish bTB eradication programme: combining stakeholder engagement and research-driven policy to tackle bovine tuberculosis.

A new Irish bovine tuberculosis (bTB) eradication strategy was launched in 2021. The strategy was formulated following extensive discussions with stakeholders, formal reviews of several aspects of the existing bTB policy and relevant inputs from the latest scientific research projects. A stakeholder discussion body, the TB Forum, had been established in 2018 and this continues under the new strategy, supported by three working groups (scientific, financial and implementation). The strategy sets out actions to address cattle-to-cattle and badger-to-cattle bTB transmission, along with actions to improve farm biosecurity and empower farmers to make their own choices to reduce bTB risk.Large scale vaccination of badgers has been rolled out under the new strategy, with over 20,000 km2 covered by the vaccination programme and 6,586 badgers captured in vaccination areas in 2021. Vaccination efforts have been complemented by intensive communications campaigns, including a web enabled software application ("app") enabling farmers to report the location of badger setts.Cattle which test inconclusive to the tuberculin skin test have been re-tested using a gamma interferon blood test since April 2021, enabling truly infected cattle to be identified more effectively due to the higher sensitivity of this test. An enhanced oversight process has been put in place for herds experiencing extended or repeat bTB breakdowns. Whole genome sequencing is being used to investigate links between breakdowns, with the results supporting operational decision making in case management.Communications, including biosecurity advice, are co-designed with stakeholders, in order to improve their effectiveness. A programme involving veterinary practitioners providing tailored biosecurity bTB advice to their clients was established in 2021 and was rolled out nationally during 2022.A core element of the new strategy is the continual improvement of policies in response to changing bTB risks, informed by scientific research and then implemented with stakeholder consultation.

Inferring bovine tuberculosis transmission between cattle and badgers via the environment and risk mapping.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is one of the most challenging and persistent health issues in many countries worldwide. In several countries, bTB control is complicated due to the presence of wildlife reservoirs of infection, i.e. European badger (Meles meles) in Ireland and the UK, which can transmit infection to cattle. However, a quantitative understanding of the role of cattle and badgers in bTB transmission is elusive, especially where there is spatial variation in relative density between badgers and cattle. Moreover, as these two species have infrequent direct contact, environmental transmission is likely to play a role, but the quantitative importance of the environment has not been assessed. Therefore, the objective of this study is to better understand bTB transmission between cattle and badgers via the environment in a spatially explicit context and to identify high-risk areas. We developed an environmental transmission model that incorporates both within-herd/territory transmission and between-species transmission, with the latter facilitated by badger territories overlapping with herd areas. Model parameters such as transmission rate parameters and the decay rate parameter of M. bovis were estimated by maximum likelihood estimation using infection data from badgers and cattle collected during a 4-year badger vaccination trial. Our estimation showed that the environment can play an important role in the transmission of bTB, with a half-life of M. bovis in the environment of around 177 days. Based on the estimated transmission rate parameters, we calculate the basic reproduction ratio (R) within a herd, which reveals how relative badger density dictates transmission. In addition, we simulated transmission in each small local area to generate a first between-herd R map that identifies high-risk areas.

Can more information be extracted from bovine TB skin test outcomes to inform animal risk management? A retrospective observational animal-level study.

Continual tailoring of control programmes of endemic pathogens during long-term eradication campaigns requires detailed analysis of surveillance data to inform evidence-based policy. Bovine tuberculosis is a disease where long-term control and eradication programs are in train in several countries. The primary diagnostic tool, the intradermal tuberculin test, used to identify infected animals can be interpreted using different criteria and cut-offs, facilitating flexibility in its use as a basis to inform interventions. We investigated the comparative risk of animals failing a single intradermal comparative tuberculin test (SICTT) based on their previous tuberculin test result following a higher risk test-type (reactor retest of an infected herd). The study was a retrospective cohort design, and the primary exposure was the test status following a reactor retest classified as mutually exclusive categories based on bovine and avian tuberculin reactions: standard interpretation inconclusive (Sdi), severe interpretation inconclusive (Svi), single intradermal test (SIT) reactors (SITr), SIT inconclusive (SITi), avian tuberculin reactors (Ar), and test negative animals. Random effects multivariable logistic regression was used to investigate future risk. Cross-validation and downscaling was used to explore model performance. Alternate models with differing outcome test types were also explored. The models were trained on 844,207 observations from June 2018 to June 2021. Sdi, Svi, SITr, SITi and Ar were associated with the following odds ratios 12.242 (95 %CIs: 5.236-28.625; p < 0.001), 4.101 (95 %CIs: 3.423-4.913; p < 0.001), 2.503 (95 %CIs: 1.878-3.338; p < 0.001), 1.741 (95 %CIs: 1.195-2.538; p = 0.004) and 1.065 (95 %CIs: 0.833-1.361; p = 0.616) for failing the next test, respectively. High model performance was achieved with inclusion of random effects for both training and test evaluation datasets (AUC: 0.94; Balanced accuracy: 0.84), but fixed-effects only predictions exhibited moderate performance (AUC: 0.70; Balanced accuracy: 0.69). This reflects that 55 % of the risk of test failure relates to between herd heterogeneity based on intra-class correlation, while controlling for fixed effects. Other factors that were associated with increasing risk included age (older cohorts were at greater risk than the youngest cohort), breakdown history of the herd (greater number of breakdowns prior to the study period), and the time between exposure test and outcome test. These results provide further evidence to inform risk-based management policies for TB, including the removal of Sdi animals in higher risk situations, supplementary testing of cattle based on tuberculin responses and the provision of risk management advice to herd owners. The results characterise the future animal-level risk posed by Svis and suggest this risk may require policy led interventions.

Revisiting the relative effectiveness of slaughterhouses in Ireland to detect tuberculosis lesions in cattle (2014-2018).

Slaughterhouse or meat factory surveillance to detect factory lesions (FL) at slaughter is an important part of the bovine tuberculosis (bTB) eradication program in Ireland. The objective of this study was to quantify the effectiveness of Irish slaughterhouses or factories in submitting FL and the proportion of those submitted FL confirmed as being due to bTB in slaughtered cattle, and to identify and quantify the association of risk factors at animal, herd, and factory level with FL submission and confirmation. The data consisted of 6,611,854 animals slaughtered in Irish factories from 2014 to 2018 obtained from the Department of Agriculture, Food and Marine (DAFM), Ireland. Selected risk factors for this study included factory, year and month of slaughter, age, sex, breed, animal movement, ever inconclusive in the standard or severe skin test, herd type, herd size, and bTB history. The association of each risk factor on the FL submission and confirmation risk were analysed with univariable followed by a multivariable logistic regression with herd as random effect. Factories were ranked and compared based on the odds ratio (OR) obtained from the univariable (crude OR) and multivariable (adjusted OR) analysis. The average submission risk of all factories was 20 per 10,000 animals slaughtered, ranging from 1 to 42 per 10,000 animals slaughtered, and the average confirmation risk over all factories was 40.72%, ranging from 0.00 to 61.84%. The odds of submitting and confirming FL as bTB positive were higher in animals over eight years old compared to animals 1-2 years old (OR = 1.91, 95 CI 95% 1.77-2.06 and OR = 4.05, 95% CI 3.17-5.18, respectively), and were higher in animals that ever had inconclusive skin result based on severe interpretation (OR = 2.83, 95% CI 2.44-3.27 and OR = 4.48, 95% CI 2.66-7.54, respectively), animals originating from sucklers herds (OR = 1.08, 95% CI 1.02-1.14 and OR = 1.31, 95% CI 1.11-1.55, respectively), or herds with bTB history in the past three years (OR = 4.46, 95% CI 4.28-4.66 and OR = 319.90, 95% CI 237.98-430.04, respectively). The odds of FL submission and confirmation decreased as the herd size increased (OR = 0.95, 95% CI 0.93-0.96 and OR = 0.82, 95% CI 0.78-0.86, respectively). An inverse relationship of FL submission and confirmation was present for variable sex and inconclusive skin result with standard interpretation, where submission odds were higher in males (OR = 1.05, 95% CI 1.00-1.10) and ever inconclusive animals (OR = 74.24, 95% CI 69.39-79.43), although the confirmation odds were lower (males OR = 0.66, 95% CI 0.56-0.76; ever inconclusive OR = 0.44, 95% CI 0.36-0.54). The crude and adjusted ranking of factories did not differ greatly for FL submission, indicating that factory-related factors may contribute significantly to the submission variation between factories. However, a substantial difference between crude and adjusted confirmation ranking was present which may indicate that animal and herd-related factors were associated to variation in confirmation risk between factories.

Simulating partial vaccine protection: BCG in badgers.

In wildlife disease management there are few diseases for which vaccination is a viable option. The human vaccine BCG has been used for the control of bovine tuberculosis in badgers since 2010 and is expected to increase. Understanding the long-term effects of repeated vaccination campaigns on disease prevalence is vital, but modelling thus far has generally assumed that a vaccine provides perfect protection to a proportion of the population, and that animals exposed to a repeated vaccination have a second independent chance of becoming protected. We held a workshop with experts in the field to obtain consensus over the main pathways for partial protection in the badger, and then simulated these using an established model. The available data supported the possibility that some individuals receive no benefit from the BCG vaccine, others may result in a delayed disease progression and in the remaining animals, vaccine protected the individual from any onward transmission. Simulating these pathways using different levels of overall efficacy demonstrated that partial protection leads to a reduced effect of vaccination, but in all of the identified scenarios it was still possible to eradicate disease in an isolated population with no disease introduction. We also identify those potential vaccination failures that require further investigation to determine which of our proposed pathways is the more likely.

Disturbance Ecology Meets Bovine Tuberculosis (bTB) Epidemiology: A Before-and-After Study on the Association between Forest Clearfelling and bTB Herd Risk in Cattle Herds.

Disturbance ecology refers to the study of discrete processes that disrupt the structure or dynamics of an ecosystem. Such processes can, therefore, affect wildlife species ecology, including those that are important pathogen hosts. We report on an observational before-and-after study on the association between forest clearfelling and bovine tuberculosis (bTB) herd risk in cattle herds, an episystem where badgers (Meles meles) are the primary wildlife spillover host. The study design compared herd bTB breakdown risk for a period of 1 year prior to and after exposure to clearfelling across Ireland at sites cut in 2015-2017. The percent of herds positive rose from 3.47% prior to clearfelling to 4.08% after exposure. After controlling for confounders (e.g., herd size, herd type), we found that cattle herds significantly increased their odds of experiencing a bTB breakdown by 1.2-times (95%CIs: 1.07-1.36) up to 1 year after a clearfell risk period. Disturbance ecology of wildlife reservoirs is an understudied area with regards to shared endemic pathogens. Epidemiological observational studies are the first step in building an evidence base to assess the impact of such disturbance events; however, such studies are limited in inferring the mechanism for any changes in risk observed. The current cohort study suggested an association between clearfelling and bTB risk, which we speculate could relate to wildlife disturbance affecting pathogen spillback to cattle, though the study design precludes causal inference. Further studies are required. However, ultimately, integration of epidemiology with wildlife ecology will be important for understanding the underlying mechanisms involved, and to derive suitable effective management proposals, if required.

Bovine tuberculosis in youngstock cattle: A narrative review.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a high-priority global pathogen of concern. The role of youngstock animals in the epidemiology of bTB has not been a focus of contemporary research. Here we have aimed to collate and summarize what is known about the susceptibility, diagnosis, transmission (infectiousness), and epidemiology to M. bovis in youngstock (up to 1-year of age). Youngstock are susceptible to M. bovis infection when exposed, with the capacity to develop typical bTB lesions. Calves can be exposed through similar routes as adults, via residual infection, contiguous neighborhood spread, wildlife spillback infection, and the buying-in of infected but undetected cattle. Dairy systems may lead to greater exposure risk to calves relative to other production systems, for example, via pooled milk. Given their young age, calves tend to have shorter bTB at-risk exposure periods than older cohorts. The detection of bTB varies with age when using a wide range of ante-mortem diagnostics, also with post-mortem examination and confirmation (histological and bacteriological) of infection. When recorded as positive by ante-mortem test, youngstock appear to have the highest probabilities of any age cohort for confirmation of infection post-mortem. They also appear to have the lowest false negative bTB detection risk. In some countries, many calves are moved to other herds for rearing, potentially increasing inter-herd transmission risk. Mathematical models suggest that calves may also experience lower force of infection (the rate that susceptible animals become infected). There are few modeling studies investigating the role of calves in the spread and maintenance of infection across herd networks. One study found that calves, without operating testing and control measures, can help to maintain infection and lengthen the time to outbreak eradication. Policies to reduce testing for youngstock could lead to infected calves remaining undetected and increasing onwards transmission. Further studies are required to assess the risk associated with changes to testing policy for youngstock in terms of the impact for within-herd disease control, and how this may affect the transmission and persistence of infection across a network of linked herds.

Is there an association between road building and bovine tuberculosis herd risk? A three time-point study in Ireland, 2011-2019.

Bovine tuberculosis (bTB) is a chronic infectious disease caused by Mycobacterium bovis which results in a significant economic cost to cattle industries and governments where it is endemic. In Ireland, the European badger is the main wildlife reservoir of infection. In this study, we investigated whether (motorway) road construction was associated with an increased risk of bTB in associated cattle herds. For this study, we considered three observation periods: pre-construction (2011-2014), construction (2015-2017) and post-construction (2018-2019). We selected 1543 herds situated, based on proximity, between >50 m and <5 km of the roadworks, and extracted information about their herd-size, herd-type, inward animal movements, bTB history, and distance to the roadworks. Generalized linear mixed models were performed, whose outcome were whether a herd experienced a bTB breakdown with ≥1 or ≥3 standard reactor/s, respectively. Herds located at a distance of >3 km from the roadworks were found to be at reduced risk of a bTB breakdown over the construction period compared with those situated within 1 km of the roadworks for ≥1 reactor/s (>3 km and construction vs. <1 km: OR: 0.595, 95 % Confidence Interval (CI): 0.354-0.999) or ≥3 reactors (>3 km and construction vs. <1 km: OR: 0.431, 95 % CI: 0.174-1.067). Other previously reported risk factors such as inward movements, herd-size and herd-type were also associated with bTB risk in the final models (≥1 reactor/s and ≥3 reactors). These findings appear to be consistent with bTB breakdowns being a consequence as opposed to coincident to road construction, given the temporal and spatial consistency of the evidence. The potential for badger social group disturbance leading to the spatial spread of infection to cattle herds, as previously described in the United Kingdom, could be a hypothetical mechanism to explain these findings. However, our findings are not consistent with previous Irish studies, including recent work from another road construction project, albeit running alongside and cross over an existing road rather than construction of a new road as in this case, or experiences from national targeted badger removal. Further research is warranted to verify this pattern occurs elsewhere, and the underlying biological mechanism. Until further data are available, we recommend that badgers are vaccinated, as a precautionary measure, in advance of the commencement of major roadworks.

Future Risk of Bovine Tuberculosis (Mycobacterium bovis) Breakdown in Cattle Herds 2013-2018: A Dominance Analysis Approach.

Bovine tuberculosis (bTB) remains a significant endemic pathogen of cattle herds, despite multi-decadal control programmes being in place in several countries. Understanding the risks of future bTB breakdown (BD) and the associated characteristics of herds and index breakdowns could help inform risk categorisation. Such risk categories could then contribute to tailored management and policies. Here, we estimated the future risk of herd BD for the cohort of herds that were derestricted during 2013 in Ireland using multivariable logit regression models, with a dominance analysis approach. One third of herds that were derestricted in 2013 experienced a breakdown during the follow-up five year period (1469/4459; 33%). BD length was a significant predictor of future risk, primarily driven by long BDs > 230 days relative to short BDs < 130 days (OR 95%CI: 1.157-1.851), as was having had a previous BD (OR 95%CI: 1.012-1.366). Herd-size was the dominant predictor of future risk (accounted for 46% of predicted variance), suggesting significant increase in risk of future breakdown with increasing (log) herd-size (OR 95%CI: 1.378-1.609). There was significant spatial variation in future risk across counties, and it was the second most dominant predictor of future risk (25% of predicted variance). The size of index breakdowns was not a strong predictor of future risk over a 5-year period. These findings can inform a risk-based policy development.

Bovine Tuberculosis (Mycobacterium bovis) Outbreak Duration in Cattle Herds in Ireland: A Retrospective Observational Study.

Bovine tuberculosis (bTB) outbreaks, caused by Mycobacterium bovis infection, are a costly animal health challenge. Understanding factors associated with the duration of outbreaks, known as breakdowns, could lead to better disease management policy development. We undertook a retrospective observational study (2012-2018) and employed Finite Mixture Models (FMM) to model the outcome parameter, and to investigate how factors were associated with duration for differing subpopulations identified. In addition to traditional risk factors (e.g., herd size, bTB history), we also explored farm geographic area, parcels/farm fragmentation, metrics of intensity via nitrogen loading, and whether herds were designated controlled beef finishing units (CBFU) as potential risk factors for increased duration. The final model fitted log-normal distributions, with two latent classes (k) which partitioned the population into a subpopulation around the central tendency of the distribution, and a second around the tails of the distribution. The latter subpopulation included longer breakdowns of policy interest. Increasing duration was positively associated with recent (<3 years) TB history and the number of reactors disclosed, (log) herd size, beef herd-type relative to other herd types, number of land parcels, area, being designated a CBFU ("feedlot") and having high annual inward cattle movements within the "tails" subpopulation. Breakdown length was negatively associated with the year of commencement of breakdown (i.e., a decreasing trend) and non-significantly with the organic nitrogen produced on the farm (N kg/hectare), a measure of stocking density. The latter finding may be due to confounding effects with herd size and area. Most variables contributed only moderately to explaining variation in breakdown duration, that is, they had moderate size effects on duration. Herd-size and CBFU had greater effect sizes on the outcome. The findings contribute to evidence-based policy formation in Ireland.

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.

Post-mortem surveillance in Ireland discloses skin-test negative cattle with presumptive evidence of infection of Mycobacterium bovis (lesions at routine slaughter (LRS)), the causative agent of bovine tuberculosis (bTB). Laboratory confirmation of lesions has impacts on trade restrictions for herds, therefore if laboratory capacity was diminished, how herds are treated would require an informed risk policy. Here we report the proportion of herds with subsequent evidence of within-herd transmission, based on skin-test results. We assess how herd-size, herd-type, and bTB-history affect the probability of additional reactors at follow-up test using univariable and multivariable random-effects models. The study represents a rapid response to developing an evidential base for policy demands during an extraordinary event, the COVID-19 epidemic in Ireland. A dataset from 2005 to 2019 of breakdowns were collated. Overall, 20,116 breakdowns were initiated by LRS cases. During the index tests of these breakdowns, 3931 revealed ≥1 skin-test reactor animals (19.54%; ≥1 standard reactors: 3827; 19.02%). Increasing herd-size was associated with reactor disclosure on follow-up. For small herds (<33 animals), 11.74% of follow-up tests disclosed ≥1 reactor; 24.63% of follow-up tests from very large herds (>137) disclosed ≥1 reactors. Beef (13.87%) and "other" (13%) herd production types had lower proportion of index tests with reactors in comparison with dairy (28.27%) or suckler (20.48%) herds. Historic breakdown size during the previous 3-years was associated reactor disclosure risk on follow-up. Our results are useful for rapid tailored policy development aimed at identifying higher risk herds.