Modelling dynamics between free-living amoebae and bacteria.

Free-living amoebae (FLA) serve as hosts for a variety of endosymbionts, which are microorganisms that reside and multiply within the FLA. Some of these endosymbionts pose a pathogenic threat to humans, animals, or both. The symbiotic relationship with FLA not only offers these microorganisms protection but also enhances their survival outside their hosts and assists in their dispersal across diverse habitats, thereby escalating disease transmission. This review is intended to offer an exhaustive overview of the existing mathematical models that have been applied to understand the dynamics of FLA, especially concerning their interactions with bacteria. An extensive literature review was conducted across Google Scholar, PubMed, and Scopus databases to identify mathematical models that describe the dynamics of interactions between FLA and bacteria, as published in peer-reviewed scientific journals. The literature search revealed several FLA-bacteria model systems, including Pseudomonas aeruginosa, Pasteurella multocida, and Legionella spp. Although the published mathematical models account for significant system dynamics such as predator-prey relationships and non-linear growth rates, they generally overlook spatial and temporal heterogeneity in environmental conditions, such as temperature, and population diversity. Future mathematical models will need to incorporate these factors to enhance our understanding of FLA-bacteria dynamics and to provide valuable insights for future risk assessment and disease control measures.

A scoping review on bovine tuberculosis highlights the need for novel data streams and analytical approaches to curb zoonotic diseases.

Zoonotic diseases represent a significant societal challenge in terms of their health and economic impacts. One Health approaches to managing zoonotic diseases are becoming more prevalent, but require novel thinking, tools and cross-disciplinary collaboration. Bovine tuberculosis (bTB) is one example of a costly One Health challenge with a complex epidemiology involving humans, domestic animals, wildlife and environmental factors, which require sophisticated collaborative approaches. We undertook a scoping review of multi-host bTB epidemiology to identify trends in species publication focus, methodologies, and One Health approaches. We aimed to identify knowledge gaps where novel research could provide insights to inform control policy, for bTB and other zoonoses. The review included 532 articles. We found different levels of research attention across episystems, with a significant proportion of the literature focusing on the badger-cattle-TB episystem, with far less attention given to tropical multi-host episystems. We found a limited number of studies focusing on management solutions and their efficacy, with very few studies looking at modelling exit strategies. Only a small number of studies looked at the effect of human disturbances on the spread of bTB involving wildlife hosts. Most of the studies we reviewed focused on the effect of badger vaccination and culling on bTB dynamics with few looking at how roads, human perturbations and habitat change may affect wildlife movement and disease spread. Finally, we observed a lack of studies considering the effect of weather variables on bTB spread, which is particularly relevant when studying zoonoses under climate change scenarios. Significant technological and methodological advances have been applied to bTB episystems, providing explicit insights into its spread and maintenance across populations. We identified a prominent bias towards certain species and locations. Generating more high-quality empirical data on wildlife host distribution and abundance, high-resolution individual behaviours and greater use of mathematical models and simulations are key areas for future research. Integrating data sources across disciplines, and a "virtuous cycle" of well-designed empirical data collection linked with mathematical and simulation modelling could provide additional gains for policy-makers and managers, enabling optimised bTB management with broader insights for other zoonoses.

BVD seroprevalence in the Irish cattle population as the national BVD programme progresses toward eradication.

BACKGROUND: Bovine Viral Diarrhoea Virus (BVDV) infection remains endemic in many countries worldwide. Ireland, in common with several other European counties, commenced an BVDV eradication programme in the last decade, Managing eradication programmes requires careful monitoring of diseases prevalence and understanding factors associated with disease exposure to ensure eradication programmes remain evidence based and tailored to the evolving epidemiological situation. METHODS: In this study, we explore the seroprevalence of BVDV exposure over a four-year period (2017 to 2020) in Ireland from a cohort of animals (n = 6,449) under 30 months of age sampled at slaughter, who were born subsequent to the commencement of a compulsory national eradication programme. Temporal trends and risk factor analysis were undertaken using multilevel logit regression models. RESULTS: There was a declining temporal trend in seroprevalence over the sample years of the study, and risk varied at both county- and herd-levels. The unadjusted marginal animal-level seroprevalence reduced from 9.1% in 2017 (95%; CI: 7.2-10.9) to 3.9% in 2020 (95%; CI: 3.2-4.6). The final model suggested that seropositivity in study cattle was strongly related with the presence of a PI animal in the herd during the year of the animal's birth, and to a lesser extent the status of the herd from which the animal was slaughtered. The risk of seroconversion increased significantly with increasing size of the herd of slaughter, in females relative to males, and in dairy relative to suckler herds. CONCLUSIONS: This study has shown that the BVDV serostatus of cattle at slaughter is correlated to the BVD infection history of the herd into which the animal was born and the herd from which it was slaughtered. Herd location, increased herd size and dairy production were associated with increased probability of serconversion. These findings will be used to inform the targeting of surveillance strategies once BVDV freedom has been achieved.

Identification and epidemiological analysis of Perostrongylus falciformis infestation in Irish badgers.

BACKGROUND: The lungworm, Perostrongylus falciformis (fomerly known as Aelurostrongylus falciformis) has been identified in badgers (Meles meles) in Britain, the Russian Federation, Italy, Norway, Poland, Ukraine, Bosnia Herzegovina and Romania, while Aelurostrongylus pridhami has been reported from badgers in Spain. RESULTS: Pulmonary tissue from 1580 Irish badgers was examined and an estimated prevalence of 32.09% (95% CI: 29.79-34.45%) of this parasite was detected. Confirmation of its occurrence was made by PCR analysis on a subset of the population. CONCLUSION: Infestation was widely distributed throughout the Republic of Ireland, with a trend towards higher infestation risk in western versus eastern counties. In addition males were at a higher risk of infestation than females and juveniles were at a significantly higher risk than adult badgers.

Seasonal variation of Fasciola hepatica antibodies in dairy herds in Northern Ireland measured by bulk tank milk ELISA.

Bovine fasciolosis, caused by the infection of the trematode parasite Fasciola hepatica, remains a problem in dairy herds causing significant production losses. In this study, bulk milk tank samples were utilised to generate a comprehensive survey of the variation in liver fluke exposure over the four seasons of 2016 in Northern Ireland (NI). Samples were tested using an antibody ELISA test; within-herd prevalence levels were categorised relative to sample-to-positive ratio (S/P%). Overall, 1494 herds (~ 50% of all active dairy farms in NI) were sampled. In total, 5750 samples were tested with 91% of herds having a sample result for each season. The proportion of herds with evidence of liver fluke exposure was very high across the year, with 93.03% of all bulk milk samples having some indication of liver fluke antibody presence. A high proportion of samples (2187/5750; 38.03%) fell within the highest infection class (indicating high within-herd prevalence). There was significant seasonal variation in the mean S/P%. A multivariable random effect ordinal logit model suggested that the greatest probability of being in a higher infection class was in winter, whilst the lowest was recorded during summer. There was a significant negative association between increasing herd liver fluke infection class and herd size. Furthermore, there was significant variation in infection levels across regions of Northern Ireland, with higher infection levels in northern administrative areas. This study demonstrates the very high liver fluke exposure in this region of Europe, and that risk is not equally distributed spatially or across seasons in dairy herds.

Bovine tuberculosis visible lesions in cattle culled during herd breakdowns: the effects of individual characteristics, trade movement and co-infection.

BACKGROUND: 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. RESULTS: 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). CONCLUSIONS: 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.

In situ adaptive response to climate and habitat quality variation: spatial and temporal variation in European badger (Meles meles) body weight.

Variation in climatic and habitat conditions can affect populations through a variety of mechanisms, and these relationships can act at different temporal and spatial scales. Using post-mortem badger body weight records from 15 878 individuals captured across the Republic of Ireland (7224 setts across ca. 15 000 km(2) ; 2009-2012), we employed a hierarchical multilevel mixed model to evaluate the effects of climate (rainfall and temperature) and habitat quality (landscape suitability), while controlling for local abundance (unique badgers caught/sett/year). Body weight was affected strongly by temperature across a number of temporal scales (preceding month or season), with badgers being heavier if preceding temperatures (particularly during winter/spring) were warmer than the long-term seasonal mean. There was less support for rainfall across different temporal scales, although badgers did exhibit heavier weights when greater rainfall occurred one or 2 months prior to capture. Badgers were also heavier in areas with higher landscape habitat quality, modulated by the number of individuals captured per sett, consistent with density-dependent effects reducing weights. Overall, the mean badger body weight of culled individuals rose during the study period (2009-2012), more so for males than for females. With predicted increases in temperature, and rainfall, augmented by ongoing agricultural land conversion in this region, we project heavier individual badger body weights in the future. Increased body weight has been associated with higher fecundity, recruitment and survival rates in badgers, due to improved food availability and energetic budgets. We thus predict that climate change could increase the badger population across the Republic of Ireland. Nevertheless, we emphasize that, locally, populations could still be vulnerable to extreme weather variability coupled with detrimental agricultural practice, including population management.

Should they stay, or should they go? Relative future risk of bovine tuberculosis for interferon-gamma test-positive cattle left on farms.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a serious infectious disease that remains an ongoing concern for cattle farming worldwide. Tuberculin skin-tests are often used to identify infected animals (reactors) during test-and-cull programs, however, due to relatively poor sensitivity, additional tests can be implemented in parallel. For example, in Northern Ireland interferon-gamma (IFN-g) testing is used in high-risk herds. However, skin-test negative animals which are positive to the IFN-g test are not required by law to be slaughtered - therefore the final choice for these animals' fate is left with the owner. During this study we investigated whether these animals represented a greater risk of becoming a skin reactor, relative to IFN-g test negative animals from the same herds. Our study population included 1107 IFN-g positive animals from 239 herds. A Cox-proportional hazard model indicated that animals which tested IFN-g positive were 2.31 times (95% CI: 1.92-2.79; P < 0.001) more likely to become a reactor compared with IFN-g negative animals. Animals from dairy herds, and from herds in the south-east, were of higher risk than animals from beef herds and other regions, respectively. Our findings suggest that IFN-g positive animals represent a higher risk of failing a skin-test in the future, indicating the value of IFN-g testing for identifying early-stage infected animals. These IFN-g positive animals are not under any disease restriction, and may move freely (trade), which may put recipient herds at increased risk. Our findings provide important evidence for stakeholders engaged in bTB eradication programs.

Risk of tuberculosis cattle herd breakdowns in Ireland: effects of badger culling effort, density and historic large-scale interventions.

Bovine tuberculosis (bTB) continues to be a problem in cattle herds in Ireland and Britain. It has been suggested that failure to eradicate this disease is related to the presence of a wildlife reservoir (the badger). A large-scale project was undertaken in the Republic of Ireland during 1997-2002 to assess whether badger removal could contribute to reducing risk of cattle herd breakdowns in four areas. During the period of that "four area" study, there was a significant decrease in risk in intensively culled (removal) areas relative to reference areas. In the present study, we revisit these areas to assess if there were any residual area effects of this former intervention a decade on (2007-2012). Over the study period there was an overall declining trend in bTB breakdown risk to cattle herds. Cattle herds within former removal areas experienced significantly reduced risk of breakdown relative to herds within former reference areas or herds within non-treatment areas (OR: 0.53; P < 0.001). Increased herd breakdown risk was associated with increasing herd size (OR: 1.92-2.03; P < 0.001) and herd bTB history (OR: 2.25-2.40; P < 0.001). There was increased risk of herd breakdowns in areas with higher badger densities, but this association was only significant early in the study (PD*YEAR interaction; P < 0.001). Badgers were culled in areas with higher cattle bTB risk (targeted culling). Risk tended to decline with cumulative culling effort only in three counties, but increased in the fourth (Donegal). Culling badgers is not seen as a viable long-term strategy. However, mixed policy options with biosecurity and badger vaccination, may help in managing cattle breakdown risk.

Large-scale movements in European badgers: has the tail of the movement kernel been underestimated?

Characterizing patterns of animal movement is a major aim in population ecology, and yet doing so at an appropriate spatial scale remains a major challenge. Estimating the frequency and distances of movements is of particular importance when species are implicated in the transmission of zoonotic diseases. European badgers (Meles meles) are classically viewed as exhibiting limited dispersal, and yet their movements bring them into conflict with farmers due to their potential to spread bovine tuberculosis in parts of their range. Considerable uncertainty surrounds the movement potential of badgers, and this may be related to the spatial scale of previous empirical studies. We conducted a large-scale mark-recapture study (755 km(2); 2008-2012; 1935 capture events; 963 badgers) to investigate movement patterns in badgers, and undertook a comparative meta-analysis using published data from 15 European populations. The dispersal movement (>1 km) kernel followed an inverse power-law function, with a substantial 'tail' indicating the occurrence of rare long-distance dispersal attempts during the study period. The mean recorded distance from this distribution was 2.6 km, the 95 percentile was 7.3 km and the longest recorded was 22.1 km. Dispersal frequency distributions were significantly different between genders; males dispersed more frequently than females, but females made proportionally more long-distance dispersal attempts than males. We used a subsampling approach to demonstrate that the appropriate minimum spatial scale to characterize badger movements in our study population was 80 km(2), substantially larger than many previous badger studies. Furthermore, the meta-analysis indicated a significant association between maximum movement distance and study area size, while controlling for population density. Maximum long-distance movements were often only recorded by chance beyond the boundaries of study areas. These findings suggest that the tail of the badger movement distribution is currently underestimated. The implications of this for understanding the spatial ecology of badger populations and for the design of disease intervention strategies are potentially significant.

Emerging and Endemic Infections in Wildlife: Epidemiology, Ecology and Management in a Changing World.

The importance of gaining a greater understanding of the infectious diseases of wild animal populations and the impact of emerging and re-emerging pathogens has never been more sharply in focus than in the current post-COVID-19 world [...].

Antimicrobial resistance in Escherichia coli isolated from pigs and associations with aggregated antimicrobial usage in Ireland: A herd-level exploration.

AIMS: Antimicrobial resistance (AMR) is of significant global concern and is a major One Health issue. There is evidence to suggest that increased antimicrobial usage (AMU) can be associated with AMR patterns, and therefore, there have been efforts to reduce AMU in anticipation of reducing AMR emergence risk. The aim of this study was to investigate whether there were any associations between AMU and AMR patterns of commensal Escherichia coli isolated from pig herds in Ireland. METHODS AND RESULTS: Data on AMR from a panel of antimicrobials (AMDs) were gathered as part of national surveillance activities. These data were associated with reported usage of AMDs, on a year-quarter basis, measured in mg/kg at a herd-level using generalized estimating equation regression analysis. Associations were tested with AMR presence or multi-drug resistance (MDR; ≥3 classes) profiles and total AMU during the contemporaneous quarter and previous quarter, respectively. Furthermore, individual and AMD class-based associations were tested. The final dataset contained 218 observations (herd-quarter usage and AMR resistance profile) from 122 herds during 2019-2021. Apparent resistance prevalence varied according to AMD type, with the highest mean prevalence found with tetracycline at 51.57% (95% CI: 45.06%-58.09%). There were significant associations between a herd obtaining a positive AMR result for any AMDs and the overall levels of AMU during the year-quarter. Furthermore, there were significant positive associations between MDR and total AMU. At the compound level, chloramphenicol resistance was significantly associated with increased usage of trimethoprim/sulfadiazine and chlortetracycline, respectively (p < 0.010). Tetracycline resistance was associated with increased use of chlortetracycline (p = 0.008). At the antimicrobial class level, there was a significant positive relationship between the usage of phenicol and the probability of a resistance for chloramphenicol (p = 0.026) and between the usage of tetracycline and tetracycline resistance probability (p = 0.018). CONCLUSIONS: Our data provide evidence of associations between overall AMU and AMR or MDR risk at the herd-quarter level. There was also evidence of associations between specific AMDs and patterns of resistance. Associations varied depending on whether time lags in usage were modelled or how usage was modelled (e.g. dichotomized or continuous). Associations with rarely used AMDs (e.g. critically important AMDs) were precluded due to a lack of statistical power. Continued monitoring of both AMU and AMR is crucial to assess the impacts of policy changes aimed at reducing AMU.

Genotypic analysis of a localised hotspot of Pestivirus A (BVDV-1) infections in Northern Ireland.

BACKGROUND: Bovine viral diarrhoea (BVD) is caused by Pestivirus A and Pestivirus B. Northern Ireland (NI) embarked on a compulsory BVD eradication scheme in 2016, which continues to this day, so an understanding of the composition of the pestivirus genotypes in the cattle population of NI is required. METHODS: This molecular epidemiology study employed 5' untranslated region (5'UTR) genetic sequencing to examine the pestivirus genotypes circulating in samples taken from a hotspot of BVD outbreaks in the Enniskillen area in 2019. RESULTS: Bovine viral diarrhoea virus (BVDV)-1e (Pestivirus A) was detected for the first time in Northern Ireland, and at a high frequency, in an infection hotspot in Enniskillen in 2019. There was no evidence of infection with BVDV-2 (Pestivirus B), Border disease virus (pestivirus D) or HoBi-like virus/BVDV-3 (pestivirus H). LIMITATIONS: Only 5'UTR sequencing was used, so supplementary sequencing, along with phylogenetic trees that include all BVDV-1 genotype reference strains, would improve accuracy. Examination of farm locations and animal movement/trade is also required. CONCLUSIONS: Genotype BVDV-1e was found for the first time in Northern Ireland, indicating an increase in the genetic diversity of BVDV-1, which could have implications for vaccine design and highlights the need for continued pestivirus genotypic surveillance.

Trends and factors associated with dairy calf early slaughter in Ireland, 2018-2022.

Dairy systems require that each cow calves annually to have an efficient milk production cycle. In systems where milk production is maximized, the male offspring from dairy breed sires tend to have poor beef production traits and, therefore, can be of low economic value. Few studies have been published on the factors impacting early slaughtering of calves in peer-reviewed literature. Here we present an analysis of national data on calves slaughtered from 2018 to 2022 in Ireland. Data (Jan 2018-May 2022) on all cattle <6 months of age were collated at a national level and were described at calf-, herd-, and county-levels. These data were statistically analyzed at per-capita slaughter rates (calves/calf born) using negative binomial regression models with an offset. There were 125,260 calves slaughtered early (1.09% of total births) recorded in the dataset from 1,364 birth herds during the study period, of which 94.8% (118,761) were male. 51.7% were classified as Friesian-cross (FRX), 11.5% Friesian (FR) and 32.1% Jersey-cross (JEX). The median age at slaughter was 16 days (Mean: 18.9 days; IQR: 13-22). The median calves/herd slaughtered was 16 (mean: 91.8); median calves/herd/year slaughtered was 21 (mean: 42.0). There was substantial variation in counts of calves slaughtered across herds, years, and counties. Herd calf slaughter rates and per capita calf slaughter rates increased significantly in 2022, with the highest rates over the time series. Calf slaughter rates varied significantly with herd size, year, and major breed (Jersey; JE). Herds which were more recently established tended to have higher calf slaughter rates. Herds that repeatedly slaughtered calves over 2 or more years tended to be larger and slaughtered more calves/herd/year. The slaughtering of calves is not widespread across the dairy industry in Ireland. The distribution of calves slaughtered per herd demonstrate that a small number of herds contributed disproportionately to calf slaughter numbers. Such herds tended to be very large (herd size), more recently established (2016 onwards), and have higher proportions of JE/JEX breed cattle. The outcomes of the present study provide an evidential base for the development of targeted industry-lead interventions with the aim of ending the routine early slaughter of calves.

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.

Genomic epidemiology of Mycobacterium bovis infection in sympatric badger and cattle populations in Northern Ireland.

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.

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.

Engaging With Farmers to Explore Correlates of Bovine Tuberculosis Risk in an Internationally Important Heritage Landscape: The Burren, in the West of Ireland.

Bovith recene tuberculosis (bTB) continues to be a pathogen of concern in several countries globally. Analysis of areas that have higher incidences of bTB outbreaks has demonstrated how risk is not equally distributed, and local data collection, analysis and participatory engagement is required to develop tailored approaches. The Burren, an internationally important heritage landscape, has been an area of higher bTB incidence for many years in Ireland, and owing to its unique geology and farming heritage a survey was developed to engage with local farmers to gain greater insight into farming practices and bTB control to inform tailored approaches. The survey gathered data on the farm and animal management approaches being used within the Burren, including local farming techniques like the use of "winterage" (grazing exposed limestone dominated uplands). Thematic analysis of free text responses was undertaken. Quantitative data were then explored using statistical models to assess associations with recent (<3 years) self-reported bTB breakdown risk. There was a high number of responses demonstrating a high degree of willingness to engage on the issue. Thematic analysis suggested that wildlife and its management (culling and vaccination), testing quality, and its impact on the bTB scheme, and pessimism around eradication were important themes. Statistical analysis suggested that increasing bTB risk was primarily related to increasing herd-size and the percentage of herd owner's land inaccessible to those attempting to locate badger setts. There was less evidence for associations relating to the amount of time, or which season (i.e., summer), farmers utilized "winterage". The results of the study will feed back directly to local bTB management plans and further stakeholder engagement and is an exemplar for local tailoring of national control measures in situations of high incidences of bTB outbreaks in particular areas.

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.