Risk Of Bovine Tuberculosis Research Articles

Is badger culling associated with risk compensation behaviour among cattle farmers?

Risk compensation theory suggests that behaviours are modified in response to interventions that remove risks by substituting them with other risky behaviours to maintain a 'risk equilibrium'. Alternatively, risk reduction interventions may result in spill-over behaviours that seek to minimise risks further. This paper assessed evidence for these behavioural risk responses among farmers in response to badger culling that seeks to remove the risk of bovine tuberculosis in cattle. Data from the UK's randomised badger culling trial were re-analysed, comparing farmers' cattle movement practices in proactive and reactive culling areasand control areas. Analysis compared cattle movementsduring and after the trial using zero-inflated negative binomial regression. The analysis found no strong evidence of risk compensation behaviours among farmers who experienced proactive culling. However, strong evidence for a reduction in cattle movements in reactive culling areas was found. The results indicate high levels of inertia within farming systems in relation to cattle purchasing. Data do not account for the risk of cattle purchases and reflect previous policy regimens. Evidence from recent badger culling interventions should be analysed. Proactive badger culling was not associated with risk compensation behaviours, while reactive badger culling was associated with decreased risk taking among farmers.

Contribution of herd management, biosecurity, and environmental factors to the risk of bovine tuberculosis in a historically low prevalence region

Eradication of bovine tuberculosis (bTB) in certain historically low-prevalence regions remains elusive. A complete characterisation of the husbandry practices, biosecurity, and environment where farms are located is crucial to implement targeted in-farm risk mitigation protocols. Here, a detailed survey performed in 94 dairy cattle farms located in Navarra, a low-prevalence region of Spain between 2016 and 2020 was carried out. Data on 73 biosecurity, farm-, and environmental-level factors potentially associated with the risk of bTB occurrence were evaluated using an ordinal logistic regression model: farms were classified based on their prevalence index, a score linked to each farm to account for the severity and recurrence of bTB cases: 22.3% of the farms had a score of 1, 21.3% a score of 2, 26.6% a score of ≥ 3, and 29.8% were negative herds. A statistically significant association between a higher prevalence index and the frequency of badger sightings along with the lease of pastures to sheep during Winter was identified. Farms that detected badgers on a monthly to daily basis in the surroundings and those that leased pastures for sheep flocks during Winter were four [odds ratio, 95% CI (4.3; 1.1–17.5)] and three (3.1; 1.0–9.9) times more likely to have the highest prevalence index, respectively (predicted probabilityprevalence index≥3 = 0.7; 95% CI 0.3–0.9). Conversely, farms that used a vehicle to transport animals from holdings to pastures were less likely (0.1; <0.1–0.3) to present higher levels of prevalence index compared with farms that used none (on foot). Results suggested that the combined effect of farm- and environmental-level risk factors identified here may be hampering disease eradication in Navarra, highlighting the need to implement targeted protocols on farms and grazing plots. An increased awareness of monitoring sheep and wildlife in direct or indirect contact with cattle herds in historically low bTB prevalence areas should be raised.

Investigation of the association between the Enferplex bovine tuberculosis antibody test and the future risk of bovine tuberculosis in irish cattle in infected herds: a pilot field study

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

The Benefit of Healthy Hedgerows

There is an interest in hedgerows because they are home to both plants and animals and provide habitat connection corridors to enable wildlife can move around the landscape. They also deliver a number of additional benefits to farmland, beyond that of a field boundary. These can include: • shelter for livestock • regulation of water supply for crops • improvements in animal health • reduction in soil erosion • reduction in the need for pesticide use • sustaining pollinator communities which support productive farming • providing a sustainable source of wood fuel • reducing the risk of bovine tuberculosis in cattle herds • reducing the rate of climate change through carbon storage • reducing pollution

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.

Evaluating the risk of bovine tuberculosis posed by standard inconclusive reactors identified at backward-traced herd tests in Northern Ireland that disclosed no reactors

Bovine tuberculosis is a notifiable disease in Northern Ireland with the national eradication programme of compulsory testing and slaughter of reactor animals costing approximately £40 million per year. Backward tracing, known as Backward Check Tests (BCTs), of reactor animals is used to identify previous herds where the bTB positive animal has resided. The aim of this study was to quantify the bovine tuberculosis (bTB) risk posed by inconclusive reactors (ICs) at BCTs at both the individual animal and the herd level. ICs to the Comparative Intradermal Tuberculin Test (CITT) at a BCT, in which no reactors were found, were matched with CITT negative animals, based on age, sex, test ID and follow up period, in Northern Ireland between 1st January 2008 and 31st December 2017 (inclusive). A retrospective matched cohort study design was used with the outcome of interest being the bTB status of each animal and subsequent bTB herd breakdowns. After adjusting for herd size, IC animals at a BCT had 16 times the odds (95% confidence interval: 7.75 to 38.28, p < 0.001) of becoming bTB positive compared to CITT negative animals. The percentage population attributable risk was 0.0001%. The majority 75% (n = 71) of ICs that became bTB positive were identified at the 42 day retest. Of those that were not disclosed at the 42 day retest (n = 24), almost a third (29%) had moved to an unrestricted herd. However, after adjusting for herd size and type, herds that had ICs only identified at a BCT did not have an increased odds of a subsequent bTB herd breakdown compared to herds that had a CITT negative BCT. Given the increased risk posed by ICs at a BCT, it may be justifiable to remove them from the herd immediately or place them under lifetime movement restrictions to the herd where they were detected. However, further action regarding the herd of origin does not appear to be justified.

Dynamics and risk of transmission of bovine tuberculosis in the emerging dairy regions of Ethiopia.

The Ethiopian government has several initiatives to expand and intensify the dairy industry; however, the risk of bovine tuberculosis (bTB) spread is a challenge. To assess the rate of expansion and risk factors for transmission of bTB within-herds, we carried out a repeated cross-sectional survey at two time points, 2016/17 and 2018, in three regional cities, namely, Gondar, Hawassa and Mekelle, representing the emerging dairy belts of Ethiopia. The total number of herds involved was 128, comprising an average of 2303 cattle in each round. The Single Intradermal Comparative Cervical Tuberculin (SICCT) test was used to identify reactor status and data on herd-level risk factors were collected using a structured questionnaire. In the first survey, the apparent prevalence of bTB, as measured by the SICCT test, was 4.5% (95% CI 3.7-5.4%) at the individual animal-level and 24% (95% CI 17.5-32%) at the herd-level. There was no statistically significant change in the overall apparent prevalence or regional distribution at the second survey, consistent with the infection being endemic. The incidence rate was estimated at 3.6 (95% CI 2.8-4.5) and 6.6 (95% CI 3.0-12.6) cases/100 cattle (or herd)-years at the animal- and herd-levels, respectively. Risk factors significantly associated with the within-herd transmission of bTB were age group and within-herd apparent prevalence at the start of the observation period. We noted that farmers voluntarily took steps to remove reactor cattle from their herds as a consequence of the information shared after the first survey. Removal of reactors between surveys was associated with a reduced risk of transmission within these herds. However, with no regulatory barriers to the sale of reactor animals, such actions could potentially lead to further spread between herds. We therefore advocate the importance of setting up regulations and then establishing a systematic bTB surveillance programme to monitor the impact prior to implementing any control measures in Ethiopia.

Grazing cattle exposure to neighbouring herds and badgers in relation to bovine tuberculosis risk

Bovine tuberculosis (bTB) can be spread between and among cattle and wildlife hosts e.g. European badger (Meles meles). The majority of cattle in the UK and Ireland are grazed during the summer, potentially exposing them to Mycobacterium bovis. 18 farms were surveyed (39% dairy, 61% beef; fields n = 697) for one grazing season (May-November 2016, n = 148,461 field days) to quantify the co-occurrence of cattle with badger setts and latrines and adjacency to neighbouring cattle herds. 3% (n = 24) of the fields had a badger sett or latrine recorded, dairy cattle were significantly more likely to co-occur with badger setts and latrines than beef cattle. Most farms (89%) grazed cattle adjacent to a neighbouring herd, which accounted for 18% of the grazing season. Potential exposure to neighbouring herds did not differ between production systems but did vary between life stages. A significant positive association between the proportion of time cattle spent grazing fields with setts present and the historic 1-, 3- and 5- year bTB status (p = 0.007, p = 0.013 and p = 0.013 respectively) was found. However, when cattle were grazed in fields with latrines, a significant negative association was found between the proportion of time cattle spent grazing fields with latrines present and the historic 3- and 5- year bTB status (p = 0.033 and p = 0.012 respectively). Historic bTB status and percentage of days spent beside a neighbouring herd was unrelated. Idiosyncrasies at farm-level and between risk factors indicated that individual farm assessments would be beneficial to understand potential exposure risk.

Decision tree machine learning applied to bovine tuberculosis risk factors to aid disease control decision making

Identifying and understanding the risk factors for endemic bovine tuberculosis (TB) in cattle herds is critical for the control of this disease. Exploratory machine learning techniques can uncover complex non-linear relationships and interactions within disease causation webs, and enhance our knowledge of TB risk factors and how they are interrelated. Classification tree analysis was used to reveal associations between predictors of TB in England and each of the three surveillance risk areas (High Risk, Edge, and Low Risk) in 2016, identifying the highest risk herds. The main classifying predictor for farms in England overall related to the TB prevalence in the 100 nearest cattle herds. In the High Risk and Edge areas it was the number of slaughterhouse destinations and in the Low Risk area it was the number of cattle tested in surveillance tests. How long ago the last confirmed incident was resolved was the most frequent classifier in trees; if within two years, leading to the highest risk group of herds in the High Risk and Low Risk areas. At least two different slaughterhouse destinations led to the highest risk group of herds in England, whereas in the Edge area it was a combination of no contiguous low-risk neighbours (i.e. in a 1 km radius) and a minimum proportion of 6–23 month-old cattle in November. A threshold value of prevalence in 100 nearest neighbours increased the risk in all areas, although the value was specific to each area. Having low-risk contiguous neighbours reduced the risk in the Edge and High Risk areas, whereas high-risk ones increased the risk in England overall and in the Edge area specifically. The best classification tree models informed multivariable binomial logistic regression models in each area, adding statistical inference outputs. These two approaches showed similar predictive performance although there were some disparities regarding what constituted high-risk predictors. Decision tree machine learning approaches can identify risk factors from webs of causation: information which may then be used to inform decision making for disease control purposes.

Prevalence Of Bovine Tuberculosis In Different Cattle Breeds In Dairy Farm In Egypt

Due to direct economic repercussions on livestock and indirect consequences for human health, knowing the prevalence rates of bovine tuberculosis is essential to define an effective control strategy. Our study was performed in 32 dairy cattle farms as we subjected 10800 dairy cattle to the Single Intradermal Comparative Tuberculin skin Test (SICTT). The skin test was interpreted according to guidelines of the World Organization for animal health (OIE). Twenty five farms (78%) have reactors to the SICTT. We also studied the relation between physiological variables with breeds, pregnancy, lactation, size of farms and the other risk factors explained in the study. Out of the 10800 tested animals, 228 (2.1%) were reactors to the skin test. The factors identified as possibly enhancing the risk of bovine tuberculosis (bTB) were herd size, age of animal, farming (housing) conditions. Other factors including breed and physiological status of the animal did not contribute to tuberculin sensitivity. The finding that large size and intensively (often poorly) managed herds were at greater risk of bovine tuberculosis and suggests that significance of bTB is increasing in Egypt parallel to an increase in the dairy operation. This surely indicates that if measures are not taken promptly, the impact of the economy and public health could be enormous. It was concluded that bTB continues to infect animals in Egypt but the prevalence was moderate, nevertheless the continued threat of economic loss in animal industry due to the persistence of bTB that should not be ignored.

Analysis of the cattle movement network and its association with the risk of bovine tuberculosis at the farm level in Castilla y Leon, Spain.

Between-farm transmission of bovine tuberculosis (bTB) occurs mostly through fence-to-fence contact between neighbouring farms, endemic infected wildlife or movement of infected animals. Unfortunately, bTB detection is frequently delayed and identification of the source of introduction is often difficult, particularly in endemic regions. Here, we characterized the cattle movement network of Castilla y Leon, a high bTB-prevalence (1.9% at the farm level in 2015) region in Spain, over six years and analysed the distribution of bTB to ultimately assess the likelihood of spatial and movement-mediated transmission. We analysed movement and bTB data from 27,633 units located in the region, of which 87% were involved in ~1.4million movements of ~8.8million animals. Network-level connectivity was low, although a few highly connected units were identified. Up to 15% of the herds became bTB-positive at some point during the study, with the highest percentage found in bullfighting and beef herds. Although bTB-positive herds had a significantly higher degree and moved more cattle than negative herds. Results of the k-test, a permutation-based procedure, suggested that positive farms were not significantly clustered in the movement network. Location was a likely risk factor as bTB-positive farms tended to be located within 5km from each other. Results suggested that movements may be a source of bTB in cattle in Castilla y Leon, although local factors may be more influential in determining risk of disease at the farm level. The description of the movement network in Castilla y Leon may be valuable for bTB surveillance in Spain. Moreover, results are useful to assess the movement-associated risk for multiple diseases.

The prevalence of brucellosis and bovine tuberculosis in ruminants in Sidi Kacem Province, Morocco.

Bovine tuberculosis (BTB) and brucellosis are major endemic zoonoses in ruminants in Morocco that impact on both animal and human health. This study presents an assessment of the epidemiological and socioeconomic burden of bacterial zoonoses in Sidi Kacem Province in Northern Morocco from a cross-sectional survey of 125 cattle and/or small ruminant-owning households. In total, 1082 sheep and goats were examined from 81 households. The single intradermal comparative cervical test to screen for bovine tuberculosis was undertaken on 1194 cattle from 123 households and all cattle were blood sampled. Cattle and small ruminant sera were tested for brucellosis using the standard Rose Bengal Test (sRBT) and the modified Rose Bengal Test (mRBT). Bacteriology was performed on 21 milk samples obtained from cattle that were seropositive for brucellosis for isolation and phenotyping of circulating Brucella strains. Individual and herd prevalence for BTB in cattle of 20.4% (95% CI 18%-23%) and 57.7% (95% CI 48%-66%), respectively, were observed in this study. The prevalence of brucellosis in cattle at individual and herd level was 1.9% (95% CI 1.2%-2.8%) and 9% (95% CI 4.5%-1.5%), respectively. Brucella pathogens were isolated from three cattle milk samples and were identified as B. abortus using Bruceladder® multiplex PCR and B. abortus biovar 1 by classical phenotyping. All small ruminants were seronegative to sRBT, two were positive to mRBT. A higher risk of BTB and brucellosis was observed in cattle in intensive livestock systems, in imported and crossed breeds and in animals from larger herds (>15). The three risk factors were usually present in the same herds, leading to higher transmission risk and persistence of both zoonoses. These results highlight the importance of implementing control strategies for both BTB and brucellosis to reduce productivity losses and the risk of transmission to humans. Prioritising control for BTB and brucellosis in intensive livestock production systems is essential for human and animal health.

CD14 gene polymorphisms associated with increased risk of bovine tuberculosis in Chinese Holstein cows

Cluster differentiation antigen 14 (CD14) is an important pattern recognition receptor protein in innate immunity. The aim of this study was to identify and assess the association of single-nucleotide polymorphisms (SNPs) in the CD14 gene with susceptibility to bovine tuberculosis (BTB) in Chinese Holstein cows. DNA samples from 517 Chinese Holstein cows (257 tuberculosis positive cases and 259 healthy controls) were collected from dairy farms in China. SNPs in the entire CD14 gene, including exonic regions, intronic regions and close to the 5′- and 3′-terminal untranslated regions, were detected by PCR, followed by direct sequencing. Five SNPs (−5C/T, 613G/A, 1023G/A, 1306G/A and 1326G/T) were found in the CD14 gene region. Significantly increased BTB susceptibility was evident in T allele carriers of −5C/T (P<0.001; odds ratio, OR 2.02; 95% confidence interval, CI 1.57–2.77), G allele carriers of 613G/A (P<0.001; OR 2.17, 95% CI 1.50–3.08) and TG haplotype carriers of both SNPs (P<0.001; OR 3.14, 95% CI 1.24–4.50). These results suggest that −5C/T and 613G/A are risk factors for BTB in Chinese Holstein cattle and might be used as candidate genetic markers in breeding cows with natural resistance to BTB.

Toll-like receptor 2 gene polymorphisms in Chinese Holstein cattle and their associations with bovine tuberculosis

This study evaluated whether there was an association between polymorphisms within the Toll-like receptor 2 gene (TLR2) of Chinese Holstein cattle and susceptibility to bovine tuberculosis (BTB). In a case–control study including 210 BTB cases and 237 control cattle, we found only two common single-nucleotide polymorphisms (SNPs) within the entire coding region of the TLR2 gene, A631G (rs95214857) and T1707C (rs1388116488). Additionally, the allele and genotype distributions of A631G and T1707C were not different between case and control groups, indicated that these SNPs were not associated with susceptibility to BTB. These results suggested that polymorphisms in the TLR2 gene might not play a significant role in the BTB risk in Chinese Holstein cattle.

Relationship of bovine TNF-α gene polymorphisms with the risk of bovine tuberculosis in Holstein cattle.

Many studies suggest significant genetic variation in the resistance of cattle and humans to infection with Mycobacterium bovis (M. bovis), the causative agent of zoonotic tuberculosis. TNF-α promotes inflammation and induces apoptosis in response to mycobacterial infection. The aim of the present study was to investigate the influence of single nucleotide polymorphisms of the TNF-α gene on bovine tuberculosis (bTB) susceptibility. We genotyped the TNF-α gene in 74 bTB-infected Holstein cows and 90 healthy control animals. The influence in the exon 3 region of TNF-α polymorphisms on bTB susceptibility was subsequently investigated by association analysis. Our finding demonstrated that the g.27534932A>C polymorphism of the TNF-α is associated with bTB in Holstein cattle. The susceptibility of cattle with the g.27534932A>C genotype compared with the CC genotype was 4.11-fold (95% CI, 1.27–13.36; P=0.02) higher. The g.27534932A>C polymorphism located in exon 3 of the TNF-α gene, and the functional consequence was missense. The deduced amino acid sequence for the protein product revealed an arginine to serine conversion at position 159, which may affect initiation of protein synthesis and disrupt normal TNF-α function that protects animals against mycobacterial infection. A significant association was observed with the A allele as a risk factor for bTB susceptibility (OR, 3.84; 95% CI, 1.21–12.17; P=0.02). In conclusion, this is the first report showing that the g.27534932A>C polymorphism may contribute to TNF-α-mediated bTB susceptibility.

Relationship of bovine &lt;i&gt;NOS2&lt;/i&gt; gene polymorphisms to the risk of bovine tuberculosis in Holstein cattle

Many studies suggest significant genetic variation in the resistance of cattle and humans to infection with Mycobacterium bovis, the causative agent of zoonotic tuberculosis. The inducible nitric oxide synthase (iNOS which is encoded by the NOS2 gene) plays a key role in the immunological control of a broad spectrum of infectious agents. This study aimed to investigate the influence of genetic variations in the promoter of the NOS2 gene on bovine tuberculosis (bTB) susceptibility. In this study, the NOS2 genes of 74 bTB-infected Holstein cows and 90 healthy controls were genotyped using PCR followed by nucleotide sequencing. Polymorphisms at rs207692718, rs109279434, rs209895548, rs385993919, rs433717754, rs383366213, rs466730386, rs715225976, rs525673647, rs720757654 and g.19958101T>G in the promoter region of the NOS2 gene were detected. The g.19958101T>G SNP produced two different conformation patterns (TT and TG) and the TG genotype was over-represented in the bTB group (20.27%) compared with the control group (2.22%). The TG genotype frequency of the g.19958101T>G variant was significantly higher in bTB cattle than in healthy controls (OR, 11.19; 95% CI, 2.47–50.73; P=0.0002). The G allele of the g.19958101T>G polymorphism was more frequent in bTB group when compared to control group (10.14% versus 1.11%). Furthermore, the G allele was a risk factor for bTB susceptibility (OR, 10.04; 95% CI, 2.26–44.65; P=0.0002). In conclusion, the g.19958101T>G polymorphism of the NOS2 gene may contribute to the susceptibility of Holstein cattle to bTB.

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-015-0242-8) contains supplementary material, which is available to authorized users.

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.

Relationship of Bovine SLC11A1 (Formerly NRAMP1) Polymorphisms to the Risk of Bovine Tuberculosis in Holstein Cattle

Many studies suggest significant genetic variation in the resistance of cattle and humans to infection with Mycobacterium bovis, the causative agent of zoonotic tuberculosis. The natural resistance associated macrophage protein 1 (NRAMP1), encoded by the SLC11A1 gene, plays a key role in the immunological control of a broad spectrum of infectious agents. The aim of the present study was to investigate the influence of single nucleotide polymorphisms (SNPs) of the SLC11A1 gene on bovine tuberculosis (bTB) susceptibility. We genotyped the SLC11A1 gene in 60 bTB-infected Holstein cows and 90 healthy control animals. The influence in the exon 4 and intron 4 regions of SLC11A1 genetic variations on bTB susceptibility was subsequently investigated by association analysis. Our finding demonstrated that the g.107117166A>G and g.107117369C>T polymorphisms of the SLC11A1 gene associated with bTB in Holstein cattle. The susceptibility of cattle with the g.107117166A>G genotype compared with the GG genotype was 3.40 (95% CI: 1.10-10.51; p=0.048) fold higher. The g. 107117166A>G SNP located in the exon 4 of the SLC11A1 gene and the functional consequence was missense. The deduced amino acid sequence for the protein product revealed an alanine to threonine conversion at position 96, which may affect initiation of protein synthesis and disrupt normal NRAMP1 function that protects animals against mycobacterial infection. The other susceptibility of cattle with the g.107117369C>T genotype compared with the TT genotype was 0.26 (95% CI: 0.12–0.56; p=0.001) fold lower. The g.107117369C>T polymorphism, located in the intron 4 of the SLC11A1 gene, may affect elements that control transcription and splicing of the NRAMP1 leading to affect pathophysiological characteristics in tuberculosis. This is the first report showing that the g. 107117166A>G and g.107117369C>T polymorphisms may contribute to SLC11A1-mediated bTB susceptibility.

Toll-like receptor 6 gene polymorphisms increase the risk of bovine tuberculosis in Chinese Holstein cattle

Our present study aimed to investigate the effect of four SNPs (G1793A, C1859A, A1980G, G1934A) in toll-like receptor 6 (TLR6) on bovine tuberculosis (bTB) resistance in a case–control study. A total of 603 Chinese Holstein cattle (264 from a dairy farm of Henan province, 339 from Hubei province) were selected to analyze the genotype of TLR6 gene by PCR-RFLP. Genotype frequencies of C1859A and A1980G site differed significantly between bTB-infected and non-infected cows (χ2=6.062, P=0.048 and χ2=6.749, P=0.034, respectively). Relative risk of tuberculosis incidence result showed that genotypes of AA or CA had greater relative risk (OR=2.730, 95%CI=0.869–8.573; OR=1.547, 95CI%=0.803–2.982, respectively) than those with genotype CC at C1859A site between bTB-infected and non-infected animals. Genotypes of GG or GA had greater relative risk (OR=2.986, 95%CI=1.245–7.165; OR=1.582, 95%CI=0.734–3.409, respectively) than those with genotype AA at A1980G site. No significant association can be inferred from G1793A and G1934A polymorphism site. The present study suggests that variants in the TLR6 gene are associated with susceptibility to bTB and the TLR6 gene may be considered as a candidate gene for bTB resistance.