Bovine tuberculosis in working foxhounds: lessons learned from a complex public health investigation.

In 2017, Public Health England South East Health Protection Team (HPT) were involved in the management of an outbreak of Mycobacterium bovis (the causative agent of bovine tuberculosis) in a pack of working foxhounds. This paper summarises the actions taken by the team in managing the public health aspects of the outbreak, and lessons learned to improve the management of future potential outbreaks. A literature search was conducted to identify relevant publications on M. bovis. Clinical notes from the Public Health England (PHE) health protection database were reviewed and key points extracted. Animal and public health stakeholders involved in the management of the situation provided further evidence through unstructured interviews and personal communications. The PHE South East team initially provided 'inform and advise' letters to human contacts whilst awaiting laboratory confirmation to identify the infectious agent. Once M. bovis had been confirmed in the hounds, an in-depth risk assessment was conducted, and contacts were stratified in to risk pools. Eleven out of 20 exposed persons with the greatest risk of exposure were recommended to attend TB screening and one tested positive, but had no evidence of active TB infection. The number of human contacts working with foxhound packs can be large and varied. HPTs should undertake a comprehensive risk assessment of all potential routes of exposure, involve all other relevant stakeholders from an early stage and undertake regular risk assessments. Current guidance should be revised to account for the unique risks to human health posed by exposure to infected working dogs.

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.

Assessment of an ELISA method to support surveillance of bovine tuberculosis in Albania.

BACKGROUND: Bovine tuberculosis (bTB) is an important bacterial infectious disease in Albania of concern to animal and human health; its prevalence is poorly documented. METHODS: In this longitudinal study, we tested by ELISA 2661 serum samples, from 154 herds, with the aim of establishing the suitability of this approach to screen the bovine population for bTB. In a follow-on survey of 87 animals in three villages, we assessed the usefulness of the Mycobacterium bovis IDEXX ELISA (IDEXX M. bovis Antibody (Ab) Test. IDEXX Europe B.V P.O. Box 1334, 2130 EK Hoofddorp, The Netherlands) assay by comparing IDEXX results with the results of the single intradermal cervical skin test. Skin tests were performed either after or at the time of collection of blood samples, and therefore cattle were not sensitized by tuberculin before serological testing. RESULTS: The proportion of herds in which serologically positive cattle were found was 18.2 % (95 % CI, 1.9-25.8 %) and the prevalence of seropositive cattle was 1.4 % (95 % CI, 0.8-2.1 %). In the follow-up study, two of the 87 animals reacted positively to the skin test and two produced inconclusive reactions. No overlap was found between the four animals with positive IDEXX ELISA results and the four animals with non-negative skin test results. CONCLUSION: The lack of agreement between the results of the two tests may reflect different elements of the immune response (humoral and cell-mediated immunity). In future, cattle should be sensitized by the intradermal injection of tuberculin 14 days prior to the collection of blood samples, which would then be tested by the Mycobacterium bovis IDEXX ELISA Test in order to determine more accurately the prevalence of infection.

Molecular detection and characterization of the Mycobacterium tuberculosis complex subspecies responsible for bovine tuberculosis in Punjab, Pakistan.

Bovine tuberculosis (bTB), traditionally associated with Mycobacterium bovis, presents significant public health and economic challenges worldwide. This study investigated the causative agents of bTB in slaughtered cattle and buffalo in Lahore, Pakistan. Of the 3,581 animals screened, 34 were identified with gross TB-like lesions. The lesions were processed for culture, PCR, and Sanger sequencing to identify the causative agents of the disease. The results identified 10 Mycobacterium orygis and 8 Mycobacterium tuberculosis sensu stricto isolates. Whole-genome sequencing was performed on two M. orygis isolates, and the sequences were phylogenetically compared to 93 publicly available M. orygis sequences. The results also demonstrated that the JB21 and JB22 primers, which have been previously commonly applied to detect M. bovis in Pakistan, are unable to distinguish between M. tuberculosis complex subspecies. The identification of M. orygis and M. tuberculosis as causative agents of bTB in this slaughterhouse in Punjab may have important implications in identifying cases of zoonotic TB in humans and applying appropriate molecular tools to identify the prevalence of the disease. The data from this study align with recent findings suggesting M. orygis is the predominant cause of bTB in South Asia.IMPORTANCEThe study findings hold significant relevance to the Journal of Clinical Microbiology, as they directly impact the field. The first-time identification of Mycobacterium orygis and Mycobacterium tuberculosis as the predominant causative agents of bovine tuberculosis in Lahore, Pakistan underscores the urgent need for enhanced diagnostic methods. The study emphasizes the importance of improved assays for the accurate detection and differentiation of Mycobacterium subspecies. Additionally, the research addresses zoonotic risk assessment and public health implications, advocating for a multidisciplinary approach that integrates clinical microbiology with veterinary and human health sectors. These insights contribute to clinical microbiology knowledge, shaping effective strategies for disease prevention, surveillance, and control. The study's potential to advance the field makes it well suited for publication in the Microbiology Spectrum journal.

Vaccination of calves with Bacillus Calmette-Guerin Danish strain 1331 results in a duration of immunity of at least 52 weeks.

Bacillus Calmette-Guérin (BCG) Danish strain 1331 (CattleBCG) is currently the lead vaccine candidate for the control of bovine tuberculosis (TB) in cattle in GB, where prior vaccination has shown to result in a significant reduction in bovine TB pathology induced by infection with Mycobacterium bovis (M. bovis). A critical knowledge gap in our understanding of CattleBCG is the duration of immunity post vaccination at the minimum intended vaccine dose. To this end, we performed an experiment where calves were vaccinated with a targeted dose of 106 CFU and, after a period of 52 weeks, experimentally infected with M. bovis. Post mortem examination performed 13 weeks after infection revealed a statistically significant reduction in the severity of TB pathology in the CattleBCG vaccinated group compared with the unvaccinated control group. Additionally, this study allowed us to further assess the diagnostic performance of a defined antigen DIVA reagent (DST-F) developed to detect infected amongst vaccinated animals. Our results demonstrate that when used in a skin test format, DST-F showed high specificity (100 %) in BCG-vaccinated animals when tested prior to infection, whilst detecting all infected animals when re-tested after infection. Furthermore, we also present results supporting the use of the DST-F reagent in an interferon-gamma release assay. In conclusion, the results of this study demonstrate a 52-week duration of immunity following administration of a minimum dose of CattleBCG. This evidence will be a fundamental component in our efforts to apply for UK marketing authorisation to enable vaccination of cattle as a significant additional control measure in the ongoing fight against bovine TB in GB.

Prevalence and occupational exposure to zoonotic diseases in high-risk populations in the Free State Province, South Africa.

Introduction: Zoonotic diseases are responsible for 2.5 billion human cases globally and approximately 2.7 million deaths annually. Surveillance of animal handlers and livestock for zoonotic pathogens contributes to understanding the true disease burden and risk factors within a community. This study investigated the prevalence of selected zoonoses in cattle, farm workers and occupational exposure to endemic zoonotic diseases and their associated risk factors. Methods: Sputum samples from farmworkers were screened for Mycobacterium bovis. Blood specimens from farmworkers and archived sera were tested for serological evidence of Brucella sp., hantaviruses, and Leptospira sp. Communal and commercial cattle herds were tested for bovine tuberculosis and brucellosis. Results: Mycobacterium bovis was not isolated from human samples. A total of 327 human sera were screened, and 35/327 (10.7%) were Brucella sp. IgG positive, 17/327 (5.2%) Leptospira sp. IgM positive, and 38/327 (11.6%) hantavirus IgG positive (95% CI). A higher proportion of Brucella sp. IgG-positive samples were detected among veterinarians (value of p = 0.0006). Additionally, two cattle from a commercial dairy farm were bovine tuberculosis (bTB) positive using the bTB skin test and confirmatory interferon-gamma assay. A higher percentage of confirmed brucellosis-positive animals were from communal herds (8.7%) compared to commercial herds (1.1%). Discussion: These findings highlight the brucellosis and M. bovis prevalence in commercial and communal herds, the zoonotic disease risk in commercial and subsistence farming in developing countries, and the occupational and rural exposure risk to zoonotic pathogens.

Field evaluation of two commercial serological assays for detecting bovine tuberculosis.

Diagnosis of bovine tuberculosis in cattle is challenging due to complex immune host response to infection that limit the performance of available diagnostic tests. In this study, performance of two commercial serological assays developed to detect bovine tuberculosis were evaluated: Enferplex Bovine TB antibody kit including 11 antigens (EnferGroup, Ireland) and IDEXX M. bovis Ab kit (IDEXX, USA). The specificity value obtained with the ELISA IDEXX M. bovis Ab test was 97.1%, whereas it was 97.1% and 95.1% for the high specificity and sensitivity settings, respectively, with the Enferplex Bovine TB antibody kit. The sensitivity of the multiplexed Enferplex Bovine TB antibody test for SICCT-positive animals was higher (N = 172; 51.7% and 58.7% with high specificity and sensitivity settings, respectively) compared to the ELISA IDEXX M. bovis Ab test (sensitivity of 36.6%). "Antigen profiles" generated by the multiplexed Enferplex method showed that five out of 11 antigens present in the test were mostly identified as positive sera in cattle originating from bTB-outbreaks. In comparison, unique profiles appeared to be correlated with false positive results. However additional studies are needed to confirm the observed antigen profiles, and their potential use as an additional diagnostic tool. Serial interpretation of the two serological tests produced higher diagnostic specificity (>99%), reducing false positive results, which is essential for a screening test when the prevalence of bovine tuberculosis is low.

Performance of two commercial serological assays for bovine tuberculosis using plasma samples.

In the bovine tuberculosis diagnosis, the use of plasma samples (already available for IFNÉ£ assays) in serological tests might facilitate the work in the field. Here, the performance of two commercial serological tests (ELISA IDEXX M. bovis Ab test and Enferplex Bovine TB antibody test) were evaluated using plasma samples from cattle in Belgium. Specificity values estimated from 567 plasma samples collected from bTB-free cattle were 98.4% when using the ELISA IDEXX M. bovis Ab test, and were 96.5% and 93.3% when using the high specificity and high sensitivity settings of the Enferplex Bovine TB antibody test, respectively. Sensitivity values were calculated relative to SICCT-positive (N = 117) and IFNÉ£-positive (N = 132) animals originating from M. bovis-infected herds. Overall, the multiplexed Enferplex Bovine TB antibody test had better sensitivity (mean: 32.5% and 43.4% for the high specificity and sensitivity settings, respectively) compared to the ELISA IDEXX M. bovis Ab test (mean: 12%). Data obtained from plasma samples in the current study were compared to a previous study using both serological tests with sera. In conclusion, both serological tests showed comparable performance with both matrix; although overall specificity values with the Enferplex Bovine TB antibody test were lower when using plasma samples than sera.

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.

Mycobacterium bovis Strain Ravenel Is Attenuated in Cattle.

Mycobacterium tuberculosis variant bovis (MBO) has one of the widest known mammalian host ranges, including humans. Despite the characterization of this pathogen in the 1800s and whole genome sequencing of a UK strain (AF2122) nearly two decades ago, the basis of its host specificity and pathogenicity remains poorly understood. Recent experimental calf infection studies show that MBO strain Ravenel (MBO Ravenel) is attenuated in the cattle host compared to other pathogenic strains of MBO. In the present study, experimental infections were performed to define attenuation. Whole genome sequencing was completed to identify regions of differences (RD) and single nucleotide polymorphisms (SNPs) to explain the observed attenuation. Comparative genomic analysis of MBO Ravenel against three pathogenic strains of MBO (strains AF2122-97, 10-7428, and 95-1315) was performed. Experimental infection studies on five calves each, with either MBO Ravenel or 95-1315, revealed no visible lesions in all five animals in the Ravenel group despite robust IFN-γ responses. Out of 486 polymorphisms in the present analysis, 173 were unique to MBO Ravenel among the strains compared. A high-confidence subset of nine unique SNPs were missense mutations in genes with annotated functions impacting two major MBO survival and virulence pathways: (1) Cell wall synthesis & transport [espH (A103T), mmpL8 (V888I), aftB (H484Y), eccC5 (T507M), rpfB (E263G)], and (2) Lipid metabolism & respiration [mycP1(T125I), pks5 (G455S), fadD29 (N231S), fadE29 (V360G)]. These substitutions likely contribute to the observed attenuation. Results from experimental calf infections and the functional attributions of polymorphic loci on the genome of MBO Ravenel provide new insights into the strain's genotype-disease phenotype associations.

In Vitro and In Vivo Antigen Presentation and Diagnosis Development of Recombinant Overlapping Peptides Corresponding to Mtb ESAT-6/CFP-10.

Cellular immunity in Mycobacteria tuberculosis (Mtb) infection is important for the pathogenesis and final clearance of intracellular Mtb infection. In addition, it is valuable for the diagnosis of tuberculosis. In this pioneering work, we tested in vitro and in vivo antigen presentation and diagnostic application of a recombinant overlapping peptide-protein derived from two Mtb RD1 antigens ESAT-6 and CFP-10 (ROP-TB). The overlapping peptide sequence of ROP-TB is cleaved by the cathepsin S enzyme and covers the entire length of the two proteins. ROP-TB can be expressed and purified from E. coli. Once taken in by antigen-presenting cells, ROP-TB can be cleaved into a peptide pool by cathepsin S within the cells. We found that in dendritic cells, ROP-TB can be processed in 6 hours of co-culture, while the ESAT-6/CFP-10 fusion protein remained in the endosomal compartment. In Mtb-infected mice, ROP-TB stimulated stronger specific T cell responses than pooled synthetic peptides derived from ESAT-6 and CFP-10. With regard to the presentation of in vivo antigens, in a guinea pig model infected with Mtb, ROP-TB induced delayed type hypersensitivity (DTH) responses comparable to those of the tuberculin purified protein derivative (PPD) and ESAT-6/CFP-10 fusion protein. In Mycobacterium bovis (Bovine TB)-infected cattle, ROP-TB elicited DTH responses. Finally, in Mtb infected patients, ROP-TB stimulated cellular immune responses in majority of patients (16/18) of different HLA phenotypes while a single peptide derived from the same proteins did not elicit the immune responses in all patients. In summary, in vitro and in vivo data suggest that ROP-TB stimulates a strong cellular immune response irrespective of HLA phenotypes and is therefore suitable for use in vitro and in vivo diagnostics.

Human and bovine tuberculosis knowledge, attitude and practice (KAP) among cattle owners in Ethiopia.

Tuberculosis (TB) is a re-emerging disease occurring worldwide, resulting in multi-billion-dollar loss and human death annually. The situation is worse in developing countries like Ethiopia, where lower knowledge, attitude, and practice (KAP) of the people is poor about the disease. A questionnaire-based cross-sectional study was conducted to assess livestock owners' KAP level towards human and bovine Tuberculosis in Gondar, Ethiopia. A total of 349 study participants were addressed through a face-to-face interview. Descriptive statistics and Pearson's chi-squares analysis were used to analyze the data and observe the association between outcome (KAP level) and predictor variables (sociodemographic characteristics). Out of the 349 respondents, 223 (63.9%) were males, while 126 (36.1%) were females. The KAP measuring interview indicated that 97.4% of the participants are aware of human tuberculosis, while only 84 (24.1%) know about bovine tuberculosis cause and mode of transmission. Inhalation was reported as the main route of transmission for human TB (41.1%) whereas, 50% of the respondent mentioned inhalation, contact, and ingestion of raw animal products as the main route of TB transmission from animal to human. Among those who have heard of bovine tuberculosis, only 56 (66.7%) of respondents consider bovine tuberculosis as a significant threat to public health. The study showed there is a lower KAP on bovine TB among cattle owners in the study area. Therefore, community health education about the impact of the disease, transmission, control, and prevention should be integrated with one health-oriented education and research to eradicate the disease from the country.

Zoonotic Tuberculosis - The Changing Landscape.

Despite slow reductions in the annual burden of active human tuberculosis (TB) cases, zoonotic TB (zTB) remains a poorly monitored and an important unaddressed global problem. There is a higher incidence in some regions and countries, especially where close association exists between growing numbers of cattle (the major source of Mycobacterium bovis) and people, many suffering from poverty, and where dairy products are consumed unpasteurised. More attention needs to be focused on possible increased zTB incidence resulting from growth in dairy production globally and increased demand in low income countries in particular. Evidence of new zoonotic mycobacterial strains in South Asia and Africa (e.g. M. orygis), warrants urgent assessment of prevalence, potential drivers and risk in order to develop appropriate interventions. Control of M. bovis infection in cattle through detect and cull policies remain the mainstay of reducing zTB risk, whilst in certain circumstances animal vaccination is proving beneficial. New point of care diagnostics will help to detect animal infections and human cases. Given the high burden of human tuberculosis (caused by M. tuberculosis) in endemic areas, animals are affected by reverse zoonosis, including multi-drug resistant strains. This, may create drug resistant reservoirs of infection in animals. Like COVID-19, zTB is evolving in an ever-changing global landscape.

Genetic Diversity and Potential Paths of Transmission of Mycobacterium bovis in the Amazon: The Discovery of M. bovis Lineage Lb1 Circulating in South America.

Bovine tuberculosis (bTB) has yet to be eradicated in Brazil. Herds of cattle and buffalo are important sources of revenue to people living in the banks of the Amazon River basin. A better understanding of Mycobacterium bovis (M. bovis) populational structure and transmission dynamics affecting these animals can significantly contribute in efforts to improve their sanitary status. Herein, we sequenced the whole genome of 22 M. bovis isolates (15 from buffalo and 7 from cattle) from 10 municipalities in the region of the Lower Amazon River Basin in Brazil and performed phylogenomic analysis and Single Nucleotide Polymorphism (SNP)-based transmission inference to evaluate population structure and transmission networks. Additionally, we compared these genomes to others obtained in unrelated studies in the Marajó Island (n = 15) and worldwide (n = 128) to understand strain diversity in the Amazon and to infer M. bovis lineages. Our results show a higher genomic diversity of M. bovis genomes obtained in the Lower Amazon River region when compared to the Marajó Island, while no significant difference was observed between M. bovis genomes obtained from cattle and buffalo (p ≥ 0.05). This high genetic diversity is reflected by the weak phylogenetic clustering of M. bovis from the Lower Amazon River region based on geographic proximity and in the detection of only two putative transmission clusters in the region. One of these clusters is the first description of inter-species transmission between cattle and buffalo in the Amazon, bringing implications to the bTB control program. Surprisingly, two M. bovis lineages were detected in our dataset, namely Lb1 and Lb3, constituting the first description of Lb1 in South America. Most of the strains of this study (13/22) and all 15 strains of the Marajó Island carried no clonal complex marker, suggesting that the recent lineage classification better describe the diversity of M. bovis in the Amazon.

Bovine tuberculosis breakdown duration in cattle herds: an investigation of herd, host, pathogen and wildlife risk factors.

BACKGROUND: Despite rigorous controls placed on herds which disclose ante-mortem test positive cattle to bovine tuberculosis, caused by the infection of Mycobacterium bovis, many herds in Northern Ireland (NI) experience prolonged breakdowns. These herds represent a considerable administrative and financial burden to the State and farming community. METHODS: A retrospective observational study was conducted to better understand the factors associated with breakdown duration, which was modelled using both negative binomial and ordinal regression approaches. RESULTS: Six explanatory variables were important predictors of breakdown length in both models; herd size, the number of reactors testing positive in the initial SICCT test, the presence of a lesioned animal at routine slaughter (LRS), the count of M. bovis genotypes during the breakdown (MLVA richness), the local herd-level bTB prevalence, and the presence of herds linked via management factors (associated herds). We report that between 2008 and 2014, mean breakdown duration in NI was 226 days (approx. seven months; median: 188 days). In the same period, however, more than 6% of herds in the region remained under movement restriction for more than 420 days (13 months); almost twice as long as the mean. The MLVA richness variable was a particularly important predictor of breakdown duration. We contend that this variable primarily represents a proxy for beef fattening herds, which can operate by purchasing cattle and selling animals straight to slaughter, despite prolonged trading restrictions. For other herd types, the model supports the hypothesis that prolonged breakdowns are a function of both residual infection within the herd, and infection from the environment (e.g. infected wildlife, contiguous herds and/or a contaminated environment). The impact of badger density on breakdown duration was assessed by including data on main sett (burrow) density. Whilst a positive association was observed in the univariate analysis, confounding with other variables means that the contribution of badgers to prolonged breakdowns was not clear from our study. We do not fully reject the hypothesis that badgers are implicated in prolonging bTB breakdowns via spillback infection, but given our results, we posit that increased disease risk from badgers is unlikely to simply be a function of increasing badger density measured using sett metrics.

Bovine tuberculosis at the human-livestock-wildlife interface and its control through one health approach in the Ethiopian Somali Pastoralists: A review.

Pastoralism is a way of life in which food supply is produced from animals by using a variety of herding practices based on constant or partial herd mobility in the low land areas of Ethiopia. It covers 12% of the total livestock population and 61% of the total area of land in the country. As a result of their mobile lifestyle, pastoralists are almost completely excluded from the available health services. This review article focuses on bovine tuberculosis in the Ethiopian Somali Pastoralist. It describes Mycobacterium bovis in humans, livestock, and wildlife, and how the disease can be controlled by using One Health approach. Bovine tuberculosis is a chronic bacterial disease caused by Mycobacterium bovis. A study done from 2006 to 2008 on the prevalence of BTB in Ethiopian wildlife showed that sera from 20 of 87 animals (23%) were positive for BTB. In Ethiopia there is no comprehensive report about the status of M. bovis in wildlife populations that often share habitat with livestock. A study done on bovine tuberculosis in Somali pastoral livestock showed low prevalence of the disease. An individual animal prevalence of 2.0%, 0.4%, and 0.2% was reported in cattle, camels, and goats, respectively. In a simultaneous human and cattle study in a pastoralist areas of south-eastern Ethiopia, out of 163 human Mycobacterium tuberculosis complex isolates three were M. bovis. Due to the moderate resistance of the etiological agent to the environmental conditions in one hand and the capacity of its survival in acid milk for not less than 15 days on the other and the habitual consumption of unpasteurized milk by humans make this disease a vital zoonosis in Somali pastoralists in Ethiopia. M. bovis is a pathogen at the human-livestock-wildlife interface. Diseases transmitted between humans, livestock, and wildlife are increasingly challenging public and veterinary health systems. Therefore, studies concerning the burden of the diseases in wildlife, livestock and human beings in Somali Pastoralists should be undertaken. A One Health approach that takes the wellbeing of the pastoralists, the health of their livestock and environment into consideration is also necessary for the control of BTB.

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.

A review on bovine tuberculosis in India.

Bovine tuberculosis (bTB) is a chronic illness in animals, especially in cattle, leading to loss in the productivity and signifies a crucial public health risk. Regardless of the zoonotic threat and significant economic costs associated with the disease, precise estimates of bTB prevalence are deficient in many countries, including India, where national control programs are yet to be instigated. The true burden of the disease remains unknown due to lack of routine surveillance data from most of the developing countries. India is progressing well towards attaining the End TB goal, yet bTB continues to remain largely hidden. Moreover, the paucity of literature on bTB in India might lead to undue complacency and hence has to be scrupulously guarded and prevented from gaining any misconceptions in the minds of the common people. Preventing and controlling bTB at the animal interface is pivotal to evade transmission to human, increase food safety and guard the livelihood of the people. To attain this goal, implementation of strategies based on international norms and a multi-sectoral approach will empower enhanced surveillance and diagnosis of disease in animals and subsequently reduce the risk for humans. As an initiative, we step forward to address this review which briefly summarizes the available data in the literature from early 20th century to date to assess the status of bTB in India. We have discussed in detail, the epidemiology, transmission and diagnosis pertaining to bTB. The review also focuses on the interconnection between the health of people and animal, discuss the preventions and control strategies and recommend the use of vaccination in cattle to reduce the spread of infection among other animals and humans. Implementing One Health approach in India, which recognizes the interdependence of the health of people and animals will help the nation in the fight against TB.

When to kill a cull: factors affecting the success of culling wildlife for disease control.

Culling wildlife to control disease can lead to both decreases and increases in disease levels, with apparently conflicting responses observed, even for the same wildlife-disease system. There is therefore a pressing need to understand how culling design and implementation influence culling's potential to achieve disease control. We address this gap in understanding using a spatial metapopulation model representing wildlife living in distinct groups with density-dependent dispersal and framed on the badger-bovine tuberculosis (bTB) system. We show that if population reduction is too low, or too few groups are targeted, a 'perturbation effect' is observed, whereby culling leads to increased movement and disease spread. We also demonstrate the importance of culling across appropriate time scales, with otherwise successful control strategies leading to increased disease if they are not implemented for long enough. These results potentially explain a number of observations of the dynamics of both successful and unsuccessful attempts to control TB in badgers including the Randomized Badger Culling Trial in the UK, and we highlight their policy implications. Additionally, for parametrizations reflecting a broad range of wildlife-disease systems, we characterize 'Goldilocks zones', where, for a restricted combination of culling intensity, coverage and duration, the disease can be reduced without driving hosts to extinction.

The Humoral Immune Response to BCG Vaccination.

Bacillus Calmette Guérin (BCG) is the only currently available vaccine against tuberculosis (TB), but it confers incomplete and variable protection against pulmonary TB in humans and bovine TB (bTB) in cattle. Insights into the immune response induced by BCG offer an underexploited opportunity to gain knowledge that may inform the design of a more efficacious vaccine, which is urgently needed to control these major global epidemics. Humoral immunity in TB and bTB has been neglected, but recent studies supporting a role for antibodies in protection against TB has driven a growing interest in determining their relevance to vaccine development. In this manuscript we review what is known about the humoral immune response to BCG vaccination and re-vaccination across species, including evidence for the induction of specific B cells and antibodies; and how these may relate to protection from TB or bTB. We discuss potential explanations for often conflicting findings and consider how factors such as BCG strain, manufacturing methodology and route of administration influence the humoral response. As novel vaccination strategies include BCG prime-boost regimens, the literature regarding off-target immunomodulatory effects of BCG vaccination on non-specific humoral immunity is also reviewed. Overall, reported outcomes to date are inconsistent, but indicate that humoral responses are heterogeneous and may play different roles in different species, populations, or individual hosts. Further study is warranted to determine whether a new TB vaccine could benefit from the targeting of humoral as well as cell-mediated immunity.