Control Of Bovine Tuberculosis Research Articles

Field Trial with Vaccine Candidates Against Bovine Tuberculosis Among Likely Infected Cattle in a Natural Transmission Setting.

Background/Objectives: Vaccines may improve the control and eradication of bovine tuberculosis. However, the evaluation of experimental candidates requires the assessment of the protection, excretion, transmission and biosafety. A natural transmission trial among likely infected animals was conducted. Methods: Seventy-four male heifers were randomly distributed (five groups) and vaccinated subcutaneously with attenuated strains (M. bovis Δmce2 or M. bovis Δmce2-phoP), a recombinant M. bovis BCG Pasteur (BCGr) or M. bovis BCG Pasteur. Then, they cohoused with a naturally infected bTB cohort under field conditions exposed to the infection. Results: A 23% of transmission of wild-type strains was confirmed (non-vaccinated group). Strikingly, first vaccination did not induce immune response (caudal fold test and IFN-gamma release assay). However, after 74 days of exposure to bTB, animals were re-vaccinated. Although their sensitization increased throughout the trial, the vaccines did not confer significant protection, when compared to the non-vaccinated group, as demonstrated by pathology progression of lesions and confirmatory tools. Besides, the likelihood of acquiring the infection was similar in all groups compared to the non-vaccinated group (p > 0.076). Respiratory and digestive excretion of viable vaccine candidates was undetectable. To note, the group vaccinated with M. bovis Δmce2-phoP exhibited the highest proportion of animals without macroscopic lesions, compared to the one vaccinated with BCG, although this was not statistically supported. Conclusions: This highlights that further evaluation of these vaccines would not guarantee better protection. The limitations detected during the trial are discussed regarding the transmission rate of M. bovis wild-type, the imperfect test for studying sensitization, the need for a DIVA diagnosis and management conditions of the trials performed under routine husbandry conditions. Re-vaccination of likely infected bovines did not highlight a conclusive result, even suggesting a detrimental effect on those vaccinated with M. bovis BCG.

Advancing meat safety diverse approaches for bovine tuberculosis detection and control in abattoirs

Bovine tuberculosis (BTB) still represents a significant public health concern and economic issue for livestock breeders in Egypt. This research investigates the incidence of bovine tuberculosis in cattle slaughtered at the central abattoir in Aswan, Egypt, in 2023. A total of 720 cattle were checked antemortem and postmortem at the abattoir. The suspected lesions were analyzed with acid-fast staining, microscopy, histology, ELISA, and RT-PCR. Based on gross tubercle lesions, the overall occurrence of bovine tuberculosis in cattle slaughtered at Aswan abattoirs was 3.2% (23/720), with thoracic lymph nodes and lungs exhibiting the highest frequency of tubercle lesions compared to other organs. According to employed diagnostic tests, the prevalence of tuberculosis was estimated as 68.6, 61, 56.5, and 78.3% for microscopy, histopathology, ELISA, and RT-PCR, respectively. These findings highlight the incidence of bovine tuberculosis and the dissemination of tuberculous lesions among cattle slaughtered at Aswan abattoirs. Furthermore, such prevalence emphasizes the urgent need for a practical disease control approach and an organized surveillance system in the cattle population. One Health strategy is strongly advised to mitigate the zoonotic transmission to people and economic losses in the cattle industry.

Nontuberculous Mycobacteria Interfering with the Control and Eradication Program of Bovine Tuberculosis

Nontuberculous Mycobacteria Interfering with the Control and Eradication Program of Bovine Tuberculosis

Assessing the feasibility of test-and-cull and test-and-segregation approaches for the control of high-prevalence bovine tuberculosis in Ethiopian intensive dairy farms

Bovine tuberculosis (bTB) is endemic and has a substantial impact on the livestock sector in Ethiopia and other low and middle-income countries (LMICs). With a national emphasis on dairy farm intensification to boost milk production and spur economic growth, the incidence of bTB is anticipated to rise. However, Ethiopia, like other LMICs, lacks a comprehensive national bTB control strategy due to the economic and social infeasibility of traditional test-and-cull (TC) approaches. To inform the development of such a strategy, we evaluated the effectiveness and feasibility of TC and test-and-segregation (TSg) strategies for bTB control on Ethiopian dairy farms. A TC approach was used at Farm A [N = 62; comparative cervical test (CCT) > 4 mm, starting prevalence 11.3%] while TSg was implemented at Farm B (N = 45; CCT > 4 mm, prevalence 22.2%), with testing intervals of 2–4 months. Both strategies achieved a reduction in bTB prevalence to 0%, requiring seven rounds of TC over 18 months at Farm A, and five rounds of TSg over 12 months at Farm B’s negative herd. The results show that adopting more sensitive thresholds [CCT > 0 mm or single cervical test (SCT) > 2 mm] during later rounds was pivotal in identifying and managing previously undetected infections, emphasizing the critical need for optimized diagnostic thresholds. Cost analysis revealed that TC was approximately twice as expensive as TSg, primarily due to testing, labor, and cow losses in TC, versus construction of new facilities and additional labor for TSg. This underscores the economic and logistical challenges of bTB management in resource-limited settings. Taken together, our study highlights an urgent need for the exploration of alternative approaches including TSg and or vaccination to mitigate within herd transmission and enable implementation of bTB control in regions where TC is not feasible.

Intra- and interspecies infectious neighbourhoods as determinant parameters for Mycobacterium bovis infection among badgers in southwestern France

The epidemiological system for Mycobacterium bovis in France involves cattle and, in some areas, wildlife species (mainly badgers and wild boar). This multi-host aspect complicates the control and eradication prospects for bovine tuberculosis in endemic areas, despite the surveillance and control measures implemented for decades in this officially tuberculosis-free European country. To improve control measures, and to manage spillback transmission from badgers to cattle, it is necessary to clarify the transmission mechanisms of M. bovis in these epidemiological systems. We modelled a badger population from a southwestern endemic area by a Dirichlet tessellation based on a sett census conducted by local hunters and trappers between 2013 and 2015. We then used a logistic regression model to test the association between the infection status of setts and computed variables depicting three types of transmission (intraspecific, interspecific and landscape-associated). The apparent prevalence of infected setts was of 40.5%. Two variables were significantly associated with the probability for a sett to be infected: the proportion of neighbouring setts that were infected (OR: 3.19 [2.04–5.17]95%) and the presence of nearby pastures belonging to an infected farm (OR: 2.33 [1.13–4.89]95%]. While badger culling measures have been implemented according to the national TB control plan in the study area since 2012 (in the vicinity of infected farms and their pastures), our results clearly highlight the need to reinforce measures aimed at reducing both intraspecific and interspecific infection pressure. For this purpose, the promising prospect of badger vaccination could be considered, along with biosecurity measures.

A humoral diagnostic test outperforms cellular tests in a farm with a latent tuberculosis outbreak caused by a new Mycobacterium tuberculosis complex spoligotype that affected sheep but not goats.

Tuberculosis (TB) is a disease caused by members of the M. tuberculosis complex (MTC) that affects numerous species. M. caprae, a member of the complex which is close to M. bovis, is emerging and affects several different hosts that include goats, cattle, sheep, pigs, rabbits, wild boar, red deer, foxes and also humans. A new M. caprae spoligotype (SB2737) was isolated from an outbreak of sheep tuberculosis affecting a mixed sheep (323)-goat (29) farm in 2021. The index case was detected by the La Rioja slaughterhouse veterinary inspection. Tracing back to the farm of origin, both species were submitted to Comparative Intradermal Tuberculin Test (CITT) and M. bovis-specific antibody ELISA tests. A subsample was also examined by IFN-γ release assay (IGRA) and all positives were slaughtered and pathologically and microbiologically investigated. Only 1.2% of sheep and no goat were positive in the CITT, and 11.4% in the IGRA sheep subsample, while up to 36.8% were positive in two consecutive M. bovis-specific antibody ELISA tests. Goats had always tested negative in annual intradermal follow-up since 2013. Upon confirmation of the immunologically positive sheep at slaughter, all the remaining negative animals were killed and 29.2% of sheep were still found infected. This raised the final overall prevalence to 37.5%. Antibody ELISA was the most sensitive (81.4%) in vivo detection method still showing a 85.0% specificity relative to pathological and microbiological tuberculosis status. It was nearly 10 times more sensitive than skin test and had an 86.8% positive predictive value. Notwithstanding a possible singular pathogenesis of the new spoligotype, this outbreak adds up to previous reports suggesting that sheep tuberculosis could be huge reservoir of infection worldwide overlooked by skin test low sensitivity or simply lack of investigation. This makes it urgent to extend the use antibody tests to address the Trojan horse of hidden M. tuberculosis complex infections on bovine TB control programs.

Unveiling insights into bovine tuberculosis: A comprehensive review.

The frequent zoonotic disease known as "bovine tuberculosis" is brought on by the Mycobacterium bovis bacteria, which can infect both people and animals. The aim of this review article is to provide an explanation of the etiology, history, epidemiology, pathogenesis, clinical symptoms, diagnosis, transmission, risk factors, public health importance, economic impact, treatment, and control of bovine tuberculosis. Primarily, bovine tuberculosis affects cattle, but other animals may also be affected. Bovine tuberculosis is present throughout the world, with the exception of Antarctica. Cattle that contract bovine tuberculosis might suffer from a persistent, crippling illness. In the early stages of the disease, there are no symptoms. The tuberculin test is the primary method for detecting bovine tuberculosis in cows. Depending on its localized site in the infected animal, M. bovis can be found in respiratory secretions, milk, urine, feces, vaginal secretions, semen, feces, and exudates from lesions (such as lymph node drainage and some skin lesions). This illness generally lowers cattle productivity and could have a negative financial impact on the livestock business, particularly the dairy industry. The most effective first-line anti-tuberculosis chemotherapy consists of isoniazid, ethambutol, rifampin, and streptomycin. Second-line drugs used against bovine tuberculosis include ethionamide, capreomycin, thioacetazone, and cycloserine. To successfully control and eradicate bovine tuberculosis, developed nations have implemented routine testing and culling of infected animals under national mandatory programs.

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.

Assessing the potential impact of applying a higher sensitivity test to selected cattle populations for the control of bovine tuberculosis in England.

Bovine tuberculosis (bTB) continues to be the costliest, most complex animal health problem in England. The effectiveness of the test-and-slaughter policy is hampered by the imperfect sensitivity of the surveillance tests. Up to half of recurrent incidents within 24 months of a previous one could have been due to undetected infected cattle not being removed. Improving diagnostic testing with more sensitive tests, like the interferon (IFN)-gamma test, is one of the government's top priorities. However, blanket deployment of such tests could result in more false positive results (due to imperfect specificity), together with logistical and cost-efficiency challenges. A targeted application of such tests in higher prevalence scenarios, such as a subpopulation of high-risk herds, could mitigate against these challenges. We developed classification machine learning algorithms (using 80% of 2012-2019 bTB surveillance data as the training set) to evaluate the deployment of IFN-gamma testing in high-risk herds (i.e. those at risk of an incident in England) in two testing data sets: i) the remaining 20% of 2012-19 data, and ii) 2020 bTB surveillance data. The resulting model, classification tree analysis, with an area under a receiver operating characteristic (ROC) curve (AUC) >95, showed a 73% sensitivity and a 97% specificity in the 2012-2019 test dataset. Used on 2020 data, it predicted eight percent (3 510 of 41 493) of eligible active herds as at-risk of a bTB incident, the majority of them (66% or 2 328 herds) experiencing at least one. Whilst all predicted at-risk herds could have preventive measures applied, the additional application of IFN-gamma test in parallel interpretation to the statutory skin test, if the risk materialises, would have resulted in 8 585 additional IFN-gamma reactors detected (a 217% increase over the 2 710 IFN-gamma reactors already detected by tests carried out). Only 18% (330 of 1 819) of incidents in predicted high-risk herds had the IFN-gamma test applied in 2020. We therefore conclude that this methodology provides a better way of directing the application of the IFN-gamma test towards the high-risk subgroup of herds. Classification tree analysis ensured the systematic identification of high-risk herds to consistently apply additional measures in a targeted way. This could increase the detection of infected cattle more efficiently, preventing recurrence and accelerating efforts to achieve eradication by 2038. This methodology has wider application, like targeting improved biosecurity measures in avian influenza at-risk farms to limit damage to the industry in future outbreaks.

Using machine learning to improve bovine tuberculosis control in herd level outbreaks.

Bovine tuberculosis (bTB), a chronic disease of cattle, is caused by the Mycobacterium bovis infection. Despite having a serious social and economic impact in the United Kingdom and Ireland, there is no antemortem gold standard diagnostic test. Tuberculin skin tests (CICT) are commonly used as a control measure with the interferon gamma (IFN-γ) assay being applied in certain circumstances. This paper utilizes data gathered describing tuberculin regression in reactors (test positive cattle) following the CICT at 72 ± 4 h post injection in herds with large bTB outbreaks. The work then applies machine learning techniques (Decision Trees, Bagging Trees and Random Forests, alongside several balancing approaches) to predict which cattle were likely to be truly infected with tuberculosis, enabling identification of atypical breakdowns that require extra investigation and providing a mechanism for quality assurance of the existing CICT bTB surveillance scheme. The analysis showed that Random Forests (RF) trained using SMOTE balancing had the joint best performance and accuracy (0.90). The importance of the two components of the interferon gamma assay within the RF model also indicated that varying the assay threshold for large outbreaks would be beneficial. Furthermore, the combined use of the RF and IFN- γ models could lead to the improved detection of infection within breakdown herds, reducing the scale and duration of outbreaks. An additional use of these models would be for quality assuring the current bTB surveillance based on CICT and post mortem inspection. Quality control is well recognized as an essential component of a disease surveillance/eradication programme.Clinical Relevance- Bovine tuberculosis remains a disease that is hard to control on a national level. The use of the machine learning model could lead to significant improved detection of infection within breakdown herds, reducing the scale and duration of outbreaks. Advanced modelling, such as this, has the potential to strengthen the efficacy of disease surveillance and the eradication strategy and can meaningfully contribute to animal disease national control plans.

Zoonotic Tuberculosis: A Neglected Disease in the Middle East and North Africa (MENA) Region.

Mycobacterium bovis is the etiologic agent of bovine tuberculosis (BTB), a serious infectious disease in both humans and animals. BTB is a zoonotic disease primarily affecting cattle and occasionally humans infected through close contact with infected hosts or the consumption of unpasteurized dairy products. Zoonotic tuberculosis is strongly associated with poverty and poor hygiene, and low- and middle-income countries bear the brunt of the disease. BTB has been increasingly recognized as a growing public health threat in developing countries. However, the lack of effective surveillance programs in many of these countries poses a barrier to accurately determining the true burden of this disease. Additionally, the control of BTB is threatened by the emergence of drug-resistant strains that affect the effectiveness of current treatment regimens. Here, we analyzed current trends in the epidemiology of the disease as well as the antimicrobial susceptibility patterns of M. bovis in the Middle East and North Africa (MENA) region, a region that includes several developing countries. Following PRISMA guidelines, a total of 90 studies conducted in the MENA region were selected. Our findings revealed that the prevalence of BTB among humans and cattle varied significantly according to the population size and country in the MENA region. Most of the available studies were based on culture and/or PCR strategies and were published without including data on antimicrobial resistance and molecular typing. Our findings highlighted the paramount need for the use of appropriate diagnostic tools and the implementation of sustainable control measures, especially at the human/animal interface, in the MENA region.

Bovine tuberculosis: slow progress

Despite a government pledge to eradicate bovine tuberculosis by 2038, progress towards this goal has been slow. This article looks at some of the reasons for this and considers ways in which all parties involved could engage to bring about a more rapid improvement in control of bovine tuberculosis.

Moral hazard in the British bovine tuberculosis control programme

Abstract Animal disease indemnity payments create a moral hazard problem by diminishing the financial burden of on-farm infection which, in turn, can reduce private incentives to invest in biosecurity. The economic importance of the moral hazard problem is a function of the size of the indemnity payment relative to market prices and input costs, as well as farm-specific disease risks and the probability that biosecurity efforts can reduce those risks. We investigate the importance of these contributory factors on disease outcomes in the context of the British bovine tuberculosis control programme using longitudinal herd-level data for all beef cattle herds in Great Britain. We show that, by disincentivising biosecurity investment, increases in disease indemnity payments lead to more on-farm breakdowns, increase the number of on-farm disease reactors and extend the duration of infection. Our findings suggest that the disease burden created through these unintended consequences accounts for approximately one-fourth of the additional programme outlays associated with a 10% increase in the per-head indemnity payment.

Bovine tuberculosis control in Fiji: Retrospective study findings for 2015 to 2020.

Control of bovine tuberculosis (bTB) is a priority for animal health, biosecurity, and human health authorities in Fiji as evident from the long-term funding of the Bovine Brucellosis and Tuberculosis Eradication and Control program (BTEC) and notable improvements to the program described in this paper. To evaluate the performance of the Fiji BTEC program from 2015 to 2020, all available bTB data for cattle were analyzed. Data sources included BTEC bTB testing records, abattoir records and laboratory records. We integrated all information to quantify the bTB tests applied, bTB positive farms and animals, meat inspection and laboratory findings. Test coverage was highest among dairy cattle in Central Division (~73%), where bTB was highly prevalent with 7.8% of dairy cattle and 61.7% of dairy farms found to be positive between 2015 and 2020. There was no visible downward trend in the apparent prevalence of bTB over the 6-year period. During 2019 and 2020, only 21.3% (51/239) of the tested dairy farms maintained their clear status, another 8.4% (20/239) reverted to infected status after 1 year or more of being bTB clear, and most farms remained infected during these 2 years. Factors observed to be contributing to this situation were persistent infections, related in part to the significant number of untested animals, uncontrolled animal movements, and larger farm size. Similar to other developing countries, bTB remains a serious concern and further strengthening of the program targeting the main contributors to bTB persistence, along with maintenance of a comprehensive reporting and traceability system, industry awareness and government support are needed. Control of bTB in Fiji is a long-term objective that must have multiple stakeholder engagement and regular review to measure success.

Zoonotic Importance of Bovine Tuberculosis in Ethiopia: An Overview

Bovine tuberculosis (BTB) is an important zoonotic disease that affects both domestic animals as well as humans in many countries of the world. The disease is caused by Mycobacterium bovis, which is responsible for 10–15% of human tuberculosis cases. BTB poses an occupational health hazard to the cattle owners, butchers, animal attendants, and veterinarians. The source of infection is exogenous and the respiratory tract is considered the chief portal of entry of the organism. The mode of spread of bacteria is aerogenous. BTB is endemic in Ethiopia, and it is mostly transmitted to people through the consumption of unpasteurized contaminated milk. Miliary tubercular lesions, chronic cough, blockages of the airways, alimentary system, or blood vessels, and lymph node enlargement are all symptoms of tuberculosis. Single intradermal or comparative intradermal tuberculin tests are useful delayed-type hypersensitivity tools for diagnosing tuberculosis in live animals. It is also employed in tuberculosis eradication programs and international trade activity. Vaccination of calves with an attenuated BTB strain known as Bacillus of Calmette and Guerin, as well as testing and culling, is significant measures in the prevention and control of BTB in endemic areas like Ethiopia. The proper pasteurization of milk before human consumption is a significant measure to reduce the public health risk posed by BTB.

Fascioliasis may promote tuberculous infectivity in small ruminants

Fascioliasis and bovine tuberculosis (TB) are global impediments to livestock development. We investigated the co-infectivity of fascioliasis and TB in small ruminants at slaughter. A total of 84 goats and 16 sheep were investigated from different slaughter houses in Mymensingh city, Bangladesh from June 2019 to February 2020. Grossly, acute fascioliasis was characterized by hemorrhagic tracts in the liver and chronic fascioliasis with biliary cirrhosis and pipe-stem liver. Grossly, seven goats and two sheep were associated with the acute and sixty goats and seven sheep were associated with the chronic phase of fascioliasis. Five goats’ livers showed both the acute and chronic phases of fascioliasis. In TB, granulomas with central core of caseous necrosis were seen in the lymph nodes (21), livers (10) and lungs (01) of goats or in the lymph nodes (03) and liver (01) of sheep. Histopathologically, biliary cirrhosis was seen in fascioliasis and granuloma, caseous necrosis and calcification in TB. In co-infection revealed granuloma (TB) with acid-fast bacilli and widespread biliary cirrhosis in the livers of goats (14) and sheep (02). The fragments of the 16S rRNA gene (372 bp, M. tuberculosis complex) and MPB83 gene (600 bp, M. bovis) were detected in the lymph nodes, livers and lungs using polymerase chain reaction. This study showed the existence of co-infectivity of Fasciola and M. bovis in goats and sheep in Bangladesh. Chronic fascioliasis may be associated with establishing tuberculous infection in small ruminants. Therefore, extremely zoonotic bovine TB control programs require active management of fascioliasis.

Spatial distribution of Mycobacterium bovis spoligotypes in cattle from the state of Minas Gerais, Brazil.

Genotyping methods have led to a better understanding of the epidemiology of Mycobacterium bovis (M. bovis) infection, and its transmission dynamics, as well as the possible phylogenetic relationships between Mycobacterium strains, thus making bovine tuberculosis control programs more efficient. The goal of this study was to characterize the main spoligotypes of M. bovis isolated from cattle in the State of Minas Gerais, Brazil. It was carried out in 28 municipalities of "Triângulo Mineiro" and "Alto Paranaíba" regions of the state. Viscera samples were obtained from 58 bovines positive for tuberculosis according to comparative cervical tests, and from another 100 bovines with lesions suggestive of tuberculosis, which were donated by the National Agricultural Laboratory of Pedro Leopoldo, Minas Gerais. Microbiological isolation was performed in Stonebrink medium, and molecular identification of mycobacteria was performed by PCR. Genotyping was performed using the spoligotyping method at the Agrobiotechnology and Molecular Biology Institute of National Agricultural Technology Institute-National Scientific and Technical Research Council, Buenos Aires, Argentina. Among the 158 viscera samples, we obtained 40 (25%) isolates of M. bovis, and detected 11 spoligotype patterns, with a predominance of SB1142 (37.5%), SB0121 (25.0%), and SB1145 (10.0%). Other standards, SB0295, SB1050, SB0881, SB1144, SB1802, SB0140, SB0120, and SB0849, varied from 2.5 to 7.5%, heterogeneously distributed among the municipalities. The presence of spoligotypes shared with other Brazilian states and different countries indicates their possible exchange through epidemiological relationships, such as the transit of live animals and/or genetic similarity between strains that share a common ancestor.

Test performance data demonstrates utility of a cattle DIVA skin test reagent (DST-F) compatible with BCG vaccination

Bacillus Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis (M. bovis), is the lead candidate vaccine for control of bovine tuberculosis (TB) in cattle. However, BCG vaccination sensitises cattle to bovine tuberculin, thus compromising the use of the current bovine TB surveillance tests. To address this, we have developed a diagnostic skin test that is not compromised by BCG vaccination and is able to detect BCG vaccinated animals that subsequently develop bovine TB following exposure to M. bovis. Building on previous work using ‘in house’ formulated protein cocktail reagents, we herein present test performance data for a single fusion protein (DST-F) containing the mycobacterial antigens ESAT-6, CFP-10 and Rv3615c formulated as a ‘ready to use’ reagent by a commercial manufacturer. Our results demonstrate that, unlike tuberculin reagents, a diagnostic skin test using DST-F maintained high specificity in BCG vaccinated animals. Furthermore, the DST-F skin test demonstrated a high relative sensitivity in identifying M. bovis infected animals, including those where BCG vaccination failed to prevent bovine TB pathology following experimental exposure to M. bovis. The DST-F is currently undergoing field trials in Great Britain to support its licensure and commercialisation.

Potential for improved detection of bovine tuberculosis by targeting combined blood biomarkers in multi-test algorithms

Bovine tuberculosis (bTB) control programs can be improved by combined use of tests for humoral and cell-mediated immune responses targeting multiple biomarkers of Mycobacterium bovis. To further the diagnostic benefits of this approach, we used Dual Path Platform (DPP) technology to test sera from cattle with naturally acquired bTB in the United States (US) and Spain for the presence of M. bovis antigen, IgM and/or IgG antibodies to MPB70/MPB83 fusion antigen in conjunction with tuberculin skin tests (TST) or interferon-gamma release assays (IGRA). When TST was complemented with detection of IgM and IgG antibodies, the diagnostic sensitivity increased from 85.4% to 95.1% in the US and from 64.2% to 81.5% in Spain. Likewise, adding the DPP assays enhanced IGRA diagnostic sensitivity from 82.7% to 93.8% in Spain. Detection of circulating M. bovis antigen showed added value when used in combination with the DPP antibody assays but it was limited when analyzed in the context of TST or IGRA results. Present findings support the benefits of a multi-test approach for the ante-mortem diagnosis of bTB in cattle.

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.