1,031 research outputs found

    Potential benefits of cattle vaccination as a supplementary control for bovine tuberculosis

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    Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tVaccination for the control of bovine tuberculosis (bTB) in cattle is not currently used within any international control program, and is illegal within the EU. Candidate vaccines, based upon Mycobacterium bovis bacillus Calmette-Guérin (BCG) all interfere with the action of the tuberculin skin test, which is used to determine if animals, herds and countries are officially bTB-free. New diagnostic tests that Differentiate Infected from Vaccinated Animals (DIVA) offer the potential to introduce vaccination within existing eradication programs. We use within-herd transmission models estimated from historical data from Great Britain (GB) to explore the feasibility of such supplemental use of vaccination. The economic impact of bovine Tuberculosis for farmers is dominated by the costs associated with testing, and associated restrictions on animal movements. Farmers' willingness to adopt vaccination will require vaccination to not only reduce the burden of infection, but also the risk of restrictions being imposed. We find that, under the intensive sequence of testing in GB, it is the specificity of the DIVA test, rather than the sensitivity, that is the greatest barrier to see a herd level benefit of vaccination. The potential negative effects of vaccination could be mitigated through relaxation of testing. However, this could potentially increase the hidden burden of infection within Officially TB Free herds. Using our models, we explore the range of the DIVA test characteristics necessary to see a protective herd level benefit of vaccination. We estimate that a DIVA specificity of at least 99.85% and sensitivity of >40% is required to see a protective benefit of vaccination with no increase in the risk of missed infection. Data from experimentally infected animals suggest that this target specificity could be achieved in vaccinates using a cocktail of three DIVA antigens while maintaining a sensitivity of 73.3% (95%CI: 61.9, 82.9%) relative to post-mortem detection.This study was funded by Defra project SE3127 and uses nationally collected incidence and cattle-movement data sets held by Defra

    Potential Benefits of Cattle Vaccination as a Supplementary Control for Bovine Tuberculosis

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    This is the final published version of the article. It was originally published in PLOS Computational Biology (Conlan AJK, Brooks Pollock E, McKinley TJ, Mitchell AP, Jones GJ, Vordermeier M, Wood JLN, PLoS Computational Biology 2015, 11(2): e1004038. doi:10.1371/journal.pcbi.1004038).\ud \ud ? 2015 Crown Copyright. This is an open-access article distributed under the terms of the free Open Government Licence, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. See: http://www.nationalarchives.gov.uk/doc/o?pen-government-licence/open-government-l?icence.htmVaccination for the control of bovine tuberculosis (bTB) in cattle is not currently used within any international control program, and is illegal within the EU. Candidate vaccines, based upon Mycobacterium bovis bacillus Calmette-Gu?rin (BCG) all interfere with the action of the tuberculin skin test, which is used to determine if animals, herds and countries are officially bTB-free. New diagnostic tests that Differentiate Infected from Vaccinated Animals (DIVA) offer the potential to introduce vaccination within existing eradication programs. We use within-herd transmission models estimated from historical data from Great Britain (GB) to explore the feasibility of such supplemental use of vaccination. The economic impact of bovine Tuberculosis for farmers is dominated by the costs associated with testing, and associated restrictions on animal movements. Farmers? willingness to adopt vaccination will require vaccination to not only reduce the burden of infection, but also the risk of restrictions being imposed. We find that, under the intensive sequence of testing in GB, it is the specificity of the DIVA test, rather than the sensitivity, that is the greatest barrier to see a herd level benefit of vaccination. The potential negative effects of vaccination could be mitigated through relaxation of testing. However, this could potentially increase the hidden burden of infection within Officially TB Free herds. Using our models, we explore the range of the DIVA test characteristics necessary to see a protective herd level benefit of vaccination. We estimate that a DIVA specificity of at least 99.85% and sensitivity of >40% is required to see a protective benefit of vaccination with no increase in the risk of missed infection. Data from experimentally infected animals suggest that this target specificity could be achieved in vaccinates using a cocktail of three DIVA antigens while maintaining a sensitivity of 73.3% (95%CI: 61.9, 82.9%) relative to post-mortem detection.This study was funded by Defra project SE3127 and uses nationally collected incidence and cattle-movement data sets held by Defra. The funders had no role in study design, data analysis, decision to publish, or preparation of the manuscript

    Bovine tuberculosis in Swedish farmed deer

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    Bovine tuberculosis (BTB) was introduced into Swedish farmed deer herds in 1987. Epidemiological investigations showed that 10 deer herds had become infected (July 1994) and a common source of infection, a consignment of 168 imported farmed fallow deer, was identified (I). As trace-back of all imported and in-contact deer was not possible, a control program, based on tuberculin testing, was implemented in July 1994. As Sweden has been free from BTB since 1958, few practising veterinarians had experience in tuberculin testing. In this test, result relies on the skill, experience and conscientiousness of the testing veterinarian. Deficiencies in performing the test may adversely affect the test results and thereby compromise a control program. Quality indicators may identify possible deficiencies in testing procedures. For that purpose, reference values for measured skin fold thickness (prior to injection of the tuberculin) were established (II) suggested to be used mainly by less experienced veterinarians to identify unexpected measurements. Furthermore, the within-veterinarian variation of the measured skin fold thickness was estimated by fitting general linear models to data (skin fold measurements) (III). The mean square error was used as an estimator of the within-veterinarian variation. Using this method, four (6%) veterinarians were considered to have unexpectedly large variation in measurements. In certain large extensive deer farms, where mustering of all animals was difficult, meat inspection was suggested as an alternative to tuberculin testing. The efficiency of such a control was estimated in paper IV and V. A Reed Frost model was fitted to data from seven BTB-infected deer herds and the spread of infection was estimated (< 0.6 effective contacts per deer and year) (IV). These results were used to model the efficiency of meat inspection in an average extensive Swedish deer herd. Given a 20% annual slaughter and meat inspection, the model predicted that BTB would be either detected or eliminated in most herds (90%) 15 years after introduction of one infected deer. In 2003, an alternative control for BTB in extensive Swedish deer herds, based on the results of paper V, was implemented

    Could a vaccine eradicate bovine tuberculosis in Portugal before 2025?

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    ABSTRACT - Introduction: Bovine tuberculosis (bTB) is a zoonotic disease, which affects cattle. In Portugal, bTB prevalence is low and the country aims to eradicate the disease by 2025. However, the presence of wildlife reservoirs and the long latent stage complicates this objective. This work aims to understand the impact of Bacillus Calmette-Guérin (BCG) in the control of bTB in Portugal through mathematical modelling and, whether it would be possible to eradicate the disease before 2025. Methods: A mathematical model (Susceptible- Exposed- Infectious– Susceptible vaccinated- Exposed vaccinated- Infectious vaccinated) representing bTB transmission between cattle with the BCG vaccine was built and implemented in R. Parameters were abstracted from the literature and data from the Portuguese bTB eradication programme. The impact of BCG on bTB was simulated using different culling and vaccination rates. The final outputs were the basic reproduction number (R0), the number of infectious animals, the bTB prevalence and the disease reduction. Results: When vaccination is considered, at any rate, the burden of disease is similar to the model only considering test and slaughter strategy. The only difference is the number of vaccinated infectious animals, which is higher when the vaccination rate increases and there is a slight decrease in R0. The major impact on decreasing the bTB infection burden is when the culling rate is 1 with and without vaccination. Discussion and Conclusion: The results suggest that the vaccination will not eradicate bTB before 2025. However, more research is needed to understand the impact of BCG on bTB. Further projects should explore the stochastic effects of bTB and focus on herds in high-risk areas.RESUMO - Introdução: A tuberculose bovina (TBb) é uma doença zoonótica, que afeta maioritariamente o gado bovino. Em Portugal, a prevalência da TBb é baixa e o objetivo é erradicar a doença até 2025. Contudo, os reservatórios da doença em animais selvagens e o longo período de latência dificultam a sua concretização. Este trabalho tem como objetivo compreender o impacto da Bacillus Calmette-Guérin (BCG) no controlo desta doença em Portugal através de modelação matemática e se é possível erradicá-la antes de 2025. Métodos: Foi construído e implementado em R um modelo matemático (Suscetível- Exposto- Infecioso- Suscetível vacinado- Exposto vacinado- Infecioso vacinado) que representa a transmissão de TBb entre o gado bovino com a implementação da BCG. Os parâmetros foram extraídos da literatura ou da base de dados do programa de erradicação em Portugal. O impacto da vacinação foi estimado para várias taxas de abate e vacinação. Os resultados obtidos foram o número básico de reprodução (R0), o número de animais infeciosos, a prevalência de TBb e a redução da doença. Resultados: Quando a vacinação é considerada, qualquer que seja a taxa, a infeção de TBb é igual aquando apenas a estratégia de teste e abate é considerada. A única diferença é o número de animais infeciosos vacinados, que é superior quando a taxa de vacinação aumenta e o pequeno decréscimo no R0. O maior impacto no decréscimo da TBb é quando a taxa de abate é 1 com ou sem vacinação. Discussão e Conclusão: Os resultados sugerem que a vacinação não irá erradicar TBb antes de 2025. Contudo, mais investigação é necessária para analisar o impacto da BCG. Trabalhos futuros deverão explorar os efeitos estocásticos de TBb e focar em manadas das áreas de maior risco de infeção

    Evaluation of P22 antigenic complex for the immuno-diagnosis of Tuberculosis in BCG vaccinated and unvaccinated goats

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    Current eradication strategies of tuberculosis (TB) in goats mainly rely on the single intradermal tuberculin test (SIT) and single intradermal cervical comparative tuberculin tests (SICCTs). TB vaccination has been proposed as a cost-effective option in high-prevalence herds or countries where economic compensation for the slaughter of positive animals is not affordable. However, TB vaccination compromises the efficiency of tuberculin-based diagnostic tests. In this study, the performance of a new diagnostic platform, based on the P22 antigenic complex, was assessed for skin test (ST), interferon-gamma release assay (IGRA), and serology under different TB scenarios. The sensitivity (Se) of diagnostic tests was assessed in TB-infected goats from the same farm (herd A, N = 77). The specificity (Sp) was assessed in two TB-negative farms (both vaccinated against paratuberculosis): one TB unvaccinated (herd B, N = 77) and another vaccinated with bacille Calmette-Guérin (BCG) (herd C, N = 68). The single (s) P22-IGRA showed the highest Se among IGRA tests (91%), and the comparative (c) P22-ST showed the highest Sp (100% in herd B and 98% in herd C). Combined interpretation of techniques enabled the best diagnostic performances. Combining the SICCT + sP22-IGRA improved Se (97%) compared to SICCT + tuberculin-based IGRA (95%), with a reduction of Sp (95 and 100%, respectively). Besides, combination of P22-ELISA with cP22-ST or SICCT elicited a similar performance in the non-vaccination context (Se: 94 and 95%; Sp: 95 and 95%, respectively), but Sp was significantly higher for the combination with cP22-ST compared to SICCT in the TB vaccination context (95 and 79%, respectively). The combination of serological tests based on P22 and MPB83 showed higher complementarity and improved 13 percentage points the Se of P22-ELISA alone. These findings suggest that either cell-mediated or antibody-based diagnostic techniques, using the P22 antigen complex, can contribute to improve the immunodiagnostics of TB in goats under different TB control strategies.info:eu-repo/semantics/publishedVersio

    The contribution of badgers to confirmed tuberculosis in cattle in high-incidence areas in England

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    The role of badgers in the transmission and maintenance of bovine tuberculosis (TB) in British cattle is widely debated as part of the wider discussions on whether badger culling and/or badger vaccination should play a role in the government’s strategy to eradicate cattle TB. The key source of information on the contribution from badgers within high-cattle-TB-incidence areas of England is the Randomised Badger Culling Trial (RBCT), with two analyses providing estimates of the average overall contribution of badgers to confirmed cattle TB in these areas. A dynamical model characterizing the association between the estimated prevalence of Mycobacterium bovis (the causative agent of bovine TB) among badgers culled in the initial RBCT proactive culls and the incidence among sympatric cattle herds prior to culling is used to estimate the average overall contribution of badgers to confirmed TB herd breakdowns among proactively culled areas. The resulting estimate based on all data (52%) has considerable uncertainty (bootstrap 95% confidence interval (CI): 9.1-100%). Separate analyses of experimental data indicated that the largest estimated reduction in confirmed cattle TB achieved inside the proactive culling areas was 54% (overdispersion-adjusted 95% CI: 38-66%), providing a lower bound for the average overall contribution of badgers to confirmed cattle TB. Thus, taking into account both results, the best estimate of the average overall contribution of badgers is roughly half, with 38% being a robustly estimated lower bound. However, the dynamical model also suggested that only 5.7% (bootstrap 95% CI: 0.9-25%) of the transmission to cattle herds is badger-to-cattle with the remainder of the average overall contribution from badgers being in the form of onward cattle-to-cattle transmission. These estimates, confirming that badgers do play a role in bovine TB transmission, inform debate even if they do not point to a single way forward

    Evolution of IFN-gamma response against mycobacterial antigens used for the diagnosis of bovine tuberculosis in BCG vaccinated cattle under a natural transmission setting in central Chile

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    Bovine tuberculosis (bTB) is a chronic disease of animals mainly caused by Mycobacterium bovis, a zoonotic pathogen that generates economic losses in the milk and meat industry. In central Chile, the Metropolitan Region concentrates dairy herds with the highest bTB prevalence of the country and the official veterinary service has supported the evaluation of the M. bovis Bacillus Calmette-Guerin (BCG) vaccine in this area with the replacement of tuberculin purified protein derivative (PPDs) by the DIVA (Differentiating Infected from Vaccinated Animals) peptides for the bTB diagnosis in the herds. This study aimed to describe the IFN-gamma response against PPDs (bovine and avian PPD) and DIVA antigenic cocktails (ESAT-6/CFP-10 and Rv3615c) in BCG vaccinated 11-month-old heifers under a natural transmission scenario. Sixty-two animals were vaccinated via subcutaneous route with a 2-8 x 105 colony forming units of BCG Russia strain and 60 control animals received sterile saline. Blood sampling was performed at time 0, previous to vaccination, and then at 3, 6, 9, 12, 15 and 18 months post-inoculation. The follow up of the IFN-gamma response in animals determined that the BCG vaccination interferes with the diagnosis of bTB using the traditional bovine PPD between 9 and 12 months post-inoculation. Furthermore, the sensitization with non-tuberculous mycobacteria (NTM) was also interfering the diagnosis relying in PPDs, suggesting the need of using DIVA antigens under this epidemiological condition, whether or not the BCG vaccine is administered in cattle, in order to improve the accuracy of bTB diagnosis in central Chile
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