Predicting the public health benefit of vaccinating cattle against Escherichia coli O157

Identifying the major sources of risk in disease transmission is key to designing effective controls. However, understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls particularly challenging for zoonotic pathogens. One such global pathogen is Escherichia coli O157, which causes a serious and sometimes fatal gastrointestinal illness. Cattle are the main reservoir for E. coli O157, and vaccines for cattle now exist. However, adoption of vaccines is being delayed by conflicting responsibilities of veterinary and public health agencies, economic drivers, and because clinical trials cannot easily test interventions across species boundaries, lack of information on the public health benefits. Here, we examine transmission risk across the cattle–human species boundary and show three key results. First, supershedding of the pathogen by cattle is associated with the genetic marker stx2. Second, by quantifying the link between shedding density in cattle and human risk, we show that only the relatively rare supershedding events contribute significantly to human risk. Third, we show that this finding has profound consequences for the public health benefits of the cattle vaccine. A naïve evaluation based on efficacy in cattle would suggest a 50% reduction in risk; however, because the vaccine targets the major source of human risk, we predict a reduction in human cases of nearly 85%. By accounting for nonlinearities in transmission across the human–animal interface, we show that adoption of these vaccines by the livestock industry could prevent substantial numbers of human E. coli O157 cases

Beef Cattle Vaccination Principles and Recommendations

This publication provides details and recommendations on vaccinations for beef cattle

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

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

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

Peste des Petits Ruminants infection among cattle and wildlife in Northern Tanzania

We investigated peste des petits ruminants (PPR) infection in cattle and wildlife in northern Tanzania. No wildlife from protected ecosystems were seropositive. However, cattle from villages where an outbreak had occurred among small ruminants showed high PPR seropositivity, indicating that spillover infection affects cattle. Thus, cattle could be of value for PPR serosurveillance

Exploring farmer and stakeholder attitudes towards the vaccination of cattle against bovine tuberculosis

This report assesses farmer attitudes towards a cattle bTB vaccine, and the potential influence of different behavioural incentives to promote vaccine use. Three hypothetical policy scenarios relevant to England and Wales were developed to examine attitudes to cattle vaccination amongst farmers and industry stakeholders. Each scenario reflected a different model of delivery: mandatory (state-led), individual farmer-led, and collective (via local vaccination companies). Farmers and agricultural stakeholders were, in principle, generally supportive of cattle vaccination, and supported an effective, trade barrier-free vaccine

The intractable challenge of evaluating cattle vaccination as a control for bovine tuberculosis

Vaccination of cattle against bovine Tuberculosis (bTB) has been a long-term policy objective for countries where disease continues to persist despite costly test-and-slaughter programs. The potential use of vaccination within the European Union has been linked to a need for field evaluation of any prospective vaccine and the impact of vaccination on the rate of transmission of bTB. We calculate that estimation of the direct protection of BCG could be achieved with 100 herds, but over 500 herds would be necessary to demonstrate an economic benefit for farmers whose costs are dominated by testing and associated herd restrictions. However, the low and variable attack rate in GB herds means field trials are unlikely to be able to discern any impact of vaccination on transmission. In contrast, experimental natural transmission studies could provide robust evaluation of both the efficacy and mode of action of vaccination using as few as 200 animals

Could a vaccine eradicate bovine tuberculosis in Portugal before 2025?

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

Humoral and cellular response to BoHV-1 in buffalo and cattle treated with an inactivated marker vaccine

The study is aimed at assessing and comparing the immune response to BoHV-1 elicited by an inactivated marker vaccine in buffaloes and cattle. Vaccination did not produced any local or general reactions in buffaloes. Seroneutralizing antibodies and cellular response by IFN-γ- test have been detected in buffaloes and cattle after a prime/ booster vaccination strategy. Humoral and cellular responses were significantly higher in cattle than in buffaloes. Data pointed out the possibility to use the marker vaccine in buffaloes. However, further studies must be planned to assess the immune pressure of marker vaccines in terms of IBR eradicative attitude in infected buffalo herds