Bovine TB, detection, protection and control

 

Intro

Bovine TB, detection, protection and control

Bovine tuberculosis (bTB) is the most pressing animal health issue for Wales today. The disease has a significant financial and social impact on farm businesses and the wider rural community. Bovine TB is very costly to Government in terms of the cost of control programme and compensation to keepers whose animals are slaughtered because of bovine TB. The cost to Welsh Government for 2016-17 is £25m and cost to industry is approximately £6.4m.

The causative organism, Mycobacterium bovis, can be transmitted to humans and its global eradication has recently become the focus of a ‘One Health’ initiative led by the World Health Organisation (WHO), the World Organisation for Animal Health (OIE), the Food and Agriculture Organization of the United Nations (FAO) and the International Union against Tuberculosis and Lung Disease (the Union) to put an end to zoonotic TB.

The Centre of Excellence for Bovine Tuberculosis (CBTB) is backed by Sêr Cymru II, a Welsh Government, EU (ERDF) and University funded programme to grow and develop academic research expertise in Wales.  It is led by Professor Glyn Hewinson FLSW,  and has been established within IBERS to help support the long-term aim of the Welsh Government to eradicate bovine TB from Wales.

The work of the CBTB is interdisciplinary in nature.  It performs research to understand the biology of M. bovis infection to underpin the development and use of new diagnostic tests and vaccines for bTB and provides expert advice and support to government and other key stakeholders on bTB eradication.

Aims & Approaches

Aims & Approaches

Aims

The Centre of Excellence for Bovine Tuberculosis (CBTB) for Wales provides expert independent advice to Welsh Government on the control of bTB and increase capacity for livestock research in Wales through the establishment of state-of-the-art veterinary research laboratories. The CBTB aims to increase research capacity and capability in the areas of immunology, veterinary bacteriology, genomics and molecular epidemiology and to work with national and international research groups and institutes such as the Animal and Plant Health Agency, the Jenner Institute, WHO, OIE and FAO to help provide a One Health approach to the control of bovine TB.

Approaches

Host-Pathogen Interaction

We undertake systematic analysis of the host response to M. bovis infection and BCG vaccination. Our approaches involve immunological investigations, application of functional genomics-based technologies including RNAseq, proteomics and metabolomics, and the study of the interaction of M. bovis and BCG with host immune cells.

Understanding M. bovis transmission in Wales

Our approach involves working closely with the Animal and Plant Health Agency and Welsh Government to define the population structure of M. bovis in Wales using whole genome sequencing to underpin the better targeting of bTB control strategies under different epidemiological situations in Wales.  We also aim to determine whether there are phenotypic differences between dominant clones of M. bovis in Wales and if so whether these have consequences on the immune response of animals to infection.

Collaborating with Low and Middle Income Counties

Developing an evidence base to support the development of bTB control strategies in Low-and-Middle Income Countries.  This is currently done though the ETHICOBOTS Consortia (A ZELS Initiative).  The ETHICOBOTS project was awarded to a consortium of researchers in Ethiopia and the UK, consisting of epidemiologists, geneticists, immunologists, and social scientists. The aim of ETHICOBOTS is to tackle the high burden of bovine TB in the Ethiopian dairy farm sector and to investigate the consequences of the on-going centrifugal trade of potentially infected dairy cattle to low prevalence regions and farming systems on transmission.

Facilities

Facilities

Our state-of-the-art veterinary research laboratories have been equipped through a WEFO funded grant (‘Establishing Cutting Edge Veterinary Research Laboratories for Wales’).  In addition,  the EDRF funded VetHub1 laboratories provide the Category 3 containment facilities integral to our work.  Together these facilities enable cutting edge research in microbiology, immunology and microbial genetics and facilitate in-depth studies of host-pathogen interactions.

 

Key research facilities include: 

  • Containment Level 2 and 3 Laboratory Suites
  • Class I, Class II and Class III Microbiological Safety Cabinets
  • Microscopy – slide scanning, fluorescent and brightfield (Zeiss Axio Scan Z1 and Axio Imager Z2)
  • High-throughput molecular (qRT-PCR) and immunological (ELISA) assays
  • ELISPOT Reader (CTL Immunospot S6 Universal)
  • Multiplex Analyser (Luminex 200)
  • Automated liquid handling (Eppendorf EpMotion 5075t)
  • Flow Cytometry – Analyser (Beckman Coulter Cytoflex LX) and cell sorter (Miltenyi Biotec Tyto)
  • Metabolic Analysis (Agilent Seahorse XF platform)
  • Single Cell Analysis System (Becton Dickenson Rhapsody)
  • Transcriptomics (Nanostring Sprint Profiler)
  • Microinjection (WPI Microinjector MICRO ePUMP with air table

Projects

Projects

  • Sêr Cymru Centre of Excellence for Bovine Tuberculosis (CBTB) for Wales  (EDRF/Welsh Government).
  • Establishing Cutting Edge Veterinary Research Laboratories for Wales (WEFO).
  • Metabolomic and proteomic approaches to identify target biomarkers as analytes for the development of improved diagnostic tests for Bovine TB EU KESS Programme.
  • Improving the detection of bovine tuberculosis in badgers EU KESS Programme.
  • Stopping the spread of TB between wildlife and livestock (STOP) (CIDRA).
  • ETHICOBOTS (Ethiopia Control of Bovine Tuberculosis Strategies) (Zoonoses and Emerging Livestock Systems (ZELS) programme).
  • Assessing risk factors for Bovine Tuberculosis using large datasets.
  • We are also working with VetHub1 to shape animal/public health Research & Development.

Outputs & Impact

Outputs and Impact

Innovation

A diagnostic test to differentiate between BCG vaccinated cattle and those infected with M. bovis was developed by the teams of Professor Glyn Hewinson and Professor Martin Vordermeier whilst working at the Animal and Plant Health Agency.  The UK government now plans to conduct field trials to understand how well this combination of vaccine and diagnostic test works in the field as a step towards licencing them for use in cattle.   More details can be found here:

  1. DIVA skin test to complement BCG vaccination of cattle
  2. Bovine TB vaccine trials

Knowledge Exchange

AberTB Conference

We have created an annual event designed to facilitate knowledge exchange and collaboration between academia, the veterinary profession, farmers, government and other stakeholders involved in the fight against bovine TB. Follow the events on Twitter @aber_tb for the latest releases.

GRABTB 

The Global Research Alliance for Bovine TB (GRAbTB) aims to establish and sustain global research partnerships that will generate scientific knowledge and tools to contribute to the successful control and eradication of bovine TB.  Prof Hewinson helped establish this initiative and was elected Inaugural Chair of GRAbTB.

Policy and bovine TB Control

In 2018, Prof Hewinson was an author of the Review of England’s Bovine TB Strategy (the Godfray Review), a report to Rt Hon Michael Gove, Secretary of State, Defra.

In 2016, Prof Hewinson, in his role as Chair of GRAbTB, was a member of the ad hoc group organised by WHO, OIE, FAO and the Union against Tuberculosis and Lung Disease to address the issue of zoonotic TB.  This meeting provided the first consultation to galvanise action against zoonotic TB.  A roadmap for zoonotic TB arising from this meeting was published on 12 October 2017.

Principal Investigators

Principal Investigators

Picture Name Email Telephone
Prof Darrell Abernethy daa47@aber.ac.uk +44 (0) 1970 621646
Prof Glyn Hewinson glh14@aber.ac.uk +44 (0) 1970 621559
Prof Bernardo Villarreal-Ramos bev10@aber.ac.uk +44 (0) 1970 622319

Publications

Publications

Frosini, S-M, Gallow, G, Gibson, A, Menezes, J, Pomba, C & Loeffler, A 2023, 'Detecting mecA in Faecal Samples: A Tool for Assessing Carriage of Meticillin-Resistant Staphylococci in Pets and Owners in the Microbiological ‘Fast Age’?', Microbiology Research, vol. 14, no. 1, pp. 60-66. 10.3390/microbiolres14010005
Subramanian, S, Srinivasan, S, Ramaiyan Selvaraju, K, Vinoli, PM, Selladurai, S, Ramasamy, B, Kumaragurubaran, K, Bakker, D, Vordermeier, M, Kapur, V & Gopal, DR 2022, 'Defined Antigen Skin Test for Bovine Tuberculosis Retains Specificity on Revaccination With Bacillus Calmette–Guérin', Frontiers in Veterinary Science, vol. 9, 814227. 10.3389/fvets.2022.814227
Gibson, AJ, Stiens, J, Passmore, IJ, Faulkner, V, Miculob, J, Willcocks, S, Coad, M, Berg, S, Werling, D, Wren, BW, Nobeli, I, Villarreal-Ramos, B & Kendall, SL 2022, 'Defining the Genes Required for Survival of Mycobacterium bovis in the Bovine Host Offers Novel Insights into the Genetic Basis of Survival of Pathogenic Mycobacteria', mBIO, vol. 13, no. 4. 10.1128/mbio.00672-22, 10.5281/zenodo.6576716
Taylor, EN, Beckmann, M, Hewinson, G, Rooke, D, Sinclair, LA & Mur, LAJ 2022, 'Metabolomic changes in lactating multiparous naturally MAP-infected Holstein-Friesian dairy cows suggest changes in mitochondrial energy pathways', Research in Veterinary Science, vol. 152, pp. 354-363. 10.1016/j.rvsc.2022.09.001
Taylor, EN, Beckmann, M, Hewinson, G, Rooke, D, Mur, LAJ & Koets, AP 2022, 'Metabolomic changes in polyunsaturated fatty acids and eicosanoids as diagnostic biomarkers in Mycobacterium avium ssp. paratuberculosis (MAP)-inoculated Holstein–Friesian heifers', Veterinary Research, vol. 53, no. 1, 68. 10.1186/s13567-022-01087-0
Scott-Baumann, J, Pizzey, R, Beckmann, M, Villarreal-Ramos, B, King, J, Hopkins, B, Rooke, D, Hewinson, G & Mur, LAJ 2022, 'Metabotyping the Welsh population of badgers based on thoracic fluid', Metabolomics, vol. 18, no. 5, 30. 10.1007/s11306-022-01888-6
Scott-Baumann, JF, Friedersdorff, JCA, Villarreal-Ramos, B, King, J, Hopkins, B, Pizzey, R, Rooke, D, Hewinson, G & Mur, LAJ 2022, 'The Faecal Microbiome of the Wild European Badger Meles meles: A Comparison Against Other Wild Omnivorous Mammals from Across the Globe', Current Microbiology, vol. 79, no. 12, 363. 10.1007/s00284-022-03064-4
Bauman, JS, Pizzey, R, Beckmann, M, Villarreal-Ramos, B, King, J, Hopkins, B, Rooke, D, Hewinson, G & Mur, LAJ 2022, 'Untargeted metabolomic analysis of thoracic blood from badgers indicate changes linked to infection with bovine tuberculosis (Mycobacterium bovis): A pilot study', Metabolomics, vol. 18, no. 8, 61. 10.1007/s11306-022-01915-6
Ábalos, P, Valdivieso, N, de Val, BP, Vordermeier, M, Benavides, MB, Alegría-Morán, R, Saadi, K, Wistuba, M, Ortega, C, Sánchez, N & Retamal, P 2022, 'Vaccination of Calves with the Mycobacterium bovis BCG Strain Induces Protection against Bovine Tuberculosis in Dairy Herds under a Natural Transmission Setting', Animals, vol. 12, no. 9, 1083. 10.3390/ani12091083
Faulkner, V, Cox, AA, Goh, S, van Bohemen, A, Gibson, AJ, Liebster, O, Wren, BW, Willcocks, S & Kendall, SL 2021, 'Re-sensitization of Mycobacterium smegmatis to Rifampicin Using CRISPR Interference Demonstrates Its Utility for the Study of Non-essential Drug Resistance Traits', Frontiers in Microbiology, vol. 11, 619427. 10.3389/fmicb.2020.619427

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