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OIE Reference Laboratory Reports Activities Activities in 2017 This report has been submitted : 2018-03-19 14:06:55 Name of disease (or topic) for which you are a designated OIE Reference Laboratory: Bovine tuberculosis Address of laboratory: New Haw, Addlestone Surrey KT15 3NB Weybridge UNITED KINGDOM Tel.: +44-1932 34.11.11 Fax: +44-1932 34.70.46 E-mail address: glyn.hewinson@apha.gsi.gov.uk Website: https://www.gov.uk/government/organisations/animal-and-plant-health-agency Name (including Title) of Head of Laboratory (Responsible Official): Mr Chris Hadkiss, CEO Name (including Title and Position) of OIE Reference Expert: Prof Glyn Hewinson Lead Scientist for Bovine Tuberculosis Which of the following defines your laboratory? Check all that apply: Governmental OIE Reference Laboratory Reports Activities, 2017 1

ToR 1: To use, promote and disseminate diagnostic methods validated according to OIE Standards 1. Did your laboratory perform diagnostic tests for the specified disease/topic for purposes such as disease diagnosis, screening of animals for export, surveillance, etc.? (t for quality control, proficiency testing or staff training) 2 OIE Reference Laboratory Reports Activities, 2017

Diagnostic Test Indicated in OIE Manual (/) Total number of test performed last year Indirect diagnostic tests Nationally Internationally Gamma Interferon micro (2 Antigen) assay 135160 0 Gamma interferon extended micro (3 2296 0 Lateral flow serology test - camelid 1170 14 Lateral flow serology test - badger 150 0 Lateral flow serology test - other 122 0 Lateral flow serology test - other 122 0 IDEXX ELISA serology test - bovine 188 0 IDEXX serology ELISA - camelid 945 0 EnferPlex serology ELISA - camelid 1426 0 Direct diagnostic tests Nationally Internationally Culture (bovine) 9782 0 Culture (non bovine) 401 0 Spoligotyping (bovine) 3500 0 VNTR typing (bovine) 3500 0 HAIN and multiplex PCR 11 0 Spoligotyping (non bovine) 195 0 VNTR typing (non bovine) 195 0 DNA testing of cattle to confirm identity 186 0 ToR 2: To develop reference material in accordance with OIE requirements, and implement and promote the application of OIE Standards. To store and distribute to national laboratories biological reference products and any other reagents used in the diagnosis and control of the designated pathogens or disease. 2. Did your laboratory produce or supply imported standard reference reagents officially recognised by the OIE? OIE Reference Laboratory Reports Activities, 2017 3

3. Did your laboratory supply standard reference reagents (non OIE-approved) and/or other diagnostic reagents to OIE Member Countries? 4 OIE Reference Laboratory Reports Activities, 2017

Type of reagent available Related diagnostic test Produced/ provide Amount supplied nationally (ml, mg) Amount supplied internationally (ml, mg). of recipient OIE Member Countries Region of recipients Antibodies Badger Tb IGRA ELISA provide 2mg 8mg 3 Badger TB serology antibodies badger TB serology ELISA provide 0 300 mg 1 Badger IGRA controls Badger Tb IGRA ELISA provide 900 ul 0 1 MPB83 Antigen Badger TB serology provide 500 ug Cattle DIVA skin test proteins provide 6 mg 2 Cattle DIVA blood test peptide cocktail provide 48 ml 1 OIE Reference Laboratory Reports Activities, 2017 5

Bovine IL-22 provide 2 ug 1 Anti-IL-22 antibodies provide 2 mg 1 Recombinant mycobacterial proteins provide 2.5 mg 3 mg 2 Bovine tuberculin provide 5mL DIVA skin test fusion protein provide 1.5 mg Cattle sera produced 16 samples 327 4. Did your laboratory produce vaccines? 5. Did your laboratory supply vaccines to OIE Member Countries? 6 OIE Reference Laboratory Reports Activities, 2017

ToR 3: To develop, standardise and validate, according to OIE Standards, new procedures for diagnosis and control of the designated pathogens or diseases 6. Did your laboratory develop new diagnostic methods validated according to OIE Standards for the designated pathogen or disease? 7. Did your laboratory develop new vaccines according to OIE Standards for the designated pathogen or disease? ToR 4: To provide diagnostic testing facilities, and, where appropriate, scientific and technical advice on disease control measures to OIE Member Countries 8. Did your laboratory carry out diagnostic testing for other OIE Member Countries? 9. Did your laboratory provide expert advice in technical consultancies on the request of an OIE Member Country? ToR 5: To carry out and/or coordinate scientific and technical studies in collaboration with other laboratories, centres or organisations 10. Did your laboratory participate in international scientific studies in collaboration with OIE Member Countries other than the own? OIE Reference Laboratory Reports Activities, 2017 7

Title of the study Duration Purpose of the study Partners (Institutions) OIE Member Countries involved other than your country Field evaluation of BCG vaccination in cattle on-going To evaluate the efficacy of BCG in cattle in field situations in Ethiopia Armauer Hansen Research Institute and Addis Ababa University ETHIOPIA Evaluation of inactivated vaccine efficacy in badgers on-going Assess efficacy of inactivated TB vaccine in badgers Neiker Institute & SERIDA SPAIN Badger bait deployment studies on-going Investigate uptake of baits in badger population ANSES & ONCFS FRANCE Development of novel latent TB models for the assessment of pre and post exposure vaccine candidates. on-going Development of novel latent TB models for the assessment of pre and post exposure vaccine candidates. University College Dublin & INRA FRANCE IRELAND Accelerating Bovine tuberculosis Control in Developing Countries India 5 years TB control in India Penn State University, Multiple Indian partners, Cambridge University,Universidad Complutense de Madrid, Douwe BaKker INDIA THE NETHERLANDS UNITED STATES OF AMERICA ToR 6: To collect, process, analyse, publish and disseminate epizootiological data relevant to the designated pathogens or diseases 11. Did your Laboratory collect epizootiological data relevant to international disease control? 12. Did your laboratory disseminate epizootiological data that had been processed and analysed? 13. What method of dissemination of information is most often used by your laboratory? (Indicate in the appropriate box the number by category) a) Articles published in peer-reviewed journals: 24 Banos G; Winters M; Mrode R; MITCHELL AP; Bishop SC; Woolliams JA; Coffey MP 2017 Genetic evaluation for bovine tuberculosis resistance in dairy cattle. Journal of Dairy Science 100 (2) 1272-1281. http://dx.doi.org/10.3168/jds.2016-11897 R10554 Impact factor: 2.408 8 OIE Reference Laboratory Reports Activities, 2017

BRUNTON LA; Alexander N; Wint W; ASHTON A; BROUGHAN JM 2017 Using geographically weighted regression to explore the spatially heterogeneous spread of bovine tuberculosis in England and Wales. Stochastic Environmental Research and Risk Assessment 31 (2) 339-352. http://dx.doi.org/10.1007/s00477-016-1320-9 R10586 Impact factor: 2.237 BRUNTON LA; Donnelly CA; O'CONNOR H; PROSSER A; ASHFIELD S; ASHTON A; UPTON P; MITCHELL A; GOODCHILD AV; PARRY JE; DOWNS SH 2017 Assessing the effects of the first 2 years of industry-led badger culling in England on the incidence of bovine tuberculosis in cattle in 2013 2015. Ecology and Evolution 7 (18) 7213-7230. http://dx.doi.org/10.1002/ece3.3254 R10716 Impact factor: 2.44 BUSCH F; Bannerman F; Liggett S; Griffin F; Clarke J; Lyashchenko KP; RHODES S 2017 Control of bovine tuberculosis in a farmed red deer herd in England. Veterinary Record 180 (3) 68. http://dx.doi.org/10.1136/vr.103930 R10546 Impact factor: 1.741 Buzdugan SN; CHAMBERS MA; DELAHAY RJ; Drewe JA 2017 Quantitative interferon-gamma responses predict future disease progression in badgers naturally infected with Mycobacterium bovis. Epidemiology and Infection 145 (15) 3204-3213. http://dx.doi.org/10.1017/s0950268817001960 R10748 Impact factor: 2.075 Buzdugan SN; Vergne T; Grosbois V; DELAHAY RJ; Drewe JA 2017 Inference of the infection status of individuals using longitudinal testing data from cryptic populations: Towards a probabilistic approach to diagnosis. Scientific Reports 7, Article number: 1111. http://dx.doi.org/10.1038/s41598-017-00806-4 R10616 Impact factor: 5.525 CHAMBERS MA; Aldwell F; WILLIAMS GA; PALMER S; GOWTAGE S; ASHFORD R; DALLEY DJ; DAVE D; WEYER U; SALGUERO FJ; NUNEZ A; NADIAN AK; CRAWSHAW T; Corner LAL; LESELLIER S 2017 The effect of oral vaccination with Mycobacterium bovis BCG on the development of tuberculosis in captive an badgers (Meles meles). Frontiers in Cellular and Infection Microbiology 7, Article 6. https://doi.org/10.3389/fcimb.2017.00006 R10574 Impact factor: 5.218 GOWTAGE S; WILLIAMS GA; Henderson R; Aylett P; MacMorran D; PALMER S; ROBERTSON A; LESELLIER S; CARTER SP; CHAMBERS MA 2017 Testing of a palatable bait and compatible vaccine carrier for the oral vaccination of an badgers (Meles meles) against tuberculosis. Vaccine 35 (6) 987-992. http://dx.doi.org/10.1016/j.vaccine.2016.12.004 R10545 Impact factor: 3.413 Hamilton CA; Mahan S; Bell CR; VILLARREAL-RAMOS B; Charleston B; Entrican G; Hope JC 2017 Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood. Immunology 151 (1) 89-97. http://dx.doi.org/10.1111/imm.12708 OIE Reference Laboratory Reports Activities, 2017 9

R10608 Impact factor: 4.078 HARRIS KA; BRUNTON L; BROUWER A; ROMERO GARCIA MP; GIBBENS JC; SMITH NH; UPTON PA 2017 Bovine TB infection status in cattle in Great Britain in 2015. Veterinary Record 180 (7) 170-175. http://dx.doi.org/10.1136/vr.j759 R10568 Impact factor: 1.741 JONES GJ; COAD M; KHATRI B; Bezos J; Parlane NA; Buddle BM; VILLARREAL-RAMOS B; HEWINSON RG; VORDERMEIER HM 2017 Tuberculin skin testing boosts interferon gamma responses to DIVA reagents in Mycobacterium bovis-infected cattle. Clinical and Vaccine Immunology 24 (5) e00551-16. http://dx.doi.org/10.1128/cvi.00551-16 R10627 Impact factor: 2.277 Lyashchenk KP; Grandison A; Keskinen K; Sikar-Gang A; Lambotte P; Esfandiari J; Ireton GC; Vallur A; Reed SG; JONES G; VORDERMEIER HM; Stabel JR; Thacker TC; Palmer MV; Water WR 2017 Identification of novel antigens recognized by serum antibodies in bovine tuberculosis. Clinical and Vaccine Immunology 24 (12) e00259-17. http://dx.doi.org/10.1128/cvi.00259-17 R10753 Impact factor: 2.598 PALPHRAMAND K; DELAHAY R; ROBERTSON A; GOWTAGE S; WILLIAMS GA; McDonald RA; CHAMBERS M; CARTER SP 2017 Field evaluation of candidate baits for oral delivery of BCG vaccine to an badgers, Meles meles. Vaccine 35 (34) 402-4407. https://doi.org/10.1016/j.vaccine.2017.06.059 R10666 Impact factor: 3.235 Pascual-Linaza AV; Gordon AW; STRINGER LA; Menzies FD 2017 Efficiency of slaughterhouse surveillance for the detection of bovine tuberculosis in cattle in rthern Ireland. Epidemiology and Infection 145 (5) 995-1005. https://doi.org/10.1017/s0950268816003095 R10595 Impact factor: 2.515 Pepponi I; KHATRI B; Tanner R; VILLARREAL-RAMOS B; VORDERMEIER M; McShane H 2017 A mycobacterial growth inhibition assay (MGIA) for bovine TB vaccine development. Tuberculosis 106, 118-122. https://doi.org/10.1016/j.tube.2017.07.008 R10682 Impact factor: 2.873 RHODES S 2017 The science of comprehensive TB testing. Official Vet Magazine, June 2017, 14, 16. http://5mpublishing.uberflip.com/i/840550-the-official-vet-magazine-june-2017/3 R10654 Impact factor: t applicable SALGUERO FJ; Gibson S; Garcia-Jimenez W; GOUGH J; STRICKLAND TS; VORDERMEIER HM; VILLARREAL-RAMOS B 2017 10 OIE Reference Laboratory Reports Activities, 2017

Differential cell composition and cytokine expression within lymph node granulomas from BCG-vaccinated and non-vaccinated cattle experimentally infected with Mycobacterium bovis. Transboundary and Emerging Diseases 64 (6) 1734-1749. http://dx.doi.org/10.1111/tbed.12561 R10736 Impact factor: 3.585 Serrano M; Elguezabal N; Sevilla IA; Geijo MV; Molina E; Arrazuria R; Urkitza A; JONES GJ; VORDERMEIER M; Garrido JM; Juste RA 2017 Tuberculosis detection in paratuberculosis vaccinated calves: new alternatives against interference. PLoS ONE 12(1): e0169735. http://dx.doi.org/10.1371/journal.pone.0169735 R10543 Impact factor: 3.234 Silk MJ; Croft DP; DELAHAY RJ; Hodgson DJ; Weber N; Boots M; McDonald RA 2017 The application of statistical network models in disease. Methods in Ecology and Evolution 8 (9) 1026-1041. http://dx.doi.org/10.1111/2041-210x.12770 R10705 Impact factor: 6.344 Silk MJ; Weber N; Steward LC; DELAHAY RJ; Croft DP; Hodgson DJ; Boots M; McDonald RA 2017 Seasonal variation in daily patterns of social contacts in the an badger Meles meles. Ecology and Evolution 7 (21) 9006-9015. http://dx.doi.org/10.1002/ece3.3402 R10741 Impact factor: 2.44 SMITH F; ROBERTSON A; SMITH GC; Gill P; McDonald RA; Wilson G;DELAHAY RJ 2017 Estimating wildlife vaccination coverage using genetic methods. biorxiv preprint. https://doi.org/10.1101/129064 R10765 Impact factor: t applicable Stewart LD; McCallan L; McNair J; MCGOLDRICK A; MORRIS R; Moyen J-L; De Juan Ferre L; Romero B; Alonso E; Parsons SDC; Van Helden P; Araujo FR; Grant IR 2017 Multilaboratory evaluation of a novel lateral flow immunochromatographic assay for confirming isolation of Mycobacterium bovis from veterinary diagnostic specimens. Journal of Clinical Microbiology 55 (12) 3411-3425. http://dx.doi.org/10.1128/jcm.00728-17 R10750 Impact factor: 4.232 Stewart LD; Tort N; Meakin P; Argudo JM; Nzuma R; Reid N; DELAHAY RJ; ASHFORD R; Montgomery WI; Grant IR 2017 Development of a novel immunochromatographic lateral flow assay specific for Mycobacterium bovis cells and its application in combination with immunomagnetic separation to test badger faeces. BMC Veterinary Research 13:131. http://dx.doi.org/10.1186/s12917-017-1048-x R10630 OIE Reference Laboratory Reports Activities, 2017 11

Impact factor: 1.643 Waters WR; VORDERMEIER HM; RHODES S; KHATRI B; Palmer MV; Maggioli MF; Thacker TC; Nelson JT; Thomsen BV; Robbe-Austerman S; Bravo Garcia DM; Schoenbaum MA; Camacho MS; Ray JS; Esfandiari J; Lambotte P; Greenwald R; Grandison A; Sikar-Gang A; Lyashchenko KP 2017 Potential for rapid antibody detection to identify tuberculous cattle with non-reactive tuberculin skin test results. BMC Veterinary Research 13:164. http://dx.doi.org/10.1186/s12917-017-1085-5 R10644 Impact factor: 1.643 b) International conferences: 3 A brief introduction to ETHICOBOTS and its goals Meeting: ETHICOBOTS Stakeholder Meeting on the Ethiopian Dairy sector: The Importance of Animal health and Disease control. Stefan Berg TB EURL Workshop Madrid Dec 2017 Jason Sawyer International Veterinary Vaccine Congress, Barcelona, October 2017, Invited plenary presentation on DIVA test development Martin Vordermeier Mycoclub France, Versailles, May, Invited plenary talk on host biomarkers. Martin Vordermeier c) National conferences: 2 BBSRC/Defra/NC3Rs bovine TB workshop, Birmingham, Dec 2017. Presented progress with NC3Rs-funded project on a bovine alveolus model for TB studies. Mark Chambers BVZS Conference 2017, London Zoo - Control of bovine TB in deer using ancillary antibody testing. Shelley Rhodes d) Other: (Provide website address or link to appropriate information) 2 Latest statistics on the incidence of tuberculosis (TB) in cattle in Great Britain and published scientific papers can be found on the APHA website: https://www.gov.uk/government/organisations/animal-and-plant-health-agency. Scientific reports and other information on bovine tuberculosis can be found at the Defra Website: https://www.gov.uk/government/organisations/department-for-environment-food-rural-affairs. Official statistics on bovine tuberculosis in Great Britain: https://www.gov.uk/government/statistical-data-sets/tuberculosis-tb-in-cattle-in-great-britain ToR 7: To provide scientific and technical training for personnel from OIE Member Countries To recommend the prescribed and alternative tests or vaccines as OIE Standards 14. Did your laboratory provide scientific and technical training to laboratory personnel from other OIE Member Countries? a) Technical visits: 1 b) Seminars: 0 c) Hands-on training courses: 1 d) Internships (>1 month): 0 12 OIE Reference Laboratory Reports Activities, 2017

Type of technical training provided (a, b, c or d) Country of origin of the expert(s) provided with training. participants from the corresponding country a Korea 1 c Ethiopia 9 ToR 8: To maintain a system of quality assurance, biosafety and biosecurity relevant for the pathogen and the disease concerned 15. Does your laboratory have a Quality Management System certified according to an International Standard? Quality management system adopted ISO17025 ISO9001:2015 Certificate scan (PDF, JPG, PNG format) UKAS_certificate.pdf ISO9001-2015_Certificate.pdf 16. Is your laboratory accredited by an international accreditation body? Test for which your laboratory is accredited culture (bovine and non bovine) Gamma Interferon ELISA Accreditation body UKAS UKAS 17. Does your laboratory maintain a biorisk management system for the pathogen and the disease concerned? (See Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, Chapter 1.1.4) ToR 9: To organise and participate in scientific meetings on behalf of the OIE 18. Did your laboratory organise scientific meetings on behalf of the OIE? 19. Did your laboratory participate in scientific meetings on behalf of the OIE? OIE Reference Laboratory Reports Activities, 2017 13

ToR 10: To establish and maintain a network with other OIE Reference Laboratories designated for the same pathogen or disease and organise regular inter-laboratory proficiency testing to ensure comparability of results 20. Did your laboratory exchange information with other OIE Reference Laboratories designated for the same pathogen or disease? 21. Was your laboratory involved in maintaining a network with OIE Reference Laboratories designated for the same pathogen or disease by organising or participating in proficiency tests? 22. Did your laboratory collaborate with other OIE Reference Laboratories for the same disease on scientific projects for the diagnosis or control of the pathogen of interest? ToR 11: To organise inter-laboratory proficiency testing with laboratories other than OIE Reference Laboratories for the same pathogens and diseases to ensure equivalence of results 23. Did your laboratory organise or participate in inter-laboratory proficiency tests with laboratories other than OIE Reference Laboratories for the same disease? te: See Interlaboratory test comparisons in: Laboratory Proficiency Testing at: http://www.oie.int/en/our-scientific-expertise/reference-laboratories/proficiency-testing see point 1.3 ToR 12: To place expert consultants at the disposal of the OIE 24. Did your laboratory place expert consultants at the disposal of the OIE? 14 OIE Reference Laboratory Reports Activities, 2017

Kind of consultancy Location Subject (facultative) OIE ad hoc Group on Replacement of ISBT on June 6-8, 2017 in Paris OIE Headquarters, Paris Replacement of the International Standard for bovine tuberculin 25. Additional comments regarding your report: OIE Reference Laboratory Reports Activities, 2017 15