Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settings

Abstract Bovine tuberculosis (bTB) is a threat to cattle health and public safety. The current control programs are hampered by wildlife reservoirs and socioeconomic barriers. Vaccinating cattle with Bacillus Calmette-Guérin (BCG) effectively reduces transmission, offering a potential solution for c...

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Main Authors: Abebe Fromsa, Andrew J. K. Conlan, Sreenidhi Srinivasan, Balako Gumi, Wegene Bedada, Miserach Zeleke, Dawit Worku, Matios Lakew, Biniam Tadesse, Berecha Bayissa, Asegedech Sirak, Musse Girma Abdela, Getnet Abie Mekonnen, Tesfaye Chibssa, Maroudam Veerasami, Gareth J. Jones, H. Martin Vordermeier, Nick Juleff, James L. N. Wood, Gobena Ameni, Vivek Kapur
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85389-1
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author Abebe Fromsa
Andrew J. K. Conlan
Sreenidhi Srinivasan
Balako Gumi
Wegene Bedada
Miserach Zeleke
Dawit Worku
Matios Lakew
Biniam Tadesse
Berecha Bayissa
Asegedech Sirak
Musse Girma Abdela
Getnet Abie Mekonnen
Tesfaye Chibssa
Maroudam Veerasami
Gareth J. Jones
H. Martin Vordermeier
Nick Juleff
James L. N. Wood
Gobena Ameni
Vivek Kapur
author_facet Abebe Fromsa
Andrew J. K. Conlan
Sreenidhi Srinivasan
Balako Gumi
Wegene Bedada
Miserach Zeleke
Dawit Worku
Matios Lakew
Biniam Tadesse
Berecha Bayissa
Asegedech Sirak
Musse Girma Abdela
Getnet Abie Mekonnen
Tesfaye Chibssa
Maroudam Veerasami
Gareth J. Jones
H. Martin Vordermeier
Nick Juleff
James L. N. Wood
Gobena Ameni
Vivek Kapur
author_sort Abebe Fromsa
collection DOAJ
description Abstract Bovine tuberculosis (bTB) is a threat to cattle health and public safety. The current control programs are hampered by wildlife reservoirs and socioeconomic barriers. Vaccinating cattle with Bacillus Calmette-Guérin (BCG) effectively reduces transmission, offering a potential solution for controlling bTB. A key requirement for vaccination strategies using BCG is the validation of defined antigens to differentiate infections among vaccinated animals (DIVA). We compared tuberculin with DIVA peptide cocktails (ESAT-6, CFP-10, and Rv3615c) in 67 unvaccinated and 67 BCG-vaccinated cattle exposed to M. bovis in a natural setting. The cattle were tested every 4 months with a skin test and every 2 months with interferon-gamma (IFN-γ) release assays (IGRA) over a year of exposure. Before exposure, the DIVA skin, DIVA IGRA, and tuberculin tests showed 100% specificity in unvaccinated control calves. After exposure, the DIVA skin, DIVA IGRA, and comparative cervical tuberculin (CCT) tests had comparable sensitivities of 46% (95% CI 36, 56), 45% (95% CI 35, 55), and 47 (95% CI 37, 57), respectively, when assessed against animals positive by M. bovis culture PCR. The results suggest that test-and-slaughter control strategies using tests with low sensitivity are not expected to be effective in controlling bTB in high-prevalence herds, and highlight an urgent need to improve the sensitivity of diagnostic tests for bTB in these settings.
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spelling doaj-art-e620396cb38d46d3ad856cdd19865e862025-02-09T12:31:04ZengNature PortfolioScientific Reports2045-23222025-02-0115111410.1038/s41598-025-85389-1Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settingsAbebe Fromsa0Andrew J. K. Conlan1Sreenidhi Srinivasan2Balako Gumi3Wegene Bedada4Miserach Zeleke5Dawit Worku6Matios Lakew7Biniam Tadesse8Berecha Bayissa9Asegedech Sirak10Musse Girma Abdela11Getnet Abie Mekonnen12Tesfaye Chibssa13Maroudam Veerasami14Gareth J. Jones15H. Martin VordermeierNick Juleff16James L. N. Wood17Gobena Ameni18Vivek Kapur19Aklilu Lemma Institutes of Pathobiology, Addis Ababa UniversityDisease Dynamics Unit, Department of Veterinary Medicine, University of CambridgeHuck Institutes of Life Sciences, The Pennsylvania State UniversityAklilu Lemma Institutes of Pathobiology, Addis Ababa UniversityAnimal Health InstituteAklilu Lemma Institutes of Pathobiology, Addis Ababa UniversityAklilu Lemma Institutes of Pathobiology, Addis Ababa UniversityAnimal Health InstituteAnimal Health InstituteAklilu Lemma Institutes of Pathobiology, Addis Ababa UniversityAnimal Health InstituteAklilu Lemma Institutes of Pathobiology, Addis Ababa UniversityAnimal Health InstituteAnimal Health InstituteCisGen Biotech Discoveries Pvt LtdAnimal and Plant Health AgencyThe Bill & Melinda Gates FoundationDisease Dynamics Unit, Department of Veterinary Medicine, University of CambridgeAklilu Lemma Institutes of Pathobiology, Addis Ababa UniversityHuck Institutes of Life Sciences, The Pennsylvania State UniversityAbstract Bovine tuberculosis (bTB) is a threat to cattle health and public safety. The current control programs are hampered by wildlife reservoirs and socioeconomic barriers. Vaccinating cattle with Bacillus Calmette-Guérin (BCG) effectively reduces transmission, offering a potential solution for controlling bTB. A key requirement for vaccination strategies using BCG is the validation of defined antigens to differentiate infections among vaccinated animals (DIVA). We compared tuberculin with DIVA peptide cocktails (ESAT-6, CFP-10, and Rv3615c) in 67 unvaccinated and 67 BCG-vaccinated cattle exposed to M. bovis in a natural setting. The cattle were tested every 4 months with a skin test and every 2 months with interferon-gamma (IFN-γ) release assays (IGRA) over a year of exposure. Before exposure, the DIVA skin, DIVA IGRA, and tuberculin tests showed 100% specificity in unvaccinated control calves. After exposure, the DIVA skin, DIVA IGRA, and comparative cervical tuberculin (CCT) tests had comparable sensitivities of 46% (95% CI 36, 56), 45% (95% CI 35, 55), and 47 (95% CI 37, 57), respectively, when assessed against animals positive by M. bovis culture PCR. The results suggest that test-and-slaughter control strategies using tests with low sensitivity are not expected to be effective in controlling bTB in high-prevalence herds, and highlight an urgent need to improve the sensitivity of diagnostic tests for bTB in these settings.https://doi.org/10.1038/s41598-025-85389-1BCG vaccinationBovine tuberculosisDefined antigen cocktailsTuberculinIGRA and skin tests
spellingShingle Abebe Fromsa
Andrew J. K. Conlan
Sreenidhi Srinivasan
Balako Gumi
Wegene Bedada
Miserach Zeleke
Dawit Worku
Matios Lakew
Biniam Tadesse
Berecha Bayissa
Asegedech Sirak
Musse Girma Abdela
Getnet Abie Mekonnen
Tesfaye Chibssa
Maroudam Veerasami
Gareth J. Jones
H. Martin Vordermeier
Nick Juleff
James L. N. Wood
Gobena Ameni
Vivek Kapur
Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settings
Scientific Reports
BCG vaccination
Bovine tuberculosis
Defined antigen cocktails
Tuberculin
IGRA and skin tests
title Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settings
title_full Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settings
title_fullStr Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settings
title_full_unstemmed Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settings
title_short Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settings
title_sort comparative performance of tuberculin and defined antigen cocktails for detecting bovine tuberculosis in bcg vaccinated cattle in natural settings
topic BCG vaccination
Bovine tuberculosis
Defined antigen cocktails
Tuberculin
IGRA and skin tests
url https://doi.org/10.1038/s41598-025-85389-1
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