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 controlling bTB. A key component of the vaccination strategy is the use of defined antigens to differentiate infections among vaccinated animals (DIVA). We compared tuberculin with a DIVA peptide cocktails (ESAT-6, CFP-10, and Rv3615c) in 67 unvaccinated and 67 BCG-vaccinated cattle exposed to M. bovis in natural settings. The cattle were tested every four months with a skin test and every two months with interferon-gamma 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. In vaccinated calves, the DIVA IGRA and DIVA skin tests had specificities of 98.5% and 94.0%, respectively, while tuberculin tests induced greater skin thickness and INF-γ production, showing a lack of specificity. After exposure, the DIVA skin, DIVA IGRA, and comparative cervical tuberculin (CCT) tests had relative sensitivities of 47%, 42%, and 43%, respectively, indicating comparable performance and potential utility of DIVA antigens with BCG vaccination. All tests had positive predictive values (PV+) of over 90% but low negative predictive values (PV-) of less than 18%. In high-prevalence herds, test and slaughter control strategies using tests with low sensitivity and predictive value are expected to be ineffective in controlling bTB. Therefore, BCG vaccination is recommended, which reduces disease transmission. Overall, this study highlights the need to improve the sensitivity of diagnostic tests for bTB.