Comparative performance and age dependence of tuberculin and defined antigen bovine tuberculosis skin tests assessed with Bayesian latent class analysis

Abstract

Tuberculin skin tests (TST), the primary diagnostic tool for bovine tuberculosis (bTB), cross-react with BCG vaccine. Recently developed defined antigen skin tests (DSTs) aim to differentiate infected amongst vaccinated animals. We evaluated the field performance of different interpretations of the TST and DSTs relative to IGRA and IDEXX M. bovis antibody tests. This panel of tests was assessed in 446 unvaccinated cattle across 22 Ethiopian dairy herds using Bayesian latent class models. We extended the standard Walter-Hui model to include age-related effects to explore evidence of the presence of diagnostic anergy. The latent class models estimate sensitivity and specificity of the DSTs to be between 84-88% and 79-85% respectively. The DSTs perform intermediately between the comparative intradermal test (CIT, sensitivity 77%, specificity 100%) and single intradermal test (SIT, sensitivity 99%, specificity 76%). We observed significant age-related declines in test sensitivity, most notably for CIT (declining from 75 to 52% over 9 years) and DST10 (83% to 68%), while other tests showed more stable sensitivity across age groups. This variable pattern across tests suggests mechanisms beyond simple age-related anergy. Together, these findings demonstrate that DSTs' superior sensitivity to CIT and comparable or better specificity than SIT, combined with their ability to distinguish vaccinated animals, creates a viable pathway for implementing BCG vaccination programs. Given the absence of any gold standard definition of infection with bTB, latent class analyses are essential to assess the relative performance of different diagnostic tests. While our results provide encouraging news for the sensitivity of the new DST tests, the high prevalence of bTB within our study population makes our design underpowered to assess the specificity of the DSTs. Future research, including assessment of the specificity of DSTs in disease-free populations and optimization of test formulation and validation through large-scale field trials is essential to fully establish the case for use in vaccination and surveillance programs.