The association between age and bovine tuberculosis diagnosis, using the interferon-gamma (IFN-γ) assay or post-mortem examination in high-risk Irish cattle herds: A retrospective cohort study

Mycobacterium bovis causes bovine tuberculosis (bTB), a chronic infectious disease with significant veterinary, public health, and economic consequences. The interferon-gamma (IFN-γ) assay is increasingly used alongside the Single Intradermal Comparative Tuberculin Test (SICTT) in Ireland's national bTB eradication programme, but age-specific patterns associated with IFN-γ positivity or post-mortem visible lesion detection (VLD) have not been fully characterised. This retrospective cohort study includes 267,674 SICTT-negative cattle tested with IFN-γ between May 2019 and December 2023 in high-risk Irish herds. Mixed-effects logistic regression models quantify associations between age and (i) IFN-γ positivity and (ii) VLD at slaughter among IFN-γ-positive cattle. Models adjust for sex, herd type, prior inconclusive SICTTs, number of prior 'risky' SICTT tests, and herd-level breakdown size (% of animals positive). Overall, 9.6% of SICTT-negative cattle test positive to IFN-γ. Our findings show that IFN-γ positivity increases with age, peaks in cattle aged 4-6 years, plateaus until 8 years, and declines thereafter. Relative to beef breeding herds, dairy, mixed, and 'other' herd types are associated with higher IFN-γ positivity, as is a history of prior inconclusive SICTTs, and fewer prior 'risky' SICTT exposures. Among IFN-γ-positive cattle, 21.9% exhibit VLD at slaughter. VLD positivity shows a U-shaped relationship with age, highest in the youngest (0-2 years), reducing in cattle aged 2-4, then increasing linearly to oldest (>8 years) cattle. The VLD odds are approximately half in dairy herds compared with beef breeding herds and are elevated in herds in the largest quartile of breakdowns (>6.25% of animals positive). The interpretation of these results should consider that IFN-γ-positivity and VLD likely reflect different stages of bTB infection, with early immune responses detected ante-mortem and visible lesions at post-mortem representing later stage disease; the absence of visible lesions therefore does not exclude M. bovis infection. It appears that age-specific IFN-γ positivity and VLD in high-risk herds are likely shaped by production systems, prior risky SICTT exposures, and herd-level outbreak dynamics rather than simple cumulative risk. The IFN-γ testing helps to identify infected cattle missed by SICTT, particularly in the early infection or large herd breakdowns and serves to support targeted, risk-based deployment to optimize Ireland's bTB eradication programme.