Interferon-γ release assays for diagnostic evaluation of tuberculosis

A multicenter cohort study evaluated the diagnostic performance of four interferon gamma release assays (IGRAs) in over 800 patients presenting with suspected active tuberculosis across English hospitals. Researchers compared traditional tests—T-SPOT.TB and QFT-GIT—to newer second-generation assays designed to incorporate novel M. tuberculosis antigens. The within-patient testing design minimized variability and allowed a robust head-to-head comparison of test characteristics.

The study found that T-SPOT.TB had moderately high sensitivity (81.4%) and specificity (86.2%), whereas QFT-GIT showed lower sensitivity (67.3%) and slightly lower specificity (80.4%). These findings align with prior reports indicating limited diagnostic accuracy of existing IGRAs in distinguishing active tuberculosis from latent infection or other conditions. In practical terms, neither T-SPOT.TB nor QFT-GIT demonstrated sufficient predictive values to function as reliable rule-in or rule-out tools in routine care.

By contrast, the second-generation IGRAs achieved sensitivity near 90% and negative predictive values approaching 90%, significantly outperforming older tests. This improvement was particularly notable in smear-negative and extrapulmonary tuberculosis cases, where conventional diagnostics often struggle. However, specificity was modest (around 80%), highlighting the persistent challenge of false positives in low-prevalence populations.

Importantly, the proportion of indeterminate results was lower for second-generation assays, suggesting they may be more robust in diverse clinical settings, including among patients with HIV and diabetes. The study also showed that adjusting test cutoffs did not meaningfully improve accuracy, underscoring that current assays are unlikely to achieve major gains simply by changing interpretive thresholds.

Overall, this work provides compelling evidence that while traditional IGRAs remain limited in their clinical utility, newer assays offer incremental benefits that could inform diagnostic pathways. These findings are relevant for clinicians, policymakers, and laboratories considering the adoption of advanced immunodiagnostic tools to support tuberculosis management.

References:

1. Whitworth, H.S., Badhan, A., Boakye, A.A., Takwoingi, Y., Rees-Roberts, M., Partlett, C., Lambie, H., Innes, J., Cooke, G., Lipman, M. and Conlon, C., 2019. Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study. The Lancet Infectious Diseases, 19(2), pp.193-202.