New meta-analysis of 307 studies finds that T-SPOT.TB is the most sensitive test for TB infection.

The most widely used tests for TB infection are the tuberculin skin test (TST), or the recently recommended antigen-based skin tests, or IGRAs. The recommended and widely used IGRAs are the T-SPOT™.TB, the QuantiFERON (QFT), and the TB-IGRA². Most guidelines worldwide state that any approved test can be used, except in specific situations like in BCG vaccinated individuals, where the traditional TST would cross-react^2,4,5. While the antigen-based skin tests and the recommended IGRAs use very similar antigens, the test methodologies are different, which can lead to variability in test performance^6,7. As all TB infection tests rely on testing immune responses, this variability can be even more pronounced when testing populations with suppressed immune systems, for example, people living with HIV⁸.

A new systematic review and meta-analysis by Rana, et al (2026)⁹ has comprehensively compared the sensitivities of recommended TB infection tests among different populations. This study showed that T-SPOT.TB had the highest pooled sensitivity, both in populations without HIV, and in populations with HIV, where sensitivity decreased across all tests included the study. In this blog we will dig a little deeper into this study and its key findings, and what they mean for TB infection testing.

Findings: T-SPOT.TB outperforms other TB infection tests

The study by Rana, et al (2026)⁹ is a large systemic review and meta-analysis, which included 307 studies that evaluated TB infection tests in individuals with microbiologically confirmed TB disease. 107 of the studies evaluated T-SPOT.TB, 110 studies evaluated TST, 185 evaluated QFT, 10 evaluated antigen-based skin tests, and just 5 evaluated TB-IGRA.

In people without HIV, T-SPOT.TB achieved the highest pooled sensitivity of any test evaluated in the study – 88.2%. This sensitivity exceeded QFT (82.6%) and the TB-IGRA (85.4%), and all IGRAs were found to perform better than the skin tests (which ranged from 75.1% to 80.3% sensitivity). This finding suggests that in the general population, T-SPOT.TB can detect more TB infected individuals.

The study then looked at test performance in more challenging populations – diagnosing TB in people living with HIV is more difficult as reduced immune function suppresses the immune response that most TB tests rely on. The study shows that this reduced immune function does cause test sensitivity to drop across all the platforms tested, but even in this challenging population, T-SPOT.TB demonstrated the highest sensitivity – 69.0% (vs. 66.5% for QFT, and 53.6% for TST ≥5mm).

Whilst this pooled sensitivity analysis in the study is interesting and could be clinically relevant for clinicians managing patients at risk of TB, the most compelling evidence in the Rana et al (2026) study comes from the 12 direct head-to-head studies comparing T-SPOT.TB and QFT in 824 participants. In people without HIV, T-SPOT.TB sensitivity was 8.8 percentages points higher than QFT. Similarly, in people living with HIV, T-SPOT.TB was 11.1 percentage points higher than QFT, although this was a smaller more limited dataset.

It is worth noting that different iterations of the QFT test were used in the 12 head-to-head studies, so further studies are needed to confirm whether the difference remains this pronounced when just the newest iteration, the QFT-Plus, is used. That being said, 8.8% and 11.1% are not marginal differences from a clinical perspective, and this higher sensitivity observed with T-SPOT.TB could translate directly into more cases detected and more lives saved. To put this into perspective, in a screening program of 1,000 high-risk individuals, an 8.8% sensitivity advantage could mean detecting an additional 88 TB cases that could otherwise be missed.

What do these results mean for clinical practice?

For healthcare providers making decisions about TB infection testing, the results of this meta-analysis are pretty clear: T-SPOT.TB comes out as the most sensitive option available across both HIV-negative and HIV-positive populations. This meta-analysis adds to a body of evidence suggesting that T-SPOT.TB could offer superior clinical performance over other IGRAs^10,11,12, and is supported by the manufacturer’s own reported performance characteristics for each product^13,14,15.

For clinicians, whether they are performing screening in a low prevalence setting, or managing high-risk patients, test sensitivity and choosing the right test is important. This publication provides the information that helps clinicians make those choices.

References:

1. World Health Organization. WHO Consolidated Guidelines on Tuberculosis. Module 1, Prevention: Tuberculosis Preventive Treatment. World Health Organization; 2020.
2. World Health Organization. WHO Consolidated Guidelines on Tuberculosis: Module 3: Diagnosis. World Health Organization; 2025.
3. Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med. 2007; 146:340-54.
4. Campbell JR, Pease C, Daley P, Pai M, Menzies D. Chapter 4: diagnosis of tuberculosis infection. Can J Respir Cri Care Sleep Med 2022; 6:49-65
5. US Centers for Disease Control and Prevention. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection – United States, 2010. United States Centers for Disease Control, 2010. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5905a1.htm. Accessed 18th August 2026.
6. Tanguay S, Killion JJ. Direct comparison of ELISPOT and ELISA-based assays for detection of individual cytokine-secreting cells. Lymphokine Cytokine Res 1994; 13:259-63.
7. Banaei N, Gaur RL, Pai M. Interferon Gamma Release Assays for Latent Tuberculosis: What Are the Sources of Variability? Journal of Clinical Microbiology. 2016; 54(4): 845-850.
8. Hamada Y, den Boon S, Cirillo DM, et al. Framework for the evaluation of new tests for tuberculosis infection. Eur Respir J. 2021; 58:2004078
9. Rana N, Noseworthy R, Jabbour E, et al. Sensitivity of Tuberculosis Infection Diagnostic Tests Among Different Populations: A Systematic Review and Meta-analysis. Open Forum Infectious Diseases. 2026. doi: 10.1093/ofid/ofag345.
10. Wong SH, Gao Q, Kelvin KF, et al. Effect of immunosuppressive therapy on interferon gamma release assay for latent tuberculosis screening in patients with autoimmune diseases: a systematic review and meta-analysis. Thorax. 2016; 71:64-72.
11. Bae W, Park KU, Song EY, et al. Comparison of the sensitivity of QuantiFERON Gold In-Tube and T-SPOT.TB according to patient age. PLoS One. 2016.
12. Abubakar I, Drobniewski F, Southern J, et al. Prognostic value of interferon-gamma release assays and tuberculin skin tests in predicting the development of active tuberculosis (UK PREDICT TB): a prospective cohort study.The Lancet Infectious Diseases. 2018;18(10);1077-1087.
13. QIAGEN. QuantiFERON-TB Gold Plus (QFT-Plus) ELISA Package Insert Jan 2023.
14. DiaSorin. LIAISON® QuantiFERON®-TB Gold Plus Solution.