Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study

Whitworth, Hilary S.; Badhan, Amarjit; Boakye, Aime A.; Takwoingi, Yemisi; Rees-Roberts, Melanie; Partlett, Christopher; Lambie, Heather; Innes, John; Cooke, Graham; Lipman, Marc; Conlon, Christopher; Macallan, Derek; Chua, Felix; Post, Frank A.; Wiselka, Martin; Woltmann, Gerrit; Deeks, Jonathan J.; Kon, Onn Min; Lalvani, Ajit; Abdoyeku, David; Davidson, Robert; Dedicoat, Martin; Kunst, Heinke; Loebingher, Michael R.; Lynn, William; Nathani, Nazim; O'Connell, Rebecca; Pozniak, Anton; Menzies, Sarah

Abstract

© 2019 Elsevier Ltd Background: The clinical utility of interferon-γ release assays (IGRAs) for diagnosis of active tuberculosis is unclear, although they are commonly used in countries with a low incidence of tuberculosis. We aimed to resolve this clinical uncertainty by determining the accuracy and utility of commercially available and second-generation IGRAs in the diagnostic assessment of suspected tuberculosis in a low-incidence setting. Methods: We did a prospective cohort study of adults with suspected tuberculosis in routine secondary care in England. Patients were tested for Mycobacterium tuberculosis infection at baseline with commercially available (T-SPOT.TB and QuantiFERON-TB Gold In-Tube [QFT-GIT]) and second-generation (incorporating novel M tuberculosis antigens) IGRAs and followed up for 6–12 months to establish definitive diagnoses. Sensitivity, specificity, positive and negative likelihood ratios, and predictive values of the tests were determined. Findings: Of the 1060 adults enrolled in the study, 845 were included in the analyses and 363 were diagnosed with tuberculosis. Sensitivity of T-SPOT.TB for all tuberculosis diagnosis, including culture-confirmed and highly probable cases, was 81·4% (95% CI 76·6–85·3), which was higher than QFT-GIT (67·3% [62·0–72·1]). Second-generation IGRAs had a sensitivity of 94·0% (90·0–96·4) for culture-confirmed tuberculosis and 89·2% (85·2–92·2) when including highly probable tuberculosis, giving a negative likelihood ratio for all tuberculosis cases of 0·13 (95% CI 0·10–0·19). Specificity ranged from 86·2% (95% CI 82·3–89·4) for T-SPOT.TB to 80·0% (75·6–83·8) for second-generation IGRAs. Interpretation: Commercially available IGRAs do not have sufficient accuracy for diagnostic evaluation of suspected tuberculosis. Second-generation tests, however, might have sufficiently high sensitivity, low negative likelihood ratio, and correspondingly high negative predictive value in low-incidence settings to facilitate prompt rule-out of tuberculosis. Funding: National Institute for Health Research.

Citation

Whitworth, H. S., Badhan, A., Boakye, A. A., Takwoingi, Y., Rees-Roberts, M., Partlett, C., Lambie, H., Innes, J., Cooke, G., Lipman, M., Conlon, C., Macallan, D., Chua, F., Post, F. A., Wiselka, M., Woltmann, G., Deeks, J. J., Kon, O. M., Lalvani, A., Abdoyeku, D., …Menzies, S. (2019). Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study. Lancet Infectious Diseases, 19(2), 193-202. https://doi.org/10.1016/s1473-3099%2818%2930613-3

• Journal Article Type: Article
• Acceptance Date: Oct 5, 2018
• Online Publication Date: Jan 14, 2019
• Publication Date: Feb 1, 2019
• Deposit Date: Apr 9, 2019
• Publicly Available Date: Jul 15, 2019
• Journal: The Lancet Infectious Diseases
• Print ISSN: 1473-3099
• Electronic ISSN: 1474-4457
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 2
• Pages: 193-202
• DOI: https://doi.org/10.1016/s1473-3099%2818%2930613-3
• Public URL: https://nottingham-repository.worktribe.com/output/1768512
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1473309918306133
• Contract Date: Apr 9, 2019