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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, and others. (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. ISSN 1473-3099. E-ISSN 1474-4457. (doi:10.1016/S1473-3099(18)30613-3) (KAR id:72863)

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Abstract

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.

Item Type: Article
DOI/Identification number: 10.1016/S1473-3099(18)30613-3
Uncontrolled keywords: tuberculosis diagnosis, interferon-γ release assays, IGRAs
Subjects: R Medicine > R Medicine (General)
Divisions: Faculties > Social Sciences > School of Social Policy Sociology and Social Research > Centre for Health Services Studies
Depositing User: Melanie Rees-Roberts
Date Deposited: 06 Mar 2019 13:44 UTC
Last Modified: 06 May 2020 03:19 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/72863 (The current URI for this page, for reference purposes)
Rees-Roberts, Melanie: https://orcid.org/0000-0002-7121-0414
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