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An observational cohort study to evaluate the clinical utility of current and second-generation interferon-gamma release-assays in diagnostic evaluation of tuberculosis

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) An observational cohort study to evaluate the clinical utility of current and second-generation interferon-gamma release-assays in diagnostic evaluation of tuberculosis. Lancet Infectious Diseases, 19 (2). pp. 193-202. ISSN 1473-3099. (doi:10.1016/S1473-3099(18)30613-3) (KAR id:70068)

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Abstract

Background: The role of interferon-gamma release assays (IGRAs) in diagnosis of active tuberculosis (TB) is unclear, yet they are commonly used in low-TB-incidence countries. This study sought to resolve this clinical uncertainty by determining the diagnostic accuracy and role of current and second-generation IGRAs in the diagnostic assessment of suspected TB in a low-incidence setting.

Methods: This was a prospective cohort study of 1,060 adults with suspected TB, conducted in routine secondary care in England. Patients were tested for M. tuberculosis (Mtb) infection at baseline using current and second-generation IGRAs, the latter incorporating novel Mtb antigens, and followed up for 6-12m to establish definitive diagnoses. Sensitivity, specificity and positive and negative likelihood ratios (LRs) and predictive values (PVs) of the tests for TB were determined.

Findings: TB was diagnosed in 363 (43%) of 845 patients included in analyses. Sensitivity of T-SPOT.TB was 81.4% (95%CI 76.6-85.3%), higher than Quantiferon-Gold In-Tube at 67.3% (95%CI 62.0-72.1%). Second-generation IGRA had higher sensitivity than current tests, at 94.0% (95%CI 90.0–96.4%) for culture-confirmed TB and 89.2% (95%CI 85.2–92.2%) when including highly-probable TB, giving a negative LR for all TB 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% (95%CI 75.6-83.8%) for second-generation IGRA.

Interpretation: Currently-available IGRAs lack sufficient accuracy for diagnostic evaluation of suspected TB. Second-generation tests, however, may have sufficiently high sensitivity, low negative LR and correspondingly high negative PV in low-incidence settings to facilitate prompt rule-out of TB.

Funding: This study was funded by the National Institute for Health Research.

Item Type: Article
DOI/Identification number: 10.1016/S1473-3099(18)30613-3
Subjects: H Social Sciences
Divisions: Faculties > Social Sciences > School of Social Policy Sociology and Social Research > Centre for Health Services Studies
Depositing User: Melanie Rees-Roberts
Date Deposited: 16 Nov 2018 14:17 UTC
Last Modified: 06 May 2020 03:18 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/70068 (The current URI for this page, for reference purposes)
Rees-Roberts, Melanie: https://orcid.org/0000-0002-7121-0414
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