Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study.
Adult
Antigens, Bacterial
/ immunology
Bacterial Proteins
/ immunology
Data Accuracy
England
/ epidemiology
Female
Follow-Up Studies
Humans
Incidence
Interferon-gamma Release Tests
/ methods
Male
Middle Aged
Mycobacterium tuberculosis
/ immunology
Predictive Value of Tests
Prospective Studies
Tuberculosis, Pulmonary
/ blood
Journal
The Lancet. Infectious diseases
ISSN: 1474-4457
Titre abrégé: Lancet Infect Dis
Pays: United States
ID NLM: 101130150
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
15
06
2018
revised:
20
09
2018
accepted:
03
10
2018
pubmed:
19
1
2019
medline:
28
5
2020
entrez:
19
1
2019
Statut:
ppublish
Résumé
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. 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. 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. 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. National Institute for Health Research.
Sections du résumé
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.
Identifiants
pubmed: 30655049
pii: S1473-3099(18)30613-3
doi: 10.1016/S1473-3099(18)30613-3
pii:
doi:
Substances chimiques
Antigens, Bacterial
0
Bacterial Proteins
0
CFP-10 protein, Mycobacterium tuberculosis
0
ESAT-6 protein, Mycobacterium tuberculosis
0
Types de publication
Comparative Study
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
193-202Subventions
Organisme : Department of Health
ID : 08/106/02
Pays : United Kingdom
Investigateurs
David Abdoyeku
(D)
Robert Davidson
(R)
Martin Dedicoat
(M)
Heinke Kunst
(H)
Michael R Loebingher
(MR)
William Lynn
(W)
Nazim Nathani
(N)
Rebecca O'Connell
(R)
Anton Pozniak
(A)
Sarah Menzies
(S)
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Type : ErratumIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.