Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study
<strong>Background</strong> 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 acc...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2019
|
| _version_ | 1797079078764806144 |
|---|---|
| author | Whitworth, H Badhan, A Boakye, A Takwoingi, Y Rees-Roberts, M Partlett, C Lambie, H Innes, J Cooke, G Lipman, M Conlon, C Macallan, D Chua, F Post, F Wiselka, M Woltmann, G Deeks, J Kon, O Lalvani, A Interferon-γ Release Assays for Diagnostic Evaluation of Active Tuberculosis study group |
| author_facet | Whitworth, H Badhan, A Boakye, A Takwoingi, Y Rees-Roberts, M Partlett, C Lambie, H Innes, J Cooke, G Lipman, M Conlon, C Macallan, D Chua, F Post, F Wiselka, M Woltmann, G Deeks, J Kon, O Lalvani, A Interferon-γ Release Assays for Diagnostic Evaluation of Active Tuberculosis study group |
| author_sort | Whitworth, H |
| collection | OXFORD |
| description | <strong>Background</strong> 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. <strong>Methods</strong> 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. <strong>Findings</strong> 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. <strong>Interpretation</strong> 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. |
| first_indexed | 2024-03-07T00:40:33Z |
| format | Journal article |
| id | oxford-uuid:82df15d7-5903-49b6-9c19-e8e3e32e74dd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:40:33Z |
| publishDate | 2019 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:82df15d7-5903-49b6-9c19-e8e3e32e74dd2022-03-26T21:40:34ZClinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:82df15d7-5903-49b6-9c19-e8e3e32e74ddEnglishSymplectic Elements at OxfordElsevier2019Whitworth, HBadhan, ABoakye, ATakwoingi, YRees-Roberts, MPartlett, CLambie, HInnes, JCooke, GLipman, MConlon, CMacallan, DChua, FPost, FWiselka, MWoltmann, GDeeks, JKon, OLalvani, AInterferon-γ Release Assays for Diagnostic Evaluation of Active Tuberculosis study group<strong>Background</strong> 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. <strong>Methods</strong> 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. <strong>Findings</strong> 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. <strong>Interpretation</strong> 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. |
| spellingShingle | Whitworth, H Badhan, A Boakye, A Takwoingi, Y Rees-Roberts, M Partlett, C Lambie, H Innes, J Cooke, G Lipman, M Conlon, C Macallan, D Chua, F Post, F Wiselka, M Woltmann, G Deeks, J Kon, O Lalvani, A Interferon-γ Release Assays for Diagnostic Evaluation of Active Tuberculosis study group Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study |
| title | Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study |
| title_full | Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study |
| title_fullStr | Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study |
| title_full_unstemmed | Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study |
| title_short | Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study |
| title_sort | clinical utility of existing and second generation interferon γ release assays for diagnostic evaluation of tuberculosis an observational cohort study |
| work_keys_str_mv | AT whitworthh clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT badhana clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT boakyea clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT takwoingiy clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT reesrobertsm clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT partlettc clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT lambieh clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT innesj clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT cookeg clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT lipmanm clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT conlonc clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT macalland clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT chuaf clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT postf clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT wiselkam clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT woltmanng clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT deeksj clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT kono clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT lalvania clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy AT interferongreleaseassaysfordiagnosticevaluationofactivetuberculosisstudygroup clinicalutilityofexistingandsecondgenerationinterferongreleaseassaysfordiagnosticevaluationoftuberculosisanobservationalcohortstudy |