Prognostic value of interferon-γ release assays and tuberculin skin test in predicting the development of active tuberculosis (UK PREDICT TB): a prospective cohort study

Abstract

SummaryBackgroundTackling tuberculosis requires testing and treatment of latent tuberculosis in high-risk groups. The aim of this study was to estimate the predictive values of the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs) for the development of active tuberculosis in high-risk groups—ie, people in recent contact with active tuberculosis cases and from high-burden countries.MethodIn this prospective cohort study, we recruited participants from 54 centres (eg, clinics, community settings) in London, Birmingham, and Leicester in the UK. Participants were eligible if they were aged 16 years or older and at high risk for latent tuberculosis infection (ie, recent contact with someone with active tuberculosis [contacts] or a migrant who had arrived in the UK in the past 5 years from—or who frequently travelled to—a country with a high burden of tuberculosis [migrants]). Exclusion criteria included prevalent cases of tuberculosis, and participants who were treated for latent tuberculosis after a positive test result in this study. Each participant received three tests (QuantiFERON-TB Gold-In Tube, T-SPOT.TB, and a Mantoux TST). A positive TST result was reported using three thresholds: 5 mm (TST-5), 10 mm (TST-10), and greater than 5 mm in BCG-naive or 15 mm in BCG-vaccinated (TST-15) participants. Participants were followed up from recruitment to development of tuberculosis or censoring. Incident tuberculosis cases were identified by national tuberculosis databases, telephone interview, and review of medical notes. Our primary objective was to estimate the prognostic value of IGRAs compared with TST, assessed by the ratio of incidence rate ratios and predictive values for tuberculosis development. The study was registered with ClinicalTrials.gov, NCT01162265, and is now complete.FindingsBetween May 4, 2010, and June 1, 2015, 10 045 people were recruited, of whom 9610 were eligible for inclusion. Of this cohort, 4861 (50·6%) were contacts and 4749 (49·4%) were migrants. Participants were followed up for a median of 2·9 years (range 21 days to 5·9 years). 97 (1·0%) of 9610 participants developed active tuberculosis (77 [1·2%] of 6380 with results for all three tests). In all tests, annual incidence of tuberculosis was very low in those who tested negatively (ranging from 1·2 per 1000 person-years, 95% CI 0·6–2·0 for TST-5 to 1·9 per 1000 person-years, 95% CI 1·3–2·7, for QuantiFERON-TB Gold In-Tube). Annual incidence in participants who tested positively were highest for T-SPOT.TB (13·2 per 1000 person-years, 95% CI 9·9–17·4), TST-15 (11·1 per 1000 person-years, 8·3–14·6), and QuantiFERON-TB Gold In-Tube (10·1 per 1000 person-years, 7·4–13·4). Positive results for these tests were significantly better predictors of progression than TST-10 and TST-5 (eg, ratio of test positivity rates in those progressing to tuberculosis compared with those not progressing T-SPOT.TB vs TST-5: 1·99, 95% CI 1·68–2·34; p<0·0001). However, TST-5 identified a higher proportion of participants who progressed to acti...

Evaluation of QuantiFERON-TB Gold Plus for Predicting Incident Tuberculosis among Recent Contacts: A Prospective Cohort Study

“…We found that the performance of QFT-Plus appeared to be comparable to that previously reported in evaluations of QFT-GIT and T-SPOT.TB, with an IRR of 10.1, 80% sensitivity for detection of incident TB, and an overall PPV for incident TB of 5.7% (8). Interferon-g responses in the TB1 and TB2 tubes were strongly correlated, and ROC curves showed a minimal difference between them for predicting incident TB.…”

“…TB disease (defined as TB diagnosed within 21 days of enrollment, as per previous work [8]) and those who accepted preventive therapy (offered in accordance with contemporary national guidance [13,14]) were excluded from the analysis. The study was approved by the UK National Research Ethics Service (ref: 14/EM/ 1208).…”

T Cell Responses to Mycobacterial Glycolipids: On the Spectrum of “Innateness”

“…The diagnosis of mycobacterial disease could be improved by leveraging the biology of mycolipid-specific T cells. Latent TB is typically diagnosed by an interferon gamma release assay, which measures T cell responses to secreted protein antigens but is a poor predictor for progression to active disease (93). The diagnosis of leprosy and Buruli ulcer are established by identifying bacilli in affected skin lesions, but this often results in false negative results because of the paucibacillary nature of these diseases.…”

Acute Miliary Tuberculosis in Pregnancy After in Vitro Fertilization and Embryo Transfer: Report of Seven Cases and Systemic Review

“…Clinical diagnosis of TB in pregnant women is often delayed, largely because of the concern about radiation exposure. The IGRA is an important diagnostic method for detecting active TB and is safe for use in pregnancy [27][28][29][30]. Both the IGRA and TST have a high consistency of 77.3-88.0% [29].…”