Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study

Abstract

Background Despite a recent decline in the annual incidence of tuberculosis (TB) in the UK, rates remain higher than in most Western European countries. The detection and treatment of latent TB infection (LTBI) is an essential component of the UK TB control programme. Objectives To assess the prognostic value and cost-effectiveness of the current two interferon gamma release assays (IGRAs) compared with the standard tuberculin skin test (TST) for predicting active TB among untreated individuals at increased risk of TB: (1) contacts of active TB cases and (2) new entrants to the UK from high-TB-burden countries. Design A prospective cohort study and economic analysis. Participants and setting Participants were recruited in TB clinics, general practices and community settings. Contacts of active TB cases and migrants who were born in high-TB-burden countries arriving in the UK were eligible to take part if they were aged ≥ 16 years. Main outcome measures Outcomes include incidence rate ratios comparing the incidence of active TB in those participants with a positive test result and those with a negative test result for each assay, and combination of tests and the cost per quality-adjusted life-year (QALY) for each screening strategy. Results A total of 10,045 participants were recruited between May 2010 and July 2015. Among 9610 evaluable participants, 97 (1.0%) developed active TB. For the primary analysis, all test data were available for 6380 participants, with 77 participants developing active TB. A positive result for TSTa (positive if induration is ≥ 5 mm) was a significantly poorer predictor of progression to active TB than a positive result for any of the other tests. Compared with TSTb [positive if induration is ≥ 6 mm without prior bacillus Calmette–Guérin (BCG) alone, T-SPOT®.TB (Oxford Immunotec Ltd, Oxford, UK), TSTa + T-SPOT.TB, TSTa + IGRA and the three combination strategies including TSTb were significantly superior predictors of progression. Compared with the T-SPOT.TB test alone, TSTa + T-SPOT.TB, TSTb + QuantiFERON® TB Gold In-Tube (QFT-GIT; QIAGEN GmbH, Hilden, Germany) and TSTb + IGRA were significantly superior predictors of progression and, compared with QFT-GIT alone, T-SPOT.TB, TSTa + T-SPOT.TB, TSTa + QFT-GIT, TSTa + IGRA, TSTb + T-SPOT.TB, TSTb + QFT-GIT and TSTb + IGRA were significantly superior predictors of progression. When evaluating the negative predictive performance of tests and strategies, negative results for TSTa + QFT-GIT were significantly poorer predictors of non-progression than negative results for TSTa, T-SPOT.TB and TSTa + IGRA. The most cost-effective LTBI testing strategies are the dual-testing strategies. The cost and QALY differences between the LTBI testing strategies were small; in particular, QFT-GIT, TSTb + T-SPOT.TB and TSTb + QFT-GIT had very similar incremental net benefit estimates. Conclusion This study found modest differences between tests, or combinations of tests, in identifying individuals who would go on to develop active TB. However, a two-step approach that combined TSTb with an IGRA was the most cost-effective testing option. Implications for practice and future research The two-step TSTb strategy, which stratified the TST by prior BCG vaccination followed by an IGRA, was the most cost-effective approach. The limited ability of current tests to predict who will progress limits the clinical utility of tests. The implications of these results for the NHS England/Public Health England national TB screening programme for migrants should be investigated. Study registration This study is registered as NCT01162265. Funding The National Institute for Health Research Health Technology Assessment programme.

SARS-CoV-2 responsive T cell numbers and anti-Spike IgG levels are both associated with protection from COVID-19: A prospective cohort study in keyworkers

“…Intriguingly, our data indicate individual level risk stratification may be possible using T-cell assays, including the standardised assay kits used in this study which, being in the same format as the widely used T-SPOT®. TB tests for latent TB infection, would be readily deployable at scale (24).…”

“…The test is similar to the widely deployed T-SPOT ® . TB test, which identifies patients infected with M. tuberculosis (24).…”

Validation of Differentially Expressed Immune Biomarkers in Latent and Active Tuberculosis by Real-Time PCR

“…Patients with PTB were also recruited at Guy’s and St Thomas’ and Royal Free London NHS Foundation Trusts, London UK (low TB incidence site; designated group UKPTB (n = 63)). Individuals with suspected LTBI (n = 103) and matched negative controls [CNTRLB (n = 102)] were recruited from individuals variably-domiciled in the UK and Asia, resident in the greater London area as part of the UK PREDICT TB study, i.e ( 4 , 42 )., by Public Health England Centre for Infections, 61 Colindale Avenue London and University College, London UK. This was a prospective cohort study, recruiting participants from 54 centers in London, Birmingham, and Leicester, at high risk for latent tuberculosis infection (i.e., 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]).…”

“…Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB) is the leading cause of infectious disease worldwide ( 1 , 2 ), accounting for the deaths of approximately 1.3 million people each year ( 3 ). The United Kingdom (UK) has seen an increase in TB since the late 1980s, with rates higher than the rest of Europe ( 4 ), and there are currently around 6000 new cases each year ( 5 ). In 2016, 73.6% of confirmed TB cases in the UK were foreign-born, with India and Pakistan the most frequent countries of origin ( 6 , 7 ).…”

BCG Vaccination Prevents Reactivation of Latent Lymphatic Murine Tuberculosis Independently of CD4+ T Cells

“…A very recent study also found no difference in the prevalence of LTBI in the UK, where the relative incidence between BCG vaccinated and naïve people was compared (47). Another very recent report predicted the possible estimation of the role of BCG vaccination on reactivation from LTBI, but the final outcome is yet to be reported (48). In a statistically underpowered Taiwanese study the percentage of T-SPOT.TB positive, HIV-infected patients, was almost 50% less in people showing a BCG scar compared with those with no evidence of BCG vaccination, therefore suggesting BCG reduces reactivation from LTBI in a HIV setting (49).…”