The University of Southampton
University of Southampton Institutional Repository

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

Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study
Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study
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.
1366-5278
1-96
Abubakar, Ibrahim
7a6eaaa0-90f8-42cd-b52f-e408a3961e4a
Lalvani, Ajit
ac754f14-ec6b-4a5b-8a72-6bb1e114b626
Southern, Jo
ad525ec6-0d60-4fce-9d88-676826fc9bf1
Sitch, Alice
a71f645f-ee23-47ee-9cad-890d0eb67789
Jackson, Charlotte
e0ec43eb-38c1-46cd-b041-99329047bc74
Onyimadu, Oluchukwu
ff168bd7-1c4f-4756-a34a-7e6b930ae29b
Lipman, Marc
5a10162e-e8d5-442b-a740-599848e9cdcd
Deeks, Jonathan J
998ba22f-f7f2-46bf-891f-02ec367881cf
Griffiths, Chris
9be94e58-34bb-43e5-a9c2-425cbf50cc86
Bothamley, Graham
41b779e2-ca09-4866-9007-f85c0adca690
Kon, Onn Min
7926b63c-abbb-44e3-96a0-5b24e7b3c096
Hayward, Andrew
fbd5098c-bd3d-455d-b09a-4f3b403baecd
Lord, Joanne
fd3b2bf0-9403-466a-8184-9303bdc80a9a
Drobniewski, Francis
4b7dd9e6-79ad-4aee-b053-86d1ab697b54
Abubakar, Ibrahim
7a6eaaa0-90f8-42cd-b52f-e408a3961e4a
Lalvani, Ajit
ac754f14-ec6b-4a5b-8a72-6bb1e114b626
Southern, Jo
ad525ec6-0d60-4fce-9d88-676826fc9bf1
Sitch, Alice
a71f645f-ee23-47ee-9cad-890d0eb67789
Jackson, Charlotte
e0ec43eb-38c1-46cd-b041-99329047bc74
Onyimadu, Oluchukwu
ff168bd7-1c4f-4756-a34a-7e6b930ae29b
Lipman, Marc
5a10162e-e8d5-442b-a740-599848e9cdcd
Deeks, Jonathan J
998ba22f-f7f2-46bf-891f-02ec367881cf
Griffiths, Chris
9be94e58-34bb-43e5-a9c2-425cbf50cc86
Bothamley, Graham
41b779e2-ca09-4866-9007-f85c0adca690
Kon, Onn Min
7926b63c-abbb-44e3-96a0-5b24e7b3c096
Hayward, Andrew
fbd5098c-bd3d-455d-b09a-4f3b403baecd
Lord, Joanne
fd3b2bf0-9403-466a-8184-9303bdc80a9a
Drobniewski, Francis
4b7dd9e6-79ad-4aee-b053-86d1ab697b54

Abubakar, Ibrahim, Lalvani, Ajit, Southern, Jo, Sitch, Alice, Jackson, Charlotte, Onyimadu, Oluchukwu, Lipman, Marc, Deeks, Jonathan J, Griffiths, Chris, Bothamley, Graham, Kon, Onn Min, Hayward, Andrew, Lord, Joanne and Drobniewski, Francis (2018) Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study. Health Technology Assessment, 22 (56), 1-96. (doi:10.3310/hta22560).

Record type: Article

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.

Text
3021419 - Version of Record
Restricted to Repository staff only until 1 October 2019.
Request a copy

More information

Accepted/In Press date: 14 August 2018
e-pub ahead of print date: 1 October 2018
Published date: 1 October 2018

Identifiers

Local EPrints ID: 425569
URI: https://eprints.soton.ac.uk/id/eprint/425569
ISSN: 1366-5278
PURE UUID: 8e6ee904-a7d5-4607-8154-bb79f42d4093
ORCID for Oluchukwu Onyimadu: ORCID iD orcid.org/0000-0002-1724-3485
ORCID for Joanne Lord: ORCID iD orcid.org/0000-0003-1086-1624

Catalogue record

Date deposited: 25 Oct 2018 16:30
Last modified: 14 Mar 2019 01:32

Export record

Altmetrics

Contributors

Author: Ibrahim Abubakar
Author: Ajit Lalvani
Author: Jo Southern
Author: Alice Sitch
Author: Charlotte Jackson
Author: Marc Lipman
Author: Jonathan J Deeks
Author: Chris Griffiths
Author: Graham Bothamley
Author: Onn Min Kon
Author: Andrew Hayward
Author: Joanne Lord ORCID iD
Author: Francis Drobniewski

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×