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Interferon-gamma release assay conversion after M. tuberculosis exposure specifically associates with greater risk of progression to tuberculosis: a prospective cohort study in Leicester (UK)

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posted on 2024-03-15, 10:40 authored by Jee-Whang KimJee-Whang Kim, Joshua Nazareth, Joanne Lee, Hemu Patel, Gerrit Woltmann, Raman Verma, Anne O'Garra, Pranabashis Haldar

Objectives

We investigated whether quantifying the serial QuantiFERON-TB Gold (QFT) response improves tuberculosis (TB) risk stratification in pulmonary TB (PTB) contacts.

Methods

297 untreated adult household PTB contacts, QFT tested at baseline and 3 months after index notification, were prospectively observed (median 1460 days). Normal variance of serial QFT responses was established in 46 extra-pulmonary TB contacts. This informed categorisation of the response in QFT-positive PTB contacts as: converters; persistently QFT-positive with significant increase (PPincrease); and without significant increase (PPno-increase).

Results

Eight co-prevalent TB (disease ≤ 3 months after index notification) and 12 incident TB (>3 months after index notification) cases were diagnosed. Genetic linkage to the index strain was confirmed in all culture-positive progressors. Cumulative 2-year incident TB risk in QFT-positive contacts was 8.4% (95% CI, 3.0% - 13.6%); stratifying by serial QFT response, significantly higher risk was observed in QFT-converters (28%), compared with PPno-increase (4.8%) and PPincrease (3.7%). Converters were characterised by exposure to index cases with a shorter interval from symptom onset to diagnosis (median reduction 50.0 days, p=0.013).

Conclusion

QFT conversion rather than quantitative changes of a persistently positive serial QFT response, associates with greater TB risk and exposure to rapidly progressive TB.

Funding

Wellcome Investigator award to A. O'Garra (215628_Z_19_Z)

National Institute for Health and Care Research (NIHR) Academic Clinical Fellowship

Francis Crick Institute (Crick 10126; Crick 10468)

BIOASTER Microbiology Technology Institute, Lyon, France (with funding from the French Government Investissement d'Avenir program ANR-10-AIRT-03) and the Medical Diagnostic Discovery Department, bioMerieux SA, France

History

Author affiliation

College of Life Sciences/Respiratory Sciences

Version

  • VoR (Version of Record)

Published in

International Journal of Infectious Diseases

Volume

141

Publisher

Elsevier BV

issn

1201-9712

eissn

1878-3511

Copyright date

2024

Available date

2024-03-15

Spatial coverage

Canada

Language

en

Deposited by

Miss Jee-Whang Kim

Deposit date

2024-03-14

Rights Retention Statement

  • No

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