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Original article
Stratification by interferon-γ release assay level predicts risk of incident TB
  1. Brita Askeland Winje1,
  2. Richard White2,
  3. Heidi Syre3,
  4. Dag Harald Skutlaberg4,5,
  5. Fredrik Oftung6,
  6. Anne Torunn Mengshoel7,
  7. Hege Salvesen Blix8,
  8. Arne Broch Brantsæter9,10,
  9. Ellen Kristine Holter11,
  10. Nina Handal12,
  11. Gunnar Skov Simonsen13,14,
  12. Jan Egil Afset15,16,
  13. Anne Marte Bakken Kran11,17
  1. 1 Department of Vaccine Preventable Diseases, Norwegian Institute of Public Health, Oslo, Norway
  2. 2 Department of Infectious Disease Epidemiology and Modelling, Norwegian Institute of Public Health, Oslo, Norway
  3. 3 Department of Medical Microbiology, Stavanger University Hospital, Stavanger, Norway
  4. 4 Department of Microbiology, Haukeland University Hospital, Bergen, Norway
  5. 5 Department of Clinical Science, University of Bergen, Bergen, Norway
  6. 6 Department of Infectious Disease Immunology, Norwegian Institute of Public Health, Oslo, Norway
  7. 7 Department of Tuberculosis, Blood Borne and Sexually Transmitted Infections, Norwegian Institute for Public Health, Oslo, Norway
  8. 8 Department of Pharmacoepidemiology, Norwegian Institute of Public Health, Oslo, Norway
  9. 9 Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway
  10. 10 Department of Acute Medicine, Oslo University Hospital, Oslo, Norway
  11. 11 Department of Microbiology, Oslo University Hospital, Oslo, Norway
  12. 12 Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway
  13. 13 Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway
  14. 14 Research Group for Host-Microbe Interaction, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromso, Norway
  15. 15 Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
  16. 16 Department of Medical Microbiology, St Olavs University Hospital, Trondheim, Norway
  17. 17 Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  1. Correspondence to Dr Brita Askeland Winje, Department of Vaccine Preventable Diseases, Norwegian Institute of Public Health, Oslo 0403, Norway; brita.winje{at}fhi.no

Abstract

Introduction Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting.

Methods In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009–30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model.

Results The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL).

Conclusions Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

  • quantiFERON TB-Gold
  • interferon-gamma release assay
  • latent tuberculosis
  • tuberculosis

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Footnotes

  • Contributors All authors were involved in planning of the study. BAW initiated the study. BAW and RW were responsible for data-management, statistical analysis and for drafting the manuscript, HS, DHS, EKH, NH, GSS, JEA and AMBK provided and cleaned QFT data for the study, HSB and ABB were responsible for classification of medical risk factors, BAW, RW, ABB, HSB, HS, DHS ATM, FO and AMBK were involved in the writing process. All authors have reviewed and approved the final version of the manuscript.

  • Funding This study was funded by the Norwegian Health Association.

  • Disclaimer The interpretation and reporting of these data are the sole responsibility of the authors, and no endorsement by the registries is intended or should be inferred.

  • Competing interests None declared.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval The Norwegian Data Protection Authority (14/01138) and the Regional Committee for Medical Research Ethics (2014/1202) approved the study. An external partner deidentified data before the researchers were given access to it.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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