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
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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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