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, 9 (4), e93986

Non-tuberculous Mycobacteria and the Performance of Interferon Gamma Release Assays in Denmark


Non-tuberculous Mycobacteria and the Performance of Interferon Gamma Release Assays in Denmark

Thomas Stig Hermansen et al. PLoS One.


Background: The QuantiFERON-TB-Gold Test (QFT) is more specific than the Mantoux skin-test to discriminate between Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterial (NTM) infections. Here we study the performance of the QFT in patients with NTM disease.

Methods: From 2005 to 2011, nationwide patient data on positive NTM cultures (n = 925) were combined with nationwide data on QFT results (n = 16,133), both retrieved from the International Reference Laboratory of Mycobacteriology, Denmark. A total of 112 patients with NTM infections had a QFT performed, 53 patients had definite NTM disease, 10 had possible disease and 49 had NTM colonization.

Results: QFT was positive in 8% (4/53) of patients with definite disease, 40% (4/10) with possible disease and 31% (15/49) with colonization. Positivity rate was lowest among patients with definite disease infected with NTM without the RD1 region 4% (2/50). None of the 15 children with MAC lymphadenitis had a positive QFT.

Conclusion: This study is one of the largest assessing IGRAs in patients with NTM disease in a TB low-incidence setting. Our study showed that the QFT holds potential to discriminate between NTM and MTB infections. We found no positive IGRA test results among children with NTM not sharing the RD1-region of MTB resulting in a 100% specificity and we suggest that a QFT in a child presenting with cervical lymphadenitis may be helpful in distinguishing NTM from TB lymphadenitis.

Conflict of interest statement

Competing Interests: The authors have the following interests. Thomas Stig Hermansen (TSH), Vibeke Østergaard Thomsen (VOT), and Troels Lillebaek (TL) are working at Statens Serum Institut in a department that analyses QuantiFERON tests from parts of Denmark. Pernille Ravn (PR) states: Hvidovre Hospital has filed a patent on the use of IP-10 as a marker for infection with mycobacterium tuberculosis, and PR is one of the registered co-inventors. PR has been an invited speaker by Cellestis and has received QFT-IT kits at a reduced price for non profit research. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. Last author Pernille Ravn has provided supplementary information on the patents regarding the biomarker IP-10 and states: “Copenhagen University Hospitals, Hvidovre, hold the following pending and issued patents disclosing the use of IP-10 as a diagnostic marker for infection with M. tuberculosis: WO2011137902 (filed 04.05.2010), WO2007DK00399 (filed 05.09.2007).” Pernille Ravn is registered as one of the inventors. This does not alter her adherence to PLOS ONE policies on sharing data and materials.


Figure 1
Figure 1. Flowchart study population.
Figure 1 illustrates the inclusion and exclusion of persons with positive NTM culture and the classification of patients into three categories on the basis of microbiological data: definite NTM disease, possible NTM disease and NTM colonization.

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Grant support

This work was supported by a research grant from the research council of Hillerød Hospital, North Zealand Hospital, Hillerød. This work was supported by a research grant from Olga Bryde Nielsens Fond, North Zealand Hospital, Hillerød. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.