Contribution of QuantiFERON-TB Gold-in-Tube to the Diagnosis of Mycobacterium tuberculosis Infection in Young Children in a Low TB Prevalence Country

Sara Debulpaep; Véronique Corbière; Jack Levy; Petra Schelstraete; Koen Vanden Driessche; Françoise Mascart; Françoise Mouchet

doi:10.3389/fped.2019.00291

Contribution of QuantiFERON-TB Gold-in-Tube to the Diagnosis of Mycobacterium tuberculosis Infection in Young Children in a Low TB Prevalence Country

Front Pediatr. 2019 Jul 18:7:291. doi: 10.3389/fped.2019.00291. eCollection 2019.

Authors

Sara Debulpaep^{1

2

3}, Véronique Corbière², Jack Levy¹, Petra Schelstraete^{3

4}, Koen Vanden Driessche^{5

6}, Françoise Mascart^{2

7}, Françoise Mouchet¹

Affiliations

¹ Pediatric Department, CHU Saint Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
² Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles, Brussels, Belgium.
³ Pediatric Department, Ghent University Hospital, Ghent, Belgium.
⁴ Division of Pediatric Pulmonology and Infectious Diseases, Pediatric Department, Ghent University Hospital, Ghent, Belgium.
⁵ Division of Pediatric Pulmonology, Pediatric Department, University Hospital Antwerp, Antwerp, Belgium.
⁶ Department of Laboratory Medicine, Radboud University Medical Center, Institute for Molecular Life Sciences, Nijmegen, Netherlands.
⁷ Immunobiology Clinic, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Abstract

Introduction: Interferon Gamma Release Assay (IGRA) has proven to be a useful test to evaluate the immune response to Mycobacterium tuberculosis antigens in children over the age of 5 years as an alternative to tuberculin skin testing (TST). Much less is known about its performance in younger children, who are at higher risk for developing tuberculosis (TB) disease after exposure. We aimed to evaluate the accuracy of using IGRA in TB screening in this population. Methods: Children below the age of 5 years at high risk for TB infection were prospectively enrolled, to compare the performance of TST and the QuantiFERON-TB Gold-In-Tube test (QFT). Children were treated in accordance with the diagnosis made at baseline and followed-up for 12 months. Results: We included a total of 60 children of which 97 blood samples were available for analysis. There was 90.72% agreement between TST and QFT (Kappa test 0.59, moderate agreement). With TST as a reference, the QFT positive predictive value was 0.72 and the negative predictive value 0.93. Discordant results were observed with 6% TST+/QFT- paired tests. When we restricted the comparison of TST and QFT to non-BCG-vaccinated children, the degree of agreement was more substantial (95%, Kappa test 0.75) and the negative predictive value was 0.99. We observed 3% discordant TST-/QFT+ results. All children with active TB disease had concordant positive QFT results, with QFT values above 4.00 IU/ml. Conclusion: In a low TB prevalence country, serial testing of QFT was found to produce a moderate agreement with TST results. False positive QFT results would have been eliminated by using a higher cutoff without misdiagnosing the children with TB disease. Some of the false negative QFT results could be explained by false positive TST results on consecutive testing. For now the most prudent approach would be to consider discordant QFT-/TST+ results as false negative QFT results, taking into account the young age of our population and the potential risk for evolution to active TB disease.

Keywords: QuantiFERON; children; contact screening; interferon gamma release assay; latent tuberculosis infection; tuberculin skin test; tuberculosis.