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Performance of Tuberculin Skin Tests and Interferon-γ Release Assays in Children Younger Than 5 Years

Velasco-Arnaiz, Eneritz, MD*,†; Soriano-Arandes, Antoni, MD, PhD; Latorre, Irene, PhD§; Altet, Neus, MD, PhD; Domínguez, José, PhD§; Fortuny, Clàudia, MD, PhD*,†,¶,‖; Monsonís, Manuel, MD**; Tebruegge, Marc, MD, MRCPCH, DTM&H, MSc, PhD††,‡‡,§§,¶¶; Noguera-Julian, Antoni, MD, PhD*,†,¶,‖

The Pediatric Infectious Disease Journal: December 2018 - Volume 37 - Issue 12 - p 1235–1241
doi: 10.1097/INF.0000000000002015
Original Studies

Background: Available data to assess the optimal diagnostic approach in infants and preschool children at risk of tuberculosis (TB) are limited.

Methods: We conducted a prospective observational study in children younger than 5 years undergoing assessment with both tuberculin skin tests (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays at 2 tertiary TB units in Barcelona, Spain.

Results: A total of 383 children were included. One of 304 participants considered uninfected developed active TB during follow-up {median [interquartile range (IQR)]: 47 [30; 48] months}, compared with none of 40 participants with latent TB infection [follow-up since completion of anti-TB treatment: 42 (32; 45) months]. Overall test agreement between TST and QFT-GIT was moderate (κ = 0.551), but very good in children screened after TB contact (κ = 0.801) and in Bacillus Calmette-Guérin (BCG)-unvaccinated children (κ = 0.816). Discordant results (16.8%, all TST+/QFT-GIT−) were mainly observed in new-entrant screening and in BCG-vaccinated children. Children with indeterminate QFT-GIT results were on average younger than those with determinate results (median age: 12 vs. 30 months; P < 0.001). The sensitivity of TSTs and QFT-GIT assays in children with confirmed active TB was 100% (95% confidence interval: 79.4%–100%) and 93.7% (95% confidence interval: 69.8%–99.8%), respectively. In patients with latent TB infection or active TB, there was no correlation between age and antigen-stimulated interferon-γ responses (r = −0.044; P = 0.714).

Conclusions: In young BCG-unvaccinated children with recent TB contact, a dual testing strategy using TST and QFT-GIT in parallel may not be necessary. However, TST+/QFT-GIT− discordance is common, and it remains uncertain if this constellation indicates TB infection or not. In active TB, QFT-GIT assays do not perform better than TSTs.

From the *Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Unitat d´Infeccions, Servei de Pediatria, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain

Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain

Institut Català de la Salut, Unitat de Tuberculosi Hospital Universitari Vall d’Hebrón-Drassanes, Barcelona, Spain

§Institut d’Investigació Germans Trias i Pujol, CIBER Enfermedades Respiratorias, Universitat Autònoma de Barcelona, Barcelona, Spain

CIBER de Epidemiología y Salud Pública, CIBERESP, Madrid, Spain

Red de Investigación Translacional en Infectología Pediátrica, RITIP, Madrid, Spain

**Servei de Microbiologia, Hospital Sant Joan de Déu, Barcelona, Spain

††Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine & Global Health Research Institute, University of Southampton, Southampton, United Kingdom

‡‡Department of Paediatric Infectious Diseases & Immunology, Evelina London Children’s Hospital, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom

§§Great Ormond Street Hospital Institute of Child Health, University College London, London, United Kingdom

¶¶Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.

Accepted for publication January 8, 2018.

The authors Tebruegge and Noguera-Julian share credit for senior authorship.

J.D. is funded by the Miguel Servet program of the Instituto de Salud Carlos III (Spain). This research was partially supported by different grants from the Instituto de Salud Carlos III (PI 13/01546, PI 13/01740 and ICI14/00228), integrated in the Plan Nacional de I+D+I and cofunded by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). Dr. Tebruegge was supported by a Clinical Lectureship provided by the UK National Institute for Health Research and funding provided by the Technology Strategy Board/Innovate U.K.

M.T. has received QuantiFERON-TB Gold assays at reduced cost for related research projects from the manufacturer (Cellestis/Qiagen). The manufacturer had no influence on the study design, data interpretation, writing of the manuscript or decision to submit the data for publication. The other authors have no potential conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Antoni Noguera-Julian, MD, PhD, Passeig de Sant Joan de Déu 2, 08950 Esplugues de Llobregat, Barcelona, Spain. E-mail: ton@sjdhospitalbarcelona.org.

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