title: Performance of interferon-γ release assay for the diagnosis of active or latent tuberculosis in children in the first 2 years of age: a multicenter study of the Italian Society of Pediatric Infectious Diseases.
abstract: BACKGROUND
  The diagnosis of latent or active tuberculosis in children is often challenging. Recently, interferon-γ release assays have been licensed, but their diagnostic accuracy in young children remains questionable as frequent false-negative or indeterminate results have been reported.
  
  
  METHODS
  We performed a multicenter, retrospective study in children 0-24 months of age who were tested at least once with QuantiFERON-TB Gold-in-tube (QTF-IT) ± tuberculin skin test (TST), to analyze its use and performance in clinical practice.
  
  
  RESULTS
  Eight-hundred and twenty-three children (449 males, median age 13.5 months) were enrolled. QTF-IT sensitivity and specificity for active tuberculosis were 92.4% and 98.6%, respectively. Indeterminate tests (4.2 %) were not related to age (P = 0.838) or gender (P = 0.223); 32 children (91.4 %) with an indeterminate QTF-IT ultimately resulted uninfected. In the 616 subjects with valid paired results of QTF-IT and TST, sensitivity and specificity were comparable (91.1% vs. 85.1% and 98.1% vs. 97.9%, respectively). Diagnostic concordance between tests was higher in Bacillus Calmétte-Guerin nonvaccinated children (κ = 0.802). A high rate of discordant tests was observed in latent infections.
  
  
  CONCLUSIONS
  QTF-IT showed good sensitivity and specificity, and a low rate of indeterminate results in the first 2 years of life, supporting its use at this age. However, considering costs and the similar performance between QTF-IT and TST, it is reasonable to suggest the latter as first-line testing in young children. The complementary use of TST and interferon-γ release assays may be considered in selected cases to improve the accuracy of testing.
authors.affiliation: From the *Department of Pediatrics, University of Turin, AOU Città della Salute e della Scienza, Regina Margherita Children's Hospital, Turin; †Department of Health Sciences, University of Florence, Anna Meyer Children's University Hospital, Florence; ‡Department of Pediatrics, University of Modena and Reggio Emilia, Modena; §Department of Pediatrics, University of Bologna, S. Orsola-Malpighi General Hospital, Bologna; ¶Unit of Microbiology, Department DIMES, University of Bologna, S. Orsola-Malpighi General Hospital, Bologna; ‖Pietro Barilla Children's Hospital, Parma; **Pediatrics and Infectious Diseases, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome; and ††Pediatric Clinic 1, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Garazzino
authors.forename: Luisa
authors.initials: L
authors.lastname: Galli
authors.forename: Elena
authors.initials: E
authors.lastname: Chiappini
authors.forename: Michele
authors.initials: M
authors.lastname: Pinon
authors.forename: Barbara Maria
authors.initials: BM
authors.lastname: Bergamini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cazzato
authors.forename: Paola
authors.initials: P
authors.lastname: Dal Monte
authors.forename: Icilio
authors.initials: I
authors.lastname: Dodi
authors.forename: Laura
authors.initials: L
authors.lastname: Lancella
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Iughetti
authors.forename: Carlotta
authors.initials: C
authors.lastname: Montagnani
authors.forename: Maurizio
authors.initials: M
authors.lastname: De Martino
authors.forename: Pier-Angelo
authors.initials: PA
authors.lastname: Tovo
mesh_terms: D001500:BCG Vaccine; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D059425:Interferon-gamma Release Tests; D007558:Italy; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012955:Societies, Medical; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology
chemical_list: D001500:BCG Vaccine