title: Performance of interferon-γ release assays in the diagnosis of confirmed active tuberculosis in immunocompetent children: a new systematic review and meta-analysis.
abstract: BACKGROUND
  Tuberculosis (TB) is a global public health problem, causing morbidity and mortality in adults and children. The most reliable diagnostic tools currently available are the in vivo Tuberculin Skin Test (TST) and the ex vivo Interferon-γ release assays (IGRAs). Several clinical, radiological, and bacteriological features make the detection of active (overt disease) TB in children difficult. Although recently developed immunological assays such as QuantiFERON-TB Gold In-Tube (QFT-IT) and T-SPOT®.TB are commonly used to identify active TB in adults, different evidence is required for diagnosis in children. The purpose of this study was to reassess the sensitivity and specificity of IGRAs in detecting microbiologically confirmed active TB in immunocompetent children.
  
  
  METHODS
  A systematic review and meta-analysis of studies reporting on the diagnostic accuracy of tests for TB in immunocompetent children aged 0-18 years, with confirmation by positive M. tuberculosis cultures, were undertaken. Electronic databases were searched up to September 2015 and study quality assessment was performed using QUADAS-2.
  
  
  RESULTS
  Fifteen studies were included in our meta-analysis. Results showed that there were no significant differences in sensitivity between TST (88.2%, 95% confidence interval [CI] 79.4-94.2%), QFT-IT (89.6%, 95% CI 79.7-95.7%) and T SPOT (88.5%, 95% CI 80.4-94.1%). However, both QFT-IT (95.4%, 95% CI 93.8-96.6%) and T-SPOT (96.8%, 95% CI 94.2-98.5%) have significantly higher specificity than TST (86.3%, 95% CI 83.9-88.6%).
  
  
  CONCLUSIONS
  QFT-IT and T-SPOT have higher specificity than TST for detecting active TB cases in immunocompetent children.
authors.affiliation: Institute of Public Health - Section of Hygiene, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1-00168, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Laurenti
authors.affiliation: Institute of Public Health - Section of Hygiene, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1-00168, Rome, Italy. matteoraponi85@gmail.com.
authors.forename: Matteo
authors.initials: M
authors.lastname: Raponi
authors.affiliation: Institute of Public Health - Section of Hygiene, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1-00168, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: de Waure
authors.affiliation: Institute of Public Health - Section of Hygiene, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1-00168, Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Marino
authors.affiliation: Institute of Public Health - Section of Hygiene, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1-00168, Rome, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Ricciardi
authors.affiliation: Institute of Public Health - Section of Hygiene, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1-00168, Rome, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Damiani
mesh_terms: D002648:Child; D002662:Child Health Services; D006801:Humans; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000097:blood*; D059425:Interferon-gamma Release Tests / Q000592:standards*; D012680:Sensitivity and Specificity; D014374:Tuberculin Test / Q000379:methods; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*
chemical_list: D007371:Interferon-gamma
keywords: Active tuberculosis; Children; Diagnosis; IGRAs; Meta-analysis; QuantiFERON-TB Gold In-Tube; T-SPOT.TB; Tuberculin skin test