Performance of interferon-γ release assays in the diagnosis of confirmed active tuberculosis in immunocompetent children: a new systematic review and meta-analysis

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-gamma 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 (R).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.