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

Abstract

BackgroundTuberculosis (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.MethodsA 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.ResultsFifteen 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 %).ConclusionsQFT-IT and T-SPOT have higher specificity than TST for detecting active TB cases in immunocompetent children.

QuantiFERON-TB Performs Better in Children, Including Infants, than in Adults with Active Tuberculosis: a Multicenter Study

“…We showed that the overall QFT-IT sensitivity in children with bacteriologically confirmed TB was significantly higher than that in adults (97.6% versus 81.0%), regardless of disease localization. Our results are in agreement with the systematic review and meta-analysis conducted by Laurenti et al, in which the QFT-IT performance in immunocompetent children with TB was 89.6% (95% CI, 79.7 to 95.7%) (26).…”

Quantitative Analysis of Gamma Interferon Release Assay Response in Children with Latent and Active Tuberculosis

“…Evaluation of IGRA performance in children remains limited due to small study sizes, resistance to phlebotomy, and difficulty in obtaining culture-confirmed results for reference (32). Sensitivity and specificity have been assessed in studies using either culture-confirmed cases or an exposure gradient as a surrogate for infection, but outcomes as well as proportion of indeterminate results are discordant, particularly in infants under 5 years (19,20,33,34). In our previous report, we showed good sensitivity (93.3%) and specificity (99.3%) of QFT-IT in comparison with TST for diagnosis of active TB (23).…”

“…IGRAs are not only tools for diagnosing LTBI but could be also used to integrate algorithms for active TB diagnosis. However, the routine use of IGRAs has not yet been extensively approved in children, due to concerns about their immature immune systems and discrepant results reported in different studies (15)(16)(17)(18)(19)(20).…”

Evaluating UK National Guidance for Screening of Children for Tuberculosis. A Prospective Multicenter Study

“…However, there has been much debate on which screening tools to use, especially for children. [11][12][13] In 2006, the National Institute for Health and Care Excellence (NICE) in the United Kingdom (UK) issued guidelines for the screening of those exposed to TB, which, for the first time, introduced interferon-gamma release assays (IGRA), a then novel bloodbased assay, into the screening algorithm. 14 Up until that point testing for evidence of sensitisation to M. tuberculosis had been via the tuberculin skin test (TST).…”