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Updated: Jun 1, 2026
An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis
Published on: August 16, 2021
Interferon-gamma release assays and childhood tuberculosis: systematic review and meta-analysis
A M Mandalakas1, A K Detjen, A C Hesseling
1Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA. anna.mandalakas@case.edu
Insights
Interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) show similar accuracy in diagnosing tuberculosis (TB) infection and disease in children. Further research with standardized methods is needed for reliable TB diagnostics in pediatric populations.
Area of Science:
- Pediatric infectious diseases
- Diagnostic test evaluation
- Mycobacterium tuberculosis research
Background:
- Children with Mycobacterium tuberculosis infection face a high risk of developing active tuberculosis (TB).
- Preventive therapy is crucial for children at risk of TB.
- Accurate diagnostic tools are essential for timely intervention.
Purpose of the Study:
- To evaluate the diagnostic value of Interferon-Gamma Release Assays (IGRAs) and the Tuberculin Skin Test (TST) in children.
- To compare the performance of IGRAs (QuantiFERON®-TB and T-SPOT.®TB) and TST for TB infection and disease diagnosis in pediatric populations.
Main Methods:
- Systematic review and meta-analysis of 33 studies.
- Inclusion of commercial IGRA tests (QFT, T-SPOT.®TB) and TST.
- Evaluation of test performance against reference standards for TB infection (incident TB, TB exposure) and disease (confirmed/clinically diagnosed TB).
Main Results:
- IGRAs and TST demonstrated similar sensitivity and specificity in diagnosing active TB disease in children.
- Positive predictive value for QFT was weak in two small studies assessing incident TB.
- Test response to TB exposure was comparable across all evaluated tests.
- Lower sensitivity was observed for all tests in younger children and those with HIV infection.
Conclusions:
- Current data indicate comparable accuracy between TST and IGRAs for detecting TB infection and diagnosing TB disease in children.
- Methodological heterogeneity across studies limited direct comparison and interpretation of results.
- There is a critical need for rigorous, standardized evaluations of TB diagnostic tests specifically designed for children.
Background:
Children infected with Mycobacterium tuberculosis have significant risk of developing tuberculosis(TB) and can therefore benefit from preventive therapy.
Objective:
To assess the value of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST)in the diagnosis of TB infection and disease in children.
Methods:
Thirty-three studies were included, assessing commercial IGRAs (QuantiFERON®-TB [QFT] andT-SPOT.®TB) and TST. Reference standards for infection were incident TB or TB exposure. Test performance for disease diagnosis was evaluated in studies assessing children with confirmed and/or clinically diagnosed TB,compared to children where TB was excluded.
Results:
Two small studies measured incident TB in children tested with QFT and found weak positive predictive value. Association of test response with exposure-categorized dichotomously or as a gradient-was similar for all tests. The sensitivity and specificity of all tests were similar in diagnosing the disease. Stratified analysis suggested lower sensitivity for all tests in young or human immuno deficiency virus infected children.
Conclusions:
Available data suggest that TST and IGRAs have similar accuracy for the detection of TB infection or the diagnosis of disease in children. Heterogeneous methodology limited the comparability of studies and the interpretation of results. A rigorous, standardized approach to evaluate TB diagnostic tests in children is needed.
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