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Interferon-gamma release assays and childhood tuberculosis: systematic review and meta-analysis [Review article]

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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] and T-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 immunodeficiency 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.

Keywords: IGRAs; TB infection; pediatrics; tuberculin skin test; tuberculosis

Document Type: Review Article

Affiliations: 1: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA; Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa 2: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa; International Union Against Tuberculosis and Lung Disease, New York, New York, USA 3: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa 4: Respiratory and Epidemiology Clinical Research Unit, Montreal Chest Institute, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Quebec, Canada 5: Respiratory and Epidemiology Clinical Research Unit, Montreal Chest Institute, Montreal, Quebec, Canada

Publication date: 01 August 2011

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  • The International Journal of Tuberculosis and Lung Disease (IJTLD) is for clinical research and epidemiological studies on lung health, including articles on TB, TB-HIV and respiratory diseases such as COVID-19, asthma, COPD, child lung health and the hazards of tobacco and air pollution. Individuals and institutes can subscribe to the IJTLD online or in print – simply email us at [email protected] for details.

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