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The Utility of an Interferon Gamma Release Assay for Diagnosis of Latent Tuberculosis Infection and Disease in Children: A Systematic Review and Meta-analysis

Machingaidze, Shingai BSc*†; Wiysonge, Charles Shey MD*†; Gonzalez-Angulo, Yulieth BSc*†; Hatherill, Mark MD*†; Moyo, Sizulu MB ChB; Hanekom, Willem FCP (Paed)*†; Mahomed, Hassan MMed*†

The Pediatric Infectious Disease Journal: August 2011 - Volume 30 - Issue 8 - p 694-700
doi: 10.1097/INF.0b013e318214b915
Review Article

Background: The utility of interferon gamma release assays (IGRAs) has been assessed in adults, but remains unclear in children. We reviewed the literature on the use of a commercial IGRA in immunocompetent children for the diagnosis of both latent tuberculosis infection (LTBI) and TB disease.

Methods: We searched PubMed for studies published before January 2010 on the diagnosis of TB in children using an IGRA. We compared the specificity and sensitivity of the tuberculin skin test (TST) and the IGRA for LTBI and conducted a random effects meta-analysis on sensitivity of the IGRA for TB disease.

Results: Of 68 studies identified, 20 were included in this review. There was increased specificity of the IGRA for LTBI in children compared with TST, but varying sensitivities. Sensitivity of the IGRA in detecting TB disease in children also varied when compared with TST (mean κ score, 0.57). For all TB cases, the pooled sensitivity was 66% (95% confidence interval [CI], 53%–78%) with heterogeneity (I 2 = 74.8%). Stratification by background TB incidence highlighted a significantly reduced IGRA sensitivity of 55% (95% CI, 37%–73%) in high incidence settings when compared with low incidence settings, 70% (95% CI, 53%–84%).

Conclusions: There was no clear evidence that IGRAs should replace TST for detecting LTBI in children. Sensitivity of the IGRA for TB disease was no different from TST, and a significantly reduced IGRA sensitivity was found in high-burden TB settings compared with low-burden TB settings. Further studies are needed to determine the value of IGRAs in LTBI and TB disease diagnosis in children.


From the *South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; and †School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.

Accepted for publication February 8, 2011.

Supported by the South African TB Vaccine Initiative (SATVI) (to S. Machingaidze) for the Master's in Public Health (Epidemiology and Biostatistics) at the University of Cape Town.

Address for correspondence: Hassan Mahomed, MMed, South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IIDMM), Room N2.10, Wernher and Beit North, Faculty of Health Sciences, University of Cape Town, Anzio Rd, Observatory, 7925, Cape Town, South Africa. E-mail:

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© 2011 by Lippincott Williams & Wilkins, Inc.