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RESEARCH ARTICLE

Interferon gamma release assay in diagnosis of pediatric tuberculosis: a meta-analysis Lin Sun, Jing Xiao, Qing Miao, Wei-xing Feng, Xi-rong Wu, Qing-qin Yin, Wei-wei Jiao, Chen Shen, Fang Liu, Dan Shen & A-dong Shen

IMMUNOLOGY & MEDICAL MICROBIOLOGY

National Key Discipline of Pediatrics, (Capital Medical University), Ministry of Education, Key Laboratory of Major Diseases in Children, (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Beijing, China

Correspondence: A-dong Shen, Beijing Pediatric Institute, Beijing Children’s Hospital affiliated to Capital Medical University, 56 Nan Li Shi Road, Xi Cheng District, Beijing 100045, China. Tel.: +8610 59718655; fax: +8610 59718662; e-mail: shenad16@hotmail.com Received 24 March 2011; revised 15 June 2011; accepted 28 June 2011. Final version published online 23 August 2011. DOI: 10.1111/j.1574-695X.2011.00838.x Editor: Patrick Brennan Keywords meta-analysis; interferon gamma; diagnosis; tuberculosis; children.

Abstract Although interferon gamma release assays (IGRAs) have been widely used for the diagnosis of latent and active tuberculosis in adults, a relative lack of validation studies in children has led to caution in their clinical interpretation. This meta-analysis systematically evaluated two IGRAs (ELISA and ELISPOT) and the tuberculin skin test (TST). We searched databases (PubMed, MEDLINE, Ovid) between January 2000 and January 2011 using search terms of latent tuberculosis infection or tuberculosis and interferon gamma release assay, or T-SPOT.TB test, or QuantiFERON-TB Gold, or ESAT-6, or CFP-10, and child, or childhood, or pediatrics. We also collected data by performing a manual search of references from relevant articles and communicating with selected authors. The meta-analysis was conducted with random effects models to account for heterogeneity between selected studies. The sensitivities of all three tests in active tuberculosis were similar. The pooled sensitivity was 70% for ELISA studies, 62% for ELISPOT studies and 71% for TST. Calculated sensitivities for IGRAs and the TST differ in culture-confirmed tuberculosis [ELISA (85%) vs. ELISPOT (76%) vs. TST (85%)] and clinical diagnosed cases [ELISA (64%) vs. ELISPOT (58%) vs. TST (66%)]. The pooled specificity was 100% for ELISA and 90% for ELISPOT, but was much lower for TST [56% in all included studies and 49% in children with bacillus Calmette-Guerin (BCG) vaccination]. The agreement between the TST and IGRAs in non-BCG-vaccinated children is higher than that in BCG-vaccinated children. In the diagnosis of active tuberculosis in children, the TST and IGRAs have similar sensitivity. By contrast, the specificity of IGRAs is far greater than the TST, particularly in children with previous BCG vaccination.

Introduction Childhood tuberculosis is commonly extra-pulmonary, disseminated and severe, especially in children under 3 years of age, and is associated with high morbidity and mortality (Marais et al., 2006). In children, diagnosis of tuberculosis is complicated by its pauci-bacillary nature, resulting in atypical clinical signs and a lower probability of bacteriological confirmation (Rigouts, 2009). Currently, the diagnosis of latent tuberculosis infection (LTBI) is hindered by the lack of a ‘gold standard’. The tuberculin FEMS Immunol Med Microbiol 63 (2011) 165–173

skin test (TST) was until recently the main method of detecting Mycobacterium tuberculosis infection and in diagnosing active tuberculosis. The TST uses a poorly defined mix of antigens from M. tuberculosis resulting in false-positive responses because of nontuberculous mycobacteria (NTM) infection or previous bacillus CalmetteGuerin (BCG) vaccination. False-negative TST results can occur when children suffer from severe active tuberculosis or immune suppression. Therefore, alternative diagnostic tools for the detection of tuberculosis have been explored. The interferon ª 2011 Federation of European Microbiological Societies Published by Blackwell Publishing Ltd. All rights reserved


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