Performance of the Interferon Gamma Release Assays in Tuberculosis Disease in Children Five Years Old or Less.

Lin Sun,Jing Xiao,Jian-Ling Tian,Wei-Wei Jiao,Qing-Qin Yin,Fang Xu,Hui Qi,Jie-Qiong Li,Guo-Shuang Feng,A-Dong Shen,Chen Shen,Xiao-Xia Peng,Ya-Jie Guo,José-María García-García

doi:10.1371/journal.pone.0143820

Lin Sun, Jing Xiao + Show 12 more

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https://doi.org/10.1371/journal.pone.0143820

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Abstract

Interferon Gamma Release Assays (IGRAs) were developed for the indirect or immunologic diagnosis of tuberculosis infection; however, they have also been used to assist in difficult to diagnose cases of tuberculosis disease in adults, and to a lesser extent, in children, especially in those under 5 years old. We evaluated the utility of using an IGRA in pediatric tuberculosis in younger children in a hospital setting. The diagnostic accuracy of T-SPOT.TB and TST was assessed in 117 children with active tuberculosis and 413 children with respiratory tract infection. Sensitivity and specificity were calculated for the tests used individually and together. Concordance was also calculated. Sensitivity of T-SPOT.TB (82.9%) was higher than TST (78.6% using a 5mm cut-off), especially in children confirmed to have TB. T-SPOT.TB was more specific than TST using a 5mm cut-off (96.1% vs. 70.9%). Combining T-SPOT.TB and TST results improved the sensitivity to 96.6%. In conclusion, the results of the current study indicate that T-SPOT.TB has good sensitivity and specificity, supporting its use among patients of this age. A combination of IGRA and TST would be useful additions to assist in the diagnosis of childhood TB.

Highlights

And accurate diagnosis of tuberculosis (TB) disease in children must be given a high priority by medical practitioners for the following reasons: children carry 6% of the global burden of TB disease[1]; in 2002 around 9% of children in China were reported to be infected with Mycobacterium tuberculosis (MTB)[2]; children under 5 years old are more likely to develop the most severe forms of disseminated and meningeal TB [3], which is due to the immature immune system [4,5]
117 were classified as having active TB, and 413 children were diagnosed as having respiratory tract infection (RTI)
One study which enrolled children with TB aged under 5 years old in a community setting, reported that T-SPOT.TB had a lower sensitivity than in older children[15], while Critselis reported that the accuracy of Interferon gamma release assays (IGRAs) is not affected by age[9]

Summary

Introduction

And accurate diagnosis of tuberculosis (TB) disease in children must be given a high priority by medical practitioners for the following reasons: children carry 6% of the global burden of TB disease[1]; in 2002 around 9% of children in China were reported to be infected with Mycobacterium tuberculosis (MTB)[2]; children under 5 years old are more likely to develop the most severe forms of disseminated and meningeal TB [3], which is due to the immature immune system [4,5].PLOS ONE | DOI:10.1371/journal.pone.0143820 December 7, 2015IGRAs and Pediatric Tuberculosis Diagnosisdiagnosis of pediatric TB is challenging because symptoms are often non-specific, specimens may be difficult to obtain, and bacteriological confirmation is less frequent than in adults[6]. Children younger than 5 are more likely to have severe extra-pulmonary TB while the most severe cases of TB are often seen in infants[7]. For these reasons, diagnosing TB in young infants warrants additional efforts. Few studies have investigated their use in young children and infants[8,9,10]. Guidelines from the American Academy of Pediatrics state that IGRAs are not recommended for routine use in children younger than five years of age due to a lack of published data[11]

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