Tuberculosis (TB) is one of the most important global public health problems and a major cause of morbidity and mortality in adults and children worldwide. Of the 10.6 million TB cases registered in 2021, approximately 1.2 million TB cases (11 %, bacteriologically confirmed or clinically diagnosed) occurred in children under 15 years of age. Of the 1.4 million TB-related deaths among HIV-negative individuals, 196,000 (approximately 14 %) occurred in HIV-negative children [1].

The latest American Thoracic Society, Infectious Diseases Society of America, and U.S. Centers for Disease Control and Prevention guidelines suggest mycobacterial culture of respiratory specimens for all children suspected of having pulmonary TB (PTB) [2]. However, the diagnosis of TB by culture remains difficult for children. Hatherill et al. reported a crude yield of TB of 10.4 % (194 culture confirmed cases), with 5.8 % by induced sputum and 6.8 % from gastric lavage [3]. Additionally, several clinical, radiological, and bacteriological features (atypical clinical signs or a low probability of bacteriological confirmation) can make the detection of active TB in children more challenging [4].

The reliable methods that are currently available for detecting TB infection are the in vivo tuberculin skin test (TST) and ex vivo interferon-gamma (IFN-γ) release assays (IGRAs). The TST has been a widely used method for diagnosing TB for more than 100 years and detects the immune response to Mycobacterium tuberculosis antigens. However, several limitations of this test exist because false-negative TST results may occur due to immunologic immaturity caused by age and/or malnutrition, disease severity, immunodeficiency, or false-positive results due to cross-reactivity with infection of mycobacteria other than M. tuberculosis complex. Other mycobacteria may include M. avium complex, the major pathogen causing non-TB mycobacteriosis, or the Bacillus Calmette-Guérin (BCG) vaccination [5]. IGRAs, which were developed more than 30 years ago as alternatives to the TST, utilize two major methods: enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot (ELISPOT) assay. For example, by utilizing ELISA, QuantiFERON-TB Gold (QFT-2G; Qiagen) and QuantiFERON-TB Gold In-Tube (QFT-3G; Qiagen) have been used to measure the concentration of IFN-γ in whole blood [6,7], and QuantiFERON-TB Gold Plus (QFT-4G; Cellestis/Qiagen) is currently available. T-SPOT evaluates the number of individual Mycobacterium-specific T cells secreting IFN-γ by the ELISPOT assay (T-SPOT) [8]. IGRAs are considered superior to TST, regarding its lack of cross-reactivity with M. avium complex infection and Bacillus Calmette-Guérin (BCG) vaccination. However, IGRAs also have several limitations, including false-negative results due to immunologic immaturity caused by age, malnutrition, disease severity, or immunodeficiency, and false-positive results due to cross-reactivity with infections other than M. tuberculosis complex, such as M. kansasii and M. marinum.

To the best of our knowledge, in the most recent systematic review and meta-analysis on the diagnostic accuracy of IGRAs in PTB confirmed by M. tuberculosis culture in immunocompetent children ≤18 years of age, the sensitivities of QFT-IT versus T-SPOT were reported as 89.6 vs. 88.5 % and the specificities as 95.4 vs. 96.8 %, respectively [9]. However, the previous report included only 15 studies in which both TST and IGRAs (QFT and/or T-SPOT) were performed. Therefore, some published data on IGRA accuracy were excluded. Additionally, new studies on the accuracy of IGRAs have been published since that systematic review and meta-analysis. Therefore, the current systematic review and meta-analysis aimed to evaluate the accuracy of IGRAs in the diagnosis of TB in children.