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This review summarizes studies evaluating the performance of the QuantiFERON-TB Gold Plus (QFT-Plus) interferon-gamma release assay (IGRA) test for Mycobacterium tuberculosis(Mtb) infection in children. Literature searching was conducted using PubMed, MEDLINE and Embase (January 2017 to December 2021) and the terms “children” or “pediatric” and “IGRAs” or “QuantiFERON-TB Gold Plus.” Selected studies (N = 14; 4646 subjects) enrolled children with Mtbinfection, tuberculosis (TB) disease or healthy children with household TB contacts. Agreement between QFT-Plus and tuberculin skin test (TST) (kappa values) ranged from –0.201 (no agreement) to 0.83 (almost perfect agreement). Assay sensitivity of QFT-Plus (against reference standard of microbiologically confirmed TB disease) was 54.5%–87.3%, with no reported difference in children less than 5 versus greater than or equal to 5 years of age. In individuals less than or equal to 18 years of age, the rate of indeterminate results was 0%–33.3% (2.6% in children <2 years). IGRAs may overcome the limitations of TST in young, Bacillus Calmette–Guérin-vaccinated children.

There are growing evidence of clinical manifestations other than acute respiratory syndrome in severe acute respiratory syndrome associated with coronavirus 2-infected children. In our multicenter retrospective analysis, we observed among 127 severe acute respiratory syndrome associated with coronavirus 2 positive children that the presence of gastrointestinal symptoms was more frequently associated with severe and critical phenotype (P= 0.029). Moreover, having gastrointestinal symptoms was more frequently reported in patients who developed cardiac impairment.

QuantiFERON-TB Gold In-Tube (QFT-GIT, Qiagen, Hilden, Germany) is an interferon-γ (IFN-γ) release assay designed to detect latent tuberculosis infection (LTBI). Although QFT-GIT has several advantages (mainly that it is not affected by the Bacille Calmette–Guérin vaccination), it has a poor sensitivity in immune-compromised individuals as it involves an immune response-based detection. Recently, QuantiFERON-TB Gold Plus (QFT-Plus) assay has been proposed as a new generation of QFT-GIT. QFT-Plus includes two tubes, TB1 and TB2 with Mycobacterium tuberculosisantigens to elicit a specific immune response. TB1 contains peptides derived from the antigens 6kDa early secretory antigenic target (ESAT-6) and 10kDa culture filtrate protein (CFP-10) (TB-7.7, present in QFT-GIT, has been removed), and it is designed to induce a specific CD4 T-cell response. TB2 contains newly designed peptides stimulating IFN-γ production by both CD4 and CD8 T cells. The additional peptides for eliciting CD8 T-cell responses have been included to increase the sensitivity of the test for LTBI detection.