Evaluating and Optimizing Quantiferon-TB Gold Plus (QFT-Plus) for Pediatric Tuberculosis (TB) and Latent TB Infection (LTBI) Screening in Northern China's Children With Underlying Health Conditions

Abstract Introduction: Children exhibit heightened susceptibility to tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (MTB) infection. Among the interferon-gamma release assays (IGRAs) recommended by the World Health Organization (WHO) for MTB infection screening is the newly included QuantiFERON-TB Gold Plus (QFT-Plus). This study assesses the implementation and optimization of QFT-Plus at the National Center for Children's Health in Northern China. Methods: We conducted a comprehensive analysis of 52,767 children who underwent IGRA testing at Beijing Children's Hospital from 2019 to 2023. The study compared QFT-Plus with the previous QFT-GIT (the other common whole blood ELISA-based IGRA assays), as well as T cell ELISPOT-based IGRA assays. The cohort included children suspected of having TB and those being screened for latent TB infection (LTBI) with various health conditions. Clinically diagnosed TB and non-TB pneumonia cases were included to ascertain the accuracy of the methods. Additionally, the plasma replacement strategy in QFT-Plus was evaluated for conditions with high indeterminate rates. Results: Among the 1,845 children admitted with suspected TB, tuberculosis ward physicians recorded an average positive rate of 48.7%, compared to 22.3% by physicians from other wards and 19.5% by outpatient clinics, with no significant differences between testing methods. In the age and gender-matched cohort of 50,879 children screened for LTBI, LTBI infection rates increased with age, and there were distinct patterns of positive and indeterminate results for each method. Specific diseases, such as severe pneumonia and Kawasaki disease, showed higher indeterminate rates with QFT-GIT, which were reduced with QFT-PLUS. The sensitivity of IGRAs in 259 confirmed TB cases was 74.3%, and the specificity was 91.5% in 11,387 children with pneumonia. QFT-Plus exhibited greater sensitivity and specificity than QFT-GIT, though it was marginally less effective than ELISPOT. In 202 Kawasaki disease cases utilizing QFT-Plus with plasma replacement, the indeterminate rate dropped from 29.2% to 6.43%, nearly aligning with ELISPOT's detection rate. Conclusion: QFT-Plus, as a new generation ELISA-based method, shows promise in pediatric TB auxiliary diagnosis and LTBI discovery. The study underscores the importance of specialized TB judgment in achieving accurate diagnoses and suggests that the use of lymphocyte culture medium in place of plasma may enhance the effectiveness of ELISA testing, especially in children with conditions that yield high indeterminate rates due to plasma component interference.