Combined use of Quantiferon and HBHA-based IGRA supports tuberculosis diagnosis and therapy management in children

Objectives: Interferon- release assays (IGRA) are designed for diagnosis of tuberculosis (TB) infection, and do not discriminate latent TB infection (LTBI) from active TB. Heparin-binding hemagglutinin antigen (HBHA) emerged as a promising antigen for TB diagnosis when used in IGRA format. Aim of this study was to prospectively evaluate the performance of an HBHAbased IGRA to support TB diagnosis and TB therapy monitoring in children with TB infection or active TB disease. Methods: Following clinical, microbiological and radiological assessment, children (0–14 years old) were tested by the QuantiFERON TB-Gold In tube (QFT) assay and an aliquot of wholeblood was stimulated with HBHA and IFN evaluated only in QFT-positive subjects. Results: Among the 550 children tested, 486 (88.4%) scored negative and 64 (11.6%) positive. None of the QFT-negative had active TB. Among the QFT-positive, 45 were with LTBI and 19 active TB. HBHA-IGRA scored positive in 41/45 children (91.1%) with LTBI and in 6/19 active TB children (31.6%) at diagnosis (p=0.001); remarkably, 5 of these 6 children with active TB scoring HBHA-positive were asymptomatic. Moreover, following TB-specific therapy, most of the non-HBHA-responding children, gained an HBHA-positive response. Conclusions: HBHA-based IGRA is a useful support in TB diagnosis and TB-therapy monitoring in children.