Michela Sali1, Danilo Buonsenso2, Pamela D'Alfonso1, Flavio De Maio1, Manuela Ceccarelli2, Basem Battah1, Ivana Palucci1, Teresa Chiacchio3, Delia Goletti3, Maurizio Sanguinetti1, Piero Valentini4, Giovanni Delogu1. 1. Institute of Microbiology, Università Cattolica del Sacro Cuore - Fondazione Policlinico Universitario Gemelli, Rome, Italy. 2. Institute of Pediatrics, Università Cattolica del Sacro Cuore - Fondazione Policlinico Universitario Gemelli, Rome, Italy. 3. Translational Research Unit, Epidemiology and Preclinical Research Department, National Institute for Infectious Diseases, IRCCS "Lazzaro Spallanzani", Rome, Italy. 4. Institute of Pediatrics, Università Cattolica del Sacro Cuore - Fondazione Policlinico Universitario Gemelli, Rome, Italy. Electronic address: piero.valentini@unicatt.it.
Abstract
OBJECTIVES: Interferon-γ 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 HBHA-based 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 whole-blood was stimulated with HBHA and IFNγ 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.
OBJECTIVES: Interferon-γ 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 HBHA-based 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 whole-blood was stimulated with HBHA and IFNγ 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.
Authors: Portia M Manngo; Andrea Gutschmidt; Candice I Snyders; Hygon Mutavhatsindi; Charles M Manyelo; Nonjabulo S Makhoba; Petri Ahlers; Andriette Hiemstra; Kim Stanley; Shirley McAnda; Martin Kidd; Stephanus T Malherbe; Gerhard Walzl; Novel N Chegou Journal: J Infect Date: 2019-07-15 Impact factor: 6.072
Authors: Noëmi R Meier; Thomas Volken; Marc Geiger; Ulrich Heininger; Marc Tebruegge; Nicole Ritz Journal: Front Pediatr Date: 2019-05-29 Impact factor: 3.418
Authors: Eva L Sudbury; Larissa Otero; Marc Tebruegge; Nicole L Messina; Carlos Seas; Martin Montes; Julia Rìos; Susie Germano; Kaya Gardiner; Vanessa Clifford; Eduardo Gotuzzo; Nigel Curtis Journal: J Clin Tuberc Other Mycobact Dis Date: 2019-04-25