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

J Infect. 2018 Dec;77(6):526-533. doi: 10.1016/j.jinf.2018.09.011. Epub 2018 Sep 26.

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.

Keywords: Biomarkers; Children; HBHA; IGRA; Monitoring of therapy; Quantiferon; Tuberculosis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Disease Management*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Interferon-gamma / blood*
  • Interferon-gamma Release Tests*
  • Italy
  • Latent Tuberculosis / diagnosis*
  • Latent Tuberculosis / drug therapy
  • Lectins / isolation & purification*
  • Male
  • Mycobacterium tuberculosis
  • Prospective Studies
  • Tuberculin Test
  • Tuberculosis / diagnosis*
  • Tuberculosis / drug therapy*

Substances

  • Biomarkers
  • Lectins
  • heparin-binding hemagglutinin
  • Interferon-gamma