Commercially available CD4 + and CD8 + IFN-γ release assays combined with an HBHA-induced IGRA improve the characterization of the tuberculosis spectrum and monitoring of treatment in children

Abstract

Commercially available Interferon-γ release assays (IGRAs), including the last-generation QuantiFERON TB-Plus (QFT-Plus), are effective in aiding the diagnosis of tuberculosis (TB) infection but cannot distinguish latent TB subjects from active TB patients. The aim of this study was to prospectively evaluate the performance of an HBHA-based IGRA, combined with commercially available IGRAs, to assess their usefulness as a prognostic biomarkers and aid in the monitoring of TB treatment in children. Following clinical, microbiological, and radiological assessment, children younger than 18 years of age classified as either LTBI or active TB were tested at baseline and during treatment by the QuantiFERON TB-Plus (QFT) assay and an aliquot of whole-blood was stimulated with HBHA. Among the 655 children evaluated, 559 (85.3%) were classified as “Non TB”, 44 patients (6.7%) with active TB, and 52 (7.9%) with LTBI. The median HBHA-IGRA IFN-gamma responses were able to discriminate active TB from LTBI (0.13 IU/ml vs 1.995, (p < 0,0001), those with asymptomatic TB from those with symptomatic TB (1.01 IU/ml vs 0.115 IU/ml, p 0.017), or more severe TB (p 0.022), and significantly raised during successful TB treatment (p < 0.0001). Conversely, CD4 + and CD8 + responses were similar in all groups of patients, although active TB patients had higher CD4 + responses and LTBI higher CD8 + responses. Conclusion: HBHA-based IGRA, combined with CD4 + and CD8 + responses assessed by commercially available IGRAs, is a useful support in the characterization of the TB spectrum in children and monitoring of TB-therapy. What is Known:• Current immune diagnostics are not able to discriminate active and latent Ttuberculosis, including the recently approved QFT-PLUS..• New immunological assays with prognostic value are highly needed. What is New:• HBHA-based IGRA, combined with CD4+ and CD8+ responses assessed by commercially available IGRAs, is a useful support for the differentiation of active and latent TB in children..• HBHA-based IGRA, combined with CD4+ and CD8+ responses assessed by commercially available IGRAs, is a useful support in the monitoring of TBtherapy in children..

Monocyte‐to‐lymphocyte, neutrophil‐to‐lymphocyte and neutrophil‐to‐monocyte plus lymphocyte ratios in children with active tuberculosis: A multicentre study

“…Since children are more likely than adults to progress to active disease and develop life‐threatening forms of TB, 4,5 early detection and treatment of latent TB infection (LTBI) is crucial to prevent the development of the overt disease. Therefore, there is an urgent need of new biomarkers with prognostic for the diagnosis of TB and to monitor the efficacy of appropriate treatment 6 …”

“…Therefore, there is an urgent need of new biomarkers with prognostic for the diagnosis of TB and to monitor the efficacy of appropriate treatment. 6 The diagnostic potential of monocyte-to-lymphocyte ratio (MLR) in the management of TB has been suggested many decades ago. In the 1920s, two different studies 7,8 conducted on rabbits and children demonstrated that increased monocytes and decreased lymphocytes counts, resulting in increased monocyte-to-lymphocyte ratios (MLR), were associated with active TB.…”

“…Overall, these tests did not significantly differ among the groups. IGRAs were similarly positive in children with active TB and LTBI, as expected 6,21. CRP was similar in children with active TB or other infections.…”