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

Sali, Michela; Buonsenso, Danilo; D’Alfonso, Pamela; Maio, Flavio De; Ceccarelli, Manuela; Battah, Basem; Palucci, Ivana; Chiacchio, Teresa; Goletti, Delia; Sanguinetti, Maurizio; Valentini, Piero; Delogu, Giovanni

doi:10.1016/j.jinf.2018.09.011

Cited by 33 publications

(34 citation statements)

References 46 publications

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“…Sali et al was able to show that combined use of the QuantiFeronGold ® with a heparin-binding hemagglutinin antigen (HBHA)-based IGRA helped to differentiate Quantiferon-positive children with LTBI from those with aTB (25). While further validation on larger cohorts of MTB-infected children will be necessary to describe the potential of this method for treatment monitoring, issues in identifying asymptomatic children with aTB appears to be its main disadvantage.…”

Section: Discussion/conclusionmentioning

confidence: 99%

The TAM-TB Assay—A Promising TB Immune-Diagnostic Test With a Potential for Treatment Monitoring

et al. 2019

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Tuberculosis (TB) epidemiology is changing in Western and Central Europe due to the rise in immigration and refugees fleeing high-TB-burden areas of war and devastation. The change in local demography and the lack of sensitive and specific TB diagnostic and monitoring tools, especially for cases of childhood TB, leads to either missed cases or over-treatment of this group. Here we present a promising new diagnostic approach, the T cell activation marker (TAM)-TB assay, and its performance in a case of extra-pulmonary TB occurring in a 16 year old refugee from Afghanistan. This assay is based on the characterization of 3 activation markers (CD38, HLA-DR, and Ki67) and one maturation marker (CD27) on M. tuberculosis-specific CD4 T cells. It was performed at time-points T0 (10 days), T1 (1 month), T2 (6 months), and T3 (12 months) post-treatment initiation. All markers were able to detect active tuberculosis (aTB) within this patient at T0 and reverted to a healthy/LTBI phenotype at the end of treatment. Tantalizingly, there was a clear trend toward the healthy/LTBI phenotype for the markers at T1 and T2, indicating a potential role in monitoring anti-TB treatment in the future. This assay may therefore contribute to improved TB diagnostic algorithms and TB treatment monitoring, potentially allowing for individualization of TB treatment duration in the future.

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Section: Discussion/conclusionmentioning

confidence: 99%

The TAM-TB Assay—A Promising TB Immune-Diagnostic Test With a Potential for Treatment Monitoring

et al. 2019

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“…Several previous studies have attempted to identify biomarkers in blood that can robustly distinguish between LTBI and active TB [34], [35], [36], [37], [38], [39], [40], but only few identified candidate biomarkers potentially allowing this distinction have been validated in subsequent, prospective studies [15], [31], [33]. Considering that currently used immune-based tests (i.e.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis-specific cytokine biomarkers for the diagnosis of childhood TB in a TB-endemic setting

Sudbury

Otero

Tebruegge

et al. 2019

Journal of Clinical Tuberculosis and Other Mycobacterial Diseas

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The tuberculin skin test and interferon-gamma release assays have limitations in diagnosing tuberculosis (TB), particularly in children. This study investigated the performance of candidate M. tuberculosis-specific cytokine biomarkers for TB in children in a TB-endemic setting. A total of 237 children with a household contact with smear-positive pulmonary TB were recruited. Importantly, a group of children with illnesses other than TB (sick controls) was included to assess specificity.Median IFN-ɣ, IL-1ra, IL-2, IL-13, IP-10, MIP-1β and TNF-α responses were significantly higher in children with active TB and latent TB infection (LTBI) than in both healthy and sick control children. Three of these cytokines – IL-2, IL-13 and IP-10 – showed better performance characteristics than IFN-ɣ, with IL-2 achieving positive and negative predictive values of 97.7% and 90.7%, respectively. Furthermore, IL-1ra and TNF-α responses differed significantly between active TB and LTBI cases, suggesting that they may be stage-specific biomarkers.Our data indicate that incorporating these biomarkers into future blood-based TB assays could result in substantial performance gains.

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“…Hence, blood-based tests are a promising alternative. A variety of blood-based immunoassays, from interferon (IFN)-g release assays to T cell activation tests, are being evaluated for treatment monitoring (Cingolani et al, 2012;Sali et al, 2018). However, in low-resource countries, these tests need to be adapted to limited laboratory equipment (MacLean et al, 2017) and a simple output (Goletti et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Association of baseline white blood cell counts with tuberculosis treatment outcome: a prospective multicentered cohort study

Chedid

Kokhreidze

Tukvadze

et al. 2020

International Journal of Infectious Diseases

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Objectives: Tuberculosis (TB) is the leading infectious cause of death in the world. Cheaper and more accessible TB treatment monitoring methods are needed. Here, we evaluated white blood cell (WBC) absolute counts, lymphocyte, and monocyte proportions during TB treatment, and characterized their association with treatment failure. Methods: This multicentered prospective cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included and followed up after two months of treatment and at the end of therapy. Blood counts were compared to treatment outcome using descriptive statistics, logistic regression, and Receiver Operating Characteristic (ROC) analyses. Results: Between December 2017 and August 2020, 198 participants were enrolled, and 152 completed treatment, including 28 (18.5%) drug-resistant patients. The rate of cure at the end of treatment was 90.8% (138/152). WBC absolute counts decreased, and lymphocyte proportions increased throughout treatment. In multivariate analyses, baseline high WBC counts and low lymphocyte proportions were associated with positive sputum culture results at the end of treatment (WBC > 11,450 cells/mm 3 : p = 0.048; lymphocytes <16.0%: p = 0.039; WBC > 11,450 cells/mm 3 and lymphocytes <16.0%: p = 0.024). Conclusion: High WBC counts and low lymphocyte proportions at baseline are significantly associated with the risk of TB treatment failure.

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

Cited by 33 publications

References 46 publications

The TAM-TB Assay—A Promising TB Immune-Diagnostic Test With a Potential for Treatment Monitoring

The TAM-TB Assay—A Promising TB Immune-Diagnostic Test With a Potential for Treatment Monitoring

Mycobacterium tuberculosis-specific cytokine biomarkers for the diagnosis of childhood TB in a TB-endemic setting

Association of baseline white blood cell counts with tuberculosis treatment outcome: a prospective multicentered cohort study

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