ArticlePloS one2012
Risk stratification of latent tuberculosis defined by combined interferon gamma release assays.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Pooled it
- Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB.The Cochrane database of systematic reviews · 2013Pooled it
- Analysis of a Combined HBHA and ESAT-6-Interferon-γ-Release Assay for the Diagnosis of Tuberculous Lymphadenopathies.Journal of clinical medicine · 2023Article
- Optimal Detection of Latent Mycobacterium tuberculosis Infection by Combined Heparin-Binding Hemagglutinin (HBHA) and Early Secreted Antigenic Target 6 (ESAT-6) Whole-Blood Interferon Gamma Release Assays.Journal of clinical microbiology · 2022Article
- Immuno-Diagnosis of Active Tuberculosis by a Combination of Cytokines/Chemokines Induced by Two Stage-Specific Mycobacterial Antigens: A Pilot Study in a Low TB Incidence Country.Frontiers in immunology · 2022Article
- Tuberculosis Risk Stratification of Psoriatic Patients Before Anti-TNF-α Treatment.Frontiers in immunology · 2021Article
- Early diagnosis of miliary tuberculosis in a hemodialysis patient by combining two interferon-γ-release assays: a case report.BMC nephrology · 2020Article
- Relevance of QuantiFERON-TB Gold Plus and Heparin-Binding Hemagglutinin Interferon-γ Release Assays for Monitoring of Pulmonary Tuberculosis Clearance: A Multicentered Study.Frontiers in immunology · 2020Article
- Tuberculosis Transmission in a Primary School and a Private Language School. An Estimation of Infectivity.Frontiers in pediatrics · 2020Article
- The pathogenesis of post-primary tuberculosis. A game changer for vaccine development.Tuberculosis (Edinburgh, Scotland) · 2019Review
- Immune Functional Assays, From Custom to Standardized Tests for Precision Medicine.Frontiers in immunology · 2018Review
- Involvement of methylated HBHA expressed from Mycobacterium smegmatis in an IFN-γ release assay to aid discrimination between latent infection and active tuberculosis in BCG-vaccinated populations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2017Article
- Stratification of Latent Mycobacterium tuberculosis Infection by Cellular Immune Profiling.The Journal of infectious diseases · 2017Article
- Immune characterization of the HBHA-specific response in Mycobacterium tuberculosis-infected patients with or without HIV infection.PloS one · 2017Article
- TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development.Frontiers in immunology · 2017Review
- Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis.The European respiratory journal · 2016Review
- Added Value of Long-Term Cytokine Release Assays to Detect Mycobacterium tuberculosis Infection in HIV-Infected Subjects in Uganda.Journal of acquired immune deficiency syndromes (1999) · 2016Article
- Tuberculosis Biomarkers: From Diagnosis to Protection.Infectious disease reports · 2016Review
- Contribution of a heparin-binding haemagglutinin interferon-gamma release assay to the detection of Mycobacterium tuberculosis infection in HIV-infected patients: comparison with the tuberculin skin test and the QuantiFERON-TB Gold In-tube.BMC infectious diseases · 2015Article
- Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost individuals infected with Mycobacterium tuberculosis develop latent tuberculosis infection (LTBI). Some may progress to active disease and would benefit from preventive treatment yet no means currently exists to predict who will reactivate. Here, we provide an approach to stratify LTBI based on IFN-γ responses to two antigens, the recombinant Early-Secreted Antigen Target-6 (rESAT-6) and the latency antigen Heparin-Binding Haemagglutinin (HBHA).
methodsWe retrospectively analyzed results from in-house IFN-γ-release assays with HBHA (HBHA-IGRA) and rESAT-6 (rESAT-6-IGRA) performed during a 12-year period on serial blood samples (3 to 9) collected from 23 LTBI subjects in a low-TB incidence country. Both the kinetics of the absolute IFN-γ concentrations secreted in response to each antigen and the dynamics of HBHA/rESAT-6-induced IFN-γ concentrations ratios were examined.
resultsThis analysis allowed the identification among the LTBI subjects of three major groups. Group A featured stable HBHA and rESAT-6-IGRA profiles with an HBHA/rESAT-6 ratio persistently higher than 1, and with high HBHA- and usually negative rESAT-6-IGRA responses throughout the study. Group B had changing HBHA/rESAT-6 ratios fluctuating from 0.0001 to 10,000, with both HBHA and rESAT-6 responses varying over time at least once during the follow-up. Group C was characterized by a progressive disappearance of all responses.
conclusionsBy combining the measures of IFN-γ concentrations secreted in response to an early and a latency antigens, LTBI subjects can be stratified into different risk groups. We propose that disappearing responses indicate cure, that persistent responses to HBHA with HBHA/rESAT-6 ratios ≥ 1 represent stable LTBI subjects, whereas subjects with ratios varying from >1 to <1 should be closely monitored as they may represent the highest-risk group, as illustrated by a case report, and should therefore be prioritized for preventive treatment.
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