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Background: Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments., Methods: Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive., Results: We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes., Conclusion: In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: M. S. received fees for participating in an advisory board with Pfizer Ltd (2 hours). The remaining authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Pérez-Recio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2-TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8 + T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2-TB1 value >0.6 IU·ml -1 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively ( P  = 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU·ml -1 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result ( P  = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of >0.6 IU·ml -1 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml -1 could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml -1 . QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing.

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents., (Copyright © 2018 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Diagnosis of latent tuberculosis infection in patients with immune-mediated inflammatory chronic diseases (IMIDs) can be challenged as diagnostic test reliability could be impaired by immunosuppression. We retrospectively analyzed the Quantiferon Gold-Test in-Tube (QFT-G-IT) results of all patients with IMIDs seen at the Department of Internal Medicine of Son Llàtzer Hospital, Palma de Mallorca (Spain), looking for the factors related to QFT-G-IT indeterminate results. During the study period (2008-2015), 520 patients met the inclusion criteria. Factors associated with indeterminate QFT-G-IT results in a univariate analysis were inflammatory bowel disease, disease activity, lymphopenia, and medium-to-high doses of corticosteroids. In a subsequent multivariate analysis, only lymphopenia (defined as < 1500 cells) was associated with indeterminate QFT-G-IT results. Lymphocyte count was the only factor independently associated with an increased number of indeterminate QFT-G-IT results in patients with different autoimmune diseases. Others factors such as the use of medium-to-high doses of corticosteroids should be considered before testing with QFT-G-IT.

Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease., Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points., Results: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%)., Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments., Clinical Trials Registration: NCT01223534., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Tuberculosis risk is increased in patients with chronic inflammatory diseases receiving any immunosuppressive treatment, notably tumor necrosis factor (TNF) antagonists therapy. Screening for the presence of latent infection with Mycobacterium tuberculosis and targeted preventive treatment to reduce the risk of progression to TB is mandatory in these patients. This Consensus Document summarizes the current knowledge and expert opinion of biologic therapies including TNF-blocking treatments. It provides recommendations for the use of interferon-gamma release assays (IGRA) and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in these patients, and for the type and duration of preventive therapy., (Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.)

Background: Interferon-γ release assays (IGRAs) are increasingly used for the diagnosis of latent tuberculosis infection (LTBI). Because of the lack of a gold standard for the diagnosis of LTBI, IGRAs are compared to the tuberculin skin test (TST) and yield conflicting results. We assessed the usefulness of an IGRA test, QuantiFERON(®)-TB Gold In-Tube (QFT-G-IT), for diagnosing LTBI compared with TST in the setting of a contact screening study., Methods: A prospective comparison between the QFT-G-IT and the TST in TB contact subjects in a low TB burden area was conducted sequentially between January 2006 and December 2012., Results: A moderate concordance between the two tests (κ = 0.44 for TST cut-off of 5 mm and κ = 0.56 for TST cut-off of 15 mm) was found. A better agreement was shown in younger contacts and in non-vaccinated contacts when using a TST of 15 mm. Independent risk factors for a TST(+)/QFT-G-IT(-) discordance were history of BCG vaccination and age between 31 and 59 years. Discordance was also more frequent using a TST cut-off value of 5 mm. QFT-G-IT(+)/TST(-) was infrequent and was found in older contacts., Conclusions: Based on our data, we cannot recommend the use of QFT-G-IT as the only test to rule out LTBI, especially in older patients.

Background/methods: Quantiferon-TB-Gold in Tube(®) test (QFT-G-IT) may have advantages if combined with TST when screening for Latent Tuberculosis Infection (LTBI) prior to initiating anti-TNF therapy in an area of intermediate tuberculosis incidence such as Spain. In a small-scale prospective study, we evaluate the use of QFT-G-IT in combination with the screening recommended in Spain (Tuberculin-Skin Test, TST retest, clinical data, and Chest X-Ray (CXR)) for LTBI in patients considered as candidates for anti-TNFα treatment., Results: From June 2008 to October 2010, 123 patients from a 300-bed hospital in Palma de Mallorca (Spain) were included in the study. The majority of patients were under immunosuppressive therapy. A positive TST and TST booster were found in 22 and 17 patients, respectively. Thus 39 (31.7%) of the 123 patients had a positive TST. QFT-G-IT was positive in 16 patients (13.6%), indeterminate in 4 (3.2%), and negative in 103 (83.7%). One of the two tests was positive and LTBI was diagnosed in 34.1% of patients. The agreement between TST and QFT-G-IT among vaccinated patients was low and not statistically significant (Kappa=0.15) and was almost perfect among non-BCG vaccinated patients (K=0.81). TST positive responses were significantly related to BCG-vaccination (p<0.05) and QFT-G-IT positive response rates were related to older age (p<0.05)., Conclusion: QFT-G-IT may have advantages when combined with TST in immunosuppressed patients especially in older patients with a negative TST; in BCG vaccinated patients with a positive TST, QFT-G-IT could avoid unnecessary treatments and toxicities related to a false-positive TST result., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)