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BACKGROUND: Screening strategies based on interferon-? 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.

Introduction: Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in low-prevalence countries. However, there is no consensus on their application. The objective of this study was to develop guidelines for the use of interferon-gamma release assays in specific clinical scenarios in Spain. Methods: A panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, formulated the clinical questions and outcomes of interest. They conducted a systematic literature search, summarized the evidence and rated its quality, and prepared the recommendations following the GRADE (Grading of Recommendations of Assessment Development and Evaluations) methodology. Results: The panel prepared recommendations on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in the contact-tracing study (both adults and children), health care workers, immunosuppressed patients (patients infected with human immunodeficiency virus, patients with chronic immunomediated inflammatory diseases due to start biological therapy and patients requiring organ transplant) and for the diagnosis of active tuberculosis. Most recommendations were weak, mainly due to the lack of good quality evidence to balance the clinical benefits and disadvantages of the interferon-gamma release assays as compared with the tuberculin skin test. Conclusion: This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at risk of tuberculosis or with suspicion of active disease. The guidelines will be applicable in specialist and primary care and in public health settings. © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Previous reports have identified interleukin-2 (IL-2), quantified in the supernatants of QuantiFERON(®)-TB Gold In-tube (QFT) after 72 h of incubation, as a potential biomarker for distinguishing between latent and active tuberculosis (TB). However, its validity has not been tested in an appropriate clinical cohort.