1,721,258 research outputs found

    The spectrum of tuberculosis infection: new perspectives in the era of biologics

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    The risk of developing active tuberculosis (TB) is higher in patients taking immunosuppressive drugs, either as a result of reactivation of a latent TB infection (LTBI) or following a new infection with Mycobacterium tuberculosis (Mtb). We discuss the pathogenesis and spectrum of Mtb infection in light of its implication for the management of patients following biologic regimens. Among recent findings, during LTBI, Mtb can persist in the host for decades, localizing in many tissues and assuming different metabolic states that protect the bacilli from the harsh host immune defenses. Despite the strong host T cell response against Mtb, the bacilli may also replicate and multiply in vivo, and any event impairing immune function may lead to active and uncontrolled bacteria replication and active disease. The classic dichotomy between active and latent disease is being reconsidered in favor of a continuous and dynamic spectrum extending from infection to disease that can coexist in the same individual. This TB spectrum results from the dynamic interaction between the host immune system and the bacilli and can be maintained in equilibrium for decades, although treatments affecting the host immune cells may result in disease reactivation

    Performance of the Tuberculin Skin Test and Interferon-γ Release Assays: An Update on the Accuracy, Cutoff Stratification, and New Potential Immune-based Approaches

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    An association between biologic agents and reactivation of active disease from latent tuberculosis infection (LTBI) has been established. Screening for LTBI is, therefore, now recommended for candidates for biologic drugs. The tuberculin skin test (TST) and interferon-γ release assays (IGRA) are the available commercial tests for detecting LTBI. We discuss their accuracy in immune-competent subjects and patients with autoimmune diseases, as well as potential new approaches to immune diagnosis. IGRA seem to be more accurate than TST in bacillus Calmette-Guerin vaccinated subjects and patients with autoimmune diseases. However, longitudinal studies are needed to estimate the risk of progression to TB after IGRA-based and/or TST-based diagnosis of LTBI in these vulnerable patients. New tests are needed to identify those patients with LTBI who will develop active TB and need prophylaxis

    The role of IGRA in the diagnosis of tuberculosis infection, differentiating from active tuberculosis, and decision making for initiating treatment or preventive therapy of tuberculosis infection

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    Objectives: The World Health Organization estimated that a quarter of the global population is infected by Mycobacterium tuberculosis (Mtb). A better control of tuberculosis (TB) is based on the ability to detect Mtb infection, identifying the progressors to TB disease, undergoing to preventive therapy and implementing strategies to register the infections and treatment completion. Design: we reviewed the literature regarding the tests available for TB infection diagnosis, the preventive therapies options and the cascade of care for controlling TB at a public health level. Results: current tests for TB infection diagnosis as IFN-γ release assays or tuberculin skin tests are based on the detection of an immune response to Mtb in the absence of clinical disease. The main limit is their low accuracy to detect progressors to disease. New preventive treatments are available with short duration that are associated with better adherence. Options to register TB infections are presented. Conclusions: Tests to diagnose TB infection are available but they lack accuracy to identify the progressors from infection to TB disease. Shorter preventive TB therapy are available but need to be implemented worldwide. A TB infection registry is crucial for improving the cascade of care leading to a better TB control

    The Mycobacterial HBHA Protein: a Promising Biomarker for Tuberculosis

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    A major goal in tuberculosis (TB) research is the identification, among the subjects infected with Mycobacterium tuberculosis (Mtb), of those with active TB, or at higher risk of developing active disease, from the latently infected subjects. The classical heterogeneity of Mtb infection and TB disease is a major obstacle toward the identification of reliable biomarkers that can stratify Mtb infected subjects based on disease risk. The heparin-binding haemagglutinin (HBHA) is a mycobacterial surface antigen that is implicated in tuberculosis (TB) pathogenesis. The host immune response against HBHA varies depending on the TB status and several studies are supporting the role of HBHA as a useful biomarker of TB

    Use of a T cell-based assay for monitoring efficacy of antituberculosis therapy

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    Monitoring the efficacy of antituberculosis therapy is crucial both for the individual patient and for better control of the spread of tuberculosis. We studied 18 patients with microbiologically confirmed tuberculosis, both at the time of diagnosis and 3 months after they started therapy, using an in vitro assay that detects T cell-mediated interferon- gamma response to selected peptides of Mycobacterium tuberculosis-specific early secretory antigenic target 6 (ESAT-6) protein. All patients had positive results at diagnosis; however, 3 months later, the response to ESAT-6 peptides was still detectable only in the 5 patients with microbiological isolation and/or absence of clinical improvement after treatment. On the basis of these data, we conclude that our assay is a useful tool in monitoring the efficacy of antituberculosis therapy
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