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      Correlation between tuberculin skin test and IGRAs with risk factors for the spread of infection in close contacts with sputum smear positive in pulmonary tuberculosis

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          Abstract

          Background

          The aim of the study was to assess the correlation between the tuberculin skin test (TST) and in vitro interferon-gamma released assays (IGRAs) with risk factors for the spread of infection in smear positive pulmonary tuberculosis (TB) contacts.

          Methods

          We recruited prospective contacts with smear positive pulmonary TB cases. We looked at human immunodeficiency virus (HIV) infection and other conditions of immunosuppression, presence of BCG vaccination and the degree of exposure to the index case. Patients underwent the TST, chest radiography, sputum analysis when necessary, and IGRA assays (QFN-G-IT and T-SPOT.TB). Presence of cough, diagnostic delay (days between first symptoms and TB diagnostic), contact conditions: room size (square meters) and index of overcrowding (square meters per person) were investigated in the index case.

          Results

          156 contacts (119 adults, 37 children) of 66 TB patients were enrolled, 2.4 (1-14) contacts per TB case. The positivity of the TST did not correlate with the risk factors studied: presence of cough (p = 0.929); delayed diagnosis (p = 0.244); room size (p = 0.462); overcrowding (p = 0.800). Both QFN-G-IT and T-SPOT.TB, showed significant association with cough (p = 0.001, and p = 0.007) and room size (p = 0.020, and p = 0.023), respectively.

          Conclusions

          Both IGRA associated better than TST with certain host-related risk factors involved in the transmission of disease, such as the presence of cough.

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          Most cited references19

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          Tuberculosis in household contacts of infectious cases in Kampala, Uganda.

          Tuberculosis remains a serious threat to public health, especially in sub-Saharan Africa. To determine the host and environmental factors responsible for tuberculosis in African households, the authors performed a prospective cohort study of 1,206 household contacts of 302 index cases with tuberculosis enrolled in Uganda between 1995 and 1999. All contacts were systematically evaluated for active tuberculosis and risk factors for active disease. Among the 1,206 household contacts, 76 secondary cases (6%) of tuberculosis were identified. Of these cases, 51 were identified in the baseline evaluation, and 25 developed during follow-up. Compared with index cases, secondary cases presented more often with minimal disease. The risk for secondary tuberculosis was greater among young children than adults (10% vs. 1.9%) and among human immunodeficiency virus-seropositive than -seronegative contacts (23% vs. 3.3%). Host risk factors could not be completely separated from the effects of environmental risk factors, suggesting that a household may represent a complex system of interacting risks for tuberculosis.
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            Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells.

            Identification of individuals latently infected with Mycobacterium tuberculosis is an important part of tuberculosis control. The current method, the tuberculin skin test (TST), has poor specificity because of the antigenic cross-reactivity of purified protein derivative (PPD) with M bovis BCG vaccine and environmental mycobacteria. ESAT-6 is a secreted antigen that is highly specific for M tuberculosis complex, but is absent from M bovis BCG. With an enzyme-linked immunospot (ELISPOT) assay for interferon gamma, we have identified ESAT-6-specific T cells as an accurate marker of M tuberculosis infection. We did a prospective, masked study of 50 healthy contacts, with varying but well defined degrees of exposure to M tuberculosis, who attended an urban contact-tracing clinic. We assessed and compared the efficacy of our assay and TST for detection of symptomless infected individuals by correlation of test results with the degree of exposure to an infectious index case. The ESAT-6 ELISPOT assay results had a strong positive relation with increasing intensity of exposure (odds ratio=9.0 per unit increase in level of exposure [95% CI 2.6--31.6], p=0.001), whereas TST results had a weaker relation with exposure (1.9 [1.0--3.5], p=0.05). By contrast, ELISPOT results were not correlated with BCG vaccination status (p=0.7), whereas TST results were significantly more likely to be positive in BCG-vaccinated contacts (12.1 [1.3--115.7], p=0.03). This new antigen-specific T cell-based assay could allow more accurate identification of symptom-free individuals recently exposed to M tuberculosis, and thereby help to improve tuberculosis control.
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              The transmission of tuberculosis in confined spaces: an analytical review of alternative epidemiological models.

              Tuberculosis (TB) is a disease that is closely associated with poverty, with transmission occurring in situations where infected persons are in close contact with others in confined spaces. While it is well recognised that overcrowding increases the risk of transmission, this increased risk has not been quantified and the relationship between overcrowding and duration of exposure is not well understood. This paper analyses three epidemiological models that have been used to predict the transmission of airborne disease in confined spaces: the Mass Action model, Riley, Murphy and Riley's model and Gammaitoni and Nucci's model. A study is presented to demonstrate the range of applicability of each model and show how they can be applied to the transmission of both TB and diseases with short incubation periods such as measles. Gammiatoni and Nucci's generalised formulation is shown to be the most suitable for modelling airborne transmission in ventilated spaces, and it is subsequently used in a parametric study to evaluate the effect of physical and environmental factors on the rate of disease transmission. The paper also presents reported quanta production data for several TB outbreaks and demonstrates that the greatest risk of TB infection is during clinical procedures that produce large quantities of aerosol, such as bronchoscopy or intubation.
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                Author and article information

                Contributors
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central
                1471-2334
                2014
                13 May 2014
                : 14
                : 258
                Affiliations
                [1 ]Unitat de Tuberculosi de Drassanes, Hospital Universitari Vall d’Hebron, Barcelona, Spain
                [2 ]IDIAP Jordi Gol Research Foundation, Barcelona, Spain
                [3 ]Universitat Autònoma of Barcelona, Barcelona, Spain
                [4 ]Servei de Microbiologia, Institut d’Investigació Germans Trias i Pujol, Badalona, Spain
                [5 ]Servei de Pneumologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
                [6 ]CIBER Enfermedades Respiratorias, Madrid, Spain
                Article
                1471-2334-14-258
                10.1186/1471-2334-14-258
                4030278
                24885850
                b84af6cd-4914-40f1-9e26-1055b208cdb2
                Copyright © 2014 de Souza-Galvão et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 February 2014
                : 9 May 2014
                Categories
                Research Article

                Infectious disease & Microbiology
                tuberculosis infection,tuberculin skin test,interferon gamma release assays,igra,overcrowding,diagnostic delay,cough

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