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      Is Open Access

      Revisiting the timetable of tuberculosis

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      1 , 2 , 3 , 3 ,
      The BMJ
      BMJ Publishing Group Ltd.

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          Abstract

          Tuberculosis has a much shorter incubation period than is widely thought, say Marcel A Behr and colleagues, and this has implications for prioritising research and public health strategies

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          Most cited references23

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          Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis.

          The risk of progression to active tuberculosis is greatest in the several years following initial infection. The extent to which latent tuberculosis infection reduces the risk of progressive disease following reexposure and reinfection is not known. Indirect estimates from population models have been highly variable. We reviewed prospective cohort studies of persons exposed to individuals with infectious tuberculosis that were published prior to the widespread treatment of latent tuberculosis to estimate the incidence of tuberculosis among individuals with latent tuberculosis infection (LTBI group) and without latent tuberculosis (uninfected; UI group). We calculated the incidence rate ratio (IRR) of tuberculosis disease following infection between these 2 groups. We then adjusted incidence for expected reactivation, proportion of each group that was infected, and median time of observation following infection during the study. We identified 18 publications reporting tuberculosis incidence among 23 paired cohorts of individuals with and without latent infection (total N = 19 886). The weighted mean adjusted incidence rate of tuberculosis in the LTBI and UI groups attributable to reinfection was 13.5 per 1000 person-years (95% confidence interval [CI]: 5.0-26.2 per 1000 person-years) and that attributable to primary infection was 60.1 per 1000 person-years (95% CI: 38.6-87.4 per 1000 person-years). The adjusted IRR for tuberculosis in the LTBI group compared with the UI group was 0.21 (95% CI: .14-.30). Individuals with latent tuberculosis had 79% lower risk of progressive tuberculosis after reinfection than uninfected individuals. The risk reduction estimated in this study is greater than most previous estimates made through population models.
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            Prospects for tuberculosis elimination.

            The target for TB elimination is to reduce annual incidence to less than one case per million population by 2050. Meeting that target requires a 1,000-fold reduction in incidence in little more than 35 years. This can be achieved only by combining the effective treatment of active TB-early case detection and high cure rates to interrupt transmission-with methods to prevent new infections and to neutralize existing latent infections. Vigorous implementation of the WHO Stop TB Strategy is needed to achieve the former, facilitated by the effective supply of, and demand for, health services. The latter calls for new technology, including biomarkers of TB risk, diagnostics, drugs, and vaccines. An important milestone en route to elimination will be reached when there is less than 1 TB death per 100,000 population, marking entry into the elimination phase. This landmark can be reached by many countries within 1-2 decades.
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              A trial of mass isoniazid preventive therapy for tuberculosis control.

              Tuberculosis is epidemic among workers in South African gold mines. We evaluated an intervention to interrupt tuberculosis transmission by means of mass screening that was linked to treatment for active disease or latent infection.
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                Author and article information

                Contributors
                Role: professor of medicine
                Role: professor of pathology and laboratory medicine
                Role: professor of immunology and infectious diseases
                Journal
                BMJ
                BMJ
                BMJ-UK
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2018
                23 August 2018
                : 362
                : k2738
                Affiliations
                [1 ]McGill International TB Centre, Infectious Diseases and Immunity in Global Health Program, McGill University Health Centre Research Institute, Montreal H4A 3J1, Canada
                [2 ]Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
                [3 ]Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
                Author notes
                Correspondence to: L Ramakrishnan lr404@ 123456cam.ac.uk
                Article
                raml045033
                10.1136/bmj.k2738
                6105930
                30139910
                026da799-eff6-4525-acbb-8182aea9fb77
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

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                Analysis

                Medicine
                Medicine

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