Is  Mycobacterium tuberculosis  infection life long?

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Abstract

People with immunoreactivity to tuberculosis are thought to have lifelong asymptomatic infection and remain at risk for active tuberculosis. Marcel A Behr and colleagues argue that most of these people are no longer infected

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Most cited references 24

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Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice.

J. L. Flynn, M M GOLDSTEIN, J. Chan … (1995)

Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-alpha (TNF alpha) contributes to this disease using murine models in which the action of TNF alpha is inhibited. TNF alpha was neutralized in vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55 kDa TNF receptor was used. The data from both models established that TNF alpha and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection. Granulomas were formed in equal numbers in control and experimental mice, but necrosis was observed only in mice deficient in TNF alpha or TNF receptor. TNF alpha and the 55 kDa TNF receptor are necessary conditions for protection against murine M. tuberculosis infection, but are not solely responsible for the tissue damage observed.

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Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

Juan Gomez-Reino, Loreto Carmona, Vicente Valverde … (2003)

The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

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False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria?

M. Farhat, C. Greenaway, M. Pai … (2006)

Despite certain drawbacks, the tuberculin skin test (TST) remains in widespread use. Important advantages of the TST are its low cost, simplicity and interpretation based on extensive published literature. However, TST specificity is reduced by bacille Calmette-Guérin (BCG) vaccination and exposure to non-tuberculous mycobacteria (NTM). To estimate TST specificity, we reviewed the published literature since 1966 regarding the effect of BCG vaccination and NTM infection on TST. Studies selected included healthy subjects with documented BCG vaccination status, including age at vaccination. Studies of NTM effect had used standardised NTM antigens in healthy subjects. In 24 studies involving 240,203 subjects BCG-vaccinated as infants, 20,406 (8.5%) had a TST of 10+ mm attributable to BCG, but only 56/5639 (1%) were TST-positive if tested > or =10 years after BCG. In 12 studies of 12,728 subjects vaccinated after their first birthday, 5314 (41.8%) had a false-positive TST of 10+ mm, and 191/898 (21.2%) after 10 years. Type of tuberculin test did not modify these results. In 18 studies involving 1,169,105 subjects, the absolute prevalence of false-positive TST from NTM cross-reactivity ranged from 0.1% to 2.3% in different regions. The effect on TST of BCG received in infancy is minimal, especially > or =10 years after vaccination. BCG received after infancy produces more frequent, more persistent and larger TST reactions. NTM is not a clinically important cause of false-positive TST, except in populations with a high prevalence of NTM sensitisation and a very low prevalence of TB infection.

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Author and article information

Contributors

Marcel A Behr: Role: professor of medicine

Paul H Edelstein: Role: professor of pathology and laboratory medicine

Lalita Ramakrishnan: Role: professor of immunology and infectious diseases

Journal

Journal ID (nlm-ta): BMJ

Journal ID (iso-abbrev): BMJ

Journal ID (publisher-id): BMJ-UK

Journal ID (hwp): bmj

Title: The BMJ

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1756-1833

Publication date Collection: 2019

Publication date (Electronic): 24 October 2019

Volume: 367

Electronic Location Identifier: l5770

Affiliations

[1 ]Department of Medicine, McGill University, McGill International TB Centre, 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: P Edelstein paul.edelstein@ 123456pennmedicine.upenn.edu

Article

Publisher ID: behm050761

DOI: 10.1136/bmj.l5770

PMC ID: 6812595

PubMed ID: 31649096

SO-VID: 2e6accbd-a16f-4bb4-82a5-958b7276b052

License:

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/.

Is Mycobacterium tuberculosis infection life long?

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Point-Of-Care Testing for Tuberculosis

Most cited references 24

Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice.

Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria?

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