Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

Author:

Pai Madhukar1,Behr Marcel1

Affiliation:

1. McGill International TB Center and Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada

Abstract

ABSTRACT The identification of individuals with latent tuberculosis infection (LTBI) is useful for both fundamental understanding of the pathogenesis of disease and for clinical and public health interventions (i.e., to prevent progression to disease). Basic research suggests there is a pathogenetic continuum from exposure to infection to disease, and individuals may advance or reverse positions within the spectrum, depending on changes in the host immunity. Unfortunately, there is no diagnostic test that resolves the various stages within the spectrum of Mycobacterium tuberculosis infection. Two main immune-based approaches are currently used for identification of LTBI: the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA). TST can use either the conventional purified protein derivative or more specific antigens. Extensive research suggests that both TST and IGRA represent indirect markers of M. tuberculosis exposure and indicates a cellular immune response to M. tuberculosis . The imperfect concordance between these two tests suggests that neither test is perfect, presumably due to both technical and biological reasons. Neither test can accurately differentiate between LTBI and active TB. Both IGRA and TST have low sensitivity in a variety of immunocompromised populations. Cohort studies have shown that both TST and IGRA have low predictive value for progression from infection to active TB. For fundamental applications, basic research is necessary to identify those at highest risk of disease with a positive TST and/or IGRA. For clinical applications, the identification of such biomarkers can help prioritize efforts to interrupt progression to disease through preventive therapy.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology

Reference54 articles.

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2. Mazurek GH Jereb J Vernon A LoBue P Goldberg S Castro K IGRA Expert Committee Centers for Disease Control and Prevention (CDC). 2010. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection: United States 2010. MMWR Recomm Rep 59 (RR-5) : 1–25. [PubMed]

3. Pai M Kunimoto D Jamieson F Menzies D. 2013. Diagnosis of latent tuberculosis infection. In Canadian Tuberculosis Standards 7th Edition. Can Respir J 20: 23A–34A.

4. National Institute for Health and Care Excellence. 2016. Tuberculosis. NICE guideline NG33. https://www.nice.org.uk/guidance/ng33. [PubMed]

5. World Health Organization. 2014. Guidelines on the Management of Latent Tuberculosis Infection . WHO Geneva Switzerland.

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