Gamma interferon release assays for detection of Mycobacterium tuberculosis infection

Madhukar Pai, Claudia M. Denkinger, Sandra V. Kik, Molebogeng X. Rangaka, Alice Zwerling, Olivia Oxlade, John Z. Metcalfe, Adithya Cattamanchi, David W. Dowdy, Keertan Dheda, Niaz Banaei

Research output: Contribution to journalArticle

Abstract

Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers.

Original languageEnglish (US)
Pages (from-to)3-20
Number of pages18
JournalClinical Microbiology Reviews
Volume27
Issue number1
DOIs
StatePublished - Jan 10 2014

ASJC Scopus subject areas

  • Epidemiology
  • Immunology and Microbiology(all)
  • Public Health, Environmental and Occupational Health
  • Microbiology (medical)
  • Infectious Diseases

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  • Cite this

    Pai, M., Denkinger, C. M., Kik, S. V., Rangaka, M. X., Zwerling, A., Oxlade, O., Metcalfe, J. Z., Cattamanchi, A., Dowdy, D. W., Dheda, K., & Banaei, N. (2014). Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clinical Microbiology Reviews, 27(1), 3-20. https://doi.org/10.1128/CMR.00034-13