title: Gamma interferon release assays for detection of Mycobacterium tuberculosis infection.
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.
authors.affiliation: McGill International TB Centre and Department of Epidemiology & Biostatistics, McGill University, Montreal, Canada.
authors.forename: Madhukar
authors.initials: M
authors.lastname: Pai
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Denkinger
authors.forename: Sandra V
authors.initials: SV
authors.lastname: Kik
authors.forename: Molebogeng X
authors.initials: MX
authors.lastname: Rangaka
authors.forename: Alice
authors.initials: A
authors.lastname: Zwerling
authors.forename: Olivia
authors.initials: O
authors.lastname: Oxlade
authors.forename: John Z
authors.initials: JZ
authors.lastname: Metcalfe
authors.forename: Adithya
authors.initials: A
authors.lastname: Cattamanchi
authors.forename: David W
authors.initials: DW
authors.lastname: Dowdy
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
authors.forename: Niaz
authors.initials: N
authors.lastname: Banaei
mesh_terms: D006801:Humans; D007159:Immunologic Tests / Q000379:methods* / Q000592:standards*; D007371:Interferon-gamma / Q000276:immunology*; D055985:Latent Tuberculosis / Q000175:diagnosis*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000175:diagnosis
chemical_list: D007371:Interferon-gamma