title: How should I interpret an interferon gamma release assay result for tuberculosis infection?
abstract: BACKGROUND
  Interferon gamma release assays (IGRAs) are the first new diagnostic tests for latent tuberculosis (TB) infection (LTBI) since the century-old tuberculin skin test (TST). They are cell-mediated immune-based blood tests that have revolutionised LTBI diagnosis and are increasingly recommended by national guidelines.
  
  
  OBJECTIVE
  With the rapid expansion of the IGRA evidence-base in recent years, the limitations of IGRA and uncertainties in clinical interpretation of IGRA results have increasingly come into focus. In LTBI diagnosis these include: prognostic power of IGRAs relative to TST for quantifying risk of progression to active disease, false-negative rates in immunocompromised patients, the clinical meaning of IGRA reversion and the significance of the size of IGRA response. Furthermore, the role of IGRAs in the diagnostic work-up of active TB is unclear, and there is little evidence supporting use of the tests in anti-TB treatment monitoring.
  
  
  METHODS
  On-going large prospective longitudinal clinical endpoint cohort studies of active and latent TB will tackle some of the uncertainties regarding IGRAs. Here we discuss clinical practice and guidance in light of the current uncertainties, based on existing evidence.
  
  
  CONCLUSIONS
  Current and planned clinical research will fill the gaps in the evidence-base, narrowing the areas of uncertainty and informing future policy. Translational research into next-generation IGRAs and new T cell-based diagnostic platforms will likely overcome the limitations of current IGRAs in the near future.
authors: Research Department of Infection and Population Health, University College London, London, UK.
authors: Ibrahim
authors: I
authors: Abubakar
authors: Helen Ruth
authors: HR
authors: Stagg
authors: Hilary
authors: H
authors: Whitworth
authors: Ajit
authors: A
authors: Lalvani
mesh_terms: D018450:Disease Progression; D006801:Humans; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000276:immunology; D017410:Practice Guidelines as Topic; D011237:Predictive Value of Tests; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology
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