title: Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.
abstract: OBJECTIVE
  Evaluation of different methods for an initial treatment decision in individuals with suspected pulmonary tuberculosis.
  
  
  BACKGROUND
  Recently, important advances regarding the diagnosis of pulmonary tuberculosis have been introduced, which influence the decision to initiate anti-tuberculosis treatment.
  
  
  METHODS
  To evaluate the impact of different methods for the presumed diagnosis of tuberculosis, individuals with suspected tuberculosis were prospectively enrolled following a specific algorithm including initial smear microscopy and Mycobacterium tuberculosis-specific nucleic acid amplification (NAAT) from sputum. In cases of negative initial test results, tuberculin skin testing, bronchoscopy with transbronchial biopsies and interferon-γ release assays (IGRAs) in peripheral blood and bronchoalveolar lavage (BAL) fluid were performed.
  
  
  RESULTS
  Amongst 135 individuals with suspected tuberculosis, 42 had tuberculosis, 10 had nontuberculous mycobacteria pulmonary infection/colonization (one had both tuberculosis and nontuberculous mycobacteria pulmonary infection/colonization) and 84 had an alternative final diagnosis. The sensitivity and specificity were 41% and 99% [positive likelihood ratio (LR+) = 40] for sputum microscopy and 31% and 98% (LR+) = 16) for BAL nucleic acid amplification, respectively. In patients with acid-fast bacilli smear-negative tuberculosis (25/42, 59.5%), M. tuberculosis-specific BAL fluid IGRA was 92% sensitive and 87% specific (LR+) = 7) for the diagnosis of tuberculosis.
  
  
  CONCLUSIONS
  None of the microbiological or immunological methods that aim to provide a rapid diagnosis of tuberculosis whilst waiting the confirmation of the M. tuberculosis culture results is on its own accurate enough to diagnose or exclude pulmonary tuberculosis. Negative sputum microscopy and M. tuberculosis-specific NAAT results should prompt bronchoscopy including BAL for M. tuberculosis-specific IGRA in individuals with suspected pulmonary tuberculosis.
authors.affiliation: Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Jafari
authors.forename: P
authors.initials: P
authors.lastname: Kessler
authors.forename: G
authors.initials: G
authors.lastname: Sotgiu
authors.forename: M
authors.initials: M
authors.lastname: Ernst
authors.forename: C
authors.initials: C
authors.lastname: Lange
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D003937:Diagnosis, Differential; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007371:Interferon-gamma