title: Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study.
abstract: BACKGROUND
  The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears.
  
  
  OBJECTIVE
  Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smear-negative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay.
  
  
  METHODS
  Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid.
  
  
  RESULTS
  Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB.
  
  
  CONCLUSIONS
  Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice.
authors: Clinical Infectious Diseases, Research Center Borstel, Borstel Germany.
authors: Claudia
authors: C
authors: Jafari
authors: Steven
authors: S
authors: Thijsen
authors: Giovanni
authors: G
authors: Sotgiu
authors: Delia
authors: D
authors: Goletti
authors: José Antonio
authors: JA
authors: Domínguez Benítez
authors: Monica
authors: M
authors: Losi
authors: Ralf
authors: R
authors: Eberhardt
authors: Detlef
authors: D
authors: Kirsten
authors: Barbara
authors: B
authors: Kalsdorf
authors: Aik
authors: A
authors: Bossink
authors: Irene
authors: I
authors: Latorre
authors: Giovanni B
authors: GB
authors: Migliori
authors: Alan
authors: A
authors: Strassburg
authors: Susanne
authors: S
authors: Winteroll
authors: Ulf
authors: U
authors: Greinert
authors: Luca
authors: L
authors: Richeldi
authors: Martin
authors: M
authors: Ernst
authors: Christoph
authors: C
authors: Lange
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D001999:Bronchoscopy / Q000379:methods / Q000706:statistics & numerical data; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods* / Q000706:statistics & numerical data; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D016017:Odds Ratio; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012882:Skin Tests / Q000379:methods / Q000706:statistics & numerical data; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000382:microbiology