title: Bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear-negative tuberculosis in HIV-infected patients.
abstract: BACKGROUND
  Peripheral blood interferon-gamma release assays (IGRAs) have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB). However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis.
  
  
  METHODS
  We enrolled HIV-infected adults with cough ≥2 weeks' duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPOT-based IGRA (T-SPOT.TB®, Oxford Immunotec, Oxford, UK) using peripheral blood and bronchoalveolar lavage (BAL) fluid mononuclear cells, and determined the accuracy of IGRAs using mycobacterial culture results as a reference standard.
  
  
  RESULTS
  94 HIV-infected patients with paired peripheral blood and BAL IGRA results were included. The study population was young (median age 34 years [IQR 28-40 years]) and had advanced HIV/AIDS (median CD4+ T-lymphocyte count 60 cells/µl [IQR 22-200 cells/µl]). The proportion of indeterminate IGRA results was higher in BAL fluid than in peripheral blood specimens (34% vs. 14%, difference 20%, 95% CI 7-33%, p = 0.002). BAL IGRA had moderate sensitivity (73%, 95% CI 50-89%) but poor specificity (48%, 95% CI 32-64%) for TB diagnosis. Sensitivity was similar (75%, 95% CI 57-89%) and specificity was higher (78%, 95% CI 63-88%) when IGRA was performed on peripheral blood.
  
  
  CONCLUSIONS
  BAL IGRA performed poorly for the diagnosis of smear-negative TB in a high HIV/TB burden setting. Further studies are needed to examine reasons for the large proportion of indeterminate results and low specificity of BAL IGRA for active TB in high HIV/TB burden settings.
authors: Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America. acattamanchi@medsfgh.ucsf.edu
authors: Adithya
authors: A
authors: Cattamanchi
authors: Isaac
authors: I
authors: Ssewenyana
authors: Rose
authors: R
authors: Nabatanzi
authors: Cecily R
authors: CR
authors: Miller
authors: Saskia
authors: S
authors: Den Boon
authors: J Lucian
authors: JL
authors: Davis
authors: Alfred
authors: A
authors: Andama
authors: William
authors: W
authors: Worodria
authors: Samuel D
authors: SD
authors: Yoo
authors: Huyen
authors: H
authors: Cao
authors: Laurence
authors: L
authors: Huang
mesh_terms: D000328:Adult; D018893:Bronchoalveolar Lavage / Q000379:methods*; D001999:Bronchoscopy; D005260:Female; D015658:HIV Infections / Q000382:microbiology*; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods*; D008297:Male; D014376:Tuberculosis / Q000175:diagnosis*; D014454:Uganda