title: Interferon-gamma assay in combination with tuberculin skin test are insufficient for the diagnosis of culture-negative pulmonary tuberculosis.
abstract: OBJECTIVE
  Early diagnosis of infectious cases and treatment of tuberculosis (TB) are important strategies for reducing the incidence of this disease. Unfortunately, traditional TB diagnostic methods are time-consuming and often unreliable. This study compared the accuracy and reliability of the tuberculin skin test (TST) and interferon (IFN)-γ-based assay (IGRA) for the diagnosis of active pulmonary TB Polish cases that could or could not be confirmed by M. tuberculosis (M.tb) culture.
  
  
  METHODS
  In total, 126 adult patients with clinically active TB or non-mycobacterial, community-acquired lung diseases (NMLD) hospitalised at the Regional Specialised Hospital of Tuberculosis, Lung Diseases and Rehabilitation in Tuszyn, Poland were enrolled in the present study. Sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), and analytic accuracy (Acc) of TST and IGRA testing for the diagnosis of culture-positive and culture-negative TB patients were calculated. The quantities of IFN-γ produced in the response to M.tb specific antigens (TB Ag - Nil) in the cultures of blood from patients with active TB and NMLD patients were also analysed.
  
  
  RESULTS
  The IGRA sensitivity in culture-positive and culture-negative TB patients was similar, measuring 65.1% and 55.6%, respectively. The sensitivity of TST did not differ from the parameters designated for IGRA, measuring 55.8% in culture-positive and 64.9% in culture-negative TB. The sensitivity of TST and IGRA was age-dependent and decreased significantly with the age of the patients. No differences in the frequency or intensity of M.tb-stimulated IFN-γ production, as assessed by IGRA testing between culture-positive and culture-negative TB were noticed. Significantly lower concentrations of IFN-γ were observed in patients with advanced TB forms compared with those with mild or moderate TB pathologies.
  
  
  CONCLUSIONS
  Our results do not show that a combination of IGRA and TST might be a step forward in the diagnosis of culture-negative TB cases. However, M. tuberculosis-stimulated IFN-γ levels might help to assess the extent of pulmonary TB lesions.
authors.affiliation: Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wlodarczyk
authors.affiliation: Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Rudnicka
authors.affiliation: Regional Specialised Hospital of Tuberculosis, Lung Diseases and Rehabilitation, Tuszyn, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Janiszewska-Drobinska
authors.affiliation: Regional Specialised Hospital of Tuberculosis, Lung Diseases and Rehabilitation, Tuszyn, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kielnierowski
authors.affiliation: Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kowalewicz-Kulbat
authors.affiliation: Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Fol
authors.affiliation: Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Druszczynska
mesh_terms: D000328:Adult; D000368:Aged; D017714:Community-Acquired Infections / Q000175:diagnosis / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology
chemical_list: D007371:Interferon-gamma