title: [Basic characteristics of a novel diagnostic method (QuantiFERON TB-2G) for latent tuberculosis infection with the use of Mycobacterium tuberculosis-specific antigens, ESAT-6 and CFP-10].
abstract: OBJECTIVE
  To determine the optimum cut-off level of a newly developed method for diagnosing tuberculosis infection based on whole-blood interferon-gamma measurement, and to study the basic characteristics of the method.
  
  
  METHODS
  1) A total of 220 young, healthy individuals having no apparent exposure to tuberculosis infection, most of whom have had a vaccination with BCG vaccine. 2) One hundred eighteen tuberculosis patients who were diagnosed by positive Mycobacterium tuberculosis on culture. 3) A group of 75 youngsters exposed to an infectious tuberculosis patient and who showed a strong tuberculin reaction (with erythema diameter of 30 mm or more).
  
  
  METHODS
  Whole-blood specimens of donors were stimulated with antigens, i.e., ESAT-6 and CFP-10, and then cultured. Plasma concentrations of interferon-gamma discharged were then determined with QuantiFERON-CMI. Correlation between interferon-gamma concentrations in response to ESAT-6 and CFP-10, and their correlation with Mantoux test results were analyzed for various categories of donors. The Receiver Operating Characteristics analysis was performed considering the loss due to misclassification. [
  
  
  CONCLUSIONS
  The optimum cut-off level was determined as 0.35 IU/ml for both ESAT-6 and CFP-10. This gave the test a sensitivity of 89.0% and specificity of 98.1% in detecting tuberculosis infection. The correlation of interferon-gamma response with tuberculin tests among BCG-vaccinated individuals was low, which suggested that the test was not influenced by previous BCG vaccination. The low correlation between ESAT-6 and CFP-10 tests suggested that the simultaneous use of the two tests was beneficial. As in the case of clinical tests in general, the cut-off should be set at a lower level when the test is applied to high prevalence situation and vice versa.
authors.affiliation: Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association (JATA), Tokyo, Japan. harada@jata.or.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Harada
authors.forename: Kazue
authors.initials: K
authors.lastname: Higuchi
authors.forename: Yukie
authors.initials: Y
authors.lastname: Sekiya
authors.forename: Jim
authors.initials: J
authors.lastname: Rothel
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitoh
authors.forename: Toru
authors.initials: T
authors.lastname: Mori
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007159:Immunologic Tests / Q000379:methods*; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011933:Reagent Kits, Diagnostic / Q000592:standards*; D014376:Tuberculosis / Q000175:diagnosis*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011933:Reagent Kits, Diagnostic; D007371:Interferon-gamma