title: Tuberculin skin testing compared with T-cell responses to Mycobacterium tuberculosis-specific and nonspecific antigens for detection of latent infection in persons with recent tuberculosis contact.
abstract: The tuberculin skin test (TST) is used for the identification of latent tuberculosis (TB) infection (LTBI) but lacks specificity in Mycobacterium bovis BCG-vaccinated individuals, who constitute an increasing proportion of TB patients and their contacts from regions where TB is endemic. In previous studies, T-cell responses to ESAT-6 and CFP-10, M. tuberculosis-specific antigens that are absent from BCG, were sensitive and specific for detection of active TB. We studied 44 close contacts of a patient with smear-positive pulmonary TB and compared the standard screening procedure for LTBI by TST or chest radiographs with T-cell responses to M. tuberculosis-specific and nonspecific antigens. Peripheral blood mononuclear cells were cocultured with ESAT-6, CFP-10, TB10.4 (each as recombinant antigen and as a mixture of overlapping synthetic peptides), M. tuberculosis sonicate, purified protein derivative (PPD), and short-term culture filtrate, using gamma interferon production as the response measure. LTBI screening was by TST in 36 participants and by chest radiographs in 8 persons. Nineteen contacts were categorized as TST negative, 12 were categorized as TST positive, and 5 had indeterminate TST results. Recombinant antigens and peptide mixtures gave similar results. Responses to TB10.4 were neither sensitive nor specific for LTBI. T-cell responses to ESAT-6 and CFP-10 were less sensitive for detection of LTBI than those to PPD (67 versus 100%) but considerably more specific (100 versus 72%). The specificity of the TST or in vitro responses to PPD will be even less when the proportion of BCG-vaccinated persons among TB contacts evaluated for LTBI increases.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. s.m.arend@lumc.nl
authors.forename: S M
authors.initials: SM
authors.lastname: Arend
authors.forename: A C
authors.initials: AC
authors.lastname: Engelhard
authors.forename: G
authors.initials: G
authors.lastname: Groot
authors.forename: K
authors.initials: K
authors.lastname: de Boer
authors.forename: P
authors.initials: P
authors.lastname: Andersen
authors.forename: T H
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: J T
authors.initials: JT
authors.lastname: van Dissel
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology; D002353:Carrier State; D003429:Cross Reactions; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology / Q000517:prevention & control
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D007371:Interferon-gamma