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Clinical and Diagnostic Laboratory Immunology, November 2001, p. 1089-1096, Vol. 8, No. 6
1071-412X/01/$04.00+0   DOI: 10.1128/CDLI.8.6.1089-1096.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Sandra M. Arend,1,* Anrik C. F. Engelhard,2,dagger Gertjan Groot,3 Kirsten de Boer,1 Peter Andersen,4 Tom H. M. Ottenhoff,5 and Jaap T. van Dissel1

Department of Infectious Diseases1 and Department of Immunohematology and Blood Transfusion,5 Leiden University Medical Center, Leiden, Department of Tuberculosis Control, Municipal Health Department `Zaanstreek en Waterland,' Zaandam,2 and Football Club Volendam, Volendam,3 The Netherlands, and Department of TB Immunology, Statens Serum Institute, Copenhagen, Denmark4

Received 19 April 2001/Returned for modification 13 June 2001/Accepted 8 August 2001

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.


* Corresponding author. Mailing address: Dept. of Infectious Diseases, C5P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Phone: 31 71 526 26 20. Fax: 31 71 526 67 58. E-mail: s.m.arend{at}lumc.nl.

dagger Current address: Royal Tropical Institute (KIT Health), Amsterdam, The Netherlands.


Clinical and Diagnostic Laboratory Immunology, November 2001, p. 1089-1096, Vol. 8, No. 6
1071-412X/01/$04.00+0   DOI: 10.1128/CDLI.8.6.1089-1096.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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