This Article Full Text Full Text (PDF) All Versions of this Article: 200509-1526OCv1 173/9/1038    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Anderson, S. T. Articles by Wilkinson, K. A. Search for Related Content PubMed PubMed Citation Articles by Anderson, S. T. Articles by Wilkinson, K. A.

Transmission of Mycobacterium tuberculosis Undetected by Tuberculin Skin Testing

Wellcome Trust Centre for Research in Clinical Tropical Medicine; Department of Pediatrics, Division of Medicine, Wright Fleming Institute, Imperial College London, London; Tuberculosis Clinic, North West London Hospitals NHS Trust, Northwick Park Hospital, Harrow, United Kingdom; Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic; and Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Rondebosch, South Africa

Correspondence and requests for reprints should be addressed to Suzanne Anderson, M.B.B.S., Department of Pediatrics, Division of Medicine, Wright Fleming Institute, Imperial College London, London W2 1PG, UK. E-mail: s.anderson{at}imperial.ac.uk

Rationale: The development of tuberculin skin test (TST) positivity following infection by Mycobacterium tuberculosis is not invariable and may depend on bacillary as well as host factors.

Objectives: First, to compare the diagnostic performance of the TST and a form of in vitro IFN- release assay (IFNGRA) in the circumstances of a contact investigation prompted by an unusually severe index case of infectious pulmonary tuberculosis. Second, to investigate the ability of the strain of M. tuberculosis responsible to induce cytokine secretion from monocytes in vitro.

Methods: A routine TST-based tuberculosis-contact screening procedure supplemented by the use of an "in house" IFNGRA that assays the T-cell response to the M. tuberculosis–specific antigens ESAT-6, CFP-10 (presented as a fusion protein within the inactivated adenylate cyclase of Bordetella pertussis), and purified protein derivative of M. tuberculosis. Isolation and genetic typing of the strain of M. tuberculosis responsible, and investigation of its ability to induce cytokine secretion from monocytes in vitro.

Measurements and Main Results: TST screening suggested a low rate of transmission with just 2/75 unequivocally positive responses. By contrast, the IFNGRA suggested an infection rate of 16/75 (22%). When compared with two reference strains of M. tuberculosis (H37Rv and CDC1551), the outbreak strain induced lower levels of tumor necrosis factor- and interleukin-12p40 (p < 0.04), cytokines associated with the development of delayed-type hypersensitivity.

Conclusions: These data suggest that infection by M. tuberculosis can be undetected by TST, and that this may partially relate to strain differences in immunogenicity.

Key Words: adenylate cyclase • diagnostic tests and procedures • ESAT-6 protein • Mycobacterium tuberculosis • tuberculin

This article has been cited by other articles:

				N. A. Knechel Tuberculosis: Pathophysiology, Clinical Features, and Diagnosis Crit. Care Nurse, April 1, 2009; 29(2): 34 - 43. [Full Text] [PDF]

				T. G. Connell, M. S. Shey, R. Seldon, M. X. Rangaka, G. van Cutsem, M. Simsova, Z. Marcekova, P. Sebo, N. Curtis, L. Diwakar, et al. Enhanced Ex Vivo Stimulation of Mycobacterium tuberculosis-Specific T Cells in Human Immunodeficiency Virus-Infected Persons via Antigen Delivery by the Bordetella pertussis Adenylate Cyclase Vector Clin. Vaccine Immunol., July 1, 2007; 14(7): 847 - 854. [Abstract] [Full Text] [PDF]

				W. W. Yew and C. C. Leung Update in Tuberculosis 2006 Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 541 - 546. [Full Text] [PDF]

				M. X. Rangaka, K. A. Wilkinson, R. Seldon, G. Van Cutsem, G. A. Meintjes, C. Morroni, P. Mouton, L. Diwakar, T. G. Connell, G. Maartens, et al. Effect of HIV-1 Infection on T-Cell-based and Skin Test Detection of Tuberculosis Infection Am. J. Respir. Crit. Care Med., March 1, 2007; 175(5): 514 - 520. [Abstract] [Full Text] [PDF]

				C. Jafari, M. Ernst, B. Kalsdorf, U. Greinert, R. Diel, D. Kirsten, K. Marienfeld, A. Lalvani, and C. Lange Rapid Diagnosis of Smear-negative Tuberculosis by Bronchoalveolar Lavage Enzyme-linked Immunospot Am. J. Respir. Crit. Care Med., November 1, 2006; 174(9): 1048 - 1054. [Abstract] [Full Text] [PDF]

				M. Pai, R. Joshi, S. Dogra, D. K. Mendiratta, P. Narang, S. Kalantri, A. L. Reingold, J. M. Colford Jr., L. W. Riley, and D. Menzies Serial Testing of Health Care Workers for Tuberculosis Using Interferon-{gamma} Assay Am. J. Respir. Crit. Care Med., August 1, 2006; 174(3): 349 - 355. [Abstract] [Full Text] [PDF]

				Skin Testing May Not Detect Recent TB Infection Journal Watch Infectious Diseases, May 5, 2006; 2006(505): 4 - 4. [Full Text]

				N. W. Schluger Assessing tuberculosis transmission and virulence: the vanishing tuberculin skin test. Am. J. Respir. Crit. Care Med., May 1, 2006; 173(9): 942 - 943. [Full Text] [PDF]