help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on July 20, 2006, doi:10.1164/rccm.200604-465OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200604-465OCv1
174/9/1048    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Related articles in AJRCCM
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jafari, C.
Right arrow Articles by Lange, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jafari, C.
Right arrow Articles by Lange, C.
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1048-1054, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200604-465OC

Original Article

Rapid Diagnosis of Smear-negative Tuberculosis by Bronchoalveolar Lavage Enzyme-linked Immunospot

Claudia Jafari, Martin Ernst, Barbara Kalsdorf, Ulf Greinert, Roland Diel, Detlef Kirsten, Kathleen Marienfeld, Ajit Lalvani and Christoph Lange

Division of Clinical Infectious Diseases and Division of Immune Cell Analytics, Research Center Borstel, Borstel; Department of Public Health, University of Düsseldorf, Düsseldorf; Center for Pulmonary Medicine and Thoracic Surgery, Hospital Großhansdorf, Großhansdorf, Germany; and Tuberculosis Immunology Group, Nuffield Department of Clinical Medicine, John Radcliff Hospital, University of Oxford, Oxford, United Kingdom

Correspondence and requests for reprints should be addressed to Christoph Lange, M.D., Ph.D., Division of Clinical Infectious Diseases, Research Center Borstel, Parkallee 35, 23845 Borstel, Germany. E-mail: clange{at}fz-borstel.de

Rationale: In a large proportion of patients with active pulmonary tuberculosis (pTB), acid-fast bacilli smear results for sputum and bronchial secretions are negative. Detectable growth of Mycobacterium tuberculosis (MTB) in cultures takes several weeks and MTB-specific DNA amplification results on sputum and bronchial secretions are variable in these patients.

Objective: We investigated whether a rapid diagnosis of pTB can be established by enumeration of MTB-specific mononuclear cells from bronchoalveolar lavage (BAL) fluid in routine clinical practice.

Methods: Patients presenting to a tertiary hospital with medical histories and pulmonary infiltrates compatible with tuberculosis, and negative acid-fast bacilli smear results (three) from sputum, were prospectively enrolled in this study. An MTB-specific enzyme-linked immunospot assay (ELISPOT [T-SPOT.TB; Oxford Immunotec, Abingdon, UK]) with early antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides was performed on peripheral blood mononuclear cells (PBMCs) and mononuclear cells from the BAL fluid (BALMCs).

Measurements and Main Results: Of 37 patients, 12 were found to have smear-negative pTB and 25 were found to have an alternative diagnosis. Patients with tuberculosis had a median number of 17 ESAT-6–specific cells and 24.5 CFP-10–specific cells per 200,000 PBMCs and 37.5 ESAT-6–specific cells and 49.5 CFP-10–specific cells per 200,000 cells in the BAL fluid. Control patients had a median of 1 ESAT-6–specific cell and 1 CFP-10–specific cell per 200,000 PBMCs and no ESAT-6– and CFP-10–specific cells per 200,000 cells in the BAL fluid (p < 0.0001). All patients with TB but none of the control subjects had more than 5 spot-forming cells per 200,000 BALMCs with either peptide in the BAL fluid ELISPOT.

Conclusion: Smear-negative pulmonary tuberculosis can be diagnosed rapidly by identification of MTB-specific cells in the BAL fluid.

Key Words: bronchoalveolar lavage • CFP-10 • ELISPOT • ESAT-6 • tuberculosis


Related articles in AJRCCM:

Finally, a Perfect Diagnostic Test for Pulmonary Tuberculosis—or Is It?
Akshay Sood and Mark Schuyler
AJRCCM 2006 174: 963-964. [Full Text]  



This article has been cited by other articles:


Home page
 ANN INTERN MEDHome page
M. Pai, A. Zwerling, and D. Menzies
Systematic Review: T-Cell-Based Assays for the Diagnosis of Latent Tuberculosis Infection: An Update
Ann Intern Med, June 30, 2008; (2008) 0000605-200808050-00241.
[Abstract] [Full Text] [PDF]

Home page
 CVIHome page
N. Khan, K. Alam, S. Nair, V. L. Valluri, K. J. R. Murthy, and S. Mukhopadhyay
Association of Strong Immune Responses to PPE Protein Rv1168c with Active Tuberculosis
Clin. Vaccine Immunol., June 1, 2008; 15(6): 974 - 980.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
A. Strassburg, C. Jafari, M. Ernst, W. Lotz, and C. Lange
Rapid diagnosis of pulmonary TB by BAL enzyme-linked immunospot assay in an immunocompromised host
Eur. Respir. J., May 1, 2008; 31(5): 1132 - 1135.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
C. Jafari, M. Ernst, A. Strassburg, U. Greinert, B. Kalsdorf, D. Kirsten, and C. Lange
Local immunodiagnosis of pulmonary tuberculosis by enzyme-linked immunospot
Eur. Respir. J., February 1, 2008; 31(2): 261 - 265.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
G. H Bothamley
New tests for tuberculosis: local immune responses have greater specificity
Thorax, January 1, 2008; 63(1): 4 - 5.
[Full Text] [PDF]

Home page
 ThoraxHome page
R A M Breen, S M Barry, C J Smith, R J Shorten, J P Dilworth, I Cropley, T D McHugh, S H Gillespie, G Janossy, and M C I Lipman
Clinical application of a rapid lung-orientated immunoassay in individuals with possible tuberculosis
Thorax, January 1, 2008; 63(1): 67 - 71.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. Losi, A. Bossink, L. Codecasa, C. Jafari, M. Ernst, S. Thijsen, D. Cirillo, M. Ferrarese, U. Greinert, L. M. Fabbri, et al.
Use of a T-cell interferon-{gamma} release assay for the diagnosis of tuberculous pleurisy
Eur. Respir. J., December 1, 2007; 30(6): 1173 - 1179.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J.-M. Hougardy, S. Place, M. Hildebrand, A. Drowart, A.-S. Debrie, C. Locht, and F. Mascart
Regulatory T Cells Depress Immune Responses to Protective Antigens in Active Tuberculosis
Am. J. Respir. Crit. Care Med., August 15, 2007; 176(4): 409 - 416.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. Lange, C. Jafari, and A. Lalvani
Rapid Diagnosis of Smear-negative Tuberculosis by Bronchoalveolar Lavage Enzyme-linked Immunospot
Am. J. Respir. Crit. Care Med., August 1, 2007; 176(3): 317 - 317.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. A. M. Breen, A. Dunleavy, and M. C. I. Lipman
Rapid Diagnosis of Smear-negative Tuberculosis by Bronchoalveolar Lavage Enzyme-linked Immunospot
Am. J. Respir. Crit. Care Med., August 1, 2007; 176(3): 316a - 317.
[Full Text] [PDF]

Home page
 ChestHome page
A. Lalvani
Diagnosing Tuberculosis Infection in the 21st Century: New Tools To Tackle an Old Enemy
Chest, June 1, 2007; 131(6): 1898 - 1906.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
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]

Home page
 JWatch Infect. DiseasesHome page
Active Pulmonary TB Diagnosed by ELISPOT of BAL Fluid
Journal Watch Infectious Diseases, November 15, 2006; 2006(1115): 4 - 4.
[Full Text]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Sood and M. Schuyler
Finally, a Perfect Diagnostic Test for Pulmonary Tuberculosis--or Is It?
Am. J. Respir. Crit. Care Med., November 1, 2006; 174(9): 963 - 964.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2006 American Thoracic Society