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Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study

Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study
Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study
RATIONALE:
The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears.

OBJECTIVES:
Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smear-negative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay.

METHODS:
Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid.

MEASUREMENTS AND MAIN RESULTS:
Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB.

CONCLUSIONS:
Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice
1073-449X
666-673
Jafari, Claudia
3cfdc102-5b75-4045-ae08-c33430986a47
Thijsen, Steven
96d9b530-90ad-425f-bd70-95fa9685e096
Sotgiu, Giovanni
eab18651-aaf9-48d0-82e1-420a85ac21dd
Goletti, Delia
ef3f9a75-ecdb-4878-bce2-c81826fb8e44
Domínguez Benítez, José Antonio
b2429318-b495-49e1-a559-ba7c9a2dd2ae
Losi, Monica
6f2acb9f-04c8-45fc-9921-7b0a0f439129
Eberhardt, Ralf
a74d17f6-8d43-4065-bc97-140687527210
Kirsten, Detlef
956e0767-7034-4c1c-9ce2-72571c597209
Kalsdorf, Barbara
e19a32e1-19ca-4270-b5ab-ce7ce44eb6d1
Bossink, Aik
9062e3e6-a76e-405b-aa1e-79876cc91300
Latorre, Irene
22620b6e-0db0-40ed-b327-18a35fba274d
Migliori, Giovanni B.
c251574e-01ff-45e1-ab38-5d61e1ff0253
Strassburg, Alan
66b1187d-0f62-4b86-acdd-5f370115e4f7
Winteroll, Susanne
e6515ef1-c2f4-4ea6-81eb-d4879ebe54a9
Greinert, Ulf
6e89b692-a1ba-47c3-8125-ede03edd5ddd
Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
Ernst, Martin
c8bb4e9a-c97f-4bf5-898d-436776695444
Lange, Christoph
f5af446d-7feb-47c6-a4b9-1718c7dcd804
Jafari, Claudia
3cfdc102-5b75-4045-ae08-c33430986a47
Thijsen, Steven
96d9b530-90ad-425f-bd70-95fa9685e096
Sotgiu, Giovanni
eab18651-aaf9-48d0-82e1-420a85ac21dd
Goletti, Delia
ef3f9a75-ecdb-4878-bce2-c81826fb8e44
Domínguez Benítez, José Antonio
b2429318-b495-49e1-a559-ba7c9a2dd2ae
Losi, Monica
6f2acb9f-04c8-45fc-9921-7b0a0f439129
Eberhardt, Ralf
a74d17f6-8d43-4065-bc97-140687527210
Kirsten, Detlef
956e0767-7034-4c1c-9ce2-72571c597209
Kalsdorf, Barbara
e19a32e1-19ca-4270-b5ab-ce7ce44eb6d1
Bossink, Aik
9062e3e6-a76e-405b-aa1e-79876cc91300
Latorre, Irene
22620b6e-0db0-40ed-b327-18a35fba274d
Migliori, Giovanni B.
c251574e-01ff-45e1-ab38-5d61e1ff0253
Strassburg, Alan
66b1187d-0f62-4b86-acdd-5f370115e4f7
Winteroll, Susanne
e6515ef1-c2f4-4ea6-81eb-d4879ebe54a9
Greinert, Ulf
6e89b692-a1ba-47c3-8125-ede03edd5ddd
Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
Ernst, Martin
c8bb4e9a-c97f-4bf5-898d-436776695444
Lange, Christoph
f5af446d-7feb-47c6-a4b9-1718c7dcd804

Jafari, Claudia, Thijsen, Steven, Sotgiu, Giovanni, Goletti, Delia, Domínguez Benítez, José Antonio, Losi, Monica, Eberhardt, Ralf, Kirsten, Detlef, Kalsdorf, Barbara, Bossink, Aik, Latorre, Irene, Migliori, Giovanni B., Strassburg, Alan, Winteroll, Susanne, Greinert, Ulf, Richeldi, Luca, Ernst, Martin and Lange, Christoph (2009) Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study. American Journal of Respiratory and Critical Care Medicine, 180 (7), 666-673. (doi:10.1164/rccm.200904-0557OC). (PMID:19590020)

Record type: Article

Abstract

RATIONALE:
The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears.

OBJECTIVES:
Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smear-negative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay.

METHODS:
Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid.

MEASUREMENTS AND MAIN RESULTS:
Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB.

CONCLUSIONS:
Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice

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More information

e-pub ahead of print date: July 2009
Published date: 1 October 2009
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 369024
URI: http://eprints.soton.ac.uk/id/eprint/369024
ISSN: 1073-449X
PURE UUID: 665b262d-7dab-43ea-a811-d620ce92482d

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Date deposited: 23 Sep 2014 13:25
Last modified: 14 Mar 2024 17:57

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Contributors

Author: Claudia Jafari
Author: Steven Thijsen
Author: Giovanni Sotgiu
Author: Delia Goletti
Author: José Antonio Domínguez Benítez
Author: Monica Losi
Author: Ralf Eberhardt
Author: Detlef Kirsten
Author: Barbara Kalsdorf
Author: Aik Bossink
Author: Irene Latorre
Author: Giovanni B. Migliori
Author: Alan Strassburg
Author: Susanne Winteroll
Author: Ulf Greinert
Author: Luca Richeldi
Author: Martin Ernst
Author: Christoph Lange

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