Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis

A Tuberculosis Network European Trialsgroup study

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

Research output: Contribution to journalArticle

111 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)666-673
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume180
Issue number7
DOIs
Publication statusPublished - Oct 1 2009

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Bronchoalveolar Lavage
Tuberculosis
Sputum
Bacillus
Enzymes
Mycobacterium tuberculosis
Blood Cells
Acids
Odds Ratio
Latent Tuberculosis
Tuberculin Test
Skin Tests
Pulmonary Tuberculosis
Nucleic Acids
Enzyme-Linked Immunospot Assay
Immunologic Tests
Bronchoalveolar Lavage Fluid
Sensitivity and Specificity
Peptides

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis : A Tuberculosis Network European Trialsgroup study. / 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; Lange, Christoph.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 180, No. 7, 01.10.2009, p. 666-673.

Research output: Contribution to journalArticle

Jafari, C, Thijsen, S, Sotgiu, G, Goletti, D, Domínguez Benítez, JA, Losi, M, Eberhardt, R, Kirsten, D, Kalsdorf, B, Bossink, A, Latorre, I, Migliori, GB, Strassburg, A, Winteroll, S, Greinert, U, Richeldi, L, Ernst, M & Lange, C 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, vol. 180, no. 7, pp. 666-673. https://doi.org/10.1164/rccm.200904-0557OC
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 ; Lange, Christoph. / Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis : A Tuberculosis Network European Trialsgroup study. In: American Journal of Respiratory and Critical Care Medicine. 2009 ; Vol. 180, No. 7. pp. 666-673.
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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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AU - Goletti, Delia

AU - Domínguez Benítez, José Antonio

AU - Losi, Monica

AU - Eberhardt, Ralf

AU - Kirsten, Detlef

AU - Kalsdorf, Barbara

AU - Bossink, Aik

AU - Latorre, Irene

AU - Migliori, Giovanni B.

AU - Strassburg, Alan

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