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Rapid diagnosis of pulmonary tuberculosis by combined molecular and immunological methods

Claudia Jafari, Ioana D. Olaru, Franziska Daduna, Martin Ernst, Jan Heyckendorf, Christoph Lange, Barbara Kalsdorf
European Respiratory Journal 2018; DOI: 10.1183/13993003.02189-2017
Claudia Jafari
1Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
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Ioana D. Olaru
1Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
2Biomedical Research and Training Institute, Harare, Zimbabwe
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Franziska Daduna
1Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
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Martin Ernst
3Division of Immune Cell-Analytics, Research Center Borstel, Borstel, Germany
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Jan Heyckendorf
1Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
4International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany
5German Center for Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel, Germany
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Christoph Lange
1Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
4International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany
5German Center for Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel, Germany
6Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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Barbara Kalsdorf
1Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
4International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany
5German Center for Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel, Germany
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Abstract

Diagnosing pulmonary tuberculosis (TB) may be delayed until culture results become available.

We ascertained the accuracy of a stepwise diagnostic algorithm for the rapid diagnosis of pulmonary TB by GeneXpert from sputum and/or bronchoalveolar-lavage (BAL) followed by a M. tuberculosis-specific BAL-enzyme-linked immunospot (ELISpot) assay in patients with a suspected diagnosis of pulmonary TB at a clinical referral center in Germany.

Among 166 patients with a presumptive diagnosis of pulmonary TB, 81 cases were confirmed by M. tuberculosis culture from sputum and/or BAL. In 66/81 (81.5%) cases patients had initially M. tuberculosis detected by GeneXpert from sputum. In addition, 6/81 (7.4%) were diagnosed by GeneXpert on BAL-fluid (together 72/81 (88.9%) patients). Out of the remaining 9 patients with negative GeneXpert results from sputum and BAL, BAL-ELISpot identified 8 patients with culture confirmed TB correctly (median time to culture positivity 26 days). At a cut-off of >4000 ESAT-6 or CFP-10-specific Interferon-γ producing lymphocytes per 1,000,0000 lymphocytes the specificity of the BAL-ELISpot for active TB was 97%.

In low incidence countries of TB, nearly all patients with active pulmonary TB can be identified within the first few days of clinical presentation using a stepwise strategy with GeneXpert and BAL-Elispot.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Jafari has nothing to disclose.

Conflict of interest: Dr. Olaru has nothing to disclose.

Conflict of interest: Mrs Daduna has nothing to disclose.

Conflict of interest: Dr. Ernst has nothing to disclose.

Conflict of interest: Dr. Heyckendorf reports personal fees from Chiesi, personal fees from Gilead, personal fees from Janssen, personal fees from Lucane, personal fees from Hain, outside the submitted work.

Conflict of interest: Dr. Lange reports personal fees from Chiesi, personal fees from Gilead, personal fees from Abbvie, personal fees from MSD, personal fees from Becton Dickinson, personal fees from Janssen, personal fees from Lucane, personal fees from Novartis, personal fees from Thermofisher, outside the submitted work.

Conflict of interest: Dr. Kalsdorf reports personal fees from Oxford Immunotec and Lucane, outside the submitted work.

This is a PDF-only article. Please click on the PDF link above to read it.

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Rapid diagnosis of pulmonary tuberculosis by combined molecular and immunological methods
Claudia Jafari, Ioana D. Olaru, Franziska Daduna, Martin Ernst, Jan Heyckendorf, Christoph Lange, Barbara Kalsdorf
European Respiratory Journal Jan 2018, 1702189; DOI: 10.1183/13993003.02189-2017

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Rapid diagnosis of pulmonary tuberculosis by combined molecular and immunological methods
Claudia Jafari, Ioana D. Olaru, Franziska Daduna, Martin Ernst, Jan Heyckendorf, Christoph Lange, Barbara Kalsdorf
European Respiratory Journal Jan 2018, 1702189; DOI: 10.1183/13993003.02189-2017
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