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Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection

BACKGROUND: Lung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant patients. Almost half of these episodes were of unknown infectious etiology despite extensi...

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Autores principales: Lewandowska, Dagmara W., Schreiber, Peter W., Schuurmans, Macé M., Ruehe, Bettina, Zagordi, Osvaldo, Bayard, Cornelia, Greiner, Michael, Geissberger, Fabienne D., Capaul, Riccarda, Zbinden, Andrea, Böni, Jürg, Benden, Christian, Mueller, Nicolas J., Trkola, Alexandra, Huber, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441588/
https://www.ncbi.nlm.nih.gov/pubmed/28542207
http://dx.doi.org/10.1371/journal.pone.0177340
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author Lewandowska, Dagmara W.
Schreiber, Peter W.
Schuurmans, Macé M.
Ruehe, Bettina
Zagordi, Osvaldo
Bayard, Cornelia
Greiner, Michael
Geissberger, Fabienne D.
Capaul, Riccarda
Zbinden, Andrea
Böni, Jürg
Benden, Christian
Mueller, Nicolas J.
Trkola, Alexandra
Huber, Michael
author_facet Lewandowska, Dagmara W.
Schreiber, Peter W.
Schuurmans, Macé M.
Ruehe, Bettina
Zagordi, Osvaldo
Bayard, Cornelia
Greiner, Michael
Geissberger, Fabienne D.
Capaul, Riccarda
Zbinden, Andrea
Böni, Jürg
Benden, Christian
Mueller, Nicolas J.
Trkola, Alexandra
Huber, Michael
author_sort Lewandowska, Dagmara W.
collection PubMed
description BACKGROUND: Lung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant patients. Almost half of these episodes were of unknown infectious etiology despite extensive routine diagnostic testing. METHODS: We re-analyzed respiratory samples of all episodes with undetermined etiology in order to detect potential viral pathogens missed/not accounted for in routine diagnostics. Respiratory samples were enriched for viruses by filtration and nuclease digestion, whole nucleic acids extracted and randomly amplified before high throughput metagenomic virus sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and quantified using specific real-time PCR. RESULTS: In completion of routine diagnostics, we identified and confirmed a viral etiology of infection by our metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B infection) despite initial negative results in specific multiplex PCR. Notably, the majority of samples were also positive for Torque teno virus (TTV) and Human Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in both throat swabs and blood samples, HHV-7 remained at low levels throughout the observation period and was restricted to the respiratory tract. CONCLUSION: This study highlights the potential of metagenomic sequencing for virus diagnostics in cases with previously unknown etiology of infection and in complex diagnostic situations such as in immunocompromised hosts.
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spelling pubmed-54415882017-06-06 Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection Lewandowska, Dagmara W. Schreiber, Peter W. Schuurmans, Macé M. Ruehe, Bettina Zagordi, Osvaldo Bayard, Cornelia Greiner, Michael Geissberger, Fabienne D. Capaul, Riccarda Zbinden, Andrea Böni, Jürg Benden, Christian Mueller, Nicolas J. Trkola, Alexandra Huber, Michael PLoS One Research Article BACKGROUND: Lung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant patients. Almost half of these episodes were of unknown infectious etiology despite extensive routine diagnostic testing. METHODS: We re-analyzed respiratory samples of all episodes with undetermined etiology in order to detect potential viral pathogens missed/not accounted for in routine diagnostics. Respiratory samples were enriched for viruses by filtration and nuclease digestion, whole nucleic acids extracted and randomly amplified before high throughput metagenomic virus sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and quantified using specific real-time PCR. RESULTS: In completion of routine diagnostics, we identified and confirmed a viral etiology of infection by our metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B infection) despite initial negative results in specific multiplex PCR. Notably, the majority of samples were also positive for Torque teno virus (TTV) and Human Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in both throat swabs and blood samples, HHV-7 remained at low levels throughout the observation period and was restricted to the respiratory tract. CONCLUSION: This study highlights the potential of metagenomic sequencing for virus diagnostics in cases with previously unknown etiology of infection and in complex diagnostic situations such as in immunocompromised hosts. Public Library of Science 2017-05-23 /pmc/articles/PMC5441588/ /pubmed/28542207 http://dx.doi.org/10.1371/journal.pone.0177340 Text en © 2017 Lewandowska et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lewandowska, Dagmara W.
Schreiber, Peter W.
Schuurmans, Macé M.
Ruehe, Bettina
Zagordi, Osvaldo
Bayard, Cornelia
Greiner, Michael
Geissberger, Fabienne D.
Capaul, Riccarda
Zbinden, Andrea
Böni, Jürg
Benden, Christian
Mueller, Nicolas J.
Trkola, Alexandra
Huber, Michael
Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection
title Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection
title_full Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection
title_fullStr Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection
title_full_unstemmed Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection
title_short Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection
title_sort metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441588/
https://www.ncbi.nlm.nih.gov/pubmed/28542207
http://dx.doi.org/10.1371/journal.pone.0177340
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