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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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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. |
format | Online Article Text |
id | pubmed-5441588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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