Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut

ABSTRACT In this study, samples from the 2013–2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were...

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Autores principales:	Miles W. Carroll, Sam Haldenby, Natasha Y. Rickett, Bernadett Pályi, Isabel Garcia-Dorival, Xuan Liu, Gary Barker, Joseph Akoi Bore, Fara Raymond Koundouno, E. Diane Williamson, Thomas R. Laws, Romy Kerber, Daouda Sissoko, Nóra Magyar, Antonino Di Caro, Mirella Biava, Tom E. Fletcher, Armand Sprecher, Lisa F. P. Ng, Laurent Rénia, N’faly Magassouba, Stephan Günther, Roman Wölfel, Kilian Stoecker, David A. Matthews, Julian A. Hiscox
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Ebola Ebola virus disease informatics Plasmodium falciparum RNA-seq bioinformatics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/15eddfa1f3bf4e41a7ea4d4bff200030
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spelling	oai:doaj.org-article:15eddfa1f3bf4e41a7ea4d4bff2000302021-11-15T15:22:04ZDeep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut10.1128/mSphereDirect.00325-172379-5042https://doaj.org/article/15eddfa1f3bf4e41a7ea4d4bff2000302017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00325-17https://doaj.org/toc/2379-5042ABSTRACT In this study, samples from the 2013–2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting. IMPORTANCE Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.Miles W. CarrollSam HaldenbyNatasha Y. RickettBernadett PályiIsabel Garcia-DorivalXuan LiuGary BarkerJoseph Akoi BoreFara Raymond KoundounoE. Diane WilliamsonThomas R. LawsRomy KerberDaouda SissokoNóra MagyarAntonino Di CaroMirella BiavaTom E. FletcherArmand SprecherLisa F. P. NgLaurent RéniaN’faly MagassoubaStephan GüntherRoman WölfelKilian StoeckerDavid A. MatthewsJulian A. HiscoxAmerican Society for MicrobiologyarticleEbolaEbola virus diseaseinformaticsPlasmodium falciparumRNA-seqbioinformaticsMicrobiologyQR1-502ENmSphere, Vol 2, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ebola Ebola virus disease informatics Plasmodium falciparum RNA-seq bioinformatics Microbiology QR1-502
spellingShingle	Ebola Ebola virus disease informatics Plasmodium falciparum RNA-seq bioinformatics Microbiology QR1-502 Miles W. Carroll Sam Haldenby Natasha Y. Rickett Bernadett Pályi Isabel Garcia-Dorival Xuan Liu Gary Barker Joseph Akoi Bore Fara Raymond Koundouno E. Diane Williamson Thomas R. Laws Romy Kerber Daouda Sissoko Nóra Magyar Antonino Di Caro Mirella Biava Tom E. Fletcher Armand Sprecher Lisa F. P. Ng Laurent Rénia N’faly Magassouba Stephan Günther Roman Wölfel Kilian Stoecker David A. Matthews Julian A. Hiscox Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut
description	ABSTRACT In this study, samples from the 2013–2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting. IMPORTANCE Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.
format	article
author	Miles W. Carroll Sam Haldenby Natasha Y. Rickett Bernadett Pályi Isabel Garcia-Dorival Xuan Liu Gary Barker Joseph Akoi Bore Fara Raymond Koundouno E. Diane Williamson Thomas R. Laws Romy Kerber Daouda Sissoko Nóra Magyar Antonino Di Caro Mirella Biava Tom E. Fletcher Armand Sprecher Lisa F. P. Ng Laurent Rénia N’faly Magassouba Stephan Günther Roman Wölfel Kilian Stoecker David A. Matthews Julian A. Hiscox
author_facet	Miles W. Carroll Sam Haldenby Natasha Y. Rickett Bernadett Pályi Isabel Garcia-Dorival Xuan Liu Gary Barker Joseph Akoi Bore Fara Raymond Koundouno E. Diane Williamson Thomas R. Laws Romy Kerber Daouda Sissoko Nóra Magyar Antonino Di Caro Mirella Biava Tom E. Fletcher Armand Sprecher Lisa F. P. Ng Laurent Rénia N’faly Magassouba Stephan Günther Roman Wölfel Kilian Stoecker David A. Matthews Julian A. Hiscox
author_sort	Miles W. Carroll
title	Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut
title_short	Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut
title_full	Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut
title_fullStr	Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut
title_full_unstemmed	Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut
title_sort	deep sequencing of rna from blood and oral swab samples reveals the presence of nucleic acid from a number of pathogens in patients with acute ebola virus disease and is consistent with bacterial translocation across the gut
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/15eddfa1f3bf4e41a7ea4d4bff200030
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Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut

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