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

Hdl Handle:
http://hdl.handle.net/10144/618996
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
Authors:
Carroll, M; Haldenby, S; Rickett, N; Pályi, B; Garcia-Dorival, I; Liu, X; Barker, G; Bore, J; Koundouno, F; Williamson, E; Laws, T; Kerber, R; Sissoko, D; Magyar, N; Di Caro, A; Biava, M; Fletcher, T; Sprecher, A; Ng, L; Rénia, L; Magassouba, N; Günther, S; Wölfel, R; Stoecker, K; Matthews, D; Hiscox, J
Journal:
mSphere
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.
Publisher:
American Society for Microbiology
Issue Date:
23-Aug-2017
URI:
http://hdl.handle.net/10144/618996
DOI:
10.1128/mSphereDirect.00325-17
PubMed ID:
28861524
Submitted date:
2017-09-05
Language:
en
ISSN:
2379-5042
Appears in Collections:
Other Diseases

Full metadata record

DC FieldValue Language
dc.contributor.authorCarroll, Men
dc.contributor.authorHaldenby, Sen
dc.contributor.authorRickett, Nen
dc.contributor.authorPályi, Ben
dc.contributor.authorGarcia-Dorival, Ien
dc.contributor.authorLiu, Xen
dc.contributor.authorBarker, Gen
dc.contributor.authorBore, Jen
dc.contributor.authorKoundouno, Fen
dc.contributor.authorWilliamson, Een
dc.contributor.authorLaws, Ten
dc.contributor.authorKerber, Ren
dc.contributor.authorSissoko, Den
dc.contributor.authorMagyar, Nen
dc.contributor.authorDi Caro, Aen
dc.contributor.authorBiava, Men
dc.contributor.authorFletcher, Ten
dc.contributor.authorSprecher, Aen
dc.contributor.authorNg, Len
dc.contributor.authorRénia, Len
dc.contributor.authorMagassouba, Nen
dc.contributor.authorGünther, Sen
dc.contributor.authorWölfel, Ren
dc.contributor.authorStoecker, Ken
dc.contributor.authorMatthews, Den
dc.contributor.authorHiscox, Jen
dc.date.accessioned2017-09-06T07:05:46Z-
dc.date.available2017-09-06T07:05:46Z-
dc.date.issued2017-08-23-
dc.date.submitted2017-09-05-
dc.identifier.citationDeep 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. 2 (4) mSphereen
dc.identifier.issn2379-5042-
dc.identifier.pmid28861524-
dc.identifier.doi10.1128/mSphereDirect.00325-17-
dc.identifier.urihttp://hdl.handle.net/10144/618996-
dc.description.abstractIn 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.en
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.rightsArchived with thanks to mSphereen
dc.titleDeep 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 Guten
dc.identifier.journalmSphereen

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