Nanopore metagenomic sequencing to investigate nosocomial transmission of human metapneumovirus from a unique genetic group among haematology patients in the United Kingdom.


Journal

The Journal of infection
ISSN: 1532-2742
Titre abrégé: J Infect
Pays: England
ID NLM: 7908424

Informations de publication

Date de publication:
05 2020
Historique:
received: 10 12 2019
revised: 05 02 2020
accepted: 08 02 2020
pubmed: 25 2 2020
medline: 19 3 2021
entrez: 25 2 2020
Statut: ppublish

Résumé

Human metapneumovirus (HMPV) infection causes a spectrum of respiratory tract disease, and may be a significant pathogen in the context of immunocompromise. Here, we report direct-from-sample metagenomic sequencing of HMPV using Oxford Nanopore Technology. We applied this sequencing approach to 25 respiratory samples that had been submitted to a clinical diagnostic laboratory in a UK teaching hospital. These samples represented 13 patients under the care of a haematology unit over a 20-day period in Spring 2019 (two sampled twice), and ten other patients elsewhere in the hospital between 2017-2019. We generated HMPV reads from 20/25 samples (sensitivity 80% compared to routine diagnostic testing) and retrieved complete HMPV genomes from 15/20 of these. Consensus sequences from Nanopore data were identical to those generated by Illumina, and represented HMPV genomes from two distinct sublineages, A2b and B2. Sequences from ten haematology patients formed a unique genetic group in the A2b sublineage, not previously reported in the UK. Among these, eight HMPV genomes formed a cluster (differing by ≤3 SNPs), likely to reflect nosocomial transmission, while two others were more distantly related and may represent independent introductions to the haematology unit. Nanopore metagenomic sequencing can be used to diagnose HMPV infection, although more work is required to optimise sensitivity. Improvements in the use of metagenomic sequencing, particularly for respiratory viruses, could contribute to antimicrobial stewardship. Generation of full genome sequences can be used to support or rule out nosocomial transmission, and contribute to improving infection prevention and control practices.

Sections du résumé

BACKGROUND
Human metapneumovirus (HMPV) infection causes a spectrum of respiratory tract disease, and may be a significant pathogen in the context of immunocompromise. Here, we report direct-from-sample metagenomic sequencing of HMPV using Oxford Nanopore Technology.
METHODS
We applied this sequencing approach to 25 respiratory samples that had been submitted to a clinical diagnostic laboratory in a UK teaching hospital. These samples represented 13 patients under the care of a haematology unit over a 20-day period in Spring 2019 (two sampled twice), and ten other patients elsewhere in the hospital between 2017-2019.
RESULTS
We generated HMPV reads from 20/25 samples (sensitivity 80% compared to routine diagnostic testing) and retrieved complete HMPV genomes from 15/20 of these. Consensus sequences from Nanopore data were identical to those generated by Illumina, and represented HMPV genomes from two distinct sublineages, A2b and B2. Sequences from ten haematology patients formed a unique genetic group in the A2b sublineage, not previously reported in the UK. Among these, eight HMPV genomes formed a cluster (differing by ≤3 SNPs), likely to reflect nosocomial transmission, while two others were more distantly related and may represent independent introductions to the haematology unit.
CONCLUSION
Nanopore metagenomic sequencing can be used to diagnose HMPV infection, although more work is required to optimise sensitivity. Improvements in the use of metagenomic sequencing, particularly for respiratory viruses, could contribute to antimicrobial stewardship. Generation of full genome sequences can be used to support or rule out nosocomial transmission, and contribute to improving infection prevention and control practices.

Identifiants

pubmed: 32092386
pii: S0163-4453(20)30085-2
doi: 10.1016/j.jinf.2020.02.003
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

571-577

Subventions

Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 110110
Pays : United Kingdom

Informations de copyright

Copyright © 2020. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest MC, RV and STP have previously received consumables free of charge from ONT, but not for the study presented here.

Auteurs

Yifei Xu (Y)

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom. Electronic address: yifei.xu@ndm.ox.ac.uk.

Kuiama Lewandowski (K)

Public Health England, National Infection Service, Porton Down, Salisbury, United Kingdom.

Katie Jeffery (K)

Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom.

Louise O Downs (LO)

Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom; Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.

Dona Foster (D)

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom.

Nicholas D Sanderson (ND)

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom.

James Kavanagh (J)

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom.

Ali Vaughan (A)

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom.

Claudia Salvagno (C)

Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom.

Richard Vipond (R)

Public Health England, National Infection Service, Porton Down, Salisbury, United Kingdom.

Miles Carroll (M)

Public Health England, National Infection Service, Porton Down, Salisbury, United Kingdom.

Robert Danby (R)

Department of Haematology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom.

Timothy Peto (T)

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom.

Derrick Crook (D)

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom.

A Sarah Walker (AS)

Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom.

Philippa C Matthews (PC)

NIHR Oxford Biomedical Research Centre, University of Oxford, United Kingdom; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom; Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.

Steven T Pullan (ST)

Public Health England, National Infection Service, Porton Down, Salisbury, United Kingdom.

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