Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit

A recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our...

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Main Authors: Chloe E. Myers, Charlotte J. Houldcroft, Sunando Roy, Ben K. Margetts, Timothy Best, Cristina Venturini, Jose A. Guerra-Assunção, Charlotte A. Williams, Rachel Williams, Helen Dunn, John C. Hartley, Kanchan Rao, Kathryn J. Rolfe, Judith Breuer
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2021.667790/full
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author Chloe E. Myers
Charlotte J. Houldcroft
Sunando Roy
Ben K. Margetts
Timothy Best
Cristina Venturini
Jose A. Guerra-Assunção
Charlotte A. Williams
Rachel Williams
Helen Dunn
John C. Hartley
Kanchan Rao
Kathryn J. Rolfe
Judith Breuer
Judith Breuer
author_facet Chloe E. Myers
Charlotte J. Houldcroft
Sunando Roy
Ben K. Margetts
Timothy Best
Cristina Venturini
Jose A. Guerra-Assunção
Charlotte A. Williams
Rachel Williams
Helen Dunn
John C. Hartley
Kanchan Rao
Kathryn J. Rolfe
Judith Breuer
Judith Breuer
author_sort Chloe E. Myers
collection DOAJ
description A recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our own database of HAdVs. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships, paired with the epidemiological data from routine infection prevention and control (IPC) records and hospital activity data. During this time period, two formal outbreaks had been declared by IPC, while WGS detected nine monophyletic clusters, seven were corroborated by epidemiological evidence and by comparison of single-nucleotide polymorphisms. One of the formal outbreaks was confirmed, and the other was not. Of the five HAdV-associated deaths, three were unlinked and the remaining two considered the source of transmission. Mixed infection was frequent (10%), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harboring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into clinical practice to influence IPC policy contemporaneously.
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spelling doaj.art-360c8e1e8b4b4d158ae7b7e350ce08d72022-12-21T18:27:51ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-07-011210.3389/fmicb.2021.667790667790Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant UnitChloe E. Myers0Charlotte J. Houldcroft1Sunando Roy2Ben K. Margetts3Timothy Best4Cristina Venturini5Jose A. Guerra-Assunção6Charlotte A. Williams7Rachel Williams8Helen Dunn9John C. Hartley10Kanchan Rao11Kathryn J. Rolfe12Judith Breuer13Judith Breuer14Cambridge Clinical Microbiology and Public Health Laboratory, Public Health England, Cambridge, United KingdomDepartment of Medicine, University of Cambridge, Cambridge, United KingdomDivision of Infection and Immunity, University College London, London, United KingdomDivision of Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, United KingdomDepartment of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, United KingdomDivision of Infection and Immunity, University College London, London, United KingdomDivision of Infection and Immunity, University College London, London, United KingdomDivision of Infection and Immunity, University College London, London, United KingdomDivision of Infection and Immunity, University College London, London, United KingdomDepartment of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, United KingdomDepartment of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, United KingdomDepartment of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, United KingdomCambridge Clinical Microbiology and Public Health Laboratory, Public Health England, Cambridge, United KingdomDivision of Infection and Immunity, University College London, London, United KingdomDepartment of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, United KingdomA recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our own database of HAdVs. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships, paired with the epidemiological data from routine infection prevention and control (IPC) records and hospital activity data. During this time period, two formal outbreaks had been declared by IPC, while WGS detected nine monophyletic clusters, seven were corroborated by epidemiological evidence and by comparison of single-nucleotide polymorphisms. One of the formal outbreaks was confirmed, and the other was not. Of the five HAdV-associated deaths, three were unlinked and the remaining two considered the source of transmission. Mixed infection was frequent (10%), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harboring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into clinical practice to influence IPC policy contemporaneously.https://www.frontiersin.org/articles/10.3389/fmicb.2021.667790/fulladenovirusepidemiologywhole genome sequencingpediatric infectious diseasenosocomial transmission
spellingShingle Chloe E. Myers
Charlotte J. Houldcroft
Sunando Roy
Ben K. Margetts
Timothy Best
Cristina Venturini
Jose A. Guerra-Assunção
Charlotte A. Williams
Rachel Williams
Helen Dunn
John C. Hartley
Kanchan Rao
Kathryn J. Rolfe
Judith Breuer
Judith Breuer
Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit
Frontiers in Microbiology
adenovirus
epidemiology
whole genome sequencing
pediatric infectious disease
nosocomial transmission
title Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit
title_full Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit
title_fullStr Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit
title_full_unstemmed Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit
title_short Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit
title_sort using whole genome sequences to investigate adenovirus outbreaks in a hematopoietic stem cell transplant unit
topic adenovirus
epidemiology
whole genome sequencing
pediatric infectious disease
nosocomial transmission
url https://www.frontiersin.org/articles/10.3389/fmicb.2021.667790/full
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