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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article number667790
Number of pages11
JournalFrontiers in Microbiology
Volume12
DOIs
Publication statusPublished - 2 Jul 2021

Bibliographical note

Funding Information: This work was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. Sequencing of 121 samples, making up the pilot study, was funded by an Action Medical Research Grant (grant number GN2424) (CH). Sequencing of subsequent samples was funded by JB who receives funding from the National Institute of Health Research University College London/University College London Hospitals NHS Foundation Trust Biomedical Research Centre. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

JB has declared that the adenovirus bait designs are used with permission from Agilent.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Publisher Copyright: © Copyright © 2021 Myers, Houldcroft, Roy, Margetts, Best, Venturini, Guerra-Assunção, Williams, Williams, Dunn, Hartley, Rao, Rolfe and Breuer.

Citation: Myers CE, Houldcroft CJ, Roy S, Margetts BK, Best T, Venturini C, Guerra-Assunção JA, Williams CA, Williams R, Dunn H, Hartley JC, Rao K, Rolfe KJ and Breuer J (2021) Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit. Front. Microbiol. 12:667790.

DOI: 10.3389/fmicb.2021.667790

Keywords

  • adenovirus
  • epidemiology
  • nosocomial transmission
  • pediatric infectious disease
  • whole genome sequencing

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