Investigation of transmission of human respiratory pathogens using whole genome sequencing
Stapleton, Patrick
Stapleton, Patrick
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Publication Date
2023-06-20
Type
Thesis
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Abstract
This doctoral thesis explores the role of whole genome sequencing in the investigation of transmission of human respiratory pathogens. It is a “PhD thesis by publication” which consists primarily of three published first-author journal articles that describe investigations of the transmission of Mumps virus, Adenovirus and Pseudomonas aeruginosa respectively. The work was undertaken in Toronto, Canada between 2016 and 2019, when the author was a Clinical and Research Fellow in Medical Microbiology at the University of Toronto, the Hospital for Sick Children and the Public Health Ontario Laboratory, as well as a PhD student with University of Galway supervised by Prof. Martin Cormican. The topics of the research were chosen for (1) their relevance to public health or hospital outbreak prevention and infection control and (2) as contexts in which best practices had yet to be established for genomic epidemiology investigations using whole genome sequencing. The majority of infections described occurred in the greater Toronto area. The introduction outlines the development of early generation pathogen typing techniques and the advent of low-cost and widely distributed whole genome sequencing technologies. The strengths and limitations of sequencing technologies that have seen widespread adoption in the field of clinical microbiology are described. An outline of the epidemiological context for each of the three articles is provided, along with rationales for using sequencing to explore transmission. The focus of the publications consists of (1) investigating the community spread of a Mumps virus outbreak in Ontario, (2) investigating a prolonged nosocomial outbreak of human Adenovirus-A31 affecting a paediatric bone marrow transplantation unit over 3 years and (3) the retrospective interrogation of a large collection of P. aeruginosa isolates from children with Cystic Fibrosis to identify cryptic nosocomial transmission. The discussion section that follows the main chapters describes how the findings from all investigations illustrate the need for clinicians to employ an approach to genomic epidemiology that can define thresholds for relatedness between pathogens where this has not already been clearly established, in order to “rule in” or “rule out” transmission as the core finding. The novelty and significance of specific findings from each study are identified and commonalities between them discussed. Finally, a post-script section explores how the lessons learned can be applied to the integration of whole genome sequencing into the routine work of clinical microbiology in hospitals laboratories in Ireland to support outbreak investigation. It briefly describes how initial steps towards this integration taken during the course of the Covid-19 pandemic through the setup of a national laboratory network for whole genome sequencing of SARS-CoV-2.
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Publisher
NUI Galway