Genomic epidemiology ofCandida aurisintroduction and outbreaks in the United Kingdom

Abstract

AbstractBackgroundCandida aurisis a globally emerging fungal pathogen that causes nosocomial invasive infections, particularly in intensive care units (ICU). Four prominent genetic clades originating from distinct geographic regions have been identified: South Asia (Clade I), East Asia (Clade II), Africa (Clade III) and South America (Clade IV) with each clade presenting differing antifungal resistance profiles. We aimed to elucidate the epidemiology of this infection in the United Kingdom (UK) 2014 - 2019 using genomic approaches.MethodsGenome sequences from 24 isolates from six patients in four London hospitals were combined with genome sequences from 183 additional outbreak isolates from nine UK hospitals. These data were used to assess the numbers and timings ofC. aurislineage introductions into the UK and to infer subsequent patterns of inter- and intra-hospital transmission.FindingsWe found evidence for at least three introductions ofC. aurisinto the UK, one from Clade I and one from Clade III. The evolutionary rate ofC. aurisClade I and Clade III were estimated at 2.764 x 10-4and 3.186 x 10-4substitutions per polymorphic site per year, respectively, with entry into the UK as 2013 and 2016 for Clades I and III respectively. We observed temporal and geographical evidence for multiple transmission events between hospitals and identified local within-hospital patient-to-patient transmission events.InterpretationThese data confirm thatC. aurisis a newly emerged infection in the UK with at least three original introductions into this country. Our analysis shows that hospital outbreaks are linked and confirms that transmission amongst patients has occurred, explaining local hospital outbreaks. Our findings argue that enhanced surveillance ofC. aurisinfection within the UK is necessary in order to protect healthcare and to curtail expansion of this emerging infection.FundingThis work was supported by a Wellcome Trust Institutional Strategic Support Fund Springboard Fellowship, and by the Medical Research Council (MR/R015600/1), the Natural Environment Research Council (NE/P001165/1) and the Wellcome Trust (219551/Z/19/Z).Research in contextSince its first description in 2009,Candida aurishas spread across the globe. For this study, authors considered all publications describing whole genome sequences of isolates within the UK up until 2020 to assess the genomic epidemiology of this fungal pathogen. This study adds value to the current understanding ofC. aurisepidemiology by undertaking the first analysis to assess transmission between and within hospitals using genomic data. We also provide the first in-depth temporal analysis to estimate likely times of introduction into the UK. These results have clinical implications, encouraging hospitals to identify yeast upon admission and to assess multiple isolates from single patients, which may harbour much diversity in terms of genetics and drug resistance.