Candida auris
National insight into the genomic epidemiology of Candida auris
Candida auris (C. auris)is an emerging fungal infection that has been identified in over 40 countries since it was first identified in Japan in 2009. Retrospective studies of strain collections identified cases dating back to 1996. C. auris preferentially colonises the skin and can disseminate to internal organs (liver, brain, lungs, bones, kidneys, and urinary tract) via a systemic bloodstream infection (candidemia). C. auris can colonise the skin, persist on surfaces and on medical equipment, and be transmitted person-to-person. It is a pathogen of increasing clinical importance due to widespread multi-drug resistance with a multi-country study revealing >90% of strains to be resistant to fluconazole, 35% resistant to amphotericin B, and over 40% exhibiting combined resistance to two or more classes of antifungals. Concerningly, this pathogen exhibits nosocomial spread with healthcare-associated outbreaks reported in numerous countries. Particularly in the USA, an increase in new cases of colonisation and infection have been reported during the COVID-19 pandemic, in part due to the increase in ICU admissions and invasive mechanical ventilation. In 2022, the CDC reported 2,377 clinical cases and 5,754 screening cases across the United States.
The C. auris genome ranges between 12.3 and 12.5 Mb with 8527 predicted genes. Although C. auris is typically a haploid organism (single-copy of the chromosome), C. auris strains have a highly plastic karyotype and can undergo rapid stress-induced karyotypic changes to diploid form. There are 5 clades of C. auris with a degree of geographical association: South Asian (clade I), East Asian (clade II), South African (clade III), South American (clade IV) and a recently emerged clade from Iran (clade V). Isolates from different clades differ by tens of thousands of single nucleotide polymorphisms (SNPs).
The first C. auris case in Australia was identified in 2015 in Perth, isolated from an overseas visitor with a history of hospitalisation in Kenya, and whole genome sequencing (WGS) revealed this isolate to belong to clade III. Thirteen other Australian C. auris isolates have undergone WGS; with nine belonging to clade III and four belonging to clade I. In Australia, the limited cases identified have been associated with travel but that does not preclude the occurrence of local acquisition or nosocomial transmission. The first C. auris in New Zealand was identified in 2023. Of growing concern is the emergence of isolates harbouring multi-drug resistance profiles, azole and echinocandin resistance have been found to be closely related to specific mutations in the ERG11 and FKS1 genes, respectively, and are recommended as diagnostic markers for drug-resistant C. auris. The recognised azole resistance mutations F126T, Y132F, K143R, and echinocandin resistance mutation S639F/P have clade-association with F126T in the South African clade, Y132F or K143R in the South Asian clade, and Y132F in the South American clade.
Reflecting the increasing awareness of this pathogen of concern, C. auris is a notifiable disease in Victoria, South Australia, and New South Wales, with Queensland and Western Australia requesting notifications for any identification. C. auris is not currently a notifiable pathogen in New Zealand. Given the global increase in C. auris in recent years it is important to initiate national surveillance to inform public health measures.
The development of a national genomic surveillance framework will provide a unified means of defining C. auris clusters. This is critical to elucidate healthcare setting outbreaks, local transmission, and importation events. A national surveillance system will strengthen the ability of public health personnel to identify and respond to outbreaks of C. auris in hospital and community settings; critically it will identify the incursion of new clades into Australia and may reveal undetected transmission within the community. Additionally, genomic surveillance will also generate insights into mechanisms of antifungal resistance and help to inform treatment.
Project Aims
Specific Aim: Develop a systematic national surveillance framework for Candida auris and integration in AusTrakka
1. To implement harmonised national analysis methodologies in AusTrakka
2. Undertake retrospective whole genome sequence analysis of Candida auris of all isolates archived and implement a 12-month prospective collection from all jurisdictions to identify the strains and clades present in Australia and New Zealand, and highlight local transmission and importation events
3. Develop a guidance document on Candida auris genomic surveillance for public health laboratories and integrate with public health agencies
