Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA: a molecular epidemiological survey

Abstract

Background: Transmission of multidrug-resistant Candida auris infection has been reported in the USA. To better understand its emergence and transmission dynamics and to guide clinical and public health responses, we did a molecular epidemiological investigation of C auris cases in the USA.

Methods: In this molecular epidemiological survey, we used whole-genome sequencing to assess the genetic similarity between isolates collected from patients in ten US states (California, Connecticut, Florida, Illinois, Indiana, Maryland, Massachusetts, New Jersey, New York, and Oklahoma) and those identified in several other countries (Colombia, India, Japan, Pakistan, South Africa, South Korea, and Venezuela). We worked with state health departments, who provided us with isolates for sequencing. These isolates of C auris were collected during the normal course of clinical care (clinical cases) or as part of contact investigations or point prevalence surveys (screening cases). We integrated data from standardised case report forms and contact investigations, including travel history and epidemiological links (ie, patients that had shared a room or ward with a patient with C auris). Genetic diversity of C auris within a patient, a facility, and a state were evaluated by pairwise differences in single-nucleotide polymorphisms (SNPs).

Findings: From May 11, 2013, to Aug 31, 2017, isolates that corresponded to 133 cases (73 clinical cases and 60 screening cases) were collected. Of 73 clinical cases, 66 (90%) cases involved isolates related to south Asian isolates, five (7%) cases were related to South American isolates, one (1%) case to African isolates, and one (1%) case to east Asian isolates. Most (60 [82%]) clinical cases were identified in New York and New Jersey; these isolates, although related to south Asian isolates, were genetically distinct. Genomic data corroborated five (7%) clinical cases in which patients probably acquired C auris through health-care exposures abroad. Among clinical and screening cases, the genetic diversity of C auris isolates within a person was similar to that within a facility during an outbreak (median SNP difference three SNPs, range 0-12).

Interpretation: Isolates of C auris in the USA were genetically related to those from four global regions, suggesting that C auris was introduced into the USA several times. The five travel-related cases are examples of how introductions can occur. Genetic diversity among isolates from the same patients, health-care facilities, and states indicates that there is local and ongoing transmission.

Funding: US Centers for Disease Control and Prevention.

Figure 1. Distribution of Candida auris clades within the USA

(A) Maximum parsimony phylogenetic tree of isolates from Colombia, India, Japan, Pakistan, South Korea, South Africa, Venezuela, and clinical cases in the USA (up to the first five clinical cases from each US state). (B) The frequency of clinical cases in the USA by clade. (C) The geographical distribution of clades; solid lines indicate introductions that are associated with patients known to have received health care abroad. CA=California. CT=Connecticut. FL=Florida. IL=Illinois. IN=Indiana. MA=Massachusetts. MD=Maryland. NY=New York. NJ=New Jersey. OK=Oklahoma. SNPs=single-nucleotide polymorphisms.

Figure 2. Identification of genetically distinct Candida auris strains in different US states

(A) Neighbour-joining phylogenetic tree of the South Asian clade, to examine isolates from clinical cases from seven US states, India, and Pakistan. (B) The principal component analysis of genetic differences between these isolates. Circles at nodes indicate separations with a bootstrap value of at least 90%. CA=California. CT=Connecticut. FL=Florida. IL=Illinois. IN=Indiana. MA=Massachusetts. MD=Maryland. NY=New York. NJ=New Jersey. OK=Oklahoma. PC1=principal component 1. PC2=principal component 2. *The 2013 case in NY.

Figure 3. Identification of five US travel-related Candida auris cases

Phylogenetic trees of the South Asian (A), South American (B), and African (C) clades, to examine isolates from clinical cases in patients known to have received medical care abroad before diagnosis of C auris infection in the USA. Numbers above branches indicate SNPs. Circles at nodes indicate separations with a bootstrap value of at least 90%. CA=California. CT=Connecticut. FL=Florida. IN=Indiana. OK=Oklahoma. SNPs=single-nucleotide polymorphisms.

Figure 4. Genetic diversity of Candida auris isolates taken from patients in the USA during transmission

(A) The mean SNP difference among several isolates taken from the same person, in 23 patients in the USA. (B) The number of SNP differences for each pairwise comparison among ten patients at a facility in New Jersey with an outbreak of C auris. (C) The number of SNP differences for each pairwise comparison among all isolates from 42 patients in New York, excluding the 2013 case, and among the epidemiologically linked pairwise comparisons in New York. The light blue diamond indicates pairwise comparisons with a single screening case in New York in 2016. SNP=single-nucleotide polymorphism.