Community outbreaks of group A Streptococcus revealed by genome sequencing

Claire E Turner,Julian Parkhill,Nicholas M Brown,Sharon J Peacock,Kim Judge,M Estée Török,Luke Bedford

doi:10.1038/s41598-017-08914-x

Abstract

The frequent occurrence of disease outbreaks in humans caused by group A Streptococcus (GAS) is an on-going public health threat. Conventional bacterial typing methods lack the discriminatory power to confidently confirm or refute outbreaks in hospital and community settings. Microbial whole genome sequencing (WGS) provides a potential solution to this, but, there has been limited population-based surveillance with accompanying sequence data. We performed retrospective genomic surveillance of 93 clinical GAS isolates from individuals in a defined geographic region. Detailed clinical information was obtained for closely related clusters of isolates. Genomic sequence data was contextualised through comparison with international data. We identified 18 different emm genotypes within our bacterial population, and revealed both highly diverse and closely related isolates. This high level of diversity was maintained even in the context of international sequence data. We also identified two emm1 clusters, and one emm3 cluster, of closely-related isolates that differed only by 1 to 4 single nucleotide polymorphisms. Analysis of clinical information identified no healthcare associated contact between patients, indicating cryptic community transmission. Our findings suggest that genomic surveillance of GAS would increase detection of transmission and highlight opportunities for intervention.

Highlights

The Lancefield group A Streptococcus (GAS; Streptococcus pyogenes) is a human pathogen capable of causing a wide spectrum of infections, ranging from self-limiting tonsillitis and pharyngitis to severe, and potentially lethal necrotising fasciitis and toxic shock syndrome
We conducted a retrospective observational cohort study at the Cambridge University Hospitals NHS Foundation Trust (CUH) in the United Kingdom (UK), and identified 93 patients with at least one GAS isolate stored between 1st January 2006 and 31st December 2012 (Supplementary Table 1)
Seventy isolates were from CUH patients, 14 from local district general and community hospitals (GCH), and 9 from general practice (GP)

Summary

Introduction

The Lancefield group A Streptococcus (GAS; Streptococcus pyogenes) is a human pathogen capable of causing a wide spectrum of infections, ranging from self-limiting tonsillitis and pharyngitis to severe, and potentially lethal necrotising fasciitis and toxic shock syndrome. The use of WGS in routine practice will require access to contextual genome databases, to enable comparison of outbreak isolates with circulating lineages. This can be used to support decisions on transmission events and outbreaks, may provide more specific information on the abundance of variant strains and disease propensity, and identify cryptic disease clusters occurring in the community. We describe retrospective genomic surveillance of clinical GAS isolated from individuals in a circumscribed geographic region This bacterial population contained 18 different emm genotypes, and both highly diverse and closely related isolates. The presence of clusters of highly similar isolates with no link to healthcare is indicative of cryptic community transmission

Methods

Results

Conclusion