Application of Whole-Genome Sequencing to an Unusual Outbreak of Invasive Group A Streptococcal Disease

Galloway-Peña, Jessica; Clement, Meredith E.; B, Kuinkel; Ruffin, Felicia; Levinson, Howard; Shelburne, Samuel A.; Moore, Zack; Fowler, Vance G.

doi:10.1093/ofid/ofw042

Cited by 13 publications

(17 citation statements)

References 15 publications

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“…WGS has been used successfully to investigate a small number of putative outbreaks, confirming a single causative strain that was distinct from the circulating population, which were otherwise indistinguishable by standard molecular typing methods 12 – 14 . Where epidemiological evidence for transmission is unclear or lacking, WGS data could potentially provide valuable supporting evidence to assist outbreak investigations 15 .…”

Section: Introductionmentioning

confidence: 99%

Community outbreaks of group A Streptococcus revealed by genome sequencing

Turner

Bedford

Brown

et al. 2017

Sci Rep

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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.

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Section: Introductionmentioning

confidence: 99%

Community outbreaks of group A Streptococcus revealed by genome sequencing

Turner

Bedford

Brown

et al. 2017

Sci Rep

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“…Outbreaks of invasive GAS disease have also been associated with acquisition of, or mutations within, genotypic regulatory systems that result in increased phenotypic virulence (20,21). However, this clonal invasive GAS outbreak differs from previously reported outbreaks (6,20,21) because it was linked primarily to the acquisition of a transposable element with no obvious virulence determinant. Widespread use of macrolides in New Zealand, particularly in elderly patients and during the winter, when this outbreak occurred (22), may well have contributed to the selection and expansion of the macrolide-resistant outbreak clone.…”

Section: Discussionmentioning

confidence: 89%

“…Outbreaks of GAS disease have previously been linked to the acquisition of mobile genetic elements, such as an ongoing polyclonal emm12 and emm1 scarlet fever outbreak in Hong Kong and mainland China associated with horizontal acquisition of multidrug resistance and a superantigen-encoding prophage (6). Outbreaks of invasive GAS disease have also been associated with acquisition of, or mutations within, genotypic regulatory systems that result in increased phenotypic virulence (20,21). However, this clonal invasive GAS outbreak differs from previously reported outbreaks (6,20,21) because it was linked primarily to the acquisition of a transposable element with no obvious virulence determinant.…”

Section: Discussionmentioning

confidence: 99%

Biphasic Outbreak of Invasive Group A Streptococcus Disease in Eldercare Facility, New Zealand

Worthing¹,

Werno²,

Pink³

et al. 2020

Emerg. Infect. Dis.

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S treptococcus pyogenes, or group A Streptococcus (GAS), is a gram-positive, human-adapted opportunistic bacterial pathogen. GAS causes a wide variety of clinical manifestations, from relatively benign self-limiting infections of the nasopharynx or skin to life-threatening invasive infections such as bacteremia, pneumonia, and necrotizing fasciitis (1). The incidence of invasive GAS infections is highest among older adults (2,3), particularly those living in longterm care facilities (2,4). Outbreaks of GAS infections are often linked with distinct epidemiologic markers such as emm type (5,6). emm typing is a sequence-based method that analyzes heterogeneity in the 5′ end of the ubiquitous emm gene that encodes the Mprotein (7). Although emm typing provides useful information about the potential relatedness of outbreak isolates, whole-genome sequencing enables outbreak investigations to proceed with a far greater level of discrimination than single-gene typing of GAS isolates (8,9). For this study, we used multiple wholegenome-based approaches to examine the genetic relationships and molecular drivers of a biphasic GAS outbreak in an eldercare facility in which 14 persons became ill and 5 died. Methods Setting During winter 2014, an outbreak of invasive and noninvasive GAS disease occurred in an eldercare facility in South Island, New Zealand. The outbreak was recognized by a senior laboratory scientist who noted the sudden increase in positive blood cultures from the facility. The outbreak occurred in 2 phases. The first phase started in late May 2014 and ended when the last case-patient (a resident) was hospitalized in early June 2014. The initial 3 case-patients were admitted within 24 hours of each other, and GAS was isolated from blood or tissue cultures from all 3 case-patients. During the first phase, 6 casepatients with confirmed GAS infection were hospitalized; 5 died of presumed sepsis. Outbreak investigations and control measures were subsequently implemented and included screening staff members and residents by collecting throat swab samples and providing targeted chemoprophylaxis for residents and staff members who were in direct contact with case-patients. These interventions continued until early July 2014; however, in late July, the outbreak recurred

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“…We previously compared the complete genome of an invasive emm4 strain isolated in 2015 (strain SSGAS001) to that of the reference emm4 strain MGAS10750, which was isolated in 2001 [6,9]. Closer examination revealed a fusion event that are characteristic of Pattern E GAS ( Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…The invasive GAS emm4 strain SSGAS001 was isolated from a point-source outbreak in 2015 and its genome described using the strain name "Duke small" [9]. We accessed the complete genomes of the 2001 pharyngeal isolate MGAS10750, considered the emm4 reference strains, and the 2015 pharyngeal emm4 isolate MEW427 from NCBI [6,10].…”

Section: Methodsmentioning

confidence: 99%

Identification of a Chimeric M4 Protein and Novel Emm Pattern in Currently Circulating Strains of Emm4 Group A Streptococcus

DebRoy

Kalia

et al. 2018

Preprint

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Group A Streptococcus (GAS) is classified by sequence of the gene encoding the M protein (emm) and the patterns into which emm types are grouped. We discovered a novel emm pattern in emm4 GAS, historically considered pattern E, arising from a fusion event between emm and the adjacent enn gene. We identified the emm/enn fusion event in 51/52 emm4 GAS strains isolated by national surveillance in 2015. GAS isolates with an emm/enn fusion event completely replaced pattern E emm4 strains over a 4-year span in Houston (2013Houston ( -2017. The novel emm/enn gene fusion and new emm pattern has potential vaccine implications.

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Application of Whole-Genome Sequencing to an Unusual Outbreak of Invasive Group A Streptococcal Disease

Cited by 13 publications

References 15 publications

Community outbreaks of group A Streptococcus revealed by genome sequencing

Community outbreaks of group A Streptococcus revealed by genome sequencing

Biphasic Outbreak of Invasive Group A Streptococcus Disease in Eldercare Facility, New Zealand

Identification of a Chimeric M4 Protein and Novel Emm Pattern in Currently Circulating Strains of Emm4 Group A Streptococcus

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