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Integration of Genomic and Other Epidemiologic Data to Investigate and Control a Cross-Institutional Outbreak of Streptococcus pyogenes.

ABSTRACT: Single-strain outbreaks of Streptococcus pyogenes infections are common and often go undetected. In 2013, two clusters of invasive group A Streptococcus (iGAS) infection were identified in independent but closely located care homes in Oxfordshire, United Kingdom. Investigation included visits to each home, chart review, staff survey, microbiologic sampling, and genome sequencing. S. pyogenes emm type 1.0, the most common circulating type nationally, was identified from all cases yielding GAS isolates. A tailored whole-genome reference population comprising epidemiologically relevant contemporaneous isolates and published isolates was assembled. Data were analyzed independently using whole-genome multilocus sequencing and single-nucleotide polymorphism analyses. Six isolates from staff and residents of the homes formed a single cluster that was separated from the reference population by both analytical approaches. No further cases occurred after mass chemoprophylaxis and enhanced infection control. Our findings demonstrate the ability of 2 independent analytical approaches to enable robust conclusions from nonstandardized whole-genome analysis to support public health practice.

SUBMITTER: Chalker VJ

PROVIDER: S-EPMC4880081 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNew Delhi metallo-β-lactamase (NDM) represents an emergent mechanism of carbapenem resistance associated with high mortality and limited antimicrobial treatment options. Because the blaNDM resistance gene is often carried on plasmids, traditional infection prevention and control (IP&C) surveillance methods like speciation, antimicrobial resistance testing, and reactive whole genome sequencing (WGS) may not detect plasmid transfer in multispecies outbreaks.MethodsInitial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance, which was performed weekly using the Illumina platform. To resolve NDM-encoding plasmids, we performed long-read Oxford Nanopore sequencing and constructed hybrid assemblies using Illumina and Nanopore sequencing data. Reports of relatedness between NDM-producing organisms and reactive WGS for suspected outbreaks were shared with the IP&C team for assessment and intervention.FindingsWe observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included seven bacterial species and each encoded the same NDM-5 plasmid, which showed high homology to NDM plasmids previously observed in Asia. WGS surveillance and epidemiologic investigation characterized ten horizontal plasmid transfer events and six bacterial transmission events between patients housed in varying hospital units. Transmission prevention focused on enhanced observation and adherence to basic infection prevention measures.InterpretationOur investigation revealed a complex, multispecies outbreak of NDM that involved multiple plasmid transfer and bacterial transmission events, increasing the complexity of outbreak identification and transmission prevention. Our investigation highlights the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks.FundingThis work was funded in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (R01AI127472) (R21AI1783691).

Project description:The disease burden of Streptococcus pyogenes is particularly high in low- and middle-income countries. However, data on the molecular epidemiology of S. pyogenes in such regions, especially sub-Saharan Africa, are scarce. To address this, whole-genome sequencing (WGS) of S. pyogenes from Gabon was performed to identify transmission clusters and provide valuable genomic data for public repositories. A total of 76 S. pyogenes isolates from 73 patients, collected between September 2012 and January 2013, were characterized by short-read whole-genome sequencing. The predominant emm types were emm58.0, emm81.2 and emm223.0 with 9.2% (7 of 76), 7.9% (6 of 76), and 6.6% (5 of 76), respectively. Single-nucleotide polymorphism analysis revealed 16 putative transmission clusters. Four of these were household transmissions. Four antimicrobial genes (lmrP, tetM, tetL, and thfT) were found in the S. pyogenes isolates from this study. All strains carried lmrP. Of the 76 isolates, 64 (84.2%) carried at least one tetracycline resistance gene (tetM or tetL). Comparisons with other publicly available African genomic data revealed a significant correlation between geographical location and genetic diversity of S. pyogenes, with Gabonese strains showing similarities to those from Kenya and certain Oceanian regions. Our study showed that transmission of S. pyogenes can occur at the community/household level and that high-resolution molecular typing is needed to monitor changes in circulating clones and to detect community outbreaks. Advocacy for the adoption of WGS for comprehensive molecular characterization of S. pyogenes and data sharing through public repositories should be encouraged to understand the molecular epidemiology and evolutionary trajectory of S. pyogenes in sub-Saharan Africa.ImportanceThe study conducted in Gabon underscores the critical importance of addressing the limited knowledge of the molecular epidemiology of Streptococcus pyogenes in low- and middle-income countries, particularly sub-Saharan Africa. Our molecular analysis identified predominant emm types and unveiled 16 putative transmission clusters, four involving household transmissions. Furthermore, the study revealed a correlation between geographical location and genetic diversity, emphasizing the necessity for a comprehensive understanding of the molecular epidemiology and evolutionary trajectory of S. pyogenes in various regions. The call for advocacy in adopting whole-genome sequencing for molecular characterization and data sharing through public repositories is crucial for advancing our knowledge and implementing effective strategies to combat the spread of S. pyogenes in sub-Saharan Africa.

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Integration of Genomic and Other Epidemiologic Data to Investigate and Control a Cross-Institutional Outbreak of Streptococcus pyogenes.

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