title: Importance of whole genome sequencing for the assessment of outbreaks in diagnostic laboratories: analysis of a case series of invasive Streptococcus pyogenes infections.
abstract: Outbreaks of Streptococcus pyogenes hypervirulent clones are constant public health threats. In western Switzerland, an increase of severe cases of S. pyogenes invasive infections was observed between December 2015 and March 2016. Our aim was (i) to investigate these cases by the use of Whole Genome Sequencing (WGS) and (ii) to determine the specific virulome and resistome of each isolate in order to undertake adequate public health measures. Eleven Streptococcus pyogenes strains isolated from 11 patients with severe invasive infections between December 13, 2015 and March 12, 2016 were included in our study. Practically, emm-typing, MLST and WGS were used to investigate the relatedness between the isolates. The presence of virulence and antibiotic resistance genes as well as mutations in transcriptional regulators of virulence and in genes encoding for antibiotic targets were assessed. Three and two groups of isolates shared the same emm-type and ST type, respectively. Single Nucleotide Polymorphism (SNP) analysis revealed 14 to 32 SNPs between the strains of the same emm-type group, ruling out the possibility of a clonal outbreak. Mutations found in covS and rocA could partially explain an increased virulence. As these reassuring results were obtained in less than 10 days, no specific hospital hygiene and no dedicated public health measures had to be undertaken. WGS is a powerful technique to discriminate between closely related strains, excluding an outbreak in less than 10 days. Moreover, WGS provided extensive data on the virulome and resistome of all these strains.
authors.affiliation: Institute of Microbiology, Department of Laboratory, University of Lausanne & Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Tagini
authors.affiliation: Unit of Pediatric Infectious Diseases and Vaccinology, Department of Pediatrics, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Aubert
authors.affiliation: Service of Infectious Diseases, Central Institute of the Valais Hospitals, Sion, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Troillet
authors.affiliation: Institute of Microbiology, Department of Laboratory, University of Lausanne & Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Pillonel
authors.affiliation: Service of Infectious Diseases, Central Institute of the Valais Hospitals, Sion, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Praz
authors.affiliation: Unit of Pediatric Infectious Diseases and Vaccinology, Department of Pediatrics, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: P A
authors.initials: PA
authors.lastname: Crisinel
authors.affiliation: Institute of Microbiology, Department of Laboratory, University of Lausanne & Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Prod'hom
authors.affiliation: Unit of Pediatric Infectious Diseases and Vaccinology, Department of Pediatrics, Lausanne University Hospital, Lausanne, Switzerland.|Service of Infectious Diseases, Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Asner
authors.affiliation: Institute of Microbiology, Department of Laboratory, University of Lausanne & Lausanne University Hospital, Lausanne, Switzerland. gilbert.greub@chuv.ch.|Service of Infectious Diseases, Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland. gilbert.greub@chuv.ch.
authors.forename: G
authors.identifier: 0000-0001-9529-3317
authors.initials: G
authors.lastname: Greub
mesh_terms: D000293:Adolescent; D000368:Aged; D001431:Bacteriological Techniques / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D058889:Molecular Typing / Q000379:methods; D013290:Streptococcal Infections / Q000175:diagnosis* / Q000453:epidemiology*; D013297:Streptococcus pyogenes / Q000302:isolation & purification*; D013557:Switzerland / Q000453:epidemiology; D037521:Virulence Factors / Q000235:genetics; D000073336:Whole Genome Sequencing / Q000379:methods*
chemical_list: D037521:Virulence Factors
keywords: Emm-typing; Group a streptococcus; MLST; Outbreak; Streptococcus pyogenes; Whole genome sequencing