title: Genomic Characteristics Behind the Spread of Bacteremic Group A Streptococcus Type emm89 in Finland, 2004-2014.
abstract: BACKGROUND
  Many countries worldwide have reported increasing numbers of emm89 group A Streptococcus (GAS) infections during last decade. Pathogen genetic factors linked to this increase need assessment.
  
  
  METHODS
  We investigated epidemiological characteristics of emm89 GAS bacteremic infections, including 7-day and 30-day case-fatality rates, in Finland during 2004-2014 and linked them to whole-genome sequencing data obtained from corresponding strains. The Fisher exact test and exact logistic regression were used to compare differences between bacteremic infections due to emm89 GAS belonging to different genetic clades and subclades.
  
  
  RESULTS
  Out of 1928 cases of GAS bacteremic infection, 278 were caused by emm89 GAS. We identified 2 genetically distinct clades, arbitrarily designated clade 2 and clade 3. Both clades were present during 2004-2008, but clade 3 increased rapidly from 2009 onward. Six subclades (designated subclades A-F) were identified within clade 3, based on phylogenetic core genome analysis. The case-fatality rate differed significantly between subclades (P < .05), with subclade D having the highest 30-day estimated case-fatality rate (19% vs 3%-14%).
  
  
  CONCLUSIONS
  A new emm89 clone, clade 3, emerged in 2009 and spread rapidly in Finland. Patients infected with certain subclades of clade 3 were significantly more likely to die. A specific polymerase chain reaction assay was developed to follow the spread of subclade D in 2015.
authors.affiliation: Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki.|European Programme for Public Health Microbiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden.
authors.forename: Francesca
authors.initials: F
authors.lastname: Latronico
authors.affiliation: Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Texas.
authors.forename: Waleed
authors.initials: W
authors.lastname: Nasser
authors.affiliation: Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki.|Department of Medical Microbiology and Immunology, University of Turku, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Puhakainen
authors.affiliation: Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki.
authors.forename: Jukka
authors.initials: J
authors.lastname: Ollgren
authors.affiliation: Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki.
authors.forename: Hanne-Leena
authors.initials: HL
authors.lastname: Hyyryläinen
authors.affiliation: Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Texas.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Beres
authors.affiliation: Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki.
authors.forename: Outi
authors.initials: O
authors.lastname: Lyytikäinen
authors.affiliation: Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki.
authors.forename: Jari
authors.initials: J
authors.lastname: Jalava
authors.affiliation: Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Texas.
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
authors.affiliation: Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki.|Department of Medical Microbiology and Immunology, University of Turku, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Vuopio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000235:genetics; D016470:Bacteremia / Q000453:epidemiology* / Q000382:microbiology* / Q000401:mortality; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D005387:Finland / Q000453:epidemiology; D016680:Genome, Bacterial; D023281:Genomics; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D017720:Molecular Epidemiology / Q000379:methods; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000379:methods; D013290:Streptococcal Infections / Q000453:epidemiology* / Q000382:microbiology* / Q000401:mortality; D013297:Streptococcus pyogenes / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein
keywords: Streptococcus pyogenes; bacteremia; bacterial genome; emm type; molecular epidemiology; surveillance; whole genome sequencing