title: Genome analysis following a national increase in Scarlet Fever in England 2014.
abstract: During a substantial elevation in scarlet fever (SF) notifications in 2014 a national genomic study was undertaken of Streptococcus pyogenes (Group A Streptococci, GAS) isolates from patients with SF with comparison to isolates from patients with invasive disease (iGAS) to test the hypotheses that the increase in SF was due to either the introduction of one or more new/emerging strains in the population in England or the transmission of a known genetic element through the population of GAS by horizontal gene transfer (HGT) resulting in infections with an increased likelihood of causing SF. Isolates were collected to provide geographical representation, for approximately 5% SF isolates from each region from 1stApril 2014 to 18thJune 2014. Contemporaneous iGAS isolates for which genomic data were available were included for comparison. Data were analysed in order to determine emm gene sequence type, phylogenetic lineage and genomic clade representation, the presence of known prophage elements and the presence of genes known to confer pathogenicity and resistance to antibiotics.
  
  
  
  555 isolates were analysed, 303 from patients with SF and 252 from patients with iGAS. Isolates from patients with SF were of multiple distinct emm sequence types and phylogenetic lineages. Prior to data normalisation, emm3 was the predominant type (accounting for 42.9% of SF isolates, 130/303 95%CI 37.5-48.5; 14.7% higher than the percentage of emm3 isolates found in the iGAS isolates). Post-normalisation emm types, 4 and 12, were found to be over-represented in patients with SF versus iGAS (p < 0.001). A single gene, ssa, was over-represented in isolates from patients with SF. No single phage was found to be over represented in SF vs iGAS. However, a "meta-ssa" phage defined by the presence of :315.2, SPsP6, MGAS10750.3 or HK360ssa, was found to be over represented. The HKU360.vir phage was not detected yet the HKU360.ssa phage was present in 43/63 emm12 isolates but not found to be over-represented in isolates from patients with SF.
  
  
  
  There is no evidence that the increased number of SF cases was a strain-specific or known mobile element specific phenomenon, as the increase in SF cases was associated with multiple lineages of GAS.
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK. vicki.chalker@phe.gov.uk.
authors.forename: Victoria
authors.identifier: 0000-0001-5751-1635
authors.initials: V
authors.lastname: Chalker
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Jironkin
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Juliana
authors.initials: J
authors.lastname: Coelho
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Shahib
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Platt
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Georgia
authors.initials: G
authors.lastname: Kapatai
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Daniel
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Chenchal
authors.initials: C
authors.lastname: Dhami
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Marisa
authors.initials: M
authors.lastname: Laranjeira
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Chambers
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Guy
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Theresa
authors.initials: T
authors.lastname: Lamagni
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Harrison
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.|Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Meera
authors.initials: M
authors.lastname: Chand
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Johnson
authors.affiliation: National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5HT, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Underwood
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001435:Bacteriophages / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D016000:Cluster Analysis; D004739:England / Q000453:epidemiology; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods; D006801:Humans; D058885:Multilocus Sequence Typing; D010802:Phylogeny; D011159:Population Surveillance; D012541:Scarlet Fever / Q000453:epidemiology / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000145:classification / Q000235:genetics* / Q000821:virology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein
keywords: Genomics; Invasive GAS; Scarlet Fever; Streptococcus pyogenes; iGAS