title: Rapid draft sequencing and real-time nanopore sequencing in a hospital outbreak of Salmonella.
abstract: BACKGROUND
  Foodborne outbreaks of Salmonella remain a pressing public health concern. We recently detected a large outbreak of Salmonella enterica serovar Enteritidis phage type 14b affecting more than 30 patients in our hospital. This outbreak was linked to community, national and European-wide cases. Hospital patients with Salmonella are at high risk, and require a rapid response. We initially investigated this outbreak by whole-genome sequencing using a novel rapid protocol on the Illumina MiSeq; we then integrated these data with whole-genome data from surveillance sequencing, thereby placing the outbreak in a national context. Additionally, we investigated the potential of a newly released sequencing technology, the MinION from Oxford Nanopore Technologies, in the management of a hospital outbreak of Salmonella.
  
  
  RESULTS
  We demonstrate that rapid MiSeq sequencing can reduce the time to answer compared to the standard sequencing protocol with no impact on the results. We show, for the first time, that the MinION can acquire clinically relevant information in real time and within minutes of a DNA library being loaded. MinION sequencing permits confident assignment to species level within 20 min. Using a novel streaming phylogenetic placement method samples can be assigned to a serotype in 40 min and determined to be part of the outbreak in less than 2 h.
  
  
  CONCLUSIONS
  Both approaches yielded reliable and actionable clinical information on the Salmonella outbreak in less than half a day. The rapid availability of such information may facilitate more informed epidemiological investigations and influence infection control practices.
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK. j.quick@bham.ac.uk.|NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, B15 2TT, UK. j.quick@bham.ac.uk.
authors.forename: Joshua
authors.initials: J
authors.lastname: Quick
authors.affiliation: Public Health England, Colindale, London, UK. philip.ashton@phe.gov.uk.
authors.forename: Philip
authors.initials: P
authors.lastname: Ashton
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK. s.t.calus@bham.ac.uk.|NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, B15 2TT, UK. s.t.calus@bham.ac.uk.
authors.forename: Szymon
authors.initials: S
authors.lastname: Calus
authors.affiliation: Public Health England, Field Epidemiology Service (Birmingham Office), Birmingham, UK. carol.chatt@phe.gov.uk.
authors.forename: Carole
authors.initials: C
authors.lastname: Chatt
authors.affiliation: Public Health England Birmingham Public Health Laboratory, Heart of England NHS Trust, Birmingham, UK. savita.gossain@heartofengland.nhs.uk.
authors.forename: Savita
authors.initials: S
authors.lastname: Gossain
authors.affiliation: Public Health England, Field Epidemiology Service (Birmingham Office), Birmingham, UK. Jeremy.Hawker@phe.gov.uk.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hawker
authors.affiliation: Public Health England, Colindale, London, UK. satheesh.nair@phe.gov.uk.
authors.forename: Satheesh
authors.initials: S
authors.lastname: Nair
authors.affiliation: Public Health England, Field Epidemiology Service (Birmingham Office), Birmingham, UK. Keith.Neal@phe.gov.uk.
authors.forename: Keith
authors.initials: K
authors.lastname: Neal
authors.affiliation: Public Health England Birmingham Public Health Laboratory, Heart of England NHS Trust, Birmingham, UK. Kathy.Nye@phe.gov.uk.
authors.forename: Kathy
authors.initials: K
authors.lastname: Nye
authors.affiliation: Public Health England, Colindale, London, UK. Tansy.Peters@phe.gov.uk.
authors.forename: Tansy
authors.initials: T
authors.lastname: Peters
authors.affiliation: Public Health England, Colindale, London, UK. Elizabeth.DePinna@phe.gov.uk.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: De Pinna
authors.affiliation: Department of Microbiology, University of Warwick, Warwick, UK. E.R.Robinson@warwick.ac.uk.
authors.forename: Esther
authors.initials: E
authors.lastname: Robinson
authors.affiliation: Public Health England Birmingham Public Health Laboratory, Heart of England NHS Trust, Birmingham, UK. keith.struthers@uhcw.nhs.uk.
authors.forename: Keith
authors.initials: K
authors.lastname: Struthers
authors.affiliation: NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, B15 2TT, UK. m.a.webber@bham.ac.uk.
authors.forename: Mark
authors.initials: M
authors.lastname: Webber
authors.affiliation: Medical Directorate, Heart of England NHS Trust, Birmingham, UK. andrew.catto@heartofengland.nhs.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Catto
authors.affiliation: Public Health England, Colindale, London, UK. Tim.Dallman@phe.gov.uk.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Dallman
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK. peter.hawkey@heartofengland.nhs.uk.|Public Health England Birmingham Public Health Laboratory, Heart of England NHS Trust, Birmingham, UK. peter.hawkey@heartofengland.nhs.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Hawkey
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK. n.j.loman@bham.ac.uk.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Loman
mesh_terms: D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D004196:Disease Outbreaks; D006760:Hospitalization; D006801:Humans; D012480:Salmonella Infections / Q000453:epidemiology* / Q000382:microbiology; D012477:Salmonella enteritidis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA / Q000379:methods*