title: Haemagglutinin and neuraminidase sequencing delineate nosocomial influenza outbreaks with accuracy equivalent to whole genome sequencing.
abstract: We describe haemagglutinin (HA) and neuraminidase (NA) sequencing in an apparent cross-site influenza A(H1N1) outbreak in renal transplant and haemodialysis patients, confirmed with whole genome sequencing (WGS).
  
  
  
  Isolates were sequenced from influenza positive individuals. Phylogenetic trees were constructed using HA and NA sequencing and subsequently WGS. Sequence data was analysed to determine genetic relatedness of viruses obtained from inpatient and outpatient cohorts and compared with epidemiological outbreak information.
  
  
  
  There were 6 patient cases of influenza in the inpatient renal ward cohort (associated with 3 deaths) and 9 patient cases in the outpatient haemodialysis unit cohort (no deaths). WGS confirmed clustered transmission of two genetically different influenza A(H1N1)pdm09 strains initially identified by analysis of HA and NA genes. WGS took longer, and in this case was not required to determine whether or not the two seemingly linked outbreaks were related.
  
  
  
  Rapid sequencing of HA and NA genes may be sufficient to aid early influenza outbreak investigation making it appealing for future outbreak investigation. However, as next generation sequencing becomes cheaper and more widely available and bioinformatics software is now freely accessible next generation whole genome analysis may increasingly become a valuable tool for real-time Influenza outbreak investigation.
authors.affiliation: Department of Infection, Southampton University Hospital NHS Trust, Public Health England Laboratory, Southampton, England, SO16 6YD, UK. Electronic address: Rebecca.Houghton@uhs.nhs.uk.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Houghton
authors.affiliation: Respiratory Virus Unit, Public Health England, London, NW9 5EQ, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ellis
authors.affiliation: Respiratory Virus Unit, Public Health England, London, NW9 5EQ, UK.
authors.forename: Monica
authors.initials: M
authors.lastname: Galiano
authors.affiliation: Department of Clinical and Experimental Sciences, University of Southampton and NIHR Respiratory Biomedical Research Unit, Southampton, England, SO16 6YD, UK.
authors.forename: Tristan W
authors.initials: TW
authors.lastname: Clark
authors.affiliation: Microbiology Department, Queen Alexandra Hospital, Portsmouth, England, PO6 3LY, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wyllie
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D003428:Cross Infection / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D004196:Disease Outbreaks / Q000517:prevention & control; D005260:Female; D016679:Genome, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D007674:Kidney Diseases / Q000150:complications; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000235:genetics*; D006435:Renal Dialysis; D014764:Viral Proteins / Q000235:genetics*
chemical_list: C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: Genomics; Healthcare associated infection; Influenza; Outbreak; Renal transplantation