title: Genetic characterisation of Malawian pneumococci prior to the roll-out of the PCV13 vaccine using a high-throughput whole genome sequencing approach.
abstract: BACKGROUND
  Malawi commenced the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunisation schedule in November 2011. Here we have tested the utility of high throughput whole genome sequencing to provide a high-resolution view of pre-vaccine pneumococcal epidemiology and population evolutionary trends to predict potential future change in population structure post introduction.
  
  
  METHODS
  One hundred and twenty seven (127) archived pneumococcal isolates from randomly selected adults and children presenting to the Queen Elizabeth Central Hospital, Blantyre, Malawi underwent whole genome sequencing.
  
  
  RESULTS
  The pneumococcal population was dominated by serotype 1 (20.5% of invasive isolates) prior to vaccine introduction. PCV13 is likely to protect against 62.9% of all circulating invasive pneumococci (78.3% in under-5-year-olds). Several Pneumococcal Molecular Epidemiology Network (PMEN) clones are now in circulation in Malawi which were previously undetected but the pandemic multidrug resistant PMEN1 lineage was not identified. Genome analysis identified a number of novel sequence types and serotype switching.
  
  
  CONCLUSIONS
  High throughput genome sequencing is now feasible and has the capacity to simultaneously elucidate serotype, sequence type and as well as detailed genetic information. It enables population level characterization, providing a detailed picture of population structure and genome evolution relevant to disease control. Post-vaccine introduction surveillance supported by genome sequencing is essential to providing a comprehensive picture of the impact of PCV13 on pneumococcal population structure and informing future public health interventions.
authors.affiliation: Malawi-Liverpool-Wellcome Clinical Research Programme, Chichiri, Blantyre 3, Malawi. Dean.Everett@liverpool.ac.uk
authors.forename: Dean B
authors.initials: DB
authors.lastname: Everett
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cornick
authors.forename: Brigitte
authors.initials: B
authors.lastname: Denis
authors.forename: Claire
authors.initials: C
authors.lastname: Chewapreecha
authors.forename: Nicholas
authors.initials: N
authors.lastname: Croucher
authors.forename: Simon
authors.initials: S
authors.lastname: Harris
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Stephen
authors.initials: S
authors.lastname: Gordon
authors.forename: Enitan D
authors.initials: ED
authors.lastname: Carrol
authors.forename: Neil
authors.initials: N
authors.lastname: French
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007223:Infant; D008295:Malawi; D008875:Middle Aged; D010802:Phylogeny; D022242:Pneumococcal Vaccines / Q000276:immunology*; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics*; D018074:Vaccines, Conjugate / Q000276:immunology; D055815:Young Adult
chemical_list: C538862:13-valent pneumococcal vaccine; D000900:Anti-Bacterial Agents; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate