title: Five winters of pneumococcal serotype replacement in UK carriage following PCV introduction.
abstract: The seven-valent pneumococcal conjugate vaccine (PCV7) was added to the UK national immunisation programme in September 2006. PCV13 replaced PCV7 in April 2010. As carriage precedes disease cases this study collected carried pneumococci from children each winter from 2006/7 to 2010/11 over PCV introduction. Conventional microbiology and whole genome sequencing were utilised to characterise pneumococcal strains. Overall prevalence of pneumococcal carriage remained stable. Vaccine serotypes (VT) decreased (p<0.0001) with concomitant increases in non-vaccine serotypes (NVT). In winter 2010/11 only one isolate of PCV7 VT was observed (6B). PCV13 unique VTs decreased between winters immediately preceding and following PCV13 introduction (p=0.04). Significant decreases for VTs 6B, 19F, 23F (PCV7) and 6A (PCV13) and increases for NVT 21, 23B, 33F and 35F were detected. The serotype replacement was accompanied by parallel changes in genotype prevalence for associated sequence types with clonal expansion contributing to replacement. By winter 2010/11, serotype coverage of PCV7 and PCV13 was 1% and 11% respectively. VT replacement was observed for PCV7 and PCV13 serotypes. Conjugate vaccine design and use requires continuous monitoring and revision.
authors.affiliation: Faculty of Medicine and Institute for Life Sciences, University of Southampton, UK.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Gladstone
authors.affiliation: Faculty of Medicine and Institute for Life Sciences, University of Southampton, UK; Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton Foundation NHS Trust, Southampton, UK.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Jefferies
authors.affiliation: Faculty of Medicine and Institute for Life Sciences, University of Southampton, UK.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Tocheva
authors.affiliation: Faculty of Medicine and Institute for Life Sciences, University of Southampton, UK.
authors.forename: Kate R
authors.initials: KR
authors.lastname: Beard
authors.affiliation: Faculty of Medicine and Institute for Life Sciences, University of Southampton, UK.
authors.forename: David
authors.initials: D
authors.lastname: Garley
authors.affiliation: Faculty of Medicine and Institute for Life Sciences, University of Southampton, UK.
authors.forename: Wei Wei
authors.initials: WW
authors.lastname: Chong
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, UK.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Faculty of Medicine and Institute for Life Sciences, University of Southampton, UK; Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton Foundation NHS Trust, Southampton, UK; NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton Foundation NHS Trust, Southampton, UK.
authors.forename: Saul N
authors.initials: SN
authors.lastname: Faust
authors.affiliation: Faculty of Medicine and Institute for Life Sciences, University of Southampton, UK; Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton Foundation NHS Trust, Southampton, UK. Electronic address: s.c.clarke@soton.ac.uk.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Clarke
mesh_terms: D002353:Carrier State / Q000382:microbiology*; D002675:Child, Preschool; D005260:Female; D016680:Genome, Bacterial; D005838:Genotype; D000069443:Heptavalent Pneumococcal Conjugate Vaccine / Q000008:administration & dosage / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012621:Seasons; D017422:Sequence Analysis, DNA; D065288:Serogroup; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D013997:Time Factors; D006113:United Kingdom; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: C538862:13-valent pneumococcal vaccine; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Next generation sequencing; Pneumococcal vaccines; Serotype replacement; Streptococcus pneumoniae; Whole genome