title: Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA.
abstract: The effect of second-generation pneumococcal conjugate vaccines on invasive pneumococcal disease (IPD) strain distributions have not yet been well described. We analysed IPD isolates recovered from children aged <5 years through Active Bacterial Core surveillance before (2008-2009; n = 828) and after (2011-2013; n = 600) 13-valent pneumococcal conjugate vaccine (PCV13) implementation. We employed conventional testing, PCR/electrospray ionization mass spectrometry and whole genome sequence (WGS) analysis to identify serotypes, resistance features, genotypes, and pilus types. PCV13, licensed in February 2010, effectively targeted all major 19A and 7F genotypes, and decreased antimicrobial resistance, primarily owing to removal of the 19A/ST320 complex. The strain complex contributing most to the remaining β-lactam resistance during 2011-2013 was 35B/ST558. Significant emergence of non-vaccine clonal complexes was not evident. Because of the removal of vaccine serotype strains, positivity for one or both pilus types (PI-1 and PI-2) decreased in the post-PCV13 years 2011-2013 relative to 2008-2009 (decreases of 32-55% for PI-1, and >95% for PI-2 and combined PI-1 + PI-2). β-Lactam susceptibility phenotypes correlated consistently with transpeptidase region sequence combinations of the three major penicillin-binding proteins (PBPs) determined through WGS analysis. Other major resistance features were predictable by DNA signatures from WGS analysis. Multilocus sequence data combined with PBP combinations identified progeny, serotype donors and recipient strains in serotype switch events. PCV13 decreased the frequency of all PCV13 serotype clones and concurrently decreased the frequency of strain subsets with resistance and/or adherence features conducive to successful carriage. Our results serve as a reference describing key features of current paediatric IPD strains in the USA after PCV13 implementation.
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Metcalf
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Gertz
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK; Department of Medicine, Addenbrookes Hospital, University of Cambridge, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Gladstone
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Walker
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Sherwood
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Jackson
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Law
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Hawkins
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chochua
authors.affiliation: Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sheth
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Rayamajhi
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK; Department of Medicine, Addenbrookes Hospital, University of Cambridge, UK.
authors.forename: S D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kim
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Whitney
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.
authors.forename: L
authors.initials: L
authors.lastname: McGee
authors.affiliation: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA. Electronic address: bbeall@cdc.gov.
authors.forename: B
authors.initials: B
authors.lastname: Beall
mesh_terms: D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D010641:Phenotype; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000382:microbiology*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D014481:United States / Q000453:epidemiology
chemical_list: C538862:13-valent pneumococcal vaccine; D022242:Pneumococcal Vaccines
keywords: Antimicrobial susceptibility; clonal complexes; pneumococcal conjugate vaccines; serotype distributions; whole genome sequence