title: Invasive pneumococcal disease: Clinical outcomes and patient characteristics 2-6 years after introduction of 7-valent pneumococcal conjugate vaccine compared to the pre-vaccine period, the Netherlands.
abstract: BACKGROUND
  Implementation of 7-valent pneumococcal conjugate vaccine (PCV7) in the Dutch national immunization program for infants led to a shift from vaccine to non-vaccine serotypes in invasive pneumococcal disease (IPD) in all age groups. We studied the impact of the serotype shift on clinical syndromes and outcomes.
  
  
  METHODS
  Pneumococcal isolates from hospitalized IPD patients obtained from nine sentinel microbiology laboratories, covering 25% of the Dutch population, were serotyped. Clinical syndromes, outcomes and patient characteristics in the post-PCV7 (2008-2012) period were compared with the pre-PCV7 period (2004-2006). Serotype specific propensity of the association with empyema, meningitis and death was calculated.
  
  
  RESULTS
  Invasive pneumonia incidence significantly decreased in children <5 years and elderly ≥65 years, but increased in 5-64 years old from 4.92 to 5.58 cases/100.000/year (RR 1.13 95% CI 0.99-1.29). Empyema incidence significantly increased in elderly 65 years and older from 0.61 to 2.60 cases/100.000/year (RR 4.28 95% CI 1.97-9.33), mainly due to serotype 1. The incidence of meningitis only declined significantly in children <5 years. IPD case-fatality decreased in children <5 years from 5% to 3%, in 5-64 years old from 9% to 7% and in elderly ≥65 years significantly from 22% to 17%, due to lower case-fatality rates for most emerging non-PCV7 serotypes.
  
  
  CONCLUSIONS
  An increase in empyema incidence was observed in persons ≥65 years old in the post-PCV7 era, mainly due to the emergence of serotype 1, although overall IPD case-fatality decreased. Extended conjugate vaccines that target serotype 1 or serotypes with high case-fatality may offer further reduction of pneumococcal disease burden.
authors.affiliation: Department of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands. Electronic address: wagenvoort@gmail.com.
authors.forename: Gertjan H J
authors.initials: GH
authors.lastname: Wagenvoort
authors.affiliation: Centre for Infectious Disease Control Netherlands (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Immunology and Infectious diseases, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
authors.affiliation: Department of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Vlaminckx
authors.affiliation: Centre for Infectious Disease Control Netherlands (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Elberse
authors.affiliation: Centre for Infectious Disease Control Netherlands (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Hester E
authors.initials: HE
authors.lastname: de Melker
authors.affiliation: Department of Medical Microbiology and the Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Arie
authors.initials: A
authors.lastname: van der Ende
authors.affiliation: Centre for Infectious Disease Control Netherlands (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Mirjam J
authors.initials: MJ
authors.lastname: Knol
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004653:Empyema / Q000453:epidemiology / Q000382:microbiology; D000069443:Heptavalent Pneumococcal Conjugate Vaccine / Q000008:administration & dosage*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control; D018571:Sentinel Surveillance; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000145:classification; D055815:Young Adult
chemical_list: D000069443:Heptavalent Pneumococcal Conjugate Vaccine
keywords: Clinical outcomes; Epidemiology; Invasive pneumococcal disease; Pneumococcal conjugate vaccine; Sentinel surveillance; Streptococcus pneumoniae