title: Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study.
abstract: BACKGROUND
  The 13-valent pneumococcal conjugate vaccine (PCV13) protects against key serotypes that increased after routine immunisation with the seven-valent vaccine (PCV7), but its potential for herd protection and serotype replacement is uncertain. The aim of this study was to analyse the effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction.
  
  
  METHODS
  We used a national dataset of electronically reported and serotyped invasive pneumococcal disease cases in England and Wales to estimate incidence rate ratios (IRRs) for vaccine and non-vaccine type invasive pneumococcal disease between July, 2013, and June, 2014, versus the pre-PCV13 and pre-PCV7 baseline. Incidence rates were corrected for missing serotype data and changes in surveillance sensitivity over time. An over-dispersed Poisson model was used to estimate IRRs and confidence intervals.
  
  
  RESULTS
  Incidence of invasive pneumococcal disease in the epidemiological year 2013/14 decreased by 32% compared with the pre-PCV13 baseline (incidence 10·14 per 100,000 in 2008-10 vs 6·85 per 100,000 in 2013/14; IRR 0·68, 95% CI 0·64-0·72). This was due to an 86% reduction of the serotypes covered by PCV7 (1·46 vs 0·20 per 100,000; IRR 0·14, 0·10-0·18) and a 69% reduction of the additional six serotypes covered by PCV13 (4·48 vs 1·40 per 100,000; IRR 0·31, 0·28-0·35). When compared with the pre-PCV7 baseline, there was a 56% overall reduction in invasive pneumococcal disease (15·63 vs 6·85 per 100,000; IRR 0·44, 95% CI 0·43-0·47). Compared with the pre-PCV13 baseline, the incidence of non-PCV13 serotypes increased (incidence all ages 4·19 vs 5·25 per 100,000; IRR 1·25, 95% CI 1·17-1·35) due to increases across a broad range of serotypes in children younger than 5 years and in people aged 45 years or more. In children younger than 5 years, incidence of non-PCV13 serotypes in 2013/14 was higher than in 2012/13 (age <2 years: 12·03 vs 10·83 per 100,000; age 2-4 years: 4·08 vs 3·63 per 100,000).
  
  
  CONCLUSIONS
  8 years of PCV use in England and Wales has reduced the overall incidence of invasive pneumococcal disease by more than 50%. The herd protection induced by PCV7 is continuing, and similar indirect protection is occurring from the additional serotypes covered by PCV13. There is, however, evidence of increasing invasive pneumococcal disease due to non-PCV13 serotypes, particularly in children younger than 5 years in 2014. If this increase continues, the maximum benefit of the PCV13 programme in children might already have been achieved.
  
  
  BACKGROUND
  Public Health England funds national surveillance of invasive pneumococcal disease.
authors: Immunisation, Hepatitis, and Blood Safety Department, Health Protection Services, Public Health England, London, UK. Electronic address: Pauline.Kaye@phe.gov.uk.
authors: Pauline A
authors: PA
authors: Waight
authors: Statistics, Modelling, and Economics Department, Health Protection Services, Public Health England, London, UK.
authors: Nicholas J
authors: NJ
authors: Andrews
authors: Immunisation, Hepatitis, and Blood Safety Department, Health Protection Services, Public Health England, London, UK.
authors: Shamez N
authors: SN
authors: Ladhani
authors: Respiratory and Vaccine Preventable Bacteria Reference Unit, Microbiology Services, Public Health England, London, UK.
authors: Carmen L
authors: CL
authors: Sheppard
authors: Institute of Hygiene and Microbiology, University of Würzburg, Würzburg, Germany; School of Medicine, Griffith University, Gold Coast Campus, Southport, QLD, Australia.
authors: Mary P E
authors: MP
authors: Slack
authors: Immunisation, Hepatitis, and Blood Safety Department, Health Protection Services, Public Health England, London, UK.
authors: Elizabeth
authors: E
authors: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004739:England / Q000453:epidemiology; D062665:Epidemiological Monitoring; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D032541:Mass Vaccination / Q000706:statistics & numerical data*; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016012:Poisson Distribution; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D018074:Vaccines, Conjugate; D014852:Wales / Q000453:epidemiology
chemical_list: C538862:13-valent pneumococcal vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate