Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites

PLoS Med. 2013;10(9):e1001517. doi: 10.1371/journal.pmed.1001517. Epub 2013 Sep 24.

Abstract

Background: Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction.

Methods and findings: Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥ 2 years before and ≥ 1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0.55, 95% CI 0.46-0.65) and remained relatively stable through year 7 (RR 0.49, 95% CI 0.35-0.68). Point estimates for VT IPD decreased annually through year 7 (RR 0.03, 95% CI 0.01-0.10), while NVT IPD increased (year 7 RR 2.81, 95% CI 2.12-3.71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18-49 year-olds [RR 0.52, 95% CI 0.29-0.91], 50-64 year-olds [RR 0.84, 95% CI 0.77-0.93], and ≥ 65 year-olds [RR 0.74, 95% CI 0.58-0.95]).

Conclusions: Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not represent the experience in low-income countries or the effects after introduction of higher valency PCVs. High-quality, population-based surveillance of serotype-specific IPD rates is needed to monitor vaccine impact as more countries, including low-income countries, introduce PCVs and as higher valency PCVs are used. Please see later in the article for the Editors' Summary.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child, Preschool
  • Databases as Topic
  • Health Planning Guidelines
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Humans
  • Meningitis, Pneumococcal / immunology
  • Meningitis, Pneumococcal / prevention & control
  • Meta-Analysis as Topic
  • Pneumococcal Infections / epidemiology
  • Pneumococcal Infections / immunology*
  • Pneumococcal Infections / prevention & control*
  • Pneumococcal Vaccines / immunology*
  • Population Surveillance*
  • Serotyping
  • Young Adult

Substances

  • Heptavalent Pneumococcal Conjugate Vaccine
  • Pneumococcal Vaccines

Grants and funding

The study was supported by grant ID# OPP1020720 from the Bill & Melinda Gates Foundation (http://www.gatesfoundation.org/Pages/home.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.