Effect of Pneumococcal Conjugate Vaccination on Serotype-Specific Carriage and Invasive Disease in England: A Cross-Sectional Study

Stefan Flasche,Pauline Waight,Albert Jan Van Hoek,Robert George,Elizabeth Sheasby,Carmen Sheppard,Elizabeth Miller,Nick Andrews,Keith P Klugman

doi:10.1371/journal.pmed.1001017

Abstract

We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7) programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines. Nasopharyngeal swabs were taken from children <5 y old and family members (n=400) 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs) were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT) carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49). The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence. Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.

Highlights

Streptococcus pneumoniae is a bacterium that frequently colonises the human nasopharynx
Because the additional serotypes included in PCV10/13 have high case:carrier ratios (CCRs) but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement
A few serotypes with high CCRs could mitigate the benefits of higher valency vaccines

Summary

Introduction

Streptococcus pneumoniae is a bacterium that frequently colonises the human nasopharynx. Since PCV7 is protective against invasive pneumococcal disease (IPD) [4] and carriage [5,6], the assumption of protection of the unvaccinated against vaccine type (VT) IPD through herd immunity played a major role in evaluating the likely impact and cost-effectiveness of vaccination [7]. Carriage of S. pneumoniae bacteria does not necessarily cause disease These bacteria can cause local, noninvasive diseases such as ear infections and sinusitis and, more rarely, they can spread into the lungs, the bloodstream, or the covering of the brain, where they cause pneumonia, septicemia, and meningitis, respectively. These invasive pneumococcal diseases (IPDs) can be successfully treated if administered early, they can be fatal. Vaccination primes the immune system to recognize and attack diseasecausing organisms (pathogens) rapidly and effectively by exposing it to weakened or dead pathogens or to pathogen molecules (antigens) that it recognizes as foreign

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