Effect of pneumococcal conjugate vaccination on serotype-specific carriage and invasive disease in England: a cross-sectional study

Abstract

Background: 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.

Methods and findings: 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.

Conclusion: 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.

Figure 1. Top: Comparison in ranked-serotype distribution prior to vaccination in children in Massachusetts to our findings in children (left) and adults (right).

For comparison with the findings with Hanage and colleagues, we aggregate 6A and 6C to 6A/C and 15B and 15C to 15B/C. Bottom: Changes in ranked serotype distribution in overall carriage in our findings from 2001/2002 to 2008/2009.

Figure 2. Age-stratified serotype distribution in carriage in 2008/2009 (below, Table S2) and CCR estimated from 2008/2009 carriage and IPD data (above, Table S1).

The colour code for the CCR represents that the corresponding serotype is included in PCV7 (green), PCV10 (light blue), PCV13 (dark blue), or is a NVT (red). The dotted line corresponds to the mean CCR for these types. Serotypes 11C, 33A, 16A, 17A, and 28F, although detected in carriage were not found among disease isolates in 2008/2009.