Pneumococcal carriage in children and their household contacts six years after introduction of the 13-valent pneumococcal conjugate vaccine in England

Abstract

Background: In April 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant immunisation schedule in England and Wales. Despite limited serotype replacement in invasive pneumococcal disease (IPD) during the first four post-PCV13 years, non-vaccine type (NVT) IPD increased substantially in 2014/15. We undertook a carriage study in 2015/16 to help understand the reasons for this increase.

Methods and findings: Families with a child aged <5 years attending a participating general practice in Gloucestershire or Hertfordshire were invited to provide nasopharyngeal swabs from all consenting members. Swabs from 650 individuals (293 under five, 73 five to twenty and 284 >twenty years) were cultured and serotyped for Streptococcus pneumoniae. Results were compared with those from three previous household studies conducted in the same populations between 2001 to 2013, and with the serotypes causing IPD to estimate case-carrier ratios (CCRs). Overall carriage prevalence did not differ between the four carriage studies with reductions in vaccine-type carriage offset by increases in NVT carriage. While no individual NVT serotype showed an increase in CCR from 2012/13, the composition of the serotypes comprising the NVT group differed such that the overall CCR of the NVT group had significantly increased since 2012/13. Carriage of two PCV13 serotypes, 3 and 19A, was found in 2015/16 (3/650 = 0.5% and 2/650 = 0.3% respectively) with no overall reduction in carriage prevalence of PCV13-7 serotypes since 2012/13, though 6C prevalence, a vaccine-related serotype, had reduced from 1.8% in 2012/13 to 2/648 (0.3%) in 2015/16, p = 0.013.

Conclusions: There was continuing evolution in carried NVTs six years after PCV13 introduction which, in addition to being vaccine-driven, could also reflect natural secular changes in certain NVTs. This poses challenges in predicting future trends in IPD. Elimination of carriage and disease due to serotypes 3 and 19A may not be achieved by PCV13.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Number of serotypes isolated in the 2015/16 survey by age group.

Non typeable pneumococcal isolates excluded.

Fig 2. The carriage of PCV13 types in the four consecutive carriage studies performed in the two study sites.

The study in 2001/02 was a longitudinal study the three subsequent studies cross-sectional. *The percentage of samples positive for serotype 6A in 2001/02 was post-hoc corrected for 6C (6A is 68% of original) as described in Flasche et al. [7].

Fig 3. Change in prevalence of serotypes (measured as the difference in proportions of all swabs taken that were culture positive for that serotype) in those aged

P values shown for serotypes where the changes was

Fig 4. Case carrier ratios in 2015/16.

The bar represents the 95% CI and vaccine serotypes are shown in red. Data includes just those aged

Fig 5. Case carrier ratios of non-vaccine serotypes in the 2012/13 survey [9] compared with the 2015/16 survey.

Fig excludes non-vaccine serotypes shown in Fig 4 but with no carriage detected in the 2012/13 study (12F, 9N, 20, 34, 37 with cases of IPD respectively 98, 47, 24, 3, 2 S1 Table).