Abstract

We used whole genome sequencing (WGS) analysis to investigate the population structure of 877 Streptococcus pneumoniae isolates from five carriage studies from 2002 (N = 346), 2010 (N = 127), 2013 (N = 153), 2016 (N = 187) and 2018 (N = 64) in UK households which covers the period pre-PCV7 to post-PCV13 implementation. The genomic lineages seen in the population were determined using multi-locus sequence typing (MLST) and PopPUNK (Population Partitioning Using Nucleotide K-mers) which was used for local and global comparisons. A Roary core genome alignment of all the carriage genomes was used to investigate phylogenetic relationships between the lineages. The results showed an influx of previously undetected sequence types after vaccination associated with non-vaccine serotypes. A small number of lineages persisted throughout, associated with both non-vaccine and vaccine types (such as ST199), or that could be an example of serotype switching from vaccine to non-vaccine types (ST177). Serotype 3 persisted throughout the study years, represented by ST180 and Global Pneumococcal Sequencing Cluster (GPSC) 12; the local PopPUNK analysis and core genome maximum likelihood phylogeny separated them into two clades, one of which is only seen in later study years. The genomic data showed that serotype replacement in the carriage studies was mostly due to a change in genotype as well as serotype, but that some important genetic lineages, previously associated with vaccine types, persisted.

Highlights

  • Understanding the population structure of pneumococci carried asymptomatically in the nasopharynx is important because carriage is a prerequisite and a reservoir for disease

  • Serotype 3 persisted throughout the study years, represented by ST180 and Global Pneumococcal Sequencing Cluster (GPSC) 12; the local PopPUNK analysis and core genome maximum likelihood phylogeny separated them into two clades, one of which is only seen in later study years

  • As many of the within-serogroup discrepancies were likely to have been due to subtyping errors with the serotyping sera as found in previous studies [15] and we were unable to fully investigate any discrepancies, the serotypes reported in this study are the result of the whole genome sequencing (WGS) analysis throughout

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Summary

Introduction

Understanding the population structure of pneumococci carried asymptomatically in the nasopharynx is important because carriage is a prerequisite and a reservoir for disease. Characterizing the epidemiology of carriage can help to predict the epidemiology of pneumococcal disease and the effect of vaccination on the pneumococcal population. The 7-valent pneumococcal vaccine (PCV7) was introduced into the routine infant program in the UK in September 2006, using a 2-, 4-, 13-month schedule and with a catch-up program for children up to 2 years. This was followed by the 13-valent vaccine (PCV13), in April 2010 with the same schedule and no catch-up program. The introduction of PCV7 vaccination resulted in a dramatic reduction in vaccine type invasive pneumococcal disease (IPD) in children and had a profound effect on vaccine type disease in adults in England and Wales [1].

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