Pre-vaccine serotype composition within a lineage signposts its serotype replacement - a carriage study over 7 years following pneumococcal conjugate vaccine use in the UK.

Rebecca A Gladstone,Vanessa Devine,Stephen D Bentley,David Cleary,Saul N Faust,Johanna M Jefferies,Stuart C Clarke,Jessica Jones

doi:10.1099/mgen.0.000119

Abstract

Serotype replacement has been reported in carriage and disease after pneumococcal conjugate vaccine (PCV) introductions in the UK and globally. We previously described concurrent expansion and decline of sequence types associated with serotype replacement over 5 years following PCV introductions in the UK. Here we use whole-genome sequencing to fully characterise the population structure of pneumococcal isolates collected over seven winters encompassing PCV7 and PCV13 introductions in the UK, investigating the importance of lineages in serotype replacement. We analysed 672 pneumococcal genomes from colonised children of 4 years old or less. The temporal prevalence of 20 lineages, defined by hierarchical Bayesian analysis of population structure (BAPS), was assessed in the context of serotype replacement. Multiple serotypes were detected in the primary winter of sampling within three vaccine-type (VT) lineages BAPS4, BAPS10 and BAPS11, in which serotype replacement were observed. In contrast, serotype replacement was not seen in the remaining three VT lineages (BAPS1, BAPS13 and BAPS14), that expressed a single serotype (6B, 6A and 3, respectively) in the primary winter. One lineage, BAPS1 serotype 6B was undetectable in the population towards the end of the study period. The dynamics of serotype replacement, in this UK population, was preceded by the presence or absence of multiple serotypes within VT lineages, in the pre-PCV population. This observation could help predict which non-vaccine types (NVTs) may be involved in replacement in future PCV introductions here and elsewhere. It could further indicate whether any antibiotic resistance associated with the lineages is likely to be affected by replacement.

Highlights

Streptococcus pneumoniae has been estimated to be responsible for 5,800 hospitalisations annually in England and Wales before the introductions of pneumococcal conjugative vaccines (PCVs) [1]
We previously reported the expansion of sequence types (STs), ST432(21) and ST439(23B), in carriage isolates after the implementation of PCV7; highlighting that clonal expansion played an important role in serotype replacement in the UK [3]
We give the first description, of the population structure for this UK carriage collection. This allowed us to observe that serotype exclusivity within a lineage during the primary sampling winter was an indicator that the lineage would go on to be removed from circulation rather than undergo replacement with unsampled non-vaccine types (NVTs)

Summary

Introduction

Streptococcus pneumoniae has been estimated to be responsible for 5,800 hospitalisations annually in England and Wales before the introductions of pneumococcal conjugative vaccines (PCVs) [1]. Since the introduction of PCV7 in 2006 and PCV13 in 2010, vaccine serotype replacement had nearly completed by winter 2012/13; non-vaccine types account for the majority of carriage pneumococcus isolates from children aged 4 or less, while the prevalence of nasopharyngeal colonisation remained unchanged [2,3,4]. We previously reported the expansion of sequence types (STs), ST432(21) and ST439(23B), in carriage isolates after the implementation of PCV7; highlighting that clonal expansion played an important role in serotype replacement in the UK [3].

Methods

Results

Discussion

Conclusion