Abstract
The effect of second-generation pneumococcal conjugate vaccines on invasive pneumococcal disease (IPD) strain distributions have not yet been well described. We analysed IPD isolates recovered from children aged <5 years through Active Bacterial Core surveillance before (2008–2009; n = 828) and after (2011–2013; n = 600) 13-valent pneumococcal conjugate vaccine (PCV13) implementation. We employed conventional testing, PCR/electrospray ionization mass spectrometry and whole genome sequence (WGS) analysis to identify serotypes, resistance features, genotypes, and pilus types. PCV13, licensed in February 2010, effectively targeted all major 19A and 7F genotypes, and decreased antimicrobial resistance, primarily owing to removal of the 19A/ST320 complex. The strain complex contributing most to the remaining β-lactam resistance during 2011–2013 was 35B/ST558. Significant emergence of non-vaccine clonal complexes was not evident. Because of the removal of vaccine serotype strains, positivity for one or both pilus types (PI-1 and PI-2) decreased in the post-PCV13 years 2011–2013 relative to 2008–2009 (decreases of 32–55% for PI-1, and >95% for PI-2 and combined PI-1 + PI-2). β-Lactam susceptibility phenotypes correlated consistently with transpeptidase region sequence combinations of the three major penicillin-binding proteins (PBPs) determined through WGS analysis. Other major resistance features were predictable by DNA signatures from WGS analysis. Multilocus sequence data combined with PBP combinations identified progeny, serotype donors and recipient strains in serotype switch events. PCV13 decreased the frequency of all PCV13 serotype clones and concurrently decreased the frequency of strain subsets with resistance and/or adherence features conducive to successful carriage. Our results serve as a reference describing key features of current paediatric IPD strains in the USA after PCV13 implementation.
Highlights
Streptococcus pneumoniae can quickly adapt to selective pressures through horizontal transfer and intrachromosomal mutation events
invasive pneumococcal disease (IPD) due to PCV13-targeted serotypes A total of 3024 isolates were collected through Active Bacterial Core surveillance (ABCs) during 2005–2013 from 3443 cases of IPD in children aged
The ability to resolve these two serotypes was included within our typing pipeline, owing to the reported low cross-reactivity of functional antibodies against serotype 15B with serotype 15C [17], which is a consideration in the formulation of new vaccines. These two serotypes accounted for 84 isolates for the years for which we provided genotyping (2008–2009 and 2011–2013), and showed a high level of genetic heterogeneity as compared with the pre-PCV7 years, when ABCs serotype 15B/15C isolates were primarily comprised of CC during 1999 (CC199) [14]
Summary
Streptococcus pneumoniae can quickly adapt to selective pressures through horizontal transfer and intrachromosomal mutation events. Metcalf et al Population-based invasive pneumococcal strain distribution in the USA 60.e10 frequency of invasive pneumococcal disease (IPD) and pneumococcal antimicrobial resistance. Individual variants that originated through serotype-switching events substantially contributed to disease burdens in the USA in the post-sevenvalent pneumococcal conjugate vaccine (PCV7) era [4,5,6,7,8]. The monitoring of pneumococcal serotypes and antimicrobial susceptibilities provides the major information for devising prevention strategies, approaches that deduce the causal chromosomal changes that lead to the emergence of individual invasive strains allow for a better biological and epidemiological understanding of pneumococcal strains. We have provided a strain reference that supplies distributions and genetic features of each invasive serotype that we detected in a US surveillance system during a key 5-year period of IPD surveillance
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