Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA

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.

Emergence of Multidrug-Resistant Pneumococcal Serotype 35B among Children in the United States

“…In the present study, the number of cases of serotype 35B IPD increased considerably after the introduction of PCV13, which is consistent with recent reports (6,8). The increase was directly related to the continued clonal expansion of CC558 and the emergence of CC156 among serotype 35B isolates.…”

“…A study from Canada also identified a serotype 35B isolate that represented an SLV of ST156 (ST9346) in 2011 (25). The two studies reported 1 or 2 occurrences of ST156 or its SLV in association with serotype 35B (8,25). Thus, ST156 did not contribute to the increased prevalence of serotype 35B in those studies.…”

“…In the United States, a recent study reported 2 capsular switching events that involved a serotype 35B donor strain (35B/ST558) and an ST156 recipient strain; the first occurred in 2009 and the second in 2012 (8). A study from Canada also identified a serotype 35B isolate that represented an SLV of ST156 (ST9346) in 2011 (25).…”

Nasopharyngeal pneumococcal carriage rates among HIV-infected adults following widespread pediatric use of conjugate pneumococcal vaccine-13

“…35 By 2015, the CDC's Active Bacterial Core Surveillance program showed that serotypes 15B/ C and 35B have emerged as 2 of the top 4 most frequent causes of IPD in children less than 5 years of age. 41 Furthermore, as serotypes 15B/C and 35B emerged, it became clear that many isolates are b-lactam resistant. 36,38,41 Strengths of this study include the prospective collection of a large number of nasopharyngeal samples from a high risk population for pneumococcal isolation.…”

“…41 Furthermore, as serotypes 15B/C and 35B emerged, it became clear that many isolates are b-lactam resistant. 36,38,41 Strengths of this study include the prospective collection of a large number of nasopharyngeal samples from a high risk population for pneumococcal isolation. Limitations of this study include the low carriage rates resulting in low number of pneumococci isolated, limiting the generalizability of serotype and antibiotic susceptibility results and factors associate with carriage.…”