High-resolution genomics identifies pneumococcal diversity and persistence of vaccine types in children with community-acquired pneumonia in the UK and Ireland

Abstract

Abstract Background Streptococcus pneumoniae is a global cause of community-acquired pneumonia (CAP) and invasive disease in children that requires antibiotic treatment. As part of the CAP-IT trial (grant No. 13/88/11; https://www.capitstudy.org.uk/), we analyzed nasopharyngeal swabs from children with clinically diagnosed CAP, and found no differences in pneumococcal susceptibility between patients receiving oral amoxicillin treatment for shorter or longer durations and at higher or lower antibiotic doses. Here, we perform high-resolution genomics to understand pneumococcal diversity and to unravel potential mechanisms underlying persistence of pneumococcal (vaccine) serotypes.Methods Three-hundred and ninety pneumococci cultured from 1132 nasopharyngeal swabs from 718 children were whole-genome sequenced (Illumina) and tested for susceptibility to penicillin and amoxicillin. Recombination analysis was performed using long-read sequenced isolates (PacBio) and publicly available sequences.Results In 390 unique pneumococcal isolates, non-susceptibility to penicillin (n = 61, 15.6%) and amoxicillin (n = 10, 2.6%) was low and independent of the amoxicillin treatment dosage and duration. Serotypes 15B/C, 11A, 15A and 23B1 were most prevalent. PCV13 serotypes 3, 19A, and 19F were also identified (n = 25, 6.4%), and recombination analysis and genome-wide comparisons with historical isolates dating from 1995 identified several potential capsule switch events in these highly recombinant vaccine serotypes 19A and 19F, in contrast to serotype 3 genomes (n = 13, 3.3%) that showed high genomic stability over the last 20 years. All 23B1 isolates (n = 27, 6.9%) were penicillin non-susceptible, and one was the result of a potential capsule-switch in 19F.Conclusions Our data suggest that vaccination strategies, but not amoxicillin use, are more likely to drive pneumococcal serotype prevalence among children in the UK and prompts consideration of PCVs with additional serotype coverage that are likely to further decrease invasive disease in this target population. Emergence of 23B1, a non-vaccine genotype with penicillin non-susceptibility, might provide a persistence strategy for vaccine serotypes, highlighting the need for continued genomic surveillance.