Introduction: Prior to the introduction of the pneumococcal conjugate vaccines (PCV7 and PCV13), invasive pneumococcal disease (IPD) was associated with high rates of morbidity and mortality in children and the elderly. However, serotype 3 infections characteristically result in severe clinical presentations. Despite the inclusion of serotype 3 in the PCV13 vaccine formulation, it continues to evade antibody-mediated clearance and remains a significant cause of IPD in Australia.
Methods: This study aimed to understand the evolution and genomic characteristics of IPD caused by Streptococcus pneumoniae serotype 3. Historical isolates of S. pneumoniae recovered from IPD cases diagnosed in New South Wales between January 1999 and December 2020 (n=134) were subjected to serotyping, whole genome sequencing (WGS) and bioinformatics analysis.
Results: The population structure of IPD isolates were determined. The S. pneumoniae genomes of serotype 3 isolates were predominately classified as sequence type (ST)-180 (86.4%, 108/125). However, the incidence of a more divergent and virulent lineage within ST-180 (Clade II, 15.2%, 19/125) emerged and increased after 2005. Internationally, Clade II has been associated with increased virulence, genetic recombination, and antimicrobial resistance to first-line agents, notably due to the acquisition of the Tn916-like conjugative transposon.
Conclusions: These findings indicate a genetic divergence in S. pneumoniae serotype 3 genomes, which is postulated to be driving the increased incidence and persistence of serotype 3 IPD in Australia.