Molecular epidemiology and comparative genomics analyses of the population structure of streptococcus pneumoniae in Hong Kong

Abstract

Streptococcus pneumoniae is an opportunistic pathogen causing severe disease burdens around the global, especially amongst young children and the elderly. Since the introduction of 7-valent pneumococcal conjugate vaccine (PVC7), reductions of the targeted serotypes amongst both carriage and invasive pneumococcal disease (IPD) populations have been observed. However, increases in non-vaccine targeted serotypes were also observed as replacements to the niches. More recently, genomics studies have found that the original pneumococcal population equilibrium could be disrupted by a widespread use of PCV7 within cities and countries. Information regarding the pneumococcal carriage rate, IPD incidence rate, and serotype replacement trends had been lacking in Asia due to delayed or lack of implementation of PCV. Even globally, only a handful of genomic studies were reported, inadequate to generalize a trend of global structural changes of the pneumococcal population. Studies on recombination and the resulting variants are scarcely available with limited coverage of genetic backgrounds. In this study, we aimed to investigate changes in the epidemiology of Hong Kong’s pneumococcal population in the post-PCV7 era, including changes in children’s pneumococcal carriage rate and carriage serotype prevalence, age-stratified IPD incidence rates and disease serotype prevalence, plus changes in pneumococcal population structure by recombination studies.

We found a significant decrease in pneumococcal carriage rate amongst young children in Hong Kong, mostly due to a drastic reduction in the prevalence of PCV7 serotypes. This reduction was accompanied by non-PCV13 serotypes, most notably serogroup 15, which increased from 3.7% (pre-PCV7) to 25.6% in the post-PCV7 collection. Molecular analysis showed the rise of serogroup 15 was a clonal expansion of pre-existing clones. A significant decrease in the prevalence of PCV7 serotypes was also observed amongst IPD cases across all age groups.

IPD incidence amongst young children and elderly had decreased significantly. Serotype replacement in IPD cases was found to be predominantly by serotype 3 (47%) and serotype 19A (8.4%), where together they contributed to more than half of the IPD cases in the post-PCV7 era.

Genomic analysis revealed Hong Kong’s pneumococcal population was disrupted and under reconstruction by the effect of the universal implementation of PCV7 in our childhood immunization program. Diversities of serotypes and genetic backgrounds had decreased significantly in the post-PCV7 era, indicating a new equilibrium has not been achieved.

Recombination analysis revealed the two predominant serotypes (serotype 3 and 19A) in post-PCV7 IPD cases in Hong Kong were both results of capsular switching recombination. The most predominant clone, ST6011-serotype 3, was not found anywhere else in the world when compared with global collections. Further analyses strongly suggested ST6011-serotype 3 was a result of a local recombination event, with ST1263-serotype 9V as the genetic background and ST180-serotype 3 as the DNA donor.

While a decrease in carriage rate and IPD incidence amongst children is encouraging, our observation of serotype replacements remains a concern particularly a capsule switched serotype 3 clone predominating post-PCV7 IPD cases. Future work should include an investigation of why this predominant clone had successfully outcompeted the other serotype 3 with a conventional ST180 background.