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Whole-Genome Analysis of Streptococcus pneumoniae Serotype 4 Causing Outbreak of Invasive Pneumococcal Disease,
Insights
Invasive pneumococcal disease caused by Streptococcus pneumoniae serotype 4 has reemerged in adults in Calgary, Canada. This resurgence is linked to specific genetic lineages and is concentrated among those experiencing homelessness or using illicit drugs.
Area of Science:
- Infectious Diseases
- Genomics
- Public Health
Background:
- Pneumococcal conjugate vaccines (PCVs) reduced invasive pneumococcal disease (IPD) globally.
- Serotype 4 IPD declined after PCV introduction in Alberta, Canada.
- A resurgence of serotype 4 IPD has been observed in adults in Calgary.
Purpose of the Study:
- To investigate the clinical and molecular characteristics of reemerging Streptococcus pneumoniae serotype 4 IPD in Calgary.
- To identify genetic factors and risk factors associated with the serotype 4 resurgence.
Main Methods:
- Clinical data review and molecular analysis of Streptococcus pneumoniae serotype 4 isolates.
- Whole-genome sequencing and phylogenetic analysis to determine genetic variability and lineage emergence.
- Multivariable logistic regression to identify associated risk factors.
Main Results:
- Whole-genome sequencing revealed significant genetic variability among serotype 4 isolates.
- Phylogenetic analysis identified an emergent ST244 lineage, with subclades clustering regionally, temporally, and by homeless status.
- Factors associated with serotype 4 IPD included male sex, age <65, homelessness, pneumonia/empyema diagnosis, and illicit drug use.
Conclusions:
- The reemergence of serotype 4 IPD in Calgary is driven by specific emergent lineages.
- Homelessness and illicit drug use are significant risk factors for serotype 4 IPD in this population.
- Targeted public health interventions may be necessary for vulnerable populations.
Abstract:
After the introduction of pneumococcal conjugate vaccines for children, invasive pneumococcal disease caused by Streptococcus pneumoniae serotype 4 declined in all ages in Alberta, Canada, but it has reemerged and spread in adults in Calgary, primarily among persons who are experiencing homelessness or who use illicit drugs. We conducted clinical and molecular analyses to examine the cases and isolates. Whole-genome sequencing analysis indicated relatively high genetic variability of serotype 4 isolates. Phylogenetic analysis identified 1 emergent sequence type (ST) 244 lineage primarily associated within Alberta and nationally distributed clades ST205 and ST695. Isolates from 6 subclades of the ST244 lineage clustered regionally, temporally, and by homeless status. In multivariable logistic regression, factors associated with serotype 4 invasive pneumococcal disease were being male, being <65 years of age, experiencing homelessness, having a diagnosis of pneumonia or empyema, or using illicit drugs.
