Manish Sadarangani (Canada)
University of British Columbia Vaccine Evaluation CenterPresenter of 7 Presentations
ESPID Young Investigator Awards Introduction (ID 2153)
Expert: (ID 2253)
WHOLE GENOME SEQUENCING OF STREPTOCOCCUS PNEUMONIAE FROM CHILDREN WITH PNEUMONIA IN CANADA BETWEEN 1991 AND 2016 FROM THE CANADIAN IMMUNIZATION MONITORING PROGRAM ACTIVE (IMPACT) (ID 441)
Abstract
Background
In children, Streptococcus pneumoniae causes up to 78% of bacterial lobar pneumonia, which may be further complicated by pleural effusion or empyema. We aimed to 1) characterize pediatric pneumonia-causing S. pneumoniae over 25 years in Canada before and after use of pneumococcal conjugate vaccines and 2) correlate bacterial genomic data with clinical features in cases.
Methods
Whole genome sequencing was performed on 297 S. pneumoniae isolates from pneumonia cases in 12 pediatric tertiary care hospitals in Canada between 1991 and 2016 from the pre-vaccine, PCV7/10 and PCV13 eras. Isolates and clinical data were obtained from the Canadian Immunization Monitoring Program ACTive (IMPACT). Genome wide associations were assessed using TreeWAS, incorporating phylogenetic data (i.e., evolutionary history) to identify associations between bacterial genomes and outcomes.
Results
Pan-genome analysis identified 4,305 genes including 1,324 which were shared by all isolates. We detected 37 Global Pneumococcal Sequence Clusters (GPSCs) including GPSCs which increased (4 and 119) and decreased (3 and 19) across vaccine eras. Genome wide association studies revealed several non-synonymous nucleotide polymorphisms or gene associations that were statistically significant in association with empyema (3 polymorphisms and 1 gene) and ICU admission >2 days (6 polymorphisms and 1 gene). One complex polymorphism (translating to a 3 amino acid change at position 207) in the gene cbpD, encoding the major pneumococcal virulence factor choline binding protein D, was significantly associated with both empyema and prolonged ICU admission.
Conclusions
The molecular epidemiology of S. pneumoniae has changed in the conjugate vaccine era in terms of GPSCs causing pediatric pneumonia. We have identified both genes and non-synonymous polymorphisms that are associated with empyema and ICU admission providing a starting point for validation studies of their role in pneumococcal pneumonia.
Clinical Trial Registration
This study does not report on the results of a controlled clinical trial
ESPID PIDJ Award Introduction (ID 2152)
ESPID Previous Fellowship Awards Introduction (ID 2154)
Introduction (ID 2337)
Expert and YE Coordinator Discussion (ID 1752)
Moderator of 3 Sessions
