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• W3123408075 abstract "Background: Pneumococcal conjugate vaccines have reduced the incidence of invasive pneumococcal disease, caused by vaccine serotypes, but non-vaccine-serotypes remain a concern. We used whole genome sequencing to study pneumococcal serotype, antibiotic resistance and invasiveness, in the context of genetic background.Methods: Our dataset of 13,454 genomes, combined with four published genomic datasets, represented Africa (40%), Asia (25%), Europe (19%), North America (12%), and South America (5%). These 20,027 pneumococcal genomes were clustered into lineages using PopPUNK, and named Global Pneumococcal Sequence Clusters (GPSCs). From our dataset, we additionally derived serotype and sequence type, and predicted antibiotic sensitivity. We then measured invasiveness using odds ratios, relating prevalence in disease to carriage.Findings: The combined collections (n=20,027) were clustered into 621 GPSCs. Thirty-five GPSCs observed in our dataset were represented by >100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed pre-PCV. Penicillin and multidrug resistance were higher (p<0.05) in a subset dominant-GPSCs (14/35, 9/35 respectively), and resistance to an increasing number of antibiotic classes was associated with increased recombination (R2=0.27 p<0.0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p<0.05) of its antibiogram (mean misclassification error 0.28, SD± 0.13). We detected increased invasiveness of six genetic backgrounds, when compared to other genetic backgrounds expressing the same serotype. Up to 1.6-fold changes in invasiveness odds ratio were observed, equivalent to the fold change in invasiveness odds ratio between serotype 35A and 18C.Interpretation: We define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing non-vaccine-serotypes in most GPSCs preclude the removal of these lineages by pneumococcal conjugate vaccines; leaving potential for serotype replacement. A subset of GPSCs have increased resistance, and/or serotype-independent invasiveness.Funding: This study was co-funded by the Bill and Melinda Gates Foundation, the Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention.Declaration of Interest: Dr. Gladstone reports PhD studentship from Pfizer, outside the submitted work; Dr. Lees reports grants from Pfizer, outside the submitted work; Dr. Madhi reports grants from BMGF, during the conduct of the study; grants and personal fees from BMGF, grants from Pfizer, grants from GSK, grants from Sanofi, grants from BIOVAC, outside the submitted work; Dr. Dagan reports grants and personal fees from Pfizer, during the conduct of the study; grants and personal fees from MSD, personal fees from MeMed, outside the submitted work; Dr. von Gottberg reports grants and other from Pfizer, during the conduct of the study; grants and other from Sanofi, outside the submitted work; Dr. Bentley reports personal fees from Pfizer, personal fees from Merck, outside the submitted work. Ethical Approval: Isolates for this study were selected from retrospective bacterial collections in each country participating in GPS. Appropriate approvals for use of isolates was obtained from each institution contributing isolates. No tissue material or other biological material was obtained from humans. All information regarding these isolates was anonymised." @default.
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• W3123408075 date "2019-01-01" @default.
• W3123408075 modified "2023-10-14" @default.
• W3123408075 title "International Genomic Definition of Pneumococcal Lineages, to Contextualise Disease, Antibiotic Resistance and Vaccine Impact" @default.
• W3123408075 doi "https://doi.org/10.2139/ssrn.3360095" @default.
• W3123408075 hasPublicationYear "2019" @default.
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