Gladstone, Rebecca, Lo, Stephanie W., Lees, John A., Croucher, Nicholas J., Van Tonder, Andries J., Corander, Jukka, Page, Andrew J., Marttinen, Pekka, Bentley, Leon J., Ochoa, Theresa J., Ho, Pak Leung, Du Plessis, Mignon, Cornick, Jennifer E., Kwambana-Adams, Brenda, Benisty, Rachel, Nzenze, Susan A., Madhi, Shabir A., Hawkins, Paulina A., Everett, Dean B., Antonio, Martin, Dagan, Ron, Klugman, Keith P., Von Gottberg, Anne, McGee, Lesley, Breiman, Robert F. and Bentley, Stephen D , (2019) International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact. EBioMedicine, 43, 338–346. (doi:10.1016/j.ebiom.2019.04.021).
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 that relating prevalence in invasive pneumococcal 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 N100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed in the years up until, and including, the first year of pneumococcal conjugate vaccine introduction. Penicillin and multidrug resistance were higher (p b .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 b .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p b .05) of its antibiogram (mean misclassification error 0.28, SD ± 0.13).
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