TY - JOUR
T1 - International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact
AU - Global Pneumococcal Sequencing Consortium
AU - Gladstone, Rebecca A
AU - Lo, Stephanie W
AU - Lees, John A
AU - Croucher, Nicholas J
AU - van Tonder, Andries J
AU - Corander, Jukka
AU - Page, Andrew J
AU - Marttinen, Pekka
AU - Bentley, Leon J
AU - Ochoa, Theresa J
AU - Ho, Pak Leung
AU - du Plessis, Mignon
AU - Cornick, Jennifer E
AU - Kwambana-Adams, Brenda
AU - Benisty, Rachel
AU - Nzenze, Susan A
AU - Madhi, Shabir A
AU - Hawkins, Paulina A
AU - Everett, Dean B
AU - Antonio, Martin
AU - Dagan, Ron
AU - Klugman, Keith P
AU - von Gottberg, Anne
AU - McGee, Lesley
AU - Breiman, Robert F
AU - Bentley, Stephen D
N1 - Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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 >100 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 < .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 < .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p < .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.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.
AB - 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 >100 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 < .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 < .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p < .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.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.
KW - Anti-Bacterial Agents/pharmacology
KW - Biodiversity
KW - Drug Resistance, Bacterial
KW - Evolution, Molecular
KW - Female
KW - Genome, Bacterial
KW - Genomics/methods
KW - Genotype
KW - Global Health
KW - Humans
KW - Male
KW - Pneumococcal Infections/drug therapy
KW - Pneumococcal Vaccines
KW - Polymorphism, Single Nucleotide
KW - Serogroup
KW - Streptococcus pneumoniae/classification
U2 - 10.1016/j.ebiom.2019.04.021
DO - 10.1016/j.ebiom.2019.04.021
M3 - Article
C2 - 31003929
SN - 2352-3964
VL - 43
SP - 338
EP - 346
JO - EBioMedicine
JF - EBioMedicine
ER -
