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@article{Gladstone:2019:10.1016/j.ebiom.2019.04.021,
author = {Gladstone, RA and Lo, SW and Lees, JA and Croucher, NJ and van, Tonder AJ and Corander, J and Page, AJ and Marttinen, P and Bentley, LJ and Ochoa, TJ and Ho, PL and du, Plessis M and Cornick, JE and Kwambana-Adams, B and Benisty, R and Nzenze, SA and Madhi, SA and Hawkins, PA and Everett, DB and Antonio, M and Dagan, R and Klugman, KP and von, Gottberg A and McGee, L and Breiman, RF and Bentley, SD},
doi = {10.1016/j.ebiom.2019.04.021},
journal = {EBioMedicine},
pages = {338--346},
title = {International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact},
url = {http://dx.doi.org/10.1016/j.ebiom.2019.04.021},
volume = {43},
year = {2019}
}

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TY  - JOUR
AB  - BackgroundPneumococcal 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.MethodsOur 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.FindingsThe 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.InterpretationWe define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing n
AU  - Gladstone,RA
AU  - Lo,SW
AU  - Lees,JA
AU  - Croucher,NJ
AU  - van,Tonder AJ
AU  - Corander,J
AU  - Page,AJ
AU  - Marttinen,P
AU  - Bentley,LJ
AU  - Ochoa,TJ
AU  - Ho,PL
AU  - du,Plessis M
AU  - Cornick,JE
AU  - Kwambana-Adams,B
AU  - Benisty,R
AU  - Nzenze,SA
AU  - Madhi,SA
AU  - Hawkins,PA
AU  - Everett,DB
AU  - Antonio,M
AU  - Dagan,R
AU  - Klugman,KP
AU  - von,Gottberg A
AU  - McGee,L
AU  - Breiman,RF
AU  - Bentley,SD
DO  - 10.1016/j.ebiom.2019.04.021
EP  - 346
PY  - 2019///
SN  - 2352-3964
SP  - 338
TI  - International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact
T2  - EBioMedicine
UR  - http://dx.doi.org/10.1016/j.ebiom.2019.04.021
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000470091600046&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/71336
VL  - 43
ER  -

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