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International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact

International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact
International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact
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).
338–346
Gladstone, Rebecca
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Lo, Stephanie W.
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Lees, John A.
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Croucher, Nicholas J.
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Van Tonder, Andries J.
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Corander, Jukka
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Page, Andrew J.
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Marttinen, Pekka
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Bentley, Leon J.
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Ochoa, Theresa J.
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Ho, Pak Leung
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Du Plessis, Mignon
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Cornick, Jennifer E.
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Kwambana-Adams, Brenda
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Benisty, Rachel
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Nzenze, Susan A.
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Madhi, Shabir A.
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Hawkins, Paulina A.
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Everett, Dean B.
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Antonio, Martin
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Dagan, Ron
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Klugman, Keith P.
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Von Gottberg, Anne
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McGee, Lesley
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Breiman, Robert F.
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Bentley, Stephen D
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Clarke, Stuart
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The Global Pneumococcal Sequencing Consortium
Gladstone, Rebecca
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Lo, Stephanie W.
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Lees, John A.
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Croucher, Nicholas J.
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Van Tonder, Andries J.
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Corander, Jukka
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Page, Andrew J.
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Marttinen, Pekka
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Bentley, Leon J.
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Ochoa, Theresa J.
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Ho, Pak Leung
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Du Plessis, Mignon
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Cornick, Jennifer E.
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Kwambana-Adams, Brenda
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Benisty, Rachel
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Nzenze, Susan A.
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Madhi, Shabir A.
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Hawkins, Paulina A.
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Everett, Dean B.
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Antonio, Martin
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Dagan, Ron
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Klugman, Keith P.
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Von Gottberg, Anne
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McGee, Lesley
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Breiman, Robert F.
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Bentley, Stephen D
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Clarke, Stuart
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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 , The Global Pneumococcal Sequencing Consortium (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).

Record type: Article

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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Accepted/In Press date: 9 April 2019
e-pub ahead of print date: 16 April 2019
Published date: May 2019

Identifiers

Local EPrints ID: 431637
URI: http://eprints.soton.ac.uk/id/eprint/431637
PURE UUID: 85447f1c-ad41-4d77-b087-a0f04e77e1ae
ORCID for Stuart Clarke: ORCID iD orcid.org/0000-0002-7009-1548

Catalogue record

Date deposited: 11 Jun 2019 16:30
Last modified: 26 Nov 2021 02:51

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Contributors

Author: Rebecca Gladstone
Author: Stephanie W. Lo
Author: John A. Lees
Author: Nicholas J. Croucher
Author: Andries J. Van Tonder
Author: Jukka Corander
Author: Andrew J. Page
Author: Pekka Marttinen
Author: Leon J. Bentley
Author: Theresa J. Ochoa
Author: Pak Leung Ho
Author: Mignon Du Plessis
Author: Jennifer E. Cornick
Author: Brenda Kwambana-Adams
Author: Rachel Benisty
Author: Susan A. Nzenze
Author: Shabir A. Madhi
Author: Paulina A. Hawkins
Author: Dean B. Everett
Author: Martin Antonio
Author: Ron Dagan
Author: Keith P. Klugman
Author: Anne Von Gottberg
Author: Lesley McGee
Author: Robert F. Breiman
Author: Stephen D Bentley
Author: Stuart Clarke ORCID iD
Corporate Author: The Global Pneumococcal Sequencing Consortium

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