The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study

Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study
Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study
Background: Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanismof serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits.Methods: We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacementby comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model.Findings: The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or morecountries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could beassociated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0·0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period.Interpretation Globally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design.
1473-3099
759-769
Lo, Stephanie W.
607ccad6-93b1-484c-ba8d-9821432fce90
Gladstone, Rebecca
6a2011bf-2561-4956-9928-46e6b927ba6d
Van Tonder, Andries J.
a600d507-76aa-48e8-b1d5-e75d90bb8e6e
Lees, John A.
3e44c908-eb48-4cb9-b178-576aea628387
Du Plessis, Mignon
22fdbb8a-0bcd-4e0d-8a32-520cb5e59e7f
Benisty, Rachel
47176607-7fda-4131-af64-c74e1f6ac770
Givon-Lavi, Noga
f5f257ae-f29e-470b-a6de-fa6f04500561
Hawkins, Paulina A.
8c2fdf53-ab4d-4484-b08b-6728fccc8bb7
Cornick, Jennifer E.
6d915388-bfcd-458a-a9f5-3593b41019bc
Kwambana-Adams, Brenda
ad0a85c9-1ee1-406e-818c-bb9fda608bdb
Law, Pierra Y
01269868-8031-433a-8fb2-19f5eeefe78e
Ho, Pak Leung
631d2e57-7dad-4413-b90b-dfa1f4f3a085
Antonio, Martin
ac8a8442-881c-4d64-af8e-6ecf34f07c83
Everett, Dean B.
6518700c-7cda-4221-b0ff-e27bb84a4bf5
Dagan, Ron
f384a61e-90a0-491d-8d51-3abea05890a4
Von Gottberg, Anne
2e435fdc-f9f3-4c37-b96a-f4d5184661f0
Klugman, Keith P.
52451fd0-e5f1-4904-ab95-66552a786a66
McGee, Lesley
8b2b4ed5-fb63-4e8f-a9b1-ee14573daab0
Breiman, Robert F.
38ff5868-bb32-43c3-97c4-d52ceba325d0
Bentley, Stephen D.
438443a4-8033-4a5d-a5a5-538dbd4e8d60
Clarke, Stuart
f7d7f7a2-4b1f-4b36-883a-0f967e73fb17
The Global Pneumococcal Sequencing Consortium
Lo, Stephanie W.
607ccad6-93b1-484c-ba8d-9821432fce90
Gladstone, Rebecca
6a2011bf-2561-4956-9928-46e6b927ba6d
Van Tonder, Andries J.
a600d507-76aa-48e8-b1d5-e75d90bb8e6e
Lees, John A.
3e44c908-eb48-4cb9-b178-576aea628387
Du Plessis, Mignon
22fdbb8a-0bcd-4e0d-8a32-520cb5e59e7f
Benisty, Rachel
47176607-7fda-4131-af64-c74e1f6ac770
Givon-Lavi, Noga
f5f257ae-f29e-470b-a6de-fa6f04500561
Hawkins, Paulina A.
8c2fdf53-ab4d-4484-b08b-6728fccc8bb7
Cornick, Jennifer E.
6d915388-bfcd-458a-a9f5-3593b41019bc
Kwambana-Adams, Brenda
ad0a85c9-1ee1-406e-818c-bb9fda608bdb
Law, Pierra Y
01269868-8031-433a-8fb2-19f5eeefe78e
Ho, Pak Leung
631d2e57-7dad-4413-b90b-dfa1f4f3a085
Antonio, Martin
ac8a8442-881c-4d64-af8e-6ecf34f07c83
Everett, Dean B.
6518700c-7cda-4221-b0ff-e27bb84a4bf5
Dagan, Ron
f384a61e-90a0-491d-8d51-3abea05890a4
Von Gottberg, Anne
2e435fdc-f9f3-4c37-b96a-f4d5184661f0
Klugman, Keith P.
52451fd0-e5f1-4904-ab95-66552a786a66
McGee, Lesley
8b2b4ed5-fb63-4e8f-a9b1-ee14573daab0
Breiman, Robert F.
38ff5868-bb32-43c3-97c4-d52ceba325d0
Bentley, Stephen D.
438443a4-8033-4a5d-a5a5-538dbd4e8d60
Clarke, Stuart
f7d7f7a2-4b1f-4b36-883a-0f967e73fb17

Lo, Stephanie W., Gladstone, Rebecca, Van Tonder, Andries J., Lees, John A., Du Plessis, Mignon, Benisty, Rachel, Givon-Lavi, Noga, Hawkins, Paulina A., Cornick, Jennifer E., Kwambana-Adams, Brenda, Law, Pierra Y, Ho, Pak Leung, Antonio, Martin, Everett, Dean B., Dagan, Ron, Von Gottberg, Anne, Klugman, Keith P., McGee, Lesley, Breiman, Robert F. and Bentley, Stephen D. , The Global Pneumococcal Sequencing Consortium (2019) Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study. The Lancet Infectious Diseases, 19 (7), 759-769. (doi:10.1016/S1473-3099(19)30297-X).

Record type: Article

Abstract

Background: Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanismof serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits.Methods: We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacementby comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model.Findings: The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or morecountries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could beassociated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0·0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period.Interpretation Globally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design.

Text
Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study - Version of Record
Available under License Creative Commons Attribution.
Download (2MB)

More information

Accepted/In Press date: 1 January 2019
e-pub ahead of print date: 10 June 2019
Published date: July 2019

Identifiers

Local EPrints ID: 431911
URI: http://eprints.soton.ac.uk/id/eprint/431911
ISSN: 1473-3099
PURE UUID: de38b5f3-adf8-44b6-a978-26b61b2063fc
ORCID for Stuart Clarke: ORCID iD orcid.org/0000-0002-7009-1548

Catalogue record

Date deposited: 21 Jun 2019 16:30
Last modified: 26 Nov 2021 02:51

Export record

Altmetrics

Contributors

Author: Stephanie W. Lo
Author: Rebecca Gladstone
Author: Andries J. Van Tonder
Author: John A. Lees
Author: Mignon Du Plessis
Author: Rachel Benisty
Author: Noga Givon-Lavi
Author: Paulina A. Hawkins
Author: Jennifer E. Cornick
Author: Brenda Kwambana-Adams
Author: Pierra Y Law
Author: Pak Leung Ho
Author: Martin Antonio
Author: Dean B. Everett
Author: Ron Dagan
Author: Anne Von Gottberg
Author: Keith P. Klugman
Author: Lesley McGee
Author: Robert F. Breiman
Author: Stephen D. Bentley
Author: Stuart Clarke ORCID iD
Corporate Author: The Global Pneumococcal Sequencing Consortium

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×