Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data

© 2019 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. Background: Pneumococcal conjugate vaccines (PCVs) have reduced pneumococcal diseases globally. Pneumococcal genomic surveys elucidate PCV effects on population structure but are rarely conduct...

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Main Authors: Chrispin Chaguza, Ellen Heinsbroek, Rebecca A. Gladstone, Terence Tafatatha, Maaike Alaerts, Chikondi Peno, Jennifer E. Cornick, Patrick Musicha, Naor Bar-Zeev, Arox Kamng'Ona, Aras Kadioglu, Lesley McGee, William P. Hanage, Robert F. Breiman, Robert S. Heyderman, Neil French, Dean B. Everett, Stephen D. Bentley
Other Authors: Public Health England
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Published: 2020
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/54618
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spelling th-mahidol.546182020-05-05T12:38:17Z Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data Chrispin Chaguza Ellen Heinsbroek Rebecca A. Gladstone Terence Tafatatha Maaike Alaerts Chikondi Peno Jennifer E. Cornick Patrick Musicha Naor Bar-Zeev Arox Kamng'Ona Aras Kadioglu Lesley McGee William P. Hanage Robert F. Breiman Robert S. Heyderman Neil French Dean B. Everett Stephen D. Bentley Public Health England Malawi Epidemiology and Intervention Research Unit Malawi-Liverpool-Wellcome Trust Clinical Research Programme University of Malawi College of Medicine Harvard T.H. Chan School of Public Health University of Cambridge University of Edinburgh Rollins School of Public Health UCL University of Liverpool Universiteit Antwerpen Mahidol University National Center for Immunization and Respiratory Diseases Nuffield Department of Clinical Medicine Johns Hopkins Bloomberg School of Public Health Wellcome Sanger Institute Medicine © 2019 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. Background: Pneumococcal conjugate vaccines (PCVs) have reduced pneumococcal diseases globally. Pneumococcal genomic surveys elucidate PCV effects on population structure but are rarely conducted in low-income settings despite the high disease burden. Methods: We undertook whole-genome sequencing (WGS) of 660 pneumococcal isolates collected through surveys from healthy carriers 2 years from 13-valent PCV (PCV13) introduction and 1 year after rollout in northern Malawi. We investigated changes in population structure, within-lineage serotype dynamics, serotype diversity, and frequency of antibiotic resistance (ABR) and accessory genes. Results: In children <5 years of age, frequency and diversity of vaccine serotypes (VTs) decreased significantly post-PCV, but no significant changes occurred in persons ≥5 years of age. Clearance of VT serotypes was consistent across different genetic backgrounds (lineages). There was an increase of nonvaccine serotypes (NVTs) - namely 7C, 15B/C, and 23A - in children <5 years of age, but 28F increased in both age groups. While carriage rates have been recently shown to remain stable post-PCV due to replacement serotypes, there was no change in diversity of NVTs. Additionally, frequency of intermediate-penicillin-resistant lineages decreased post-PCV. Although frequency of ABR genes remained stable, other accessory genes, especially those associated with mobile genetic element and bacteriocins, showed changes in frequency post-PCV. Conclusions: We demonstrate evidence of significant population restructuring post-PCV driven by decreasing frequency of vaccine serotypes and increasing frequency of few NVTs mainly in children under 5. Continued surveillance with WGS remains crucial to fully understand dynamics of the residual VTs and replacement NVT serotypes post-PCV. 2020-05-05T05:38:17Z 2020-05-05T05:38:17Z 2020-03-17 Article Clinical Infectious Diseases. Vol.70, No.7 (2020), 1294-1303 10.1093/cid/ciz404 15376591 10584838 2-s2.0-85082096197 https://repository.li.mahidol.ac.th/handle/123456789/54618 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85082096197&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Medicine
spellingShingle Medicine
Chrispin Chaguza
Ellen Heinsbroek
Rebecca A. Gladstone
Terence Tafatatha
Maaike Alaerts
Chikondi Peno
Jennifer E. Cornick
Patrick Musicha
Naor Bar-Zeev
Arox Kamng'Ona
Aras Kadioglu
Lesley McGee
William P. Hanage
Robert F. Breiman
Robert S. Heyderman
Neil French
Dean B. Everett
Stephen D. Bentley
Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data
description © 2019 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. Background: Pneumococcal conjugate vaccines (PCVs) have reduced pneumococcal diseases globally. Pneumococcal genomic surveys elucidate PCV effects on population structure but are rarely conducted in low-income settings despite the high disease burden. Methods: We undertook whole-genome sequencing (WGS) of 660 pneumococcal isolates collected through surveys from healthy carriers 2 years from 13-valent PCV (PCV13) introduction and 1 year after rollout in northern Malawi. We investigated changes in population structure, within-lineage serotype dynamics, serotype diversity, and frequency of antibiotic resistance (ABR) and accessory genes. Results: In children <5 years of age, frequency and diversity of vaccine serotypes (VTs) decreased significantly post-PCV, but no significant changes occurred in persons ≥5 years of age. Clearance of VT serotypes was consistent across different genetic backgrounds (lineages). There was an increase of nonvaccine serotypes (NVTs) - namely 7C, 15B/C, and 23A - in children <5 years of age, but 28F increased in both age groups. While carriage rates have been recently shown to remain stable post-PCV due to replacement serotypes, there was no change in diversity of NVTs. Additionally, frequency of intermediate-penicillin-resistant lineages decreased post-PCV. Although frequency of ABR genes remained stable, other accessory genes, especially those associated with mobile genetic element and bacteriocins, showed changes in frequency post-PCV. Conclusions: We demonstrate evidence of significant population restructuring post-PCV driven by decreasing frequency of vaccine serotypes and increasing frequency of few NVTs mainly in children under 5. Continued surveillance with WGS remains crucial to fully understand dynamics of the residual VTs and replacement NVT serotypes post-PCV.
author2 Public Health England
author_facet Public Health England
Chrispin Chaguza
Ellen Heinsbroek
Rebecca A. Gladstone
Terence Tafatatha
Maaike Alaerts
Chikondi Peno
Jennifer E. Cornick
Patrick Musicha
Naor Bar-Zeev
Arox Kamng'Ona
Aras Kadioglu
Lesley McGee
William P. Hanage
Robert F. Breiman
Robert S. Heyderman
Neil French
Dean B. Everett
Stephen D. Bentley
format Article
author Chrispin Chaguza
Ellen Heinsbroek
Rebecca A. Gladstone
Terence Tafatatha
Maaike Alaerts
Chikondi Peno
Jennifer E. Cornick
Patrick Musicha
Naor Bar-Zeev
Arox Kamng'Ona
Aras Kadioglu
Lesley McGee
William P. Hanage
Robert F. Breiman
Robert S. Heyderman
Neil French
Dean B. Everett
Stephen D. Bentley
author_sort Chrispin Chaguza
title Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data
title_short Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data
title_full Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data
title_fullStr Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data
title_full_unstemmed Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data
title_sort early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data
publishDate 2020
url https://repository.li.mahidol.ac.th/handle/123456789/54618
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