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Title: Early signals of vaccine-driven perturbation seen in pneumococcal carriage population genomic data
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
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
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
Keywords: Medicine
Issue Date: 17-Mar-2020
Citation: Clinical Infectious Diseases. Vol.70, No.7 (2020), 1294-1303
Abstract: © 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.
ISSN: 15376591
Appears in Collections:Scopus 2020

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