Early Signals of Vaccine-driven Perturbation Seen in Pneumococcal Carriage Population Genomic Data

• Type of Material: Article
• Authors: Chrispin Chaguza, Wellcome Sanger Institute; Ellen Heinsbroek, University of Liverpool; Rebecca A. Gladstone, Wellcome Sanger Institute; Terence Tafatatha, Malawi Epidemiology Intervention Research Unit; Maaike Alaerts, Malawi-Liverpool-Wellcome Trust Clinical Research Programme; Chikondi Peno, Malawi-Liverpool-Wellcome Trust Clinical Research Programme; Jennifer E. Cornick, University of Liverpool; Patrick Musicha, University of Liverpool; Naor Bar-Zeev, University of Liverpool; Arox Kamng'ona, University of Liverpool; Aras Kadioglu, University of Liverpool; Lesley McGee, Centers for Disease Control and Prevention; William P. Hanage, Harvard T. H. Chan School of Public Health; Robert Breiman, Emory University; Robert S. Heyderman, Malawi-Liverpool-Wellcome Trust Clinical Research Programme; Neil French, University of Liverpool; Dean B. Everett, Malawi-Liverpool-Wellcome Trust Clinical Research Programme; Stephen D. Bentley, Wellcome Sanger Institute
• Language: English
• Date: 2020-04-01
• Publisher: OXFORD UNIV PRESS INC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2019.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/cid/ciz404
• Title of Journal or Parent Work: CLINICAL INFECTIOUS DISEASES
• Volume: 70
• Issue: 7
• Start Page: 1294
• End Page: 1303
• Grant/Funding Information: This work was supported by the Bill & Melinda Gates Foundation’s funding for the Global Pneumococcal Sequencing (GPS) project (www.pneumogen.net; grant number OPP1034556 to S. D. B., L. M., and R. F. B.) and by Wellcome UK (core grant number 084679/Z/08/Z to the MLW). R. S. H. and N. F. are supported by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) grant under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union (MR/N023129/1). C. C. was funded by a PhD studentship from the Commonwealth Scholarship Commission in the United Kingdom.
• Keywords: STREPTOCOCCUS-PNEUMONIAE; CHILDREN; Life Sciences & Biomedicine; ADULTS; Science & Technology; HAEMOPHILUS-INFLUENZAE; serotypes; EVOLUTION; SEROTYPE REPLACEMENT; pneumococcus; NASOPHARYNGEAL CARRIAGE; Immunology; genomics; Microbiology; carriage; DISEASE; Infectious Diseases; CONJUGATE VACCINE; RESISTANCE
• Research Categories: Biology, Microbiology; Health Sciences, Immunology; Biology, Genetics

Abstract

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.