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

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Pneumococcal conjugate vaccines (PCV) 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 of 660 pneumococcal isolates collected through surveys from healthy carriers two years from PCV14 introduction and one-year post-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 the under-fives, frequency and diversity of vaccine serotypes (VT) decreased significantly post-PCV but no significant changes occurred in over-fives. Clearance of VT serotypes was consistent across different genetic backgrounds (lineages). There was an increase of non-vaccine serotypes (NVT) namely 7C, 15B/C, 23A in under-fives but 28F increased in both age groups. While carriage rates have been recently shown to remain stable post-PCV due replacement serotypes, there was no change in diversity of NVTs. Additionally, frequency of intermediate-penicillin-resistant lineages decreased post-PCV. While frequency of ABR genes remained stable, other accessory genes especially those associated with MGEs 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 under-fives. Continued surveillance with WGS remains crucial to fully understand dynamics of the residual VTs and replacement NVT serotypes post-PCV.

Original languageEnglish
JournalClinical Infectious Diseases
Early online date16 May 2019
DOIs
Publication statusE-pub ahead of print - 16 May 2019

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