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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1294-1303
Number of pages10
JournalClinical Infectious Diseases
Issue number7
Publication statusPublished - 17 Mar 2020

Bibliographical note

Funding Information:
Potential conflicts of interest. N. B. Z. has received investigator-initiated project grants from GlaxoSmithKline Biologicals and from Takeda Pharmaceuticals. R. A. G. has received a PhD studentship from Pfizer in 2009–2013. W. P. H. has received personal fees from Antigen Discovery. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Funding Information:
Financial support. 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.

Publisher Copyright:
© 2019 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America.


  • carriage
  • genomics
  • pneumococcus
  • serotypes


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