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Clin Infect Dis. 2020 Mar 17;70(7):1294-1303. doi: 10.1093/cid/ciz404.

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

Author information

1
Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge.
2
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, United Kingdom.
3
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre.
4
Darwin College, University of Cambridge, Silver Street, Cambridge.
5
HIV and STI Department, National Infection Service, Public Health England, London, United Kingdom.
6
Malawi Epidemiology Intervention Research Unit (formerly KPS), Chilumba.
7
Center of Medical Genetics, University of Antwerp, Belgium.
8
Medical Research Council Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, United Kingdom.
9
Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
10
Nuffield Department of Medicine, University of Oxford, United Kingdom.
11
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
12
Department of Biomedical Sciences, University of Malawi, College of Medicine, Blantyre.
13
Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
14
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
15
Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia.
16
Division of Infection and Immunity, University College London, United Kingdom.
17
Department of Pathology, University of Cambridge, United Kingdom.

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.

KEYWORDS:

carriage; genomics; pneumococcus; serotypes

PMID:
31094423
DOI:
10.1093/cid/ciz404

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