Geographical migration and fitness dynamics of Streptococcus pneumoniae

The Global Pneumococcal Sequencing Consortium

doi:10.1038/s41586-024-07626-3

Geographical migration and fitness dynamics of Streptococcus pneumoniae

The Global Pneumococcal Sequencing Consortium

Wellcome Sanger Institute
University of Cambridge
Barcelona Supercomputing Center
National Institute for Communicable Diseases
School of Pathology
Parasites and Microbes
National Center for Immunization and Respiratory Diseases
University of the Witwatersrand Faculty of Health Sciences
University of Cape Town
Instituto Nacional de Enfermedades Infecciosas
icddr,b
Child Health Research Foundation
Belarusian State Medical University
Institute Adolfo Lutz
Angkor Hospital for Children
Peking University People’s Hospital
The Chinese University of Hong Kong–Prince of Wales Hospital
Chinese University of Hong Kong
University of California San Francisco
Centre Hospitalier Intercommunal de Créteil
Université Paris-Est Créteil Val de Marne
Groupe de Pathologie Infectieuse Pédiatrique de la Société Française de Pédiatrie
University of Ghana
Christian Medical College
Kempegowda Institute of Medical Sciences
Ben-Gurion University of the Negev
Kenya Medical Research Institute
University of Malawi
Khalifa University College of Medicine and Health Sciences
The Emirates ICT Innovation Center (EBTIC)
UCSI University
University of Southampton
Manhiça Health Research Center (CISM)
University of Oxford
University of Sydney

Research output: Contribution to journal › Article › peer-review

29 Citations (SciVal)

Abstract

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location^1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

Original language	English
Pages (from-to)	386-392
Number of pages	7
Journal	Nature
Volume	631
Issue number	8020
Early online date	3 Jul 2024
DOIs	https://doi.org/10.1038/s41586-024-07626-3
Publication status	Published - 11 Jul 2024

Data Availability Statement

All data and code for figures and analysis are accessible at GitHub (https://github.com/sophbel/geomig_evo_pneumo). All whole-genome sequences were deposited into the European Nucleotide Database and accession numbers are available in the GitHub repository and on FigShare (https://doi.org/10.6084/m9.figshare.24219214)75. Associated metadata are available from the Microreact webserver (https://microreact.org/project/7wqgd2gbBBEeBLLPKonbaT-belman2024southafricapneumococcus), as well as from the GitHub repository and Global Pneumococcal Sequencing Project Monocle database (https://data.monocle.sanger.ac.uk/).

Funding

This work was supported by the Wellcome Trust (grant number WT QQ2016-2021, reference 206194, to S.B., S.L. and S.D.B.); the Bill & Melinda Gates Foundation (under Investment ID INV-003570 to S.A.M., A.v.G., M.d.P., S.D. and S.N.); the NIH (grant number R01AI160780 to H.S.); and the European Research Council (grant number 804744 to H.S. and N.L.). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. We would like to thank all Global Pneumococcal Sequencing project partners; and M.\u2009O\u2019Driscoll, S.\u2009Farr, and V.\u2009Carr for code review.

Funders	Funder number
The Wellcome Trust	206194, WT QQ2016-2021
NIH-NIA	R01AI160780
Bill & Melinda Gates Foundation	INV-003570
European Research Council	804744

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

General

Access to Document

10.1038/s41586-024-07626-3Licence: CC BY

Cite this

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title = "Geographical migration and fitness dynamics of Streptococcus pneumoniae",

abstract = "Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95\% confidence interval of 1.59{\textendash}1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.",

author = "\{The Global Pneumococcal Sequencing Consortium\} and Sophie Belman and No{\'e}mie Lefrancq and Susan Nzenze and Sarah Downs and \{du Plessis\}, Mignon and Lo, \{Stephanie W.\} and Lesley McGee and Madhi, \{Shabir A.\} and \{von Gottberg\}, Anne and Bentley, \{Stephen D.\} and Henrik Salje and Alejandra Corso and Paula Gagetti and Brooks, \{Abdullah W.\} and Md Hasanuzzaman and Saha, \{Samir K.\} and Senjuti Saha and Alexander Davydov and Leonid Titov and Almeida, \{Samanta Cristine Grassi\} and Paul Turner and Chunjiang Zhao and Hui Wang and Margaret Ip and Ho, \{Pak Leung\} and Pierra Law and Keenan, \{Jeremy D.\} and Robert Cohen and Emmanuelle Varon and Eric Sampane-Donkor and Balaji Veeraraghavan and Geetha Nagaraj and Ravikumar, \{K. L.\} and J. Yuvaraj and \{Shamanna Noga\}, Varun and Rachel Benisty and Ron Dagan and Godfrey Bigogo and Jennifer Verani and Anmol Kiran and Everett, \{Dean B.\} and Jennifer Cornick and Maaike Alaerts and Sekaran, \{Shamala Devi\} and Clarke, \{Stuart C.\} and Benild Moiane and Betuel Sigauque and Helio Mucavele and Pollard, \{Andrew J.\} and Rama Kandasamy",

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doi = "10.1038/s41586-024-07626-3",

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AU - The Global Pneumococcal Sequencing Consortium

AU - Belman, Sophie

AU - Lefrancq, Noémie

AU - Nzenze, Susan

AU - Downs, Sarah

AU - du Plessis, Mignon

AU - Lo, Stephanie W.

AU - McGee, Lesley

AU - Madhi, Shabir A.

AU - von Gottberg, Anne

AU - Bentley, Stephen D.

AU - Salje, Henrik

AU - Corso, Alejandra

AU - Gagetti, Paula

AU - Brooks, Abdullah W.

AU - Hasanuzzaman, Md

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AU - Saha, Senjuti

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AU - Titov, Leonid

AU - Almeida, Samanta Cristine Grassi

AU - Turner, Paul

AU - Zhao, Chunjiang

AU - Wang, Hui

AU - Ip, Margaret

AU - Ho, Pak Leung

AU - Law, Pierra

AU - Keenan, Jeremy D.

AU - Cohen, Robert

AU - Varon, Emmanuelle

AU - Sampane-Donkor, Eric

AU - Veeraraghavan, Balaji

AU - Nagaraj, Geetha

AU - Ravikumar, K. L.

AU - Yuvaraj, J.

AU - Shamanna Noga, Varun

AU - Benisty, Rachel

AU - Dagan, Ron

AU - Bigogo, Godfrey

AU - Verani, Jennifer

AU - Kiran, Anmol

AU - Everett, Dean B.

AU - Cornick, Jennifer

AU - Alaerts, Maaike

AU - Sekaran, Shamala Devi

AU - Clarke, Stuart C.

AU - Moiane, Benild

AU - Sigauque, Betuel

AU - Mucavele, Helio

AU - Pollard, Andrew J.

AU - Kandasamy, Rama

PY - 2024/7/11

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N2 - Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

AB - Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

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Geographical migration and fitness dynamics of Streptococcus pneumoniae

Abstract

Data Availability Statement

Funding

UN SDGs

ASJC Scopus subject areas

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