Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study

• Type of Material: Article
• Authors: Keith Klugman, Emory University; Stephanie W Lo, Wellcome Sanger Institute; Kate Mellor, Wellcome Sanger Institute; Robert Cohen, Assoc Clin & Therapeut Infantile Val de Marne; Alba Redin Alonso, Hospital Sant Joan de Deu; Sophie Belman, Wellcome Sanger Institute; Narender Kumar, Wellcome Sanger Institute; Paulina A Hawkins, Emory University; Rebecca A Gladstone, University of Oslo; Anne von Gottberg, National Institute for Communicable Diseases; Balaji Veeraraghavan, Christian Med Coll & Hosp; KL Ravikumar, Kempegowda Institute of Medical Sciences; Rama Kandasamy, University of Oxford; Sir Andrew J Pollard, University of Oxford; Samir K Saha, Child Health Research Foundation; Godfrey Bigogo, Kenya Medical Research Institute; Martin Antonio, The Gambia at The London School of Hygiene & Tropical Medicine; Brenda Kwambana-Adams, The Gambia at The London School of Hygiene & Tropical Medicine; Shaper Mirza, Lahore University of Management Sciences; Sadia Shakoor, Aga Khan University; Imran Nisar, Aga Khan University; Jennifer E Cornick, Malawi Liverpool Wellcome Trust; Deborah Lehmann, University of Western Australia; Rebecca L Ford, Papua New Guinea Institute of Medical Research; Betuel Sigauque, Centro de Investigação em Saúde da Manhiça; Paul Turner, Angkor Hospital for Children; Jennifer Moïsi, Agence de Médecine Préventive; Stephen K Obaro, University of Nebraska Medical Center; Ron Dagan, Ben-Gurion University of the Negev; Idrissa Diawara, Hassan II University of Casablanca; Anna Skoczyńska, National Medicines Institute, Warsaw; Hui Wang, Peking University People ‘s Hospital; Philip E Carter, Kenepuru Science Centre, Porirua; Gail Rodgers, Bill & Melinda Gates Foundation, Seattle; Robert Breiman, Emory University; Lesley McGee, Centers for Disease Control and Prevention, Atlanta; Stephen Bentley, Wellcome Sanger Institute; Carmen Muñoz Almagro, Hospital Sant Joan de Deu; Emmanuelle Varon, Centre Hospitalier Intercommunal de Créteil
• Language: English
• Date: 2022-10-01
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/S2666-5247(22)00158-6
• Title of Journal or Parent Work: LANCET MICROBE
• Volume: 3
• Issue: 10
• Start Page: E735
• End Page: E743
• Keywords: Life Sciences & Biomedicine; Science & Technology; ERA; DISEASE; 19A; CLONAL EVOLUTION; CHILDREN; EXPANSION; ADULTS; PNEUMOCOCCAL CONJUGATE VACCINE; Microbiology; ANTIMICROBIAL RESISTANCE; Infectious Diseases; NORWAY
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Microbiology; Environmental Sciences

Abstract

Background: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context. Methods: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590). Findings: Serotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3–5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain. Interpretation: Our work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases. Funding: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention.