Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study
Stephanie W. Lo, Kate C. Mellor, Robert Cohen, Alba Redin Alonso, Sophie Belman, Narender Kumar, Paulina A. Hawkins, Rebecca A. Gladstone, Anne von Gottberg, Balaji Veeraraghavan, K L Ravikumar, Rama Kandasamy, Sir Andrew J Pollard, Samir K. Saha, Godfrey Bigogo, Martín Antonio, Brenda Kwambana-Adams, Shaper Mirza, Sadia Shakoor, Muhammad Imran Nisar, Jennifer Cornick, Deborah Lehmann, Rebecca Ford, Betuel Sigaúque, Paul Turner, Jennifer C. Moïsi, Stephen Obaro, Ron Dagan, Idrissa Diawara, Anna Skoczyńska, Hui Wang, Philip E. Carter, Keith P. Klugman, Gail L. Rodgers, Robert F. Breiman, Lesley McGee, Stephen D. Bentley, Carmen Muñoz‐Almagro, Emmanuelle Varon, Abdullah Brooks, Alejandra Corso, Alexander Davydov, Alison Maguire, Anmol Kiran, Benild Moiane, Bernard Beall, Chunjiang Zhao, David Aanensen, Dean Everett, Diego Faccone, Ebenezer Foster-Nyarko, Ebrima Bojang, Ekaterina Egorova, Elena Voropaeva, Eric Sampane-Donkor, Ewa Sadowy, Geetha Nagaraj, Helio Mucavele, Houria Belabbès, Naima Elmdaghri, Jennifer Verani, Jeremy Keenan, John Lees, Jyothish N Nair Thulasee Bhai, Kedibone Ndlangisa, Khalid Zerouali, Leon Bentley, Leonid Titov, Linda De Gouveia, Maaike Alaerts, Margaret Ip, Maria Cristina de Cunto Brandileone, Md Hasanuzzaman, Metka Paragi, Michele Nurse-Lucas, Mignon du Plessis, Mushal Ali, Nicholas Croucher, Nicole Wolter, Noga Givon-Lavi, Nurit Porat, Özgen Köseoglu Eser, Pak-Leung Ho, Patrick Eberechi Akpaka, Paula Gagetti, Peggy-Estelle Tientcheu, Pierra Law, Rachel Benisty, Rafal Mostowy, Roly Malaker, Samanta Cristine Grassi Almeida, Sanjay Doiphode, Shabir Madhi, Shamala Devi Sekaran, Stuart Clarke, Somporn Srifuengfung, Susan Nzenze, Tamara Kastrin, Theresa Ochoa, Waleria Hryniewicz
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.