International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact.

Autor: Gladstone RA; Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK. Electronic address: rg9@sanger.ac.uk., Lo SW; Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK., Lees JA; New York University School of Medicine, New York, NY, USA., Croucher NJ; Faculty of Medicine, School of Public Health, Imperial College London, UK., van Tonder AJ; Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK., Corander J; Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK; Department of Biostatistics, University of Oslo, 0317 Oslo, Norway., Page AJ; Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK., Marttinen P; Department of Computer Science, Helsinki Institute for Information Technology HIIT, Espoo, Finland., Bentley LJ; Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK., Ochoa TJ; Instituto de Medicina Tropical, Universidad Peruana Cayetano Heredia, Lima, Peru., Ho PL; Department of Microbiology, Carol Yu Centre for Infection, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China., du Plessis M; Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa., Cornick JE; Malawi-Liverpool-Wellcome-Trust Clinical Research Programme, Blantyre, Malawi., Kwambana-Adams B; NIHR Global Health Research Unit on Mucosal Pathogens, Division of Infection and Immunity, University College London, London, UK; WHO Collaborating Centre for New Vaccines Surveillance, Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine, Atlantic Boulevard, Fajara, PO Box 273 Banjul, the Gambia., Benisty R; The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Nzenze SA; Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, South Africa; Department of Science and Technology, National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, South Africa., Madhi SA; Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, South Africa; Department of Science and Technology, National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, South Africa., Hawkins PA; Rollins School Public Health, Emory University, USA., Everett DB; Queens Research Institute, University of Edinburgh, UK., Antonio M; WHO Collaborating Centre for New Vaccines Surveillance, Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine, Atlantic Boulevard, Fajara, PO Box 273 Banjul, the Gambia; Division of Microbiology & Immunity, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK., Dagan R; The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Klugman KP; Rollins School Public Health, Emory University, USA., von Gottberg A; Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa., McGee L; Centers for Disease Control and Prevention, Atlanta, USA., Breiman RF; Rollins School Public Health, Emory University, USA; Emory Global Health Institute, Atlanta, USA., Bentley SD; Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK.
Jazyk: angličtina
Zdroj: EBioMedicine [EBioMedicine] 2019 May; Vol. 43, pp. 338-346. Date of Electronic Publication: 2019 Apr 16.
DOI: 10.1016/j.ebiom.2019.04.021
Abstrakt: Background: Pneumococcal conjugate vaccines have reduced the incidence of invasive pneumococcal disease, caused by vaccine serotypes, but non-vaccine-serotypes remain a concern. We used whole genome sequencing to study pneumococcal serotype, antibiotic resistance and invasiveness, in the context of genetic background.
Methods: Our dataset of 13,454 genomes, combined with four published genomic datasets, represented Africa (40%), Asia (25%), Europe (19%), North America (12%), and South America (5%). These 20,027 pneumococcal genomes were clustered into lineages using PopPUNK, and named Global Pneumococcal Sequence Clusters (GPSCs). From our dataset, we additionally derived serotype and sequence type, and predicted antibiotic sensitivity. We then measured invasiveness using odds ratios that relating prevalence in invasive pneumococcal disease to carriage.
Findings: The combined collections (n = 20,027) were clustered into 621 GPSCs. Thirty-five GPSCs observed in our dataset were represented by >100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed in the years up until, and including, the first year of pneumococcal conjugate vaccine introduction. Penicillin and multidrug resistance were higher (p < .05) in a subset dominant-GPSCs (14/35, 9/35 respectively), and resistance to an increasing number of antibiotic classes was associated with increased recombination (R 2  = 0.27 p < .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p < .05) of its antibiogram (mean misclassification error 0.28, SD ± 0.13). We detected increased invasiveness of six genetic backgrounds, when compared to other genetic backgrounds expressing the same serotype. Up to 1.6-fold changes in invasiveness odds ratio were observed.
Interpretation: We define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing non-vaccine-serotypes in most GPSCs preclude the removal of these lineages by pneumococcal conjugate vaccines; leaving potential for serotype replacement. A subset of GPSCs have increased resistance, and/or serotype-independent invasiveness.
(Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE