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EBioMedicine. 2019 May;43:338-346. doi: 10.1016/j.ebiom.2019.04.021. Epub 2019 Apr 16.

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

Author information

1
Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK. Electronic address: rg9@sanger.ac.uk.
2
Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK.
3
New York University School of Medicine, New York, NY, USA.
4
Faculty of Medicine, School of Public Health, Imperial College London, UK.
5
Parasites and microbes, Wellcome Sanger Institute, Hinxton, UK; Department of Biostatistics, University of Oslo, 0317 Oslo, Norway.
6
Department of Computer Science, Helsinki Institute for Information Technology HIIT, Espoo, Finland.
7
Instituto de Medicina Tropical, Universidad Peruana Cayetano Heredia, Lima, Peru.
8
Department of Microbiology, Carol Yu Centre for Infection, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
9
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa.
10
Malawi-Liverpool-Wellcome-Trust Clinical Research Programme, Blantyre, Malawi.
11
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.
12
The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
13
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.
14
Rollins School Public Health, Emory University, USA.
15
Queens Research Institute, University of Edinburgh, UK.
16
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.
17
Centers for Disease Control and Prevention, Atlanta, USA.
18
Rollins School Public Health, Emory University, USA; Emory Global Health Institute, Atlanta, USA.

Abstract

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 (R2 = 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.

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