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

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dc.contributor.author Gladstone, Rebecca A.
dc.contributor.author Lo, Stephanie W.
dc.contributor.author Lees, John A.
dc.contributor.author Croucher, Nicholas J.
dc.contributor.author van Tonder, Andries J.
dc.contributor.author Corander, Jukka
dc.contributor.author Page, Andrew J.
dc.contributor.author Marttinen, Pekka
dc.contributor.author Bentley, Leon J.
dc.contributor.author Ochoa, Theresa J.
dc.contributor.author Ho, Pak Leung
dc.contributor.author du Plessis, Mignon
dc.contributor.author Cornick, Jennifer E.
dc.contributor.author Kwambana-Adams, Brenda
dc.contributor.author Benisty, Rachel
dc.contributor.author Nzenze, Susan A.
dc.contributor.author Madhi, Shabir A.
dc.contributor.author Hawkins, Paulina A.
dc.contributor.author Everett, Dean B.
dc.contributor.author Antonio, Martin
dc.contributor.author Dagan, Ron
dc.contributor.author Klugman, Keith P.
dc.contributor.author von Gottberg, Anne
dc.contributor.author McGee, Lesley
dc.contributor.author Breiman, Robert F.
dc.contributor.author Bentley, Stephen D.
dc.date.accessioned 2019-12-06T20:57:48Z
dc.date.available 2019-12-06T20:57:48Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/7419
dc.description.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. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof urn:issn:2352-3964
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject adolescent en_US
dc.subject adult en_US
dc.subject aged en_US
dc.subject antibiotic resistance en_US
dc.subject antibiotic sensitivity en_US
dc.subject Article en_US
dc.subject child en_US
dc.subject chloramphenicol en_US
dc.subject cotrimoxazole en_US
dc.subject erythromycin en_US
dc.subject female en_US
dc.subject gene isolation en_US
dc.subject genetic database en_US
dc.subject genetic recombination en_US
dc.subject genetic variability en_US
dc.subject genome analysis en_US
dc.subject genotype en_US
dc.subject geographic distribution en_US
dc.subject human en_US
dc.subject major clinical study en_US
dc.subject male en_US
dc.subject middle aged en_US
dc.subject multidrug resistance en_US
dc.subject multilocus sequence typing en_US
dc.subject penicillin derivative en_US
dc.subject phenotype en_US
dc.subject phylogeny en_US
dc.subject pneumococcal infection en_US
dc.subject preschool child en_US
dc.subject prevalence en_US
dc.subject priority journal en_US
dc.subject sensitivity and specificity en_US
dc.subject sequence alignment en_US
dc.subject single nucleotide polymorphism en_US
dc.subject Streptococcus pneumonia en_US
dc.subject tetracycline en_US
dc.subject vaccine en_US
dc.subject whole genome sequencing en_US
dc.title International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/j.ebiom.2019.04.021
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.03
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.00.00


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