Genomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort study

<p><strong>Background</strong> Invasive meningococcal disease (IMD) is a worldwide health issue that is potentially preventable with vaccination. In view of its sporadic nature and the high diversity of Neisseria meningitidis, epidemiological surveillance incorporating detailed iso...

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Main Authors: Hill, DMC, Lucidarme, J, Gray, SJ, Newbold, LS, Ure, R, Brehony, C, Harrison, OB, Bray, JE, Jolley, KA, Bratcher, HB, Parkhill, J, Tang, CM, Borrow, R, Maiden, MCJ
Format: Journal article
Language:English
Published: Elsevier 2015
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author Hill, DMC
Lucidarme, J
Gray, SJ
Newbold, LS
Ure, R
Brehony, C
Harrison, OB
Bray, JE
Jolley, KA
Bratcher, HB
Parkhill, J
Tang, CM
Borrow, R
Maiden, MCJ
author_facet Hill, DMC
Lucidarme, J
Gray, SJ
Newbold, LS
Ure, R
Brehony, C
Harrison, OB
Bray, JE
Jolley, KA
Bratcher, HB
Parkhill, J
Tang, CM
Borrow, R
Maiden, MCJ
author_sort Hill, DMC
collection OXFORD
description <p><strong>Background</strong> Invasive meningococcal disease (IMD) is a worldwide health issue that is potentially preventable with vaccination. In view of its sporadic nature and the high diversity of Neisseria meningitidis, epidemiological surveillance incorporating detailed isolate characterisation is crucial for effective control and understanding the evolving epidemiology of IMD. The Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL) exploits whole-genome sequencing (WGS) for this purpose and presents data on a comprehensive and coherent IMD isolate collection from England and Wales via the internet. We assessed the contribution of these data to investigating IMD epidemiology.</p> <p><strong>Methods</strong> WGS data were obtained for all 899 IMD isolates available for England and Wales in epidemiological years 2010–11 and 2011–12. The data had been annotated at 1720 loci, analysed, and disseminated online. Information was also available on meningococcal population structure and vaccine (Bexsero, GlaxoSmithKline, Brentford, Middlesex, UK) antigen variants, which enabled the investigation of IMD-associated genotypes over time and by patients' age groups. Population genomic analyses were done with a hierarchical gene-by-gene approach.</p> <p><strong>Findings</strong> The methods used by MRF-MGL efficiently characterised IMD isolates and information was provided in plain language. At least 20 meningococcal lineages were identified, three of which (hyperinvasive clonal complexes 41/44 [lineage 3], 269 [lineage 2], and 23 [lineage 23]) were responsible for 528 (59%) of IMD isolates. Lineages were highly diverse and showed evidence of extensive recombination. Specific lineages were associated with IMD in particular age groups, with notable diversity in the youngest and oldest individuals. The increased incidence of IMD from 1984 to 2010 in England and Wales was due to successive and concurrent epidemics of different lineages. Genetically, 74% of isolates were characterised as encoding group B capsules: 16% group Y, 6% group W, and 3% group C. Exact peptide matches for individual Bexsero vaccine antigens were present in up to 26% of isolates.</p> <p><strong>Interpretation</strong> The MRF-MGL represents an effective, broadly applicable model for the storage, analysis, and dissemination of WGS data that can facilitate real-time genomic pathogen surveillance. The data revealed information crucial to effective deployment and assessment of vaccines against N meningitidis.</p>
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spelling oxford-uuid:3e77a800-667b-4ec3-abed-02d078b5baa02024-01-10T09:45:51ZGenomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3e77a800-667b-4ec3-abed-02d078b5baa0EnglishSymplectic Elements at OxfordElsevier2015Hill, DMCLucidarme, JGray, SJNewbold, LSUre, RBrehony, CHarrison, OBBray, JEJolley, KABratcher, HBParkhill, JTang, CMBorrow, RMaiden, MCJ<p><strong>Background</strong> Invasive meningococcal disease (IMD) is a worldwide health issue that is potentially preventable with vaccination. In view of its sporadic nature and the high diversity of Neisseria meningitidis, epidemiological surveillance incorporating detailed isolate characterisation is crucial for effective control and understanding the evolving epidemiology of IMD. The Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL) exploits whole-genome sequencing (WGS) for this purpose and presents data on a comprehensive and coherent IMD isolate collection from England and Wales via the internet. We assessed the contribution of these data to investigating IMD epidemiology.</p> <p><strong>Methods</strong> WGS data were obtained for all 899 IMD isolates available for England and Wales in epidemiological years 2010–11 and 2011–12. The data had been annotated at 1720 loci, analysed, and disseminated online. Information was also available on meningococcal population structure and vaccine (Bexsero, GlaxoSmithKline, Brentford, Middlesex, UK) antigen variants, which enabled the investigation of IMD-associated genotypes over time and by patients' age groups. Population genomic analyses were done with a hierarchical gene-by-gene approach.</p> <p><strong>Findings</strong> The methods used by MRF-MGL efficiently characterised IMD isolates and information was provided in plain language. At least 20 meningococcal lineages were identified, three of which (hyperinvasive clonal complexes 41/44 [lineage 3], 269 [lineage 2], and 23 [lineage 23]) were responsible for 528 (59%) of IMD isolates. Lineages were highly diverse and showed evidence of extensive recombination. Specific lineages were associated with IMD in particular age groups, with notable diversity in the youngest and oldest individuals. The increased incidence of IMD from 1984 to 2010 in England and Wales was due to successive and concurrent epidemics of different lineages. Genetically, 74% of isolates were characterised as encoding group B capsules: 16% group Y, 6% group W, and 3% group C. Exact peptide matches for individual Bexsero vaccine antigens were present in up to 26% of isolates.</p> <p><strong>Interpretation</strong> The MRF-MGL represents an effective, broadly applicable model for the storage, analysis, and dissemination of WGS data that can facilitate real-time genomic pathogen surveillance. The data revealed information crucial to effective deployment and assessment of vaccines against N meningitidis.</p>
spellingShingle Hill, DMC
Lucidarme, J
Gray, SJ
Newbold, LS
Ure, R
Brehony, C
Harrison, OB
Bray, JE
Jolley, KA
Bratcher, HB
Parkhill, J
Tang, CM
Borrow, R
Maiden, MCJ
Genomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort study
title Genomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort study
title_full Genomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort study
title_fullStr Genomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort study
title_full_unstemmed Genomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort study
title_short Genomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort study
title_sort genomic epidemiology of age associated meningococcal lineages in national surveillance an observational cohort study
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