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Whole-genome characterization of emergent invasive Neisseria meningitidis serogroup Y in Sweden from the two recent decades
National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background and Objective: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y has increased in Europe, especially in Scandinavia. In Sweden, serogroup Y is the dominating serogroup and in 2012 the serogroup Y disease incidence was 0.46/100,000 population. We have previously shown that a strain type belonging to ST-23 is responsible for the emergence of this serogroup in Sweden. The objective of this study was to compare the meningococcal population structure and phylogeography of Swedish invasive serogroup Y strains to other countries with different disease incidence.

Materials and Methods: Whole-genome sequencing was performed on invasive serogroup Y isolates from 1995 to 2012 in Sweden (n=186). A comparison of serogroup Y isolates was performed using a collection of isolates from England, Wales and Northern Ireland (n=143), which has relatively low incidence, and two isolates from the USA, where serogroup Y remains one of the major causes of IMD.

Results: The meningococcal population structures were similar in the investigated regions; however, different strain types were dominating in each geographic region. A number of genes, known or hypothesized to have an impact on meningococcal virulence, were shown to be associated with different strain types and subtypes.

Conclusions: The emergence of serogroup Y is most likely not associated with a previously described strain type that has been introduced into the Swedish meningococcal population. The reasons for the disease increase are most probably multifactorial; both increased virulence and host adaptive immunity influence infection and transmission. Future genomewide association studies could reveal additional genes associated with serogroup Y meningococcal disease.

Keyword [en]
Neisseria meningitidis, genome sequencing, epidemiology, serogroup Y, invasive meningococcal disease
National Category
Biomedical Laboratory Science/Technology
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-36120OAI: oai:DiVA.org:oru-36120DiVA: diva2:740576
Available from: 2014-08-25 Created: 2014-08-25 Last updated: 2017-10-17Bibliographically approved
In thesis
1. Genome-based characterization of Neisseria meningitidis with focus on the emergent serogroup Y disease
Open this publication in new window or tab >>Genome-based characterization of Neisseria meningitidis with focus on the emergent serogroup Y disease
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neisseria meningitidis, also referred to as meningococcus, is one of the leading causes of epidemic meningitis and septicaemia worldwide. Despite modern treatment, meningococcal disease remains associated with a high mortality (about 10%). Meningococcal disease is mainly restricted to specific hypervirulent lineages and specific capsular groups (serogroups), which have a changing global distribution over time. At the end of the 2000s, the previously unusual serogroup Y emerged, corresponding to half of all of the invasive meningococcal disease (IMD) cases in Sweden by the beginning of the 2010s. The aim of this thesis is to describe the emergence of serogroup Y meningococci genetically in an effort to understand some of the factors involved in the successful spread of this group throughout Sweden. In addition, genetic typing schemes were evaluated for surveillance and outbreak investigation.

Our results indicate that the currently recommended typing for surveillance of meningococci could be altered to include the factor H-binding protein (fHbp). A highly variable multilocus variable number tandem repeat analysis (HV-MLVA) was able to confirm connected cases in a suspected small outbreak. In addition, a strain type sharing the same porA, fetA, porB, fHbp, penA and multilocus sequence type was found to be the principal cause of the increase in serogroup Y disease. However, a deeper resolution obtained from the core genomes revealed a subtype of this strain, which was mainly responsible for the increase. Finally, when the Swedish serogroup Y genomes were compared internationally, different strains seemed to dominate in different regions. This indicates that the increase was probably not due to one or more point introductions of a strain previously known internationally but more probably multifactorial.

Place, publisher, year, edition, pages
Örebro: Örebro university, 2014. 92 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 109
Keyword
Neisseria meningitidis, meningococcal disease, serogroup Y, molecular characterization, epidemiology, genome sequencing
National Category
Medical and Health Sciences Biomedical Laboratory Science/Technology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-35997 (URN)
Public defence
2014-09-26, Universitetssjukhuset, hörsal C3, Södra Grev Rosengatan, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2014-08-21 Created: 2014-08-21 Last updated: 2017-10-17Bibliographically approved

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Hedberg, Sara [Thulin]Unemo, MagnusFredlund, Hans

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