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Characteristics of Neisseria meningitidis isolates causing fatal disease
Örebro University, School of Health and Medical Sciences.
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2008 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 9, p. 734-744Article in journal (Refereed) Published
Abstract [en]

The objectives of the present study were to describe a selection of characteristics of all available fatal meningococcal isolates (n=62) and to compare these with all the other invasive isolates (non-fatal, n=474) collected in Sweden from 1995 to 2004 (fatality rate of 12%). The coverage of the fatal isolates by presently discussed outer membrane vesicle (OMV) vaccines was also estimated. The isolates were characterized by serogroup, serotype, genosubtype, multilocus sequence type and antibiogram. Basic epidemiological data were gathered. The results of the fatal isolates showed 55% serogroup B, 27% C, 15% Y and 3% W-135, with a fatality rate of 11% for B, 12% for C, 17% for Y and 8% for W-135. Characteristics associated with higher mortality were age, gender, serogroup Y, serotype 14 and 15 and genosubtypes P1.7,16-29,35 and P1.5-1,10-4,36-2. In contrast, non-14/non-15 serotypes, the genosubtypes P1.5-1,10-8,36-2; P1.7-2,4,37 and P1.7,16,35, as well as reduced sensitivity for penicillin G were associated with decreased mortality. The presently discussed OMV vaccines could, based solely on the complete genosubtype, theoretically cover up to 44% of the fatal serogroup B cases and up to 100% if every variable region by itself is capable to induce protective immunity.

Place, publisher, year, edition, pages
London: Taylor & Francis , 2008. Vol. 40, no 9, p. 734-744
National Category
Medical and Health Sciences Infectious Medicine
Research subject
Infectious Diseases
Identifiers
URN: urn:nbn:se:oru:diva-3456DOI: 10.1080/00365540802029565PubMedID: 18609211OAI: oai:DiVA.org:oru-3456DiVA, id: diva2:137753
Available from: 2008-12-08 Created: 2008-12-08 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Characterisation of Neisseria meningitidis from a virulence and immunogenic perspective that includes variations in novel vaccine antigens
Open this publication in new window or tab >>Characterisation of Neisseria meningitidis from a virulence and immunogenic perspective that includes variations in novel vaccine antigens
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neisseria meningitidis, also referred to as meningococcus, is a Gram-negative diplococcal bacterium best known as an important cause of meningitis and septicaemia worldwide. Meningococcal disease is a rare but life-threatening illness that may progress to death despite optimal medical care including appropriate antibiotic therapy. Case fatality remains high and survivors may suffer from significant sequelae because of impaired circulation and/or damages to the central nervous system. Prevention through vaccination remains a most effective approach to control disease. The main problem, however, is the absence of an effective vaccine against disease caused by a broad spectrum of group B isolates.

Understanding how the meningococcus can be both a common commensal and a devastating human pathogen is a major task for researchers in the area of meningococcal disease. In paper I, we investigated and described the characteristics of fatal meningococcal isolates and compared these with non-fatal invasive meningococcal isolates. The diversity was high within the isolates from both patient groups. Group Y, serotypes 14 and 15 and genosubtypes P1.7,16-29,35 and P1.5-1,10-4,36-2 were more common in fatal cases as were being elderly and female.

The second major task in the area of meningococcal disease is to develop a group B vaccine. Six genes encoding antigens identified as promising vaccine candidates were examined in papers II & III. Based on our results, the prevalence of these genes and their sequence variation have the potential to constitute a meningococcal vaccine of broad range that also cover group B isolates in Sweden and other countries with a similar distribution of disease causing meningococci.

In paper IV, we investigated the levels of IgG antibodies in serum directed against fHbp and NadA, two of the antigens included in papers II & III. Overall, the immune response to fHbp seems to be higher than the immune response to NadA, with a clear rise of anti-fHbp in the young adult groups (20-29 years).

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2009. p. 92
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 31
Keywords
Neisseria meningitidis, meningococcal disease, risk factors, vaccine, genome-derived neisserial antigens (GNA), polymerase chain reaction (PCR), sequencing
National Category
Medical and Health Sciences
Research subject
Medicine; Biomedicine
Identifiers
urn:nbn:se:oru:diva-6638 (URN)978-91-7668-670-6 (ISBN)
Public defence
2009-06-05, Wilandersalen, Universitetssjukhuset Örebro, Örebro, 09:00 (Swedish)
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Available from: 2009-05-06 Created: 2009-05-06 Last updated: 2017-10-18Bibliographically approved

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Jacobsson, SusanneFredlund, Hans

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