The molecular characterisation of Neisseria meningitidis in Scotland before, during and after the initial introduction of the meningococcal serogroup C conjugate (MenC) vaccines

Diggle, Mathew A. (2004) The molecular characterisation of Neisseria meningitidis in Scotland before, during and after the initial introduction of the meningococcal serogroup C conjugate (MenC) vaccines. PhD thesis, University of Glasgow.

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Printed Thesis Information: https://eleanor.lib.gla.ac.uk/record=b2252829

Abstract

The aim of this project was to develop and introduce an MLST system for all meningococci causing invasive disease in Scotland starting in 1999, and subsequently throughout 2000, 2001 and 2002. MLST was introduced because strains within the electrophoretic type 37 (ET-37) complex, particularly those of ST11, are often indistinguishable by traditional methods. Nucleotide sequencing was performed on seven housekeeping genes and one outer membrane protein gene, porA. Data was analysed using databases and software available through the MLST website (www.mlst.net) and the porA websites (neisseria.org/nm/typing/porA/ and http://www.show.scot.nhs.uk/smprl/). The introduction of MLST in Scotland was used as a routine method for the characterization of Neisseria meningitidis isolates in 1999. Coincidentally this is just prior to the introduction of the MenC vaccines in November 1999. All N. meningitidis isolates from invasive disease were analysed. This has given valuable data highlighting the effect the MenC has on Serogroup C disease and its decline over the length of the vaccination campaign. At the same time, the overall numbers of cases were monitored including the effect on serogroup B between 1999 and 2002. This has been linked with historical data such as the typical cyclical pattern seen with serogroups B and C over the past decade. The incidences of ET-37 strains in serogroup C disease were assessed along with ET-37 strains of other serogroups. The number of different ST's isolated were monitored from the introduction of the MenC vaccine and this has been linked with their corresponding serogroups and subtypes. A decrease in serogroup C disease was observed, however this has been accompanied by an increase in serogroup B disease. The occurrence of capsule switch has been assessed and applied to the whole data set for subsequent conclusion. This thesis clearly shows that MLST is extremely important for the surveillance of meningococcal disease over a period of years and, and that this study, has been effective not only in monitoring the impact of the MenC vaccines, but also providing a detailed genotypic representation of strains now commonly associated with disease. In addition to enhanced sequence based characterisation, development of a fluorescent -based PCR protocol using N. meningitidis specific probes has been developed to markedly improved sensitivity and specificity of meningococcal DNA detection. Using an automated platform employing Taqman chemistry, a detection system employs fluorescence-based chemistry that eliminates post PCR processing and has provided accurate real-time quantitative PCR. This development has identified previously undetectable quantities of meningococcal DNA, which have been subsequently used in a modified MLST system to produce genotypic results, which would not normally be created.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Clarke, Dr. S. C. and Mitchell, Prof. T.
Date of Award: 2004
Depositing User: Mrs Monika Milewska-Fiertek
Unique ID: glathesis:2004-30951
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 25 Oct 2018 11:00
Last Modified: 09 Apr 2019 08:22
URI: http://theses.gla.ac.uk/id/eprint/30951
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