Molecular characterization of non-groupable Neisseria meningitidis causing invasive disease in South Africa

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dc.contributor.authorGanesh, Karistha
dc.date.accessioned2018-07-05T08:36:20Z
dc.date.available2018-07-05T08:36:20Z
dc.date.issued2017
dc.descriptionThe University of the Witwatersrand, Faculty of Health Sciences In fulfilment of the requirements for the degree of Master of Science in Medicine. 27 October 2017.en_ZA
dc.description.abstractBackground The meningococcal capsule is an important virulence determinant. Unencapsulated meningococci lacking capsule biosynthesis genes and containing the capsule null locus (cnl) are predominantly non-pathogenic. Rare cases of invasive meningococcal disease caused by cnl isolates belonging to sequence types (ST) and clonal complexes (cc) ST-845 (cc845), ST-198 (cc198), ST-192 (cc192) and ST-53 (cc53) have been documented. The clinical significance of these isolates however remains unclear. We identified four invasive cnl meningococci through laboratory-based surveillance in South Africa from 2003 through 2013, which we aimed to characterize using whole genome data. Results One isolate [NG: P1.7-2,30: F1-2: ST-53 (cc53)] contained cnl allele 12, and caused empyema in an adult male with bronchiectasis from tuberculosis, diabetes mellitus and a smoking history. Three isolates were NG: P1.18-11,42-2: FΔ: ST-192 (cc192) and contained cnl allele 2. One patient was an adolescent male with meningitis. The remaining two isolates were from recurrent disease episodes (eight months apart) in a male child with deficiency of the sixth complement component, and with the exception of two single nucleotide polymorphisms, contained identical core genomes. The ST-53 (cc53) isolate possessed alleles for NHBA peptide 191 and fHbp variant 2; whilst the ST-192 (cc192) isolates contained NHBA peptide 704 and fHbp variant 3. All four isolates lacked nadA. Comparison of the South African genomes to 65 additional cnl genomes on the PubMLST Neisseria database (http://pubmlst.org/neisseria/), determined that most putative virulence genes could be found in both invasive and carriage phenotypes. Conclusions Although rare, invasive disease by cnl meningococci may be associated with host immunodeficiency and such patients may benefit from protein-based meningococcal vaccines.en_ZA
dc.description.librarianLG2018en_ZA
dc.identifier.urihttps://hdl.handle.net/10539/24741
dc.language.isoenen_ZA
dc.subject.meshNeisseria Meningitidis
dc.titleMolecular characterization of non-groupable Neisseria meningitidis causing invasive disease in South Africaen_ZA
dc.typeThesisen_ZA
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