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Title: Viral infections as predisposing factors for bacterial meningitis
Author: Raza, Muhammad Waqar
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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Epidemiological data suggest that viral infections might be predisposing factors for bacterial meningitis and carriage of type b Haemophilus influenzae (Hib), Neisseria meningitidis or Streptococcus pneumoniae, the three pathogens most commonly associated with bacterial meningitis. Non-secretors of ABO blood group antigens are over-represented among patients with bacterial meningitis and in populations affected by some outbreaks. The first objective of the study was to examine the hypothesis that non-secretors were also over-represented among patients with respiratory viral infections. Compared with the local population, there was a significantly higher proportion of secretors among patients with disease due to respiratory syncytial virus (RSV), influenza A virus, rhinovirus and ECHO virus. The hypothesis that Leb and/or H-type 1 antigens present on cells or in body fluids of secretors might be receptor(s) for RSV was examined. Affinity purified molecules with Leb or H type 1 determinants or synthetic receptor analogues did not decrease the infectivity of RSV for HEp-2 cells. Bacterial attachment to mucosal surfaces is an important prerequisite for infection. The second major objective was to assess the effect of RSV infection of HEp-2 cells (a human epithelial cell line) on binding of bacteria responsible for meningitis. Binding of bacteria labelled with fluorescein isothiocyanate (FITC) to HEp-2 cells and RSV-infected HEp-2 cells was compared by flow cytometry. Strains of meningococci (3) and Hib (5) expressing antigens of different serogroups, serotypes and subtypes and a strain of Staphylococcus aureus bound significantly more effectively to virus infected cells. Similar patterns of increased binding of unlabelled meningococci to monolayers of RSV-infected cells were also observed. Studies to identify the changes on the cell surface associated with RSV infection responsible for enhanced binding were carried out with one strain of meningococcus. Viral infection of HEp-2 cells did not enhance the expression of Lewisa antigen, a proposed receptor for bacteria in non-secretors. Monoclonal antibodies to the attachment glycoprotein G of RSV decreased the bacterial binding to infected HEp-2 cells; but monoclonal antibodies to the fusion glycoprotein F did not affect binding.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available