Winter, Andrew John (1997)
Ph.D. thesis, University of Birmingham.
Experimental meningitis was induced in pigmented guinea pigs by subarachnoid inoculation of \(1 \times 10^9\) Escherichia coli K-12 or \(3 \times 10^7\) CFU Streptococcus pneumoniae serotype 2 D39 (NCTC 7466) or PLN-A, \(\Delta\)NA1 or \(\Delta\)HY1, defined isogenic derivatives of D39 deficient in pneumolysin, neuraminidase or hyaluronidase respectively. All animals developed a meningeal inflammatory response and a labyrinthitis. Hearing loss in pneumococcal meningitis was measured by recording the evoked auditory nerve compound action potential from the round window membrane. Animals infected with PLN-A sustained significantly less hearing loss than those infected with wild-type D39 (12 dB vs. 50 dB 12 h post inoculation; P<0.0001), Neuraminidase deficiency did not alter the course of the meningeal inflammatory response nor affect hearing loss. The \(\Delta\)HY1 mutant survived poorly in the cerebrospinal fluid and blood but still caused hearing loss. Both pneumococcal and E. coli meningitis induced specific ultrastructural lesions in the organ of Corti as judged by high-resolution scanning and transmission electron microscopy, and these lesions were most severe with pneumolysin-sufficient pneumococcal infection. Microperfusion of \(5\times10^6\) CFU S.pneumoniae D39 directly into the scala tympani of guinea pigs also resulted in electrophysiological and ultrastructural damage to the organ of Corti that could be diminished by pretreatment with antibiotics. The data confirm the cochlea as the site of meningogenic deafness. They suggest that pneumolysin expression is chiefly responsible for meningogenic deafness and that if pneumococci invade the inner ear during bacterial meningitis, cochlear deafhess will rapidly ensue.
|Type of Work:||Ph.D. thesis.|
|School/Faculty:||Faculties (to 1997) > Faculty of Medicine and Dentistry|
|Department:||Department of Infection|
RC Internal medicine
|Institution:||University of Birmingham|
|Library Catalogue:||Check for printed version of this thesis|
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