Pathogenesis of bacterial meningitis. Studies on the route of meningeal invasion following Hemophilus influenzae inoculation of infant rats
Ostrow, P.T.; Moxon, E.R.; Vernon, N.; Kapko, R.
Laboratory Investigation; a Journal of Technical Methods and Pathology 40(6): 678-685
1979
ISSN/ISBN: 0023-6837 PMID: 312973 Document Number: 153548
Colonization of the nasopharynx with H. influenzae type b may result in invasive disease causing meningitis. The route by which these bacteria spread to the subarachnoid space is not known. Two possible routes are contiguous spread via the olfactory nerves and hematogenous invasion secondary to bacteremia. These possibilities were investigated in infant rats following intranasal or i.p. inoculation of H. influenzae type b. Serial blood cultures were obtained from 5 min. to 72 h following inoculation and rats were sacrificed at consecutive intervals for culture of CSF. The skulls were sectioned through the midcoronal plane so as to include nasal cavity, olfactory nerves, cribriform plate, and olfactory lobes of brain which were examined by routine histopathology and direct immunofluorescence staining of bacteria. After intranasal inoculation, bacteria and inflammatory cells were seen in the nasal mucosa and perineural spaces of olfactory nerves. This was followed by localized inflammation, without bacteria, immediately above the cribriform plate. At this stage, CSF cultures were always sterile. Culture-positive leptomeningitis was only observed after bacteremia was present for at least 6 h and was always most intense immediately above the cribriform plate. I.p. inoculation produced bacteremia without any concomitant local disturbance in the meninges. This led to meningitis that was generalized from the outset with a diffuse or random distribution of inflammation and bacteria in the subarachnoid space. The establishment of local inflammation by intranasal inoculation of nonvirulent unencapsulated H. influenzae altered the course of meningitis produced i.p. so that these rats resembled those in which the pathogenic organisms were given intranasally. Bacteria may reach the meninges via the hematogenous route. Local nonspecific inflammation above the cribriform plate may facilitate hematogenous invasion at that site.