Pathogenesis and pathophysiology of bacterial meningitis

Abstract

Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

Peptide mimicry of the meningococcal group C capsular polysaccharide.

“…Infections caused by encapsulated bacteria such as Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli are a major cause of morbidity and mortality in neonates and infants (1)(2)(3). The capsular polysaccharide is a major virulence factor in these organisms.…”

A gonococcal homologue of meningococcal γ-glutamyl transpeptidase gene is a new type of bacterial pseudogene that is transcriptionally active but phenotypically silent

“…N. meningitidis causes meningitis, which is due to the meningococcal invasion into the human central nervous system, including cerebrospinal fluid (CSF) [36-38]. It has been shown that meningococcal GGT has a physiological function of acquiring cysteine from environmental γ-glutamyl-cysteinyl peptides under cysteine-limited environments such as the CSF [39].…”

Prevention of pneumococcal meningitis

“…Each of these cytokines in turn can stimulate the production of other inflammatory mediators (eg, interleukin-6, platelet activating factor, interferons, other interleukins), activate and attract leukocytes, and activate the coagulation cascade. The end result is an increased permeability of the blood-brain barrier, thrombosis of vessels and decreased cerebral blood flow, cerebral edema, and increased intracranial pressure; these findings may be exaggerated with certain pneumococcal serotypes, resulting in more severe tissue damage and sequelae [17,21,22]. Pneumococcal meningitis occurs more frequently in children between the ages of 6 and 18 months; it is important to note, however, that in this age group presentation with the classic signs and symptoms of meningitis are least likely until fairly late in the disease course.…”