Current concepts in the pathogenesis of meningitis caused by Streptococcus pneumoniae

Abstract

In spite of improved antimicrobial therapy, bacterial meningitis still results in brain damage leading to significant long-term neurological sequelae in a substantial number of survivors, as confirmed by several recent studies. Meningitis caused by Streptococcus pneumoniae is associated with a particularly severe outcome. Experimental studies over the past few years have increased our understanding of the molecular mechanisms underlying the events that ultimately lead to brain damage during meningitis. Necrotic damage to the cerebral cortex is at least partly mediated by ischemia and oxygen radicals and therefore offers a promising target for adjunctive therapeutic intervention. Neuronal apoptosis in the hippocampus may represent the major pathological process responsible for cognitive impairment and learning disabilities in survivors. However, the mechanisms involved in causing this damage remain largely unknown. Anti-inflammatory treatment with corticosteroids aggravates hippocampal damage, thus underlining the potential shortcomings of current adjuvant strategies. In contrast, the combined inhibition of matrix metalloproteinase and tumour necrosis factor-alpha converting enzyme protected both the cortex and hippocampus in experimental meningitis, and may represent a promising new approach to adjunctive therapy. It is the hope that a more refined molecular understanding of the pathogenesis of brain damage during bacterial meningitis will lead to new adjunctive therapies.

Antibacterial Activity of a Competence-Stimulating Peptide in Experimental Sepsis Caused by Streptococcus pneumoniae

“…route) was set up to enable the direct inoculation of CSP into an infected organ and/or anatomical district (the blood). Other animal models of pneumococcal infection that are available, like the model of pneumonia and sepsis after intranasal inoculation or the model of sepsis after intraperitoneal inoculation, do not allow this type of study, and the involvement of host components in the meningitis model (29,46,47) may hide beneficial antipneumococcal therapeutic effects. Animal models of disease are dependent both on the infecting pneumococcal strain and on the genetic background of the mice (7,14,21,54).…”

Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice

“…Pneumococcal meningitis is preceded by nasopharyngeal colonization, followed by bacteremia and invasion of the CNS (8,9). However, little is known about the complement of factors required for invasion of, and survival in, the brain by pneumococci.…”

Chemotactic Factors in Cerebrospinal Fluid during Bacterial Meningitis

“…Bacterial meningitis is a devastating infectious disease, with a worldwide mortality rate of 20 to 30% despite antibiotic treatment (43,45,58). As many as 50% of survivors encounter neurological sequelae, such as hearing impairment, seizure disorders, and learning and behavioral problems (22,32,65).…”

“…Leukocyte recruitment is a key aspect of the protective response against invading microorganisms, but over recent years, evidence has accumulated that leukocytes also contribute importantly to tissue damage in bacterial meningitis (30,43,46,65,85). Although leukocytes within the CSF are important for host defense, it has been demonstrated repeatedly that inhibition of leukocyte recruitment does not necessarily reduce bacterial clearance in the CNS (15,51,82).…”