title: Pathogenesis and pathophysiology of pneumococcal meningitis.
abstract: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.
authors: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, The Netherlands.
authors: Barry B
authors: BB
authors: Mook-Kanamori
authors: Madelijn
authors: M
authors: Geldhoff
authors: Tom
authors: T
authors: van der Poll
authors: Diederik
authors: D
authors: van de Beek
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000382:microbiology* / Q000503:physiopathology*; D013296:Streptococcus pneumoniae / Q000502:physiology*