Pathogenesis and Pathophysiology of Pneumococcal Meningitis

Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

doi:10.1128/cmr.00008-11

Cited by 492Bacterial Infections and VaccinesPneumonia and Respiratory InfectionsStreptococcal Infections and Treatments

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

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Mook-Kanamori, Barry B., Geldhoff, Madelijn, van der Poll, Tom, van de Beek, Diederik·2011·Clinical Microbiology Reviews

DOI 10.1128/cmr.00008-11PMC PMC3131058

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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.

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In cases of bacterial meningitis, infections usually start as skin, gastrointestinal or respiratory infections that spread to the blood, and bacteria accumulate in the leptomeningeal vasculature and move into the meninges by inducing BBB breakdown.
“In cases of bacterial meningitis, infections usually start as skin, gastrointestinal or respiratory infections that spread to the blood”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Mook-Kanamori et al., 2011
Bacterial presence in the meninges induces a strong inflammatory response, including production of multiple cytokines (TNF-alpha, IL-1-beta, and IL-6), and a massive infiltration of neutrophils, and these cytokines and neutrophils work to quell the infection but also drive the breakdown of endothelial cell tight junctions.
“Bacterial presence in the meninges induces a strong inflammatory response, including production of multiple cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6), and a massive infiltration of neutrophils”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Mook-Kanamori et al., 2011

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Authors: Mook-Kanamori, B. B., Geldhoff, M., van der Poll, T., & van de Beek, D.
Affiliations: Amsterdam UMC Location University of Amsterdam (NL)
Department of Neurology and Center for Experimental and Molecular Medicine (CEMM), Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, P.O. Box 22660, 1100DD Amsterdam, The Netherlands
Venue: Clinical Microbiology Reviews
Publisher: American Society for Microbiology
Published: 2011-07
Volume: 24
Issue: 3
Pages: 557-591
ISSN: 0893-8512 (ISSN-L)
1098-6618
DOI: 10.1128/cmr.00008-11
PMC: PMC3131058
OpenAlex: W2171827842
Cited by: 492
References: 569
Citations by year: 2026: 13 · 2025: 33 · 2024: 32 · 2023: 28 · 2022: 29 · 2021: 45 · 2020: 48 · 2019: 38 · 2018: 22 · 2017: 28 · 2016: 46 · 2015: 37 · 2014: 39 · 2013: 24 · 2012: 27
FWCI: 3.37
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Clinical Microbiology Reviews (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
Keywords: pneumococcal meningitis, Streptococcus pneumoniae, pathogenesis, pathophysiology, nasopharyngeal carriage, epithelial cell adhesion, blood-brain barrier penetration, complement activation, coagulation, microglia, neutrophil recruitment, cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, cerebrovascular complications, animal models, adjunctive therapy, antimicrobial therapy
MeSH terms: Animals, Humans, Inflammation, Meningitis, Pneumococcal, Streptococcus pneumoniae

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Pathogenesis and Pathophysiology of Pneumococcal Meningitis

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