Meningococcal Meningitis

Infectious Disease MONDO:0018059 Pathograph 9 Show in embeddings browser Bacterial meningitis

Meningococcal meningitis is an acute, life-threatening bacterial infection of the leptomeninges and subarachnoid space caused by encapsulated Neisseria meningitidis (serogroups A, B, C, W, X, and Y). Following nasopharyngeal colonization and bloodstream invasion, meningococci cross the blood-brain barrier and replicate in the cerebrospinal fluid, where lipooligosaccharide (endotoxin) release and two-partner secretion system virulence factors trigger complement activation (C1q, MBL, C3a, C5a, sC5b-9) and canonical/non-canonical inflammasome pyroptosis (caspase-1, caspase-11, gasdermin-D, IL-1beta, IL-18), often accompanied by meningococcemia and a characteristic petechial or purpuric rash.

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⚙

Pathophysiology

3
Nasopharyngeal Mucosal Colonization and Epithelial Invasion
Encapsulated Neisseria meningitidis adheres to and colonizes the human nasopharyngeal mucosa and translocates across the epithelial barrier into the submucosa and bloodstream in susceptible individuals.
adhesion of symbiont to host GO:0044406 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased adhesion of symbiont to host (GO:0044406). GO:0044406 is a biological process from the Gene Ontology.
nasopharynx UBERON:0001728 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in nasopharynx (UBERON:0001728). UBERON:0001728 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Polysaccharide Capsule and Factor H-Binding Protein Complement Evasion and Meningococcemia Translocation across the nasopharyngeal epithelium seeds encapsulated meningococci into the systemic circulation.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs it is frequently severe and potentially life threatening."
Establishes mucosal acquisition and progression to severe invasive meningococcal infection.
Polysaccharide Capsule and Factor H-Binding Protein Complement Evasion and Meningococcemia
Within the bloodstream, the meningococcal polysaccharide capsule and factor H-binding protein (fHbp) inhibit alternative-pathway opsonophagocytosis and complement-mediated bactericidal lysis, enabling intravascular survival and meningococcemia.
complement activation GO:0006956 ↓ DECREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased complement activation (GO:0006956). GO:0006956 is a biological process from the Gene Ontology.
blood UBERON:0000178 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in blood (UBERON:0000178). UBERON:0000178 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Cerebrospinal Fluid Complement Activation and Inflammasome Pyroptosis Bacteremic meningococci adhere to cerebral microvascular endothelium and breach the blood-brain barrier to enter the subarachnoid space.
Sepsis Intravascular meningococcal replication and endotoxin release produce meningococcal sepsis.
Petechiae Microvascular endothelial invasion and thrombosis during meningococcemia cause a petechial or purpuric rash.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
Links invasive meningococcal bloodstream infection (sepsis with petechial rash) to meningitis.
Cerebrospinal Fluid Complement Activation and Inflammasome Pyroptosis
Within the subarachnoid space and brain parenchyma, Neisseria meningitidis triggers classical, lectin, and common-pathway complement activation in the cerebrospinal fluid (elevated C1q, MBL, C3a, iC3b, C5a, sC5b-9, and CFH) and activates canonical and non-canonical inflammasome pyroptosis via caspase-1, caspase-11, and gasdermin-D cleavage (promoted by the HrpB two-partner secretion system), releasing mature IL-1beta and IL-18 and driving intense meningeal inflammation.
complement activation GO:0006956 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased complement activation (GO:0006956). GO:0006956 is a biological process from the Gene Ontology. pyroptosis GO:0070269 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased pyroptosis, annotated with pyroptotic inflammatory response (GO:0070269). GO:0070269 is a biological process from the Gene Ontology. inflammatory response GO:0006954 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
cerebrospinal fluid UBERON:0001359 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in cerebrospinal fluid (UBERON:0001359). UBERON:0001359 is an anatomical location from the Uberon multi-species anatomy ontology. meninx UBERON:0002360 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in meninx (UBERON:0002360). UBERON:0002360 is an anatomical location from the Uberon multi-species anatomy ontology. brain UBERON:0000955 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in brain (UBERON:0000955). UBERON:0000955 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Meningitis Complement anaphylatoxins (C3a, C5a) and pyroptotic IL-1beta/IL-18 release drive purulent meningeal inflammation.
Show evidence (2 references)
PMID:24412248 SUPPORT Human clinical
"Complement factors C1q and MBL as well as common complement pathway factors C3a, iC3b, C5a, sC5b-9 and complement regulator CFH were all elevated in patients with bacterial meningitis as compared to the controls."
Demonstrates widespread CSF complement cascade activation (C1q, MBL, C3a, iC3b, C5a, sC5b-9) in patients with meningococcal and pneumococcal meningitis.
DOI:10.3389/fcimb.2024.1384072 SUPPORT Model organism
"Furthermore, western blot analysis of brain samples during the infection demonstrated that: i. N. meningitidis activated canonical and non-canonical inflammasome pyroptosis pathways in the mouse brain; ii. the activation of caspase-11, caspase-1, and gasdermin-D was markedly reduced in the hrpB..."
Shows that N. meningitidis activates caspase-1/caspase-11/gasdermin-D pyroptosis and IL-1beta/IL-18 release in the brain during meningitis.
⬡

Pathograph

Use Group by to collapse related nodes into one box. Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Meningococcal Meningitis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

3
Blood 1
Petechiae FREQUENT HP:0000967 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Petechiae (HP:0000967). HP:0000967 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
Highlights petechial rash as a hallmark clinical sign of invasive meningococcal disease.
Immune 2
Meningitis VERY_FREQUENT HP:0001287 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Meningitis (HP:0001287). HP:0001287 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
Identifies meningitis as a primary clinical manifestation of invasive meningococcal infection.
Sepsis FREQUENT HP:0100806 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sepsis (HP:0100806). HP:0100806 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
Identifies sepsis as a major presentation of invasive meningococcal infection.
🧬

Genetic Associations

1
Terminal Complement Pathway Deficiency (C5-C9) (Risk Factor / Predisposition)
Show evidence (1 reference)
PMID:31440263 SUPPORT Human clinical
"Our study confirms the strong association of meningococcal infections with terminal pathway deficiency and highlights the risk of pneumococcal and auto-immune diseases in the classical and alternative pathways."
Confirms the strong genetic association between terminal complement pathway deficiencies and invasive meningococcal infections.
💊

Medical Actions

3
Quadrivalent Meningococcal Conjugate Vaccination (MenACWY / MCV4)
Action: vaccinationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is vaccination (NCIT:C15346). NCIT:C15346 is a clinical intervention from the NCI Thesaurus. Ontology label: Vaccination NCIT:C15346
Platform: Vaccine
Polysaccharide-protein conjugate vaccines against Neisseria meningitidis serogroups A, C, W, and Y convert T-independent capsular polysaccharides into T-dependent antigens, inducing high-titer serum bactericidal antibodies and mucosal carriage reduction that have markedly reduced non-B invasive meningococcal disease.
Mechanism Target:
INHIBITS Polysaccharide Capsule and Factor H-Binding Protein Complement Evasion and Meningococcemia — Anti-capsular IgG antibodies induced by MenACWY conjugate vaccination trigger complement-mediated serum bactericidal lysis of serogroup A, C, W, and Y meningococci.
Show evidence (1 reference)
PMID:23830646 SUPPORT INDIRECT Human clinical
"Vaccines have reduced the incidence of infection with certain non-B meningococcal serogroups, and new serotype B vaccines are on the horizon."
Documents reduction of non-B invasive meningococcal infection incidence by serogroup-specific meningococcal vaccines.
Effect differs by subgroup:
genotype terminal complement pathway deficiency (C5-C9) or C5 inhibitor recipients vs complement-sufficient individuals — smaller effect on serum bactericidal lysis and protection against invasive meningococcal disease
Because meningococcal killing relies heavily on membrane attack complex (C5b-9) serum bactericidal activity, patients with terminal complement pathway deficiencies remain at elevated risk of invasive meningococcal disease despite vaccination.
Show evidence (1 reference)
PMID:31440263 SUPPORT Human clinical
"Our study confirms the strong association of meningococcal infections with terminal pathway deficiency and highlights the risk of pneumococcal and auto-immune diseases in the classical and alternative pathways."
Confirms the dependence of anti-meningococcal host defense on intact terminal complement pathway activity.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Vaccines have reduced the incidence of infection with certain non-B meningococcal serogroups, and new serotype B vaccines are on the horizon."
Confirms effectiveness of non-B meningococcal conjugate vaccines in reducing disease incidence.
Meningococcal Group B Protein Vaccination (4CMenB / MenB-FHbp)
Action: vaccinationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is vaccination (NCIT:C15346). NCIT:C15346 is a clinical intervention from the NCI Thesaurus. Ontology label: Vaccination NCIT:C15346
Platform: Vaccine
Because the alpha(2-8)-linked polysialic acid capsule of serogroup B Neisseria meningitidis mimics human neural cell adhesion molecule (NCAM) and is poorly immunogenic, MenB vaccines (4CMenB / Bexsero and MenB-FHbp / Trumenba) target subcapsular outer-membrane proteins (fHbp, NadA, NHBA, PorA OMVs). Infant 4CMenB vaccination in England achieved 82.9% two-dose vaccine effectiveness (94.2% against covered strains) and a 75% reduction in MenB disease incidence.
Mechanism Target:
INHIBITS Polysaccharide Capsule and Factor H-Binding Protein Complement Evasion and Meningococcemia — Antibodies against subcapsular antigens (fHbp, NadA, NHBA, PorA) block factor H recruitment and promote classical-pathway bactericidal lysis of serogroup B meningococci.
Show evidence (1 reference)
PMID:31971676 SUPPORT INDIRECT Human clinical
"From September 2015 through August 2018, the incidence of meningococcal group B disease in England (average annual birth cohort, approximately 650,000 infants) was significantly lower in vaccine-eligible cohorts than the expected incidence (63 observed cases as compared with 253 expected cases;..."
Demonstrates 75% reduction in invasive MenB disease in 4CMenB-eligible infant cohorts.
Show evidence (2 references)
PMID:31971676 SUPPORT Human clinical
"From September 2015 through August 2018, the incidence of meningococcal group B disease in England (average annual birth cohort, approximately 650,000 infants) was significantly lower in vaccine-eligible cohorts than the expected incidence (63 observed cases as compared with 253 expected cases;..."
Provides population-level effectiveness of infant 4CMenB immunization.
PMID:28100432 SUPPORT Human clinical
"Two-dose vaccine effectiveness was 82·9% (95% CI 24·1-95·2) against all MenB cases, equivalent to a vaccine effectiveness of 94·2% against the highest predicted MenB strain coverage of 88%."
Reports 82.9% two-dose vaccine effectiveness against all MenB cases and 94.2% against vaccine-covered strains.
Early Parenteral Antimicrobial Therapy
Action: antibiotic therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is antibiotic therapy (NCIT:C15620). NCIT:C15620 is a clinical intervention from the NCI Thesaurus. Ontology label: Antibiotic Therapy NCIT:C15620
Immediate empirical and targeted parenteral antimicrobial therapy (such as third-generation cephalosporins or penicillin G) is essential to eradicate cerebrospinal fluid and bloodstream meningococci.
Mechanism Target:
INHIBITS Cerebrospinal Fluid Complement Activation and Inflammasome Pyroptosis — Bactericidal beta-lactam antibiotics clear viable N. meningitidis from the CSF and bloodstream.
Show evidence (1 reference)
PMID:23830646 SUPPORT INDIRECT Human clinical
"Suspected patients should receive early appropriate antimicrobial therapy concomitantly with confirmatory invasive diagnostic tests."
Establishes early antimicrobial therapy as standard-of-care treatment for suspected invasive meningococcal disease.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Suspected patients should receive early appropriate antimicrobial therapy concomitantly with confirmatory invasive diagnostic tests."
Supports prompt antimicrobial therapy upon clinical suspicion of meningococcal meningitis or sepsis.
🔬

Diagnosis

1
Confirmatory Invasive Diagnostic Testing (CSF Analysis, Culture, and PCR)
Confirmatory microbiological and molecular diagnostic testing (cerebrospinal fluid examination, blood and CSF culture, and PCR) performed concomitantly with early empirical antimicrobial therapy in patients with suspected meningococcal meningitis or sepsis.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Suspected patients should receive early appropriate antimicrobial therapy concomitantly with confirmatory invasive diagnostic tests."
Establishes confirmatory invasive diagnostic testing alongside empirical antimicrobial therapy as standard diagnostic practice.
📈

Progression

2
Nasopharyngeal Carriage and Acute Meningococcemic Invasion Phase
Following asymptomatic nasopharyngeal colonization, encapsulated meningococci invade the bloodstream in susceptible hosts, causing acute meningococcemia frequently accompanied by a non-blanching petechial rash.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
Documents the acute invasive bloodstream presentation (sepsis with petechial rash) alongside meningitis.
Acute Purulent Meningitis Phase
Bacteremic meningococci breach the blood-brain barrier and replicate in the cerebrospinal fluid, triggering fulminant complement- and pyroptosis-driven meningitis that requires immediate parenteral antimicrobial therapy.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Suspected patients should receive early appropriate antimicrobial therapy concomitantly with confirmatory invasive diagnostic tests."
Emphasizes the rapid clinical progression of invasive meningococcal meningitis requiring immediate empirical antimicrobial therapy.
📊

Prevalence

1
Global invasive meningococcal disease cohorts
Annual incidence Unknown
Invasive meningococcal infection is relatively uncommon overall in non-epidemic settings, with serogroup-specific conjugate and protein vaccines substantially reducing disease incidence in immunized cohorts.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs it is frequently severe and potentially life threatening."
Characterizes invasive meningococcal infection as a relatively uncommon but severe and potentially life-threatening disease.
🦠

Infectious Agent

1
Neisseria meningitidis
Encapsulated, Gram-negative diplococcus colonizing the human nasopharynx; invasive disease is caused predominantly by polysaccharide-encapsulated serogroups A, B, C, W, X, and Y.
Neisseria meningitidis NCBITaxon:487 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs it is frequently severe and potentially life threatening."
Identifies Neisseria meningitidis as the causative bacterium of severe invasive meningococcal infection and meningitis.
↔️

Transmission

1
Respiratory droplet and close-contact transmission from nasopharyngeal carriers
Neisseria meningitidis colonizes the human nasopharynx and is transmitted from person to person via respiratory droplets or oral secretions, with invasive bloodstream and meningeal invasion occurring in a subset of newly colonized susceptible hosts.
Show evidence (1 reference)
PMID:23830646 SUPPORT Human clinical
"Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs it is frequently severe and potentially life threatening."
Identifies Neisseria meningitidis as an invasive human pathogen causing severe meningococcal infection.
{ }

Source YAML

click to show 
name: Meningococcal Meningitis
creation_date: '2026-10-25T20:10:00Z'
category: Infectious Disease
description: >-
  Meningococcal meningitis is an acute, life-threatening bacterial infection of
  the leptomeninges and subarachnoid space caused by encapsulated Neisseria
  meningitidis (serogroups A, B, C, W, X, and Y). Following nasopharyngeal
  colonization and bloodstream invasion, meningococci cross the blood-brain
  barrier and replicate in the cerebrospinal fluid, where lipooligosaccharide
  (endotoxin) release and two-partner secretion system virulence factors trigger
  complement activation (C1q, MBL, C3a, C5a, sC5b-9) and canonical/non-canonical
  inflammasome pyroptosis (caspase-1, caspase-11, gasdermin-D, IL-1beta, IL-18),
  often accompanied by meningococcemia and a characteristic petechial or
  purpuric rash.
disease_term:
  preferred_term: meningococcal meningitis
  term:
    id: MONDO:0018059
    label: meningococcal meningitis
parents:
- Bacterial meningitis
synonyms:
- Cerebrospinal fever
- Epidemic cerebrospinal meningitis
- Meningococcal cerebrospinal meningitis
infectious_agent:
- name: Neisseria meningitidis
  description: >-
    Encapsulated, Gram-negative diplococcus colonizing the human nasopharynx;
    invasive disease is caused predominantly by polysaccharide-encapsulated
    serogroups A, B, C, W, X, and Y.
  infectious_agent_term:
    preferred_term: Neisseria meningitidis
    term:
      id: NCBITaxon:487
      label: Neisseria meningitidis
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs it is frequently severe and potentially life threatening."
    explanation: Identifies Neisseria meningitidis as the causative bacterium of severe invasive meningococcal infection and meningitis.
agent_life_cycle:
  description: >-
    Neisseria meningitidis is an obligate human pathogen maintained by
    asymptomatic carriage in the human nasopharynx and transmitted person to
    person via respiratory droplets.
  hosts:
  - preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
    role: obligate human reservoir and definitive host
transmission:
- name: Respiratory droplet and close-contact transmission from nasopharyngeal carriers
  description: >-
    Neisseria meningitidis colonizes the human nasopharynx and is transmitted
    from person to person via respiratory droplets or oral secretions, with
    invasive bloodstream and meningeal invasion occurring in a subset of newly
    colonized susceptible hosts.
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs it is frequently severe and potentially life threatening."
    explanation: Identifies Neisseria meningitidis as an invasive human pathogen causing severe meningococcal infection.
prevalence:
- population: Global invasive meningococcal disease cohorts
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: UNKNOWN
  rate_denominator: POPULATION_PER_YEAR
  notes: >-
    Invasive meningococcal infection is relatively uncommon overall in
    non-epidemic settings, with serogroup-specific conjugate and protein
    vaccines substantially reducing disease incidence in immunized cohorts.
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs it is frequently severe and potentially life threatening."
    explanation: Characterizes invasive meningococcal infection as a relatively uncommon but severe and potentially life-threatening disease.
progression:
- phase: Nasopharyngeal Carriage and Acute Meningococcemic Invasion Phase
  notes: >-
    Following asymptomatic nasopharyngeal colonization, encapsulated
    meningococci invade the bloodstream in susceptible hosts, causing acute
    meningococcemia frequently accompanied by a non-blanching petechial rash.
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
    explanation: Documents the acute invasive bloodstream presentation (sepsis with petechial rash) alongside meningitis.
- phase: Acute Purulent Meningitis Phase
  notes: >-
    Bacteremic meningococci breach the blood-brain barrier and replicate in the
    cerebrospinal fluid, triggering fulminant complement- and pyroptosis-driven
    meningitis that requires immediate parenteral antimicrobial therapy.
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Suspected patients should receive early appropriate antimicrobial therapy concomitantly with confirmatory invasive diagnostic tests."
    explanation: Emphasizes the rapid clinical progression of invasive meningococcal meningitis requiring immediate empirical antimicrobial therapy.
pathophysiology:
- name: Nasopharyngeal Mucosal Colonization and Epithelial Invasion
  description: >-
    Encapsulated Neisseria meningitidis adheres to and colonizes the human
    nasopharyngeal mucosa and translocates across the epithelial barrier into
    the submucosa and bloodstream in susceptible individuals.
  role: trigger
  biological_scale: CELLULAR
  locations:
  - preferred_term: nasopharynx
    term:
      id: UBERON:0001728
      label: nasopharynx
  biological_processes:
  - preferred_term: adhesion of symbiont to host
    modifier: INCREASED
    term:
      id: GO:0044406
      label: adhesion of symbiont to host
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs it is frequently severe and potentially life threatening."
    explanation: Establishes mucosal acquisition and progression to severe invasive meningococcal infection.
  downstream:
  - target: Polysaccharide Capsule and Factor H-Binding Protein Complement Evasion and Meningococcemia
    description: Translocation across the nasopharyngeal epithelium seeds encapsulated meningococci into the systemic circulation.
    causal_link_type: DIRECT
- name: Polysaccharide Capsule and Factor H-Binding Protein Complement Evasion and Meningococcemia
  conforms_to: "polysaccharide_conjugate_t_dependent_switching#Polysaccharide Capsule-Mediated Mucosal Colonization and Complement Evasion"
  description: >-
    Within the bloodstream, the meningococcal polysaccharide capsule and factor
    H-binding protein (fHbp) inhibit alternative-pathway opsonophagocytosis and
    complement-mediated bactericidal lysis, enabling intravascular survival and
    meningococcemia.
  role: amplifier
  biological_scale: TISSUE
  locations:
  - preferred_term: blood
    term:
      id: UBERON:0000178
      label: blood
  biological_processes:
  - preferred_term: complement activation
    modifier: DECREASED
    term:
      id: GO:0006956
      label: complement activation
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
    explanation: Links invasive meningococcal bloodstream infection (sepsis with petechial rash) to meningitis.
  downstream:
  - target: Cerebrospinal Fluid Complement Activation and Inflammasome Pyroptosis
    description: Bacteremic meningococci adhere to cerebral microvascular endothelium and breach the blood-brain barrier to enter the subarachnoid space.
    causal_link_type: DIRECT
  - target: Sepsis
    description: Intravascular meningococcal replication and endotoxin release produce meningococcal sepsis.
  - target: Petechiae
    description: Microvascular endothelial invasion and thrombosis during meningococcemia cause a petechial or purpuric rash.
- name: Cerebrospinal Fluid Complement Activation and Inflammasome Pyroptosis
  description: >-
    Within the subarachnoid space and brain parenchyma, Neisseria meningitidis
    triggers classical, lectin, and common-pathway complement activation in the
    cerebrospinal fluid (elevated C1q, MBL, C3a, iC3b, C5a, sC5b-9, and CFH) and
    activates canonical and non-canonical inflammasome pyroptosis via caspase-1,
    caspase-11, and gasdermin-D cleavage (promoted by the HrpB two-partner
    secretion system), releasing mature IL-1beta and IL-18 and driving intense
    meningeal inflammation.
  role: central_effector
  biological_scale: TISSUE
  locations:
  - preferred_term: cerebrospinal fluid
    term:
      id: UBERON:0001359
      label: cerebrospinal fluid
  - preferred_term: meninx
    term:
      id: UBERON:0002360
      label: meninx
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  biological_processes:
  - preferred_term: complement activation
    modifier: INCREASED
    term:
      id: GO:0006956
      label: complement activation
  - preferred_term: pyroptosis
    modifier: INCREASED
    term:
      id: GO:0070269
      label: pyroptotic inflammatory response
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:24412248
    reference_title: "Cerebrospinal fluid complement activation in patients with pneumococcal and meningococcal meningitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Complement factors C1q and MBL as well as common complement pathway factors C3a, iC3b, C5a, sC5b-9 and complement regulator CFH were all elevated in patients with bacterial meningitis as compared to the controls."
    explanation: Demonstrates widespread CSF complement cascade activation (C1q, MBL, C3a, iC3b, C5a, sC5b-9) in patients with meningococcal and pneumococcal meningitis.
  - reference: DOI:10.3389/fcimb.2024.1384072
    reference_title: "Neisseria meningitidis activates pyroptotic pathways in a mouse model of meningitis: role of a two-partner secretion system"
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Furthermore, western blot analysis of brain samples during the infection demonstrated that: i. N. meningitidis activated canonical and non-canonical inflammasome pyroptosis pathways in the mouse brain; ii. the activation of caspase-11, caspase-1, and gasdermin-D was markedly reduced in the hrpB mutant; iii. the increase in the amount of IL-1β and IL-18, which are an important end point of pyroptosis, occurs in the brains of mice infected with the wild-type strain 93/4286 and is strongly reduced in those infected with 93/4286ΩhrpB."
    explanation: Shows that N. meningitidis activates caspase-1/caspase-11/gasdermin-D pyroptosis and IL-1beta/IL-18 release in the brain during meningitis.
  downstream:
  - target: Meningitis
    description: Complement anaphylatoxins (C3a, C5a) and pyroptotic IL-1beta/IL-18 release drive purulent meningeal inflammation.
phenotypes:
- name: Meningitis
  category: Neurological
  frequency: VERY_FREQUENT
  description: Acute purulent meningitis is a cardinal presentation of invasive Neisseria meningitidis infection.
  phenotype_term:
    preferred_term: Meningitis
    term:
      id: HP:0001287
      label: Meningitis
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
    explanation: Identifies meningitis as a primary clinical manifestation of invasive meningococcal infection.
- name: Sepsis
  category: Systemic
  frequency: FREQUENT
  description: Meningococcemia (meningococcal sepsis) frequently accompanies or occurs alongside meningococcal meningitis.
  phenotype_term:
    preferred_term: Sepsis
    term:
      id: HP:0100806
      label: Sepsis
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
    explanation: Identifies sepsis as a major presentation of invasive meningococcal infection.
- name: Petechiae
  category: Dermatological
  frequency: FREQUENT
  description: A non-blanching petechial or purpuric rash is a classic diagnostic clue of meningococcal meningitis and sepsis.
  phenotype_term:
    preferred_term: Petechiae
    term:
      id: HP:0000967
      label: Petechiae
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Meningococcus should be considered and investigated promptly as a potentially etiologic pathogen in any patient with meningitis, or sepsis accompanied by a petechial rash."
    explanation: Highlights petechial rash as a hallmark clinical sign of invasive meningococcal disease.
diagnosis:
- name: Confirmatory Invasive Diagnostic Testing (CSF Analysis, Culture, and PCR)
  description: >-
    Confirmatory microbiological and molecular diagnostic testing (cerebrospinal
    fluid examination, blood and CSF culture, and PCR) performed concomitantly
    with early empirical antimicrobial therapy in patients with suspected
    meningococcal meningitis or sepsis.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Suspected patients should receive early appropriate antimicrobial therapy concomitantly with confirmatory invasive diagnostic tests."
    explanation: Establishes confirmatory invasive diagnostic testing alongside empirical antimicrobial therapy as standard diagnostic practice.
treatments:
- name: Quadrivalent Meningococcal Conjugate Vaccination (MenACWY / MCV4)
  description: >-
    Polysaccharide-protein conjugate vaccines against Neisseria meningitidis
    serogroups A, C, W, and Y convert T-independent capsular polysaccharides
    into T-dependent antigens, inducing high-titer serum bactericidal antibodies
    and mucosal carriage reduction that have markedly reduced non-B invasive
    meningococcal disease.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  target_mechanisms:
  - target: Polysaccharide Capsule and Factor H-Binding Protein Complement Evasion and Meningococcemia
    treatment_effect: INHIBITS
    description: >-
      Anti-capsular IgG antibodies induced by MenACWY conjugate vaccination
      trigger complement-mediated serum bactericidal lysis of serogroup A, C, W,
      and Y meningococci.
    evidence:
    - reference: PMID:23830646
      reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "Vaccines have reduced the incidence of infection with certain non-B meningococcal serogroups, and new serotype B vaccines are on the horizon."
      explanation: Documents reduction of non-B invasive meningococcal infection incidence by serogroup-specific meningococcal vaccines.
  effect_modifiers:
  - effect_modifier_type: GENOTYPE
    stratum: terminal complement pathway deficiency (C5-C9) or C5 inhibitor recipients
    comparator_stratum: complement-sufficient individuals
    modified_outcome: serum bactericidal lysis and protection against invasive meningococcal disease
    effect_in_stratum: SMALLER_EFFECT
    description: >-
      Because meningococcal killing relies heavily on membrane attack complex
      (C5b-9) serum bactericidal activity, patients with terminal complement
      pathway deficiencies remain at elevated risk of invasive meningococcal
      disease despite vaccination.
    evidence:
    - reference: PMID:31440263
      reference_title: "Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Our study confirms the strong association of meningococcal infections with terminal pathway deficiency and highlights the risk of pneumococcal and auto-immune diseases in the classical and alternative pathways."
      explanation: Confirms the dependence of anti-meningococcal host defense on intact terminal complement pathway activity.
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Vaccines have reduced the incidence of infection with certain non-B meningococcal serogroups, and new serotype B vaccines are on the horizon."
    explanation: Confirms effectiveness of non-B meningococcal conjugate vaccines in reducing disease incidence.
- name: Meningococcal Group B Protein Vaccination (4CMenB / MenB-FHbp)
  description: >-
    Because the alpha(2-8)-linked polysialic acid capsule of serogroup B
    Neisseria meningitidis mimics human neural cell adhesion molecule (NCAM) and
    is poorly immunogenic, MenB vaccines (4CMenB / Bexsero and MenB-FHbp /
    Trumenba) target subcapsular outer-membrane proteins (fHbp, NadA, NHBA, PorA
    OMVs). Infant 4CMenB vaccination in England achieved 82.9% two-dose vaccine
    effectiveness (94.2% against covered strains) and a 75% reduction in MenB
    disease incidence.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  target_mechanisms:
  - target: Polysaccharide Capsule and Factor H-Binding Protein Complement Evasion and Meningococcemia
    treatment_effect: INHIBITS
    description: >-
      Antibodies against subcapsular antigens (fHbp, NadA, NHBA, PorA) block
      factor H recruitment and promote classical-pathway bactericidal lysis of
      serogroup B meningococci.
    evidence:
    - reference: PMID:31971676
      reference_title: "Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "From September 2015 through August 2018, the incidence of meningococcal group B disease in England (average annual birth cohort, approximately 650,000 infants) was significantly lower in vaccine-eligible cohorts than the expected incidence (63 observed cases as compared with 253 expected cases; incidence rate ratio, 0.25; 95% confidence interval [CI], 0.19 to 0.36), with a 75% reduction in age groups that were fully eligible for vaccination."
      explanation: Demonstrates 75% reduction in invasive MenB disease in 4CMenB-eligible infant cohorts.
  evidence:
  - reference: PMID:31971676
    reference_title: "Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "From September 2015 through August 2018, the incidence of meningococcal group B disease in England (average annual birth cohort, approximately 650,000 infants) was significantly lower in vaccine-eligible cohorts than the expected incidence (63 observed cases as compared with 253 expected cases; incidence rate ratio, 0.25; 95% confidence interval [CI], 0.19 to 0.36), with a 75% reduction in age groups that were fully eligible for vaccination."
    explanation: Provides population-level effectiveness of infant 4CMenB immunization.
  - reference: PMID:28100432
    reference_title: "Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Two-dose vaccine effectiveness was 82·9% (95% CI 24·1-95·2) against all MenB cases, equivalent to a vaccine effectiveness of 94·2% against the highest predicted MenB strain coverage of 88%."
    explanation: Reports 82.9% two-dose vaccine effectiveness against all MenB cases and 94.2% against vaccine-covered strains.
- name: Early Parenteral Antimicrobial Therapy
  description: >-
    Immediate empirical and targeted parenteral antimicrobial therapy (such as
    third-generation cephalosporins or penicillin G) is essential to eradicate
    cerebrospinal fluid and bloodstream meningococci.
  treatment_term:
    preferred_term: antibiotic therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
  target_mechanisms:
  - target: Cerebrospinal Fluid Complement Activation and Inflammasome Pyroptosis
    treatment_effect: INHIBITS
    description: Bactericidal beta-lactam antibiotics clear viable N. meningitidis from the CSF and bloodstream.
    evidence:
    - reference: PMID:23830646
      reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "Suspected patients should receive early appropriate antimicrobial therapy concomitantly with confirmatory invasive diagnostic tests."
      explanation: Establishes early antimicrobial therapy as standard-of-care treatment for suspected invasive meningococcal disease.
  evidence:
  - reference: PMID:23830646
    reference_title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Suspected patients should receive early appropriate antimicrobial therapy concomitantly with confirmatory invasive diagnostic tests."
    explanation: Supports prompt antimicrobial therapy upon clinical suspicion of meningococcal meningitis or sepsis.
genetic:
- name: Terminal Complement Pathway Deficiency (C5-C9)
  association: Risk Factor / Predisposition
  notes: >-
    Congenital deficiencies of terminal complement pathway components (C5
    through C9) impair membrane attack complex-mediated serum bactericidal
    lysis and strongly predispose affected individuals to invasive
    meningococcal infections.
  evidence:
  - reference: PMID:31440263
    reference_title: "Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our study confirms the strong association of meningococcal infections with terminal pathway deficiency and highlights the risk of pneumococcal and auto-immune diseases in the classical and alternative pathways."
    explanation: Confirms the strong genetic association between terminal complement pathway deficiencies and invasive meningococcal infections.
references:
- reference: PMID:23830646
  title: "Severe meningococcal infection: a review of epidemiology, diagnosis, and management."
  findings: []
- reference: PMID:31971676
  title: "Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England."
  findings: []
- reference: PMID:28100432
  title: "Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study."
  findings: []
- reference: PMID:24412248
  title: "Cerebrospinal fluid complement activation in patients with pneumococcal and meningococcal meningitis."
  findings: []
- reference: PMID:31440263
  title: "Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies."
  findings: []
- reference: DOI:10.3389/fcimb.2024.1384072
  title: "Neisseria meningitidis activates pyroptotic pathways in a mouse model of meningitis: role of a two-partner secretion system"
  findings: []
📚

References & Deep Research

References

6
PMID:23830646
Severe meningococcal infection: a review of epidemiology, diagnosis, and management.
No top-level findings curated for this source.
PMID:31971676
Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England.
No top-level findings curated for this source.
PMID:28100432
Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study.
No top-level findings curated for this source.
PMID:24412248
Cerebrospinal fluid complement activation in patients with pneumococcal and meningococcal meningitis.
No top-level findings curated for this source.
PMID:31440263
Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies.
No top-level findings curated for this source.
DOI:10.3389/fcimb.2024.1384072
Neisseria meningitidis activates pyroptotic pathways in a mouse model of meningitis: role of a two-partner secretion system
No top-level findings curated for this source.