Neisseria meningitidis
Gram-negative, encapsulated diplococcus; obligate human pathogen. Colonises the nasopharynx of ~10% of healthy adults asymptomatically and causes invasive meningococcal disease (IMD) in a small fraction. IMD manifests as bacterial meningitis, fulminant meningococcal septicaemia (purpuric non-blanching rash, DIC, Waterhouse-Friderichsen syndrome), or both. The polysaccharide capsule is antiphagocytic and the primary vaccine antigen for serogroups A, C, W, Y. Serogroup B capsule is polysialic acid identical to host neural cell adhesion molecule (NCAM) — intrinsically non-immunogenic — requiring the 4-component protein vaccines Bexsero and Trumenba. LOS (lipooligosaccharide) drives endotoxic shock via TLR4 → massive cytokine storm → endothelial apoptosis + DIC. Terminal complement deficiency (C5–C9) raises IMD risk 500–1000-fold; eculizumab (anti-C5) raises it 1000–2000-fold requiring mandatory MenACWY + MenB vaccination before initiation.
Classification & Structure
| Gram reaction | Gram-negative diplococcus (kidney/coffee-bean shaped pairs, ~0.6–1.0 µm); aerobic; oxidase-positive; fastidious (requires enriched media, 5% CO⊂2;); Thayer-Martin selective medium for clinical specimens |
| Morphology | Non-motile; encapsulated; ferments glucose and maltose (not lactose/sucrose); distinguishes from N. gonorrhoeae (glucose only); oxidase-positive (all Neisseria) |
| Cell wall / Capsule | Polysaccharide capsule defines serogroup (A: N-acetyl-mannosamine-1-phosphate; B: polysialic acid = human NCAM; C: poly-α-2,9-NeuNAc; W/Y: distinct hexose-containing repeat units). LOS (lipooligosaccharide): lacks O-antigen repeat; potent TLR4 agonist; primary mediator of endotoxic shock. LOS sialylation recruits factor H → ↓complement activation |
| Key virulence factors | Polysaccharide capsule (antiphagocytic, serum resistance); fHbp (factor H binding protein — complement evasion; MenB vaccine antigen); NadA (β1-integrin binding; Bexsero antigen); NHBA (heparan sulfate binding; Bexsero antigen); PorA OMV (Bexsero antigen); IgA1 protease; Type IV pili (nasopharyngeal adhesion via CEACAM1) |
Pathogenesis
1 · Nasopharyngeal colonisation
Type IV pili bind CEACAM1 on nasopharyngeal columnar epithelial cells → initial attachment → pilus retraction (PilT ATPase) → tight microcolony formation. IgA1 protease cleaves secretory IgA1 → ↓mucosal antibody defence. Bacteria undergo transcytosis through the mucosal epithelium into the subepithelial space, then enter the bloodstream.
2 · Bacteraemia and complement evasion
In blood, the polysaccharide capsule prevents C3b deposition; fHbp recruits factor H → ↓C3b opsonisation and MAC formation; LOS sialylation further recruits factor H. Terminal complement (MAC, C5b–C9) is the critical bactericidal effector: C5–C9 deficiency raises IMD risk 500–1000×; properdin deficiency causes fulminant meningococcaemia; eculizumab (anti-C5) raises risk 1000–2000× → mandatory dual vaccination before initiation.
3 · LOS-driven endotoxic shock and DIC
LOS binds TLR4/MD-2 on monocytes, macrophages, and endothelium → MyD88/TRIF → NF-κB + IRF3 → massive TNF-α, IL-1β, IL-6, IL-8, IL-12 release → endothelial apoptosis + ↑tissue factor expression → DIC. Purpuric rash progresses from petechiae → ecchymoses → skin confluence → gangrene requiring amputation. Waterhouse-Friderichsen syndrome (bilateral adrenal haemorrhage → acute cortisol deficiency → refractory shock) occurs in ~10% of fulminant septicaemia. LOS serum concentration correlates directly with disease severity and mortality.
4 · Meningeal seeding and CNS injury
Bacteria adhere to blood-brain barrier (BBB) endothelium via CEACAM1, NadA, and pili → transcytosis → subarachnoid space. CSF is poor in complement, antibody, and immune cells → unrestricted replication. LOS → IL-8/CXCL8 → massive neutrophilic pleocytosis (>1000 WBC/µL) → ↑ICP → cerebral oedema → herniation (primary cause of acute death). Subarachnoid vessel vasculitis → thrombosis → brain infarcts. Cochlear blood vessel inflammation → sensorineural hearing loss in 5–10% of survivors.
Host Immune Response
Disease Spectrum
| Syndrome | Frequency | Key features |
|---|---|---|
| Meningococcal meningitis | ~50% of IMD | Headache, photophobia, neck stiffness, fever; Kernig’s/Brudzinski’s signs; CSF turbid, WBC >1000 (neutrophils), ↑protein, ↓glucose; ↑ICP → herniation risk; do not delay treatment for LP |
| Meningococcal septicaemia | ~30–40% of IMD | Purpuric/petechial non-blanching rash (pathognomonic); high fever; haemodynamic instability; DIC; MODS; Waterhouse-Friderichsen syndrome; rapidly expanding purpura is a medical emergency |
| Combined meningitis + septicaemia | ~20% of IMD | Features of both; worst prognosis; highest mortality |
| Serogroup Y pneumonia | Rare | Lobar/multilobar pneumonia; elderly; consider in culture-negative pneumonia |
| Arthritis / pericarditis | Rare | Post-infectious immune-complex manifestations; generally favourable outcome with treatment |
Treatment & Prophylaxis
| IV ceftriaxone 2 g (adult) | GIVE IMMEDIATELY if IMD clinically suspected — before LP if not immediately available. Bactericidal; excellent CSF penetration; penicillin G alternative if susceptibility confirmed. |
| Dexamethasone | 0.15 mg/kg IV before/with first antibiotic dose; reduces hearing loss in bacterial meningitis; benefit less certain specifically for meningococcal but recommended. |
| ICU support | Aggressive fluid resuscitation; vasopressors (distributive shock + adrenal insufficiency); hydrocortisone in refractory shock; limb viability monitoring and surgery for gangrenous extremities. |
| Close contact prophylaxis | Rifampicin 2 days, or ciprofloxacin single dose, or ceftriaxone IM single dose for household contacts within 24 h; eradicates nasopharyngeal carriage, preventing secondary cases. |
| MenACWY conjugate vaccine | Covers serogroups A, C, W, Y; routine at 11–12 years + booster at 16 (US); high-risk groups from ≥2 months; near-eliminates serogroup C IMD in vaccinated populations. Mandatory before eculizumab. |
| MenB vaccines | Bexsero (4CMenB: fHbp, NHBA, NadA, PorA OMV) or Trumenba (bivalent fHbp); 16–23 years or outbreak/complement-deficient/eculizumab populations; 2–3 dose series. Mandatory before anti-C5 therapy. |
Cross-Atlas Connections
References
- Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020.
- Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. 9th ed. Elsevier; 2021.
Contribute to the Pathogen Atlas
This entry covers meningococcal biology, complement evasion, and IMD management. Planned expansions: serogroup X vaccine development, genomic epidemiology of hypervirulent lineages CC11/CC32, and eculizumab-era prophylaxis data.