Neisseria meningitidis

Snapshot

• An 18-year-old man presents to the emergency department for an intractable headache and generalized malaise. His symptoms began 3 days ago and have progressively worsened. Physical examination is significant for nuchal rigidity, diffuse petechia, and an inability to extend at the knee while the hips are flexed at 90°. A lumbar puncture is performed and cerebral spinal fluid studies demonstrate an elevated opening pressure, elevated protein, decreased glucose, and a leukocytosis. Gram stain of the cerebral spinal fluid demonstrates gram-negative diplococci.

Introduction

• Classification
  • a gram-negative diplococcus
• Epidemiology
  • risk factors 
    • college students
    • military
    • infants and the elderly
    • no meningococcus vaccine
• Transmission
  • respiratory and oral secretions
• Microbiology
  • properties
    • metabolizes glucose
    • produces IgA proteases
    • contains lipooligosaccharides (has strong endotoxin activity)
    • aerobic or facultatively anaerobic
    • maltose fermenter 
  • reservoir
    • nasopharynx
      • penetrates mucosal epithelium and enters circulation
        • pharynx → hematogenous spread (blood) → choroid plexus → meninges 
  • molecular biology
    • virulence factors
      • polysaccharide capsule 
        • an important virulence factor
          • provides resistance against phagocytosis
      • IgA protease
        • allows oropharynx colonization
      • endotoxin (lipooligosaccharide) 
        • analogous to LPS from other gram-negative bacteria
        • causes hemorrhage and sepsis
        • responsible for petechial rash
          • small red dots of hemorrhage
      • pili
        • enables attachment to the nasopharynx 
        • antigenic variation avoids the immune system attack
• Pathogenesis
  • begins as asymptomatic colonization in the nasopharynx in healthy patients
    • in rare cases, the bacteria invade through the mucosa, resulting in bacteremia, which can allow seeding of the microbe to the meninges
    • an inflammatory response against the microbe (due to its endotoxin) ensues, leading to tissue injury
      • procoagulant pathways can also be activated, causing intravascular thrombosis (e.g., purpura and petechiae)
  • Patients deficient in components of the alternative and terminal complement (C5b-C9 – membrane attack complex) pathways have increased susceptibility to recurrent Neisseria bacteremia
• Prevention
  • meningococcal vaccine
    • indication
      • all patients 11-18 years of age
      • ≤ 10 years of age and ≥ 19 years of age who are high risk for invasive meningococcal disease
• Associated conditions
  • meningitis
  • meningococcemia
  • purpural fulminans
  • Waterhouse-Friderichsen syndrome  
    • adrenal infarction leading to adrenal insufficiency 
• Prognosis
• poor prognosis include shock, young and old age, coma, purpura fulminans, and disseminated intravascular coagulation

Presentation

• Symptoms
  • headache
  • fever
  • neck stiffness
  • nausea and vomiting
  • myalgias
• Physical
  • petechial rash 
  • nuchal rigidity
  • Brudzinki sign
    • spontaneous flexion of the hips during passive neck flexion
  • Kernig sign
• inability to extend the knees while the hips are flexed at 90°

Studies

• Culture
  • perform a Gram stain of the cerebral spinal fluid or blood
• gold standard for the diagnosis

Differential

• Meningitis caused by other organisms
  • Streptococcus pneumoniae
  • Listeria monocytogenes
  • differentiating factors
• different organisms are isolated with microbiologic testing

Treatment

• Medical
  • empiric antibiotic therapy
    • indication
      • preferably given after cerebral spinal fluid cultures and blood cultures are obtained
        • given antibiotics first will impair diagnostic testing
    • regimen
      • third-generation cephalosporin
        • e.g., ceftriaxone or cefotaxime 
  • antimicrobial chemoprophylaxis
    • indication
      • ideally given within 24 hours
        • household members
        • roommates or intimate contacts
        • direct exposure to oral or respiratory secretions (e.g., kissing and endotracheal intubation)
        • sitting next to the infectious person for ≥ 8 hours
        • patients who work in a childcare center
    • medication
      • rifampin
      • ciprofloxacin
• ceftriaxone

Complications

• Sepsis
• Hypovolemic shock
• Cerebral edema and hydrocephalus
• Cognitive impairment