Meningococcal Disease

Background

• Meningococcal disease refers to invasive disease caused by the bacteria Neisseria meningitidis, which usually manifests as meningitis and/or septicemia.
  • Although 13 serogroups of N. meningitidis have been identified, 90% of cases are caused by serogroups A, B, C, W135, X, or Y.
  • The prevalence of the infecting serogroup varies by geography and risk group.
• Approximately 500,000 cases occur worldwide each year, but incidence varies widely across geographic regions and age groups.
  • Less than 1 case per 100,000 persons occurs in North America and Europe, but 10-1,000 cases per 100,000 persons occur in countries across the meningitis belt in sub-Saharan Africa, where epidemics occur irregularly.
  • Anyone may be affected. The peak incidence occurs in infants < 1 year old and again in teenagers and young adults.
• The risk of meningococcal disease is associated with social situations as well as environment and immune status.
  • Living and social situations with a high likelihood of close person-to-person contact are associated with increased risk of invasive meningococcal disease.
  • Injury to the nasopharyngeal mucosa due to smoking, upper respiratory tract infection, very low humidity, dust, wind, and low nighttime temperatures increases the risk of disease after acquisition of the organism.
  • Both congenital and acquired immunodeficiency are associated with increased risk of meningococcal disease.

Evaluation

• Clinical manifestations of meningococcal infection vary with age.
  • Infants and young children are more likely to present with nonspecific symptoms, which may lead to misdiagnosis.
    • They tend to progress to symptoms associated with sepsis or meningitis more rapidly than older children, including:
      • symptoms of raised intracranial pressure, including decreased consciousness, bradycardia, focal neural signs, papilledema, or bulging fontanelle (in infants < 18 months old) with meningitis
      • cold hands and feet, leg pain, abnormal skin color, and skin lesions (progressing to hemorrhagic rash)
  • Older children and adults may present with fever, chills, nausea, muscle ache, and vomiting before progressing to:
    • headache, stiff neck, photophobia, agitation, decreased consciousness, and meningismus with meningitis
    • circulatory insufficiency, shock, coagulopathy, and petechial/purpuric rash with septicemia
• The most recognizable feature of invasive meningococcal disease is a rapidly progressing nonblanching purpuric rash.
• Meningitis and septicemia may develop alone or in combination.
• Coagulopathy, ultimately culminating in purpura fulminans, complicates 15%-25% of meningococcemia cases.
• Diagnosis is based on clinical suspicion of meningococcal disease with laboratory confirmation of invasive N. meningitidis.
  • The diagnostic gold standard is growth of N. meningitidis in culture of normally sterile body fluid (usually blood or cerebrospinal fluid [CSF]).
  • Other confirmatory tests may include polymerase chain reaction (PCR) and/or Gram stain of blood, CSF, or other specimens (for example, respiratory secretions or skin lesion aspirate).

Management

• Give parenteral antibiotics as soon as possible and transfer the patient to the nearest appropriate hospital if meningococcal disease is suspected.
  • While cultures and other test results are pending, broad-spectrum coverage for bacterial and viral etiologies of meningitis should be initiated, covering not only meningococcal infection, but other potential etiologies as well.
  • For children, give parenteral cefotaxime as soon as meningococcal disease is suspected using age- and weight-based dosing (Strong recommendation):
    • for neonates aged 0-7 days, give 100-150 mg/kg/day in divided doses every 8-12 hours
    • for neonates aged 8-28 days, give 150-200 mg/kg/day in divided doses every 6-8 hours
    • for infants and children > 28 days old, give 225-300 mg/kg/day in divided doses every 6-8 hours
  • For adults, give either (Strong recommendation):
    • ceftriaxone 2 g every 12 hours
    • cefotaxime 1.33-2 g every 4 hours or 2-3 g every 6 hours
  • Consider adjusting antibiotics after meningococcal infection is confirmed based on penicillin minimal inhibitory concentration (MIC).
• Additional supportive care in patients with shock due to meningococcal septicemia:
  • Give fluid resuscitation with rapid infusion of IV crystalloids ≥ 30 mL/kg in adults and ≥ 20 mL/kg in children, with further resuscitation guided by reassessment of hemodynamic status (Strong recommendation).
  • Give inotropes and vasopressors early if there are signs of fluid-resistant shock (Strong recommendation in adults, Weak recommendation in children).
  • Give steroids if shock does not adequately respond to fluid and vasopressors (Weak recommendation).
  • Use insulin if necessary to maintain blood glucose level ≤ 180 mg/dL (10 mmol/L) (Strong recommendation in adults, Weak recommendation in children).
  • Mechanical ventilation or renal replacement therapy may be necessary in severe cases.
  • For adults, consider venous thromboembolism prophylaxis with anticoagulant (unless contraindicated) (Strong recommendation) or mechanical prophylaxis (Weak recommendation).
  • For adults, consider stress ulcer prophylaxis in patients with gastrointestinal bleeding risk factors (Strong recommendation).
• In patients with meningococcal meningitis without shock:
  • Give maintenance fluids to correct dehydration, avoid hypoglycemia, and maintain electrolyte balance if there is no evidence of raised intracranial pressure or antidiuretic hormone secretion.
  • Consider hyperosmolar therapy for management of cerebral edema.
  • There is insufficient evidence to recommend dexamethasone in adults or children with meningococcal meningitis.
  • In adults, consider venous thrombosis prophylaxis in high-risk patients without coagulopathy (Weak recommendation).

Prevention

• In the United States, vaccination with a conjugate meningococcal vaccine protective against serotypes A, C, W, and Y is recommended for adolescents aged 11-18 years, military recruits, and college students (without previous vaccination) as well as children and adults with increased risk of meningococcal disease due to (Strong recommendation):
  • anatomical or functional asplenia
  • persistent complement component deficiencies
  • use of complement inhibitor (such as eculizumab or ravulizumab)
  • HIV infection
  • occupational exposure (microbiologist routinely exposed to N. meningitidis isolates)
  • travel to endemic or hyperendemic areas (for example, meningitis belt or pilgrimage to the Hajj)
  • meningococcal serotypes A, C, W, or Y outbreak
• In the United States, vaccination with meningococcal B vaccine is recommended for special populations, including (Strong recommendation):
  • anatomical or functional asplenia
  • persistent complement component deficiencies
  • use of complement inhibitor (such as eculizumab or ravulizumab)
  • occupational exposure
  • meningococcal serotype B outbreak
• For adolescents and young adults aged 16-23 years not otherwise at increased risk for meningococcal disease as above, consider 2-dose series of meningococcal B vaccine based on shared clinical decision-making. Factors to consider include risk of serious complications of invasive meningococcal infection, increased risk among college students, particularly students living in on-campus housing, and overall low number of serogroup B cases in United States.
• Antibiotic chemoprophylaxis may also be warranted for persons with close contact to the patient with meningococcal disease in the 7 days before symptom onset - such as household members, childcare center contacts, and persons directly exposed to the patient's oral or respiratory secretions (Weak recommendation).