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Meningococcal Disease
Han Q. Bui, MD, MPH
image BASICS
  • Meningococcemia is a blood-borne infection caused by Neisseria meningitidis.
  • Bacteremia without meningitis: Patient is acutely ill and may have skin manifestations (rashes, petechiae, and ecchymosis) and hypotension.
  • Bacteremia with meningitis: sudden onset of fever, nausea, vomiting, headache, decreased ability to concentrate, and myalgias
  • Disease progresses rapidly within a matter of hours.
  • Meningococcal bacteremia rarely occurs without frank sepsis.
  • Skin findings and hypotension may be present.
    • A petechial rash appears as discrete lesions 1 to 2 mm in diameter; most frequently on the trunk and lower portions of the body and will be seen in >50% of patients on presentation.
    • Purpura fulminans is a severe complication of meningococcal disease and occurs in up to 25% of cases. It is characterized by acute onset of cutaneous hemorrhage and necrosis due to vascular thrombosis and disseminated intravascular coagulopathy.
  • The mortality rate is ˜13%.
    • 11-19% of survivors suffer serious sequelae, including deafness, neurologic deficit, or limb loss due to peripheral ischemia.
  • Disease is seasonal, peaking in December/January.
  • Annually, ˜1,000 cases of invasive meningococcal disease occur in the United States (1).
    • Most common in adolescents and young adults, followed by infants <1 year
  • N. meningitidis is a gram-negative diplococcus with at least 13 serotypes.
  • N. meningitidis has an outer coat that produces disease—causing endotoxin.
  • Major serogroups in the United States are B, C, Y, and W-135
    • Serogroup B is the predominant cause of meningococcemia in children <1 year.
    • Serogroup C is the most common cause of meningococcal disease in the United States.
    • Serogroup Y is the predominant cause of meningococcemia in the elderly (2).
  • Major serogroups worldwide are A, B, C, Y, and W-135
    • W-135 is the major cause of disease in the “meningitis belt” of sub-Saharan Africa.
Late complement component deficiency has an autosomal recessive inheritance.
  • Age: 3 months to 1 year
  • Late complement component deficiency (C5, C6, C7, C8, or C9)
  • Asplenia (1)
  • Living in close quarters (e.g., household contacts, nursery/daycare centers, dormitories, military barracks)
  • Exposure to active and passive tobacco smoke (1)
  • Two vaccines are currently licensed for use in the United States. Each contains antigens to serogroups A, C, Y, and W-135. Neither provides immunity against serotype B, which is responsible for 1/3 of U.S. cases (3)
    • Meningococcal polysaccharide vaccine (MPSV4): recommended for patients ≥55 years who are at elevated risk (1)
      • Duration of protection is short: 1 to 3 years for patients <5 years; 3 to 5 years for adolescents and adults (3)
      • Often used for patients requiring short duration of protection—traveling to endemic areas, college freshmen, community outbreaks (3)
    • Meningococcal conjugate vaccine (MCV4): recommended for patients 2 to 55 years (1)
  • In October 2014, the Food and Drug Administration (FDA) licensed the first serogroup B meningococcal (MenB) vaccine (MenB-FHbp) as a 3-dose series. In January 2015, FDA licensed a second MenB vaccine (MenB-4C) as a 2-dose series. Both vaccines were approved for use in persons aged 10 to 25 years. Individuals aged ≥10 years who are at increased risk for meningococcal disease due to persistent complement component deficiencies, anatomic or functional asplenia should receive MenB vaccine (3).
  • Protective levels of antibody are achieved ˜7 to 10 days after primary immunization (2).
  • Vaccine is recommended for all persons 11 to 18 years and persons 19 to 55 years at increased risk for the disease.
    • Guillain-Barré syndrome has been associated with the MCV4 vaccine, so a personal history of Guillain-Barré is a relative contraindication for receiving this vaccine.
  • CDC International Travel Advisory
    • Vaccine is required by the government of Saudi Arabia for Hajj pilgrims >2 years of age.
    • The vaccine should be given to travelers to sub-Saharan Africa (“meningitis belt”).
  • Fever, hypotension, tachycardia
  • Neurologic: nuchal rigidity, focal neurologic findings, coma, seizure
    • Focal neurologic findings and seizures are more commonly seen with Haemophilus influenzae or Streptococcus pneumoniae.
  • Cardiopulmonary: signs of heart failure with pulmonary edema—gallop, rales
  • Dermatologic: maculopapular rash, petechiae, ecchymosis, purpura
  • Median time of onset of specific meningitis symptoms (e.g., neck stiffness, photophobia, bulging fontanelle) is as fast as 12 to 15 hours after onset of illness (4).
  • Late signs of meningitis (e.g., unconsciousness, delirium, or seizures) occur ˜15 hours in infants <1 year and ˜24 hours in older children (5).
  • Sepsis; bacterial meningitis (other organisms)
  • Gonococcemia
  • Acute bacterial endocarditis
  • Rocky mountain spotted fever
  • Hemolytic uremic syndrome
  • Gonococcal arthritis dermatitis syndrome
  • Influenza
Initial Tests (lab, imaging)
  • CBC with differential
    • Leukocytosis (left shift; toxic granulation) or leukopenia, thrombocytopenia
  • Lactic acidosis
  • Coagulation studies
    • Prolonged prothrombin time/partial thromboplastin time
    • Low fibrinogen
    • Elevated fibrin degradation products
  • Blood culture
    • Blood culture positive for N. meningitidis
    • Cultures positive in 50-60% of cases
  • CSF
    • Grossly cloudy
    • Increased WBCs with polymorphonuclear predominance
    • Gram stain showing gram-negative diplococci
    • Glucose-to-blood glucose ratio <0.4
    • Protein >45 mg/dL
    • Positive for N. meningitidis antigen (MAT or PCR)
    • CSF culture for N. meningitidis: positive in 80-90% of cases
  • CT scan of head if concern for space-occupying lesions
Test Interpretation
  • Disseminated intravascular coagulation (DIC)
  • Exudates on meninges
  • Polymorphonuclear infiltration of meninges
  • Hemorrhage of adrenal glands
First Line
  • Antibiotics
    • Begin treatment as soon as meningococcal meningitis is suspected.
    • P.657

    • Age influences empiric treatment based on common etiologic organisms.
      • Preterm to <1 month: ampicillin plus cefotaxime or ampicillin plus gentamicin
        • Cefotaxime
          • 0 to7 days: 50 mg/kg q12h
          • 8 to 28 days: 50 mg/kg q8h
        • Ampicillin
          • >2,000 g
            • 0 to 7 days: 50 mg/kg q8h
            • 8 to 28 days: 50 mg/kg q6h
          • <2,000 g
            • 0 to 7 days: 50 mg/kg q12h
            • 8 to 28 days: 50 mg/kg q8h
      • 1 month to 50 years: cefotaxime or ceftriaxone plus vancomycin
        • If severe penicillin allergy: chloramphenicol plus trimethoprim-sulfamethoxazole (TMP-SMX) plus vancomycin
      • >50 years of age or patients with alcoholism, debilitating disease, or impaired immunity: ampicillin plus ceftriaxone plus vancomycin
        • Ampicillin: 2 g IV q4h
        • Ceftriaxone: 2 g IV q12h
        • Vancomycin: 30 to 45 mg/kg/day IV divided q6h
        • If severe penicillin allergy: TMP-SMX plus vancomycin
    • Penicillin G
      • Effective if the isolate is penicillin sensitive
      • Penicillin can be used if the isolate has a penicillin minimum inhibitory concentration (MIC) of <0.1 &mgr;g/mL.
      • For isolates with a penicillin MIC of 0.1 to 1 &mgr;g/mL, treatment with high-dose penicillin is effective, but a 3rd-generation cephalosporin is preferred (5).
      • Penicillin G: 4 million units IV q4h (pediatric dose: 0.25 mU/kg/day IV divided q4-6h) OR ampicillin: 2 g IV q4h (pediatric dose: 200 to 300 mg/kg/day IV divided q6h)
  • Duration of treatment: 7 days (6)
  • Dexamethasone
    • Indications
      • Known or suspected pneumococcal meningitis in selected adults
      • Children with H. influenzae type B meningitis
  • Dexamethasone is often given initially in adults and children with suspected bacterial meningitis while awaiting microbiologic data.
  • Dexamethasone has not been shown to be of benefit in meningococcal meningitis and should be discontinued once this diagnosis is established.
  • Dosage
    • Infants and children >6 weeks: IV 0.15 mg/kg/dose q6h for the first 2 to 4 days of antibiotic treatment
    • Start 10 to 20 minutes before or with the first dose of antibiotic.
  • Chemoprophylaxis
    • Indications
      • Close contacts: Those who have had prolonged (>8 hours) contact while in close proximity (<3 feet) to the patient or who have been directly exposed to the patient's oral secretions between 1 week before the onset of the patient's symptoms and until 24 hours after initiation of appropriate antibiotic therapy (2).
        • Examples: household members and personnel in nurseries, daycare centers, nursing homes, dormitories, military barracks, correctional facilities, and other closed institutional settings
      • No chemoprophylaxis is indicated for casual contacts, including most health care workers, unless there is exposure to respiratory secretion.
    • Timing
      • Ideally <24 hours after case identification
      • Chemoprophylaxis should not be administered if identified >14 days after exposure.
    • Prophylactic regimens
      • Rifampin, ciprofloxacin, and ceftriaxone
        • Ceftriaxone
          • Recommended for pregnant women
          • Adults: 250 mg IM as a single dose
        • Rifampin (meningococcal meningitis prophylaxis)
          • Adult: 600 mg IV or PO q12h for 2 days
          • Pediatric
            • <1 month: 10 mg/kg/day in divided doses q12h for 2 days
            • Infants and children: 20 mg/kg/day in divided doses q12h for 2 days (max 600 mg/dose)
        • Ciprofloxacin
          • Adults: 500 mg PO as a single dose (7)[B]
  • Vaccination
    • For household contacts (if the case is from a vaccine-preventable serogroup)
  • Precautions
    • Adjust the dosage of medications in patients with severe renal dysfunction.
Second Line
  • For meningitis
    • Chloramphenicol: 1 g IV q6h (pediatric dose: 75 to 100 mg/kg/day divided q6h) or ceftriaxone 2 g IV q12h (pediatric dose: 80 to 100 mg/kg/day divided q12-24h)
    • In large outbreaks, a single dose of long-acting chloramphenicol has been used. Single-dose ceftriaxone shows equal efficacy in one randomized controlled trial.
  • Precautions
    • Ceftriaxone should not be used in patients with a history of anaphylactic reactions to penicillin (e.g., hypotension, laryngeal edema, wheezing, hives).
    • Chloramphenicol may cause aplastic anemia.
Potential complications
  • Seizure activity
  • DIC
  • Acute respiratory distress syndrome
  • Renal failure
  • Adrenal failure
  • Multisystem organ failure
Admission Criteria/Initial Stabilization
  • If meningitis is suspected, initiate antibiotics (± corticosteroids), and proceed immediately to lumbar puncture.
  • Droplet isolation for 24 hours from the beginning of antibiotic therapy
IV Fluids
Replace volume as needed; with septic shock, large volumes of crystalloid may be required.
Educate family and close contacts regarding the risk of contracting meningococcal infections.
Overall mortality is 13%.
1. Centers for Disease Control and Prevention. Factsheet: meningococcal disease and meningococcal vaccine. http://www.cdc.gov/meningococcal/clinical-info.html. Accessed 2014.
2. Gardner P. Clinical practice. Prevention of meningococcal disease. N Engl J Med. 2006;355(14):1466-1473.
3. Folaranmi T, Rubin L, Martin SW, et al. Use of serogroup B meningococcal vaccines in persons aged ≥10 years at increased risk for serogroup B meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(22):608-612.
4. Rodríguez CL, Octavio JG, Isea C, et al. Acute polyarthritis as sole manifestation of meningococcal disease. J Clin Rheumatol. 2012;18(1):42-43.
5. Thompson MJ, Ninis N, Perera R, et al. Clinical recognition of meningococcal disease in children and adolescents. Lancet. 2006;367(9508):397-403.
6. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267-1284.
7. Fraser A, Gafter-Gvili A, Paul M, et al. Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev. 2005;(1):CD004785.
Additional Reading
  • Visintin C, Mugglestone MA, Fields EJ, et al. Management of bacterial meningitis and meningococcal septicaemia in children and young people: summary of NICE guidance. BMJ. 2010;340:c3209.
  • Wright C, Wordsworth R, Glennie L. Counting the cost of meningococcal disease: scenarios of severe meningitis and septicemia. Paediatr Drugs. 2013;15(1):49-58.
  • A39.4 Meningococcemia, unspecified
  • A39.0 Meningococcal meningitis
  • A39.2 Acute meningococcemia
Clinical Pearls
  • Invasive meningococcal disease can be rapidly fatal. Therefore, rapid identification of cases with early treatment is essential for good clinical outcomes. Treat then test in suspected cases
  • Provide chemoprophylaxis to close contacts.
  • Vaccinate at-risk populations as a preventive measure.