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Meningococcal Disease
Han Q. Bui, MD, MPH
image BASICS
DESCRIPTION
  • 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.
EPIDEMIOLOGY
Incidence
  • 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
ETIOLOGY AND PATHOPHYSIOLOGY
  • 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.
Genetics
Late complement component deficiency has an autosomal recessive inheritance.
RISK FACTORS
  • 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)
GENERAL PREVENTION
  • 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”).
image DIAGNOSIS
PHYSICAL EXAM
  • 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).
DIFFERENTIAL DIAGNOSIS
  • Sepsis; bacterial meningitis (other organisms)
  • Gonococcemia
  • Acute bacterial endocarditis
  • Rocky mountain spotted fever
  • Hemolytic uremic syndrome
  • Gonococcal arthritis dermatitis syndrome
  • Influenza
DIAGNOSTIC TESTS & INTERPRETATION
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
image TREATMENT
MEDICATION
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.
ISSUES FOR REFERRAL
Potential complications
  • Seizure activity
  • DIC
  • Acute respiratory distress syndrome
  • Renal failure
  • Adrenal failure
  • Multisystem organ failure
INPATIENT CONSIDERATIONS
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.
image ONGOING CARE
PATIENT EDUCATION
Educate family and close contacts regarding the risk of contracting meningococcal infections.
PROGNOSIS
Overall mortality is 13%.
REFERENCES
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
&NA;
  • 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.
Codes
&NA;
ICD10
  • A39.4 Meningococcemia, unspecified
  • A39.0 Meningococcal meningitis
  • A39.2 Acute meningococcemia
Clinical Pearls
&NA;
  • 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.