Description

A systemic infection caused by the relatively fastidious gram-negative diplococcus Neisseria meningitidis. Despite treatment with appropriate antibiotics, this disease may have a fulminant course (i.e., significant complications within hours of presentation) with a high likelihood of mortality.

Epidemiology

• The rates of meningococcal disease in the United States have been declining since the 1990s. In 2015, there were 375 cases with an annual incidence of 0.18 cases per 100,000.
• In North America, infants and children are most often affected, with a secondary peak occurring in adolescents, who are the population predominantly responsible for disease carriage. Indeed, it has been shown that 23.7% of adolescents carry meningococcus in their nasopharynx.
• The disease occurs most commonly in winter and spring months.
• Increased disease activity may follow an influenza A outbreak.
• 13 serogroups have been described on the basis of capsular polysaccharide antigens.
  • In the United States, serogroup B causes approximately 60% of cases in children <5 years of age.
  • Serogroups C, Y, or W cause approximately 2/3 cases of meningococcal disease among persons 11 years old and older.

Risk Factors

• Patients with asplenia, deficiencies of properdin C3, or a terminal complement component (C5 to C9), and HIV are at increased risk for invasive and recurrent disease.
• People who take eculizumab for treatment of atypical hemolytic uremic syndrome or paroxysmal nocturnal hemoglobinuria are also at increased risk.
• Other risk groups include microbiologists who are routinely exposed to isolates of N. meningitidis, military recruits, college students living in residence halls, and those traveling to a country where meningococcal disease is endemic.
• Organism virulence factors, such as differences in the bacterial cell wall lipopolysaccharide, play a role in disease severity. Less virulent organisms are more likely in chronic meningococcemia, which has a favorable prognosis.

General Prevention

• Exposed contacts, including household, day care, and nursery school, should receive the following:
  • Rifampin, 10 mg/kg (maximum 600 mg) PO q12h for 4 doses
  • Contacts <1 month of age should receive rifampin 5 mg/kg PO q12h for 4 doses.
  • Alternatively, ceftriaxone is also effective prophylaxis for contacts ≤15 years of age; a single dose of 125 mg IM is recommended.
  • For contacts >15 years old, ceftriaxone 250 mg IM is recommended. Its safety profile is preferred for pregnant women.
• Medical personnel should receive prophylaxis only if they had close contact with respiratory secretions.
• Vaccines for types A, B, C, W, and Y are available and produce an immune response in 10 to 14 days.
• A tetravalent conjugate meningococcal vaccine, MCV4, is licensed for use in people in the age range of 2 to 55 years. It is recommended in all unimmunized 11- to 12-year-old adolescents, with a booster dose at age 16 years.
• Serotype B vaccine was recently approved by the U.S. Food and Drug Administration (FDA) and is licensed for use in people 10 to 25 years of age. The Centers for Disease Control and Prevention (CDC) recommends that:
  • All adolescents and young adults aged 16 to 23 years may be vaccinated, ideally at aged 16 to 18 years, to give protection during this stage of increased risk.
  • Certain adolescents and young adults should receive this vaccine. This includes those identified at increased risk at times of an outbreak and those with medical conditions, including complement deficiencies and functional or anatomic asplenia.
• The CDC continues to recommend routine adolescent immunization with the exception of persons with a history of Guillain-Barré syndrome (GBS) who are not in a high-risk group for invasive meningococcal disease. An updated fact sheet on GBS and MCV4 is available at: https://www.cdc.gov/vaccinesafety/concerns/history/gbs-menactra-faqs.html. Two large studies published in 2012 did not support an association between GBS and MCV4 vaccination.

Pathophysiology

• Fulminant disease is signified by diffuse microvascular damage and disseminated intravascular coagulation (DIC); see “Diagnosis” section.
• Death results from effects of endotoxic shock, including circulatory collapse and myocardial dysfunction.

Etiology

• Colonization and infection of the upper respiratory tract occurs after inhalation of, or direct contact with, the organism, usually in oral secretions.
• Disseminated disease occurs when the organism penetrates the nasal mucosa and enters the bloodstream, where it replicates.

Commonly Associated Conditions

• Terminal complement deficiencies
• Asplenia
• HIV disease

History

• Fever
• Malaise
• Rash
• Bacteremia without sepsis presents with fever, malaise, myalgias, and headache. Patients may clear the infection spontaneously, or it may invade meninges, joints, lungs, and so forth.
• Meningococcemia without meningitis occurs after initial bacteremia with systemic sepsis. A rash erupts, which may be nonspecific maculopapular, morbilliform, or urticarial. Progression to petechiae or purpura signifies evolution of disease.
• Fulminant disease can manifest within 1 to 2 hours of onset of signs or symptoms and is signified by hypotension, oliguria, DIC, myocardial dysfunction, and vascular collapse.

Physical Exam

• Tachycardia
• Delayed capillary refill
• Petechiae
• Abnormal mental status
• Physical examination of a child with fever should include careful evaluation of the skin for petechiae and signs of early shock (tachycardia, delayed capillary refill, abnormal mental status, etc.).
• Nuchal rigidity, lethargy, and irritability should be carefully but expeditiously evaluated.

Differential Diagnosis

• Meningitis due to N. meningitidis is indistinguishable from that of other causes, except for 1/3 of children who have a petechial rash.
• Sepsis from other microbial causes (e.g., Streptococcus, Rocky Mountain spotted fever, viruses) may have a very similar clinical presentation, including the petechiae or purpuric rash.

Diagnostic Tests and Interpretation

The organism can be cultured from blood, CSF, and skin lesions.

General Measures

• Because of the rapidly progressing nature of meningococcemia in some, patients with acute onset of petechial rash and fever should receive a prompt initial dose of antibiotics (if possible and practical, after blood culture or lumbar puncture).
• Patients require close clinical monitoring, often in an intensive care unit (ICU) setting.

Medication (Drugs)

• Cefotaxime or ceftriaxone can be initiated as presumptive therapy. After sensitivity is confirmed, penicillin is preferred.
• After isolate is proven sensitive to penicillin, treatment of choice is aqueous penicillin G IV at a dose of 300,000 IU/kg/24 h q4–6h (max, 12 million U/24 h) for 5 to 7 days.
• In penicillin-allergic patients, 3rd-generation cephalosporins, or chloramphenicol are acceptable alternatives.

Inpatient Consideratons

• Patients with meningococcemia require respiratory isolation until 24 hours after initiation of appropriate antibiotic therapy.
• Health care personnel with direct exposure to respiratory secretions require antibiotic prophylaxis.
• Close monitoring of vital signs and clinical status is necessary, with prompt transfer to an ICU setting, if deemed clinically appropriate.

Follow-Up Recommendations

Prognosis

• Fatality rate of meningococcemia is 15–20%, even when recognized and treated.
• Fatality rate of meningococcal meningitis is 5%. The most severe cases often have a rapid progression from onset of symptoms to death over a matter of hours. At the time of hospital admission, the following signs predict poor survival:
  • Lack of meningitis
  • Shock
  • Coma
  • Purpura
  • Neutropenia
  • Thrombocytopenia
  • DIC
  • Myocarditis

Complications

• Complications may result directly from the infection or be classified as allergic immune complex mediated.
• Approximately 10–20% of survivors have significant sequelae, including hearing loss in 5–10% and other neurologic complications such as subdural effusions and cranial nerve palsies.
• Meningococcemia may also be complicated by
  • Myocarditis
  • Arthritis
  • Hemorrhage
  • Pneumonia
  • Digit or limb amputation
  • Skin scarring
• Immunologic complications include
  • Arthritis
  • Vasculitis
  • Pericarditis
  • Episcleritis

ICD-9

036.2 Meningococcemia

ICD-10

• A39.4 Meningococcemia, unspecified
• A39.3 Chronic meningococcemia
• A39.2 Acute meningococcemia

SNOMED

• 4089001 Meningococcemia (disorder)
• 240426001 chronic meningococcemia (disorder)
• 186365005 Acute meningococcemia