Basics
Description
- A systemic infection with the bacterium Neisseria meningitidis, a gram-negative diplococcus that is relatively fastidious. 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.
- 13 serogroups have been described on the basis of capsular polysaccharide antigens; serotypes B, C, and Y account for most of the cases in the United States. Serogroup Y accounted for 30% of cases between 1996 and 1998.
General Prevention
- Isolation of the hospitalized patient; hospitalized patients require respiratory isolation until 24 hours after initiation of appropriate antibiotic therapy.
- 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, C, Y, and W-135 are available and produce an immune response in 10 " “14 days.
- A tetravalent conjugate meningococcal vaccine, MCV4, is licensed for use in people in the age range of 2 " “55 years. It is recommended in all unimmunized 11 " “12-year-old adolescents, with a booster dose at age 16 years.
- Serotype B vaccine was recently approved by the FDA and is licensed for use in people 10 " “25 years of age.
- The Centers for Disease Control and Prevention (CDC) continues to recommend routine adolescent immunization with the exception of persons with a history of Guillain-Barre 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 http://www.cdc.gov/vaccinesafety/Concerns/gbsfactsheet.html. A study published in 2012 did not support an association between GBS and MCV4 vaccination.
Epidemiology
- The rates of meningococcal disease in the United States have remained stable at 0.9 " “1.5 cases per 100,000 population per year.
- Children <5 years of age are most often affected, with peak incidence between 3 and 5 months of age.
- During epidemics, more school-aged children may be affected.
- The disease occurs most commonly in winter and spring months.
- Increased disease activity may follow an influenza A outbreak.
Risk Factors
- Patients with asplenia, deficiencies of properdin C3, or a terminal complement component (C5 " “C9), and HIV are at increased risk for invasive and recurrent disease.
- 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.
Genetics
- Inherited deficiency of terminal complement may be found in 5 " “10% of patients during epidemics. The frequency increases to 30% in patients with recurrent disease.
- A number of other immune function " “related genes associated with either susceptibility or protection from infection have been identified.
Pathophysiology
- Fulminant disease is signified by diffuse microvascular damage and disseminated intravascular coagulation (DIC); see "Diagnosis " ť 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.
Diagnosis
Signs and Symptoms
- Fever
- Malaise
- Rash
- Petechiae
- Tachycardia
- Delayed capillary fill
- Abnormal mental status
- 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 " “2 hours of onset of signs or symptoms and is signified by hypotension, oliguria, DIC, myocardial dysfunction, and vascular collapse. Death occurs in 15 " “20% of these patients.
History
Time of onset of fever, malaise, and rash ‚
Physical Exam
- 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.).
- Recognition of abnormal vital signs and lethargy is necessary.
- Nuchal rigidity, lethargy, and irritability should be carefully but expeditiously evaluated.
Diagnostic Tests & Interpretation
The organism can be cultured from blood, CSF, and skin lesions. ‚
Lab
- Gram stain of CSF or scraped petechial lesion (pressed against a glass slide) revealing gram-negative diplococci will give a presumptive diagnosis.
- Rapid test for antigen detection
- Supports diagnosis if found in CSF but not sensitive for serogroup B
- CBC
- One study showed that 94% of children show abnormalities in 1 or more of the following parameters: abnormalities in absolute neutrophil count ( ≤1,000/mm3 or ≥10,000/mm3), immature neutrophil count ( ≥500/mm3), and/or immature-to-total neutrophil ratio ( ≥0.20).
Diagnostic Procedures/Other
Lumbar puncture: antigen detection although culture remains the gold standard ‚
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.
Treatment
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).
- Close monitoring of vital signs and clinical status should follow, preferably in an ICU setting.
Medication
- 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 " “7 days.
- In penicillin-allergic patients, 3rd-generation cephalosporins, or chloramphenicol are acceptable alternatives.
Issues for Referral
Public health officials should be notified of N. meningitidis cases. ‚
Ongoing Care
Follow-up Recommendations
Patient Monitoring
Patients with bacterial meningitis should have a hearing test as a follow-up. ‚
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.
- Meningococcemia may be complicated by myocarditis, arthritis, hemorrhage, and pneumonia; digit or limb amputation, and skin scarring.
- Meningococcal meningitis is most commonly complicated by deafness in 5 " “10% of survivors.
- Other complications of meningitis include seizures, subdural effusions, and cranial nerve palsies.
- Immunologic complications include arthritis, vasculitis, pericarditis, and episcleritis.
Additional Reading
- Brouwer ‚ MC, Spanjaard ‚ L, Prins ‚ JM, et al. Association of chronic meningococcemia with infection by meningococci with underacylated lipopolysaccharide. J Infect. 2011;62(6):479 " “483.
- Centers for Disease Control and Prevention. Update: Guillain-Barre syndrome among recipients of Menactra meningococcal conjugate vaccine " ”United States, June 2005 " “September 2006. MMWR Morb Mortal Wkly Rep. 2006;55(43):1120 " “1124.
- Demissie ‚ DE, Kaplan ‚ SL, Romero ‚ JR, et al. Altered neutrophil counts at diagnosis of invasive meningococcal infection in children. Pediatr Infect Dis J. 2013;32(10):1070 " “1072. ‚ [View Abstract]
- Pathan ‚ N, Faust ‚ SN, Levin ‚ M. Pathophysiology of meningococcal meningitis and septicaemia. Arch Dis Child. 2003;88(7):601 " “607. ‚ [View Abstract]
- Rosenstein ‚ NE, Perkins ‚ BA, Stephens ‚ DS, et al. Medical progress: meningococcal disease. N Engl J Med. 2001;344(18):1378 " “1388. ‚ [View Abstract]
- Velentgas ‚ P, Amato ‚ AA, Bohn ‚ RL, et al. Risk of Guillain-Barre syndrome after meningococcal conjugate vaccination. Pharmacoepidemiol Drug Saf. 2012;21(12):1350 " “1358. ‚ [View Abstract]
- Welch ‚ SB, Nadel ‚ S. Treatment of meningococcal infection. Arch Dis Child. 2003;88(7):608 " “614. ‚ [View Abstract]
Codes
ICD09
ICD10
- A39.4 Meningococcemia, unspecified
- A39.3 Chronic meningococcemia
- A39.2 Acute meningococcemia
SNOMED
- 4089001 Meningococcemia (disorder)
- 240426001 chronic meningococcemia (disorder)
- 186365005 Acute meningococcemia
FAQ
- Q: How long should antibiotic therapy be given to a patient with septic shock?
- A: 7 days
- Q: Is MCV4 meningococcal vaccine indicated for all adolescents?
- A: Yes, MCV4 is now recommended in all previously unimmunized adolescents at the doctor visit from 11 to 12 years or at high school entry, whichever comes first. A booster dose is recommended at age 16 years.
- Q: How does 1 approach MCV4 immunization of adolescents who previously received MPSV4?
- A: If 3 " “5 years have elapsed since their MPSV4 vaccination, then MCV4 immunization is indicated.
- Q: When should 1 test for complement deficiency?
- A: In patients with recurrent disease
- Q: Which hospital personnel should receive prophylaxis?
- A: Only those with direct exposure to index patient 's secretions.