AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Meningococcal disease is a communicable infection caused by Neisseria meningitidis. It is transmitted from person to person via respiratory secretions. N meningitidis infection can be clinically polymorphic. The most common disease presentation is meningitis. Rarely, N meningitidis infection may manifest as chronic meningococcemia that resembles the arthritis-dermatitis syndrome of gonococcemia; however, acute meningococcal septicemia (also called meningococcemia) is the most devastating form of the disease.

Meningococcemia can kill more rapidly than any other infectious disease. Early recognition is critical to implement prompt antibiotic therapy and supportive care. Treatment must be instituted rapidly because irreversible shock and death may occur within hours of the onset of symptoms. Cutaneous manifestations in meningococcemia may be important clues to the diagnosis. Skin involvement can be the most dramatic aspect of the disease and is often the first sign that leads to the clinical consideration of meningococcemia.

Pathophysiology

N meningitidis is an obligate, nonmotile, aerobic, encapsulated, gram-negative diplococcus that can only be cultured on blood-enriched media in a 5-10% carbon dioxide–enriched environment. The outer polysaccharide capsule of N meningitidis serves as the basis of serologic grouping. To date, at least 13 different serogroups have been identified; however, groups A, B, C, Y, and W-135 are the major pathogens involved in human disease.

Transmission of N meningitidis occurs from person to person through respiratory secretions. The human upper respiratory tract is the only known reservoir. Carrier rates depend on age. Approximately 2% of children younger than 2 years, 5% of children up to 17 years, and 20-40% of young adults are carriers of N meningitidis. Overcrowded conditions (eg, schools, military camps) can significantly increase the carrier rate. Screening of military recruits performed during recent epidemics demonstrated that although as many as 95% of recruits were oropharyngeal carriers, only 1% developed systemic disease. Because very few recruits with meningococcal disease had ever been in contact with another such patient, asymptomatic carriers are thought to be the major source of transmission of pathogenic strains.

A complex interaction between host factors and the organism determines the outcome of exposure to N meningitidis. Colonization and invasion of meningococci are facilitated by pili that attach to mucosal epithelial cells. A concomitant viral infection may facilitate the invasion of N meningitidis into the bloodstream or lower respiratory tract. Once in the bloodstream, N meningitidis causes profound effects on small blood vessels, related to both direct invasion of endothelial cells and indirect damage from endotoxin release. Endotoxin from the lipopolysaccharide of meningococci causes endothelial cells, monocytes, and macrophages to release tumor necrosis factor-alpha, interleukin 1, interleukin 6, and interferon-gamma.

The deleterious effects of these cytokines play a major role in the pathogenesis of meningococcemia by causing severe hypotension, reduced cardiac output, and increased endothelial permeability. Multiple organ failure, shock, and death may ensue as a result of anoxia in vital organs and massive disseminated intravascular coagulation (DIC).

Frequency

United States

An estimated 2600 cases of meningococcemia occur each year.

Mortality/Morbidity

The mortality rate is approximately 5% in children and 5-10% in adults; however, meningococcemia associated with DIC has a mortality rate of higher than 90%.

Age

Children younger than 4 years have the highest risk of developing meningococcal disease. Neonates are often resistant to disease because passively acquired maternal immunoglobulin G antibodies are present until approximately age 6 months. As the child grows older, asymptomatic exposure to a variety of encapsulated and nonencapsulated N meningitidis strains increases protective bacterial immunity. Protective immunoglobulin M and immunoglobulin G are found in up to 95% of young adults.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Meningococcemia follows an upper respiratory tract infection and is associated with headache, nausea, vomiting, myalgias, and arthralgias.
• Not all patients appear toxic.
• The initial presentation may be difficult to distinguish from a viral syndrome.
• While a slower clinical presentation can occur in persons with a milder form of disease, fever may increase dramatically with rapid clinical deterioration.
• In fulminant meningococcemia, a hemorrhagic eruption, hypotension, and cardiac depression may be apparent within hours of the initial presentation.

Physical

• Cutaneous manifestations of meningococcemia are common and can be the presenting sign of disease.
• Petechiae are the most common sign, occurring in 50-60% of patients with meningococcemia; however, urticarial and maculopapular lesions also may occur initially. Petechiae are most often located on the extremities and trunk but may progress to involve any part of the body. Petechiae may appear in groups under areas of pressure.
• With progression of meningococcemia, pustules, bullae, and hemorrhagic lesions with central necrosis can develop. Stellate purpura with a central gunmetal-gray hue is characteristic and should be considered highly suggestive of meningococcemia.
• Large maplike purpuric and necrotic areas related to the development of DIC are characteristic of fulminant meningococcemia.
• Noncutaneous physical findings are as follows:
• • Altered mental status
  • Neck stiffness
  • Irritability
  • Seizures
  • Nerve palsies
  • Gait disturbance
  • Nausea
  • Vomiting
  • Unstable vital signs

Causes

• Most patients with meningococcal disease are previously healthy individuals; however, patients with certain medical conditions are at increased risk for developing meningococcal infection.
• Meningococcemia is particularly common among individuals with deficiencies of terminal complement components C5-C9 or properdin.
• • These late complement components are required for bacteriolysis of meningococci.
  • An estimated 50-60% of individuals with late complement component deficiencies develop at least one episode of meningococcal disease.
  • Many of these patients experience multiple episodes of infection.
• Acquired complement deficiencies that occur in association with systemic lupus erythematosus, multiple myeloma, severe liver disease, enteropathies, and the nephrotic syndrome also predispose to meningococcal infection.
• An association has been described between increased risk of mortality in children with meningococcal disease and polymorphisms in the interleukin 1 cluster.
• Other risk factors include immunoglobulin deficiency, asplenia, and HIV infection.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Bacterial sepsis (gonococcemia, Haemophilus influenzae infection, Streptococcus pneumoniae infection)
Endocarditis (Staphylococcus aureus infection)
Rocky Mountain spotted fever
Viral illness, especially with enterovirus infection
Toxic shock syndrome
Leptospirosis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Meningococcemia can be confirmed with blood culture, lumbar puncture, and a Gram stain of lesional skin biopsy or aspirate specimens.
• Blood culture
• • Perform the blood culture before the administration of antibiotics, if possible, unless this delays the start of treatment.
  • In meningococcemia, organisms have been isolated by blood culture in almost 100% of patients, yet the results are not available for 12-24 hours.
• Throat culture
• • A throat culture should be obtained; however, the diagnosis of meningococcemia cannot be made solely based on a positive result from throat culture because asymptomatic colonization is not uncommon.
  • Complement deficiencies should be sought for complicated infections and recurrent or familial disease.

Imaging Studies

• Deep muscle and bone involvement can be evaluated with magnetic resonance imaging.

Procedures

• Lumbar puncture
• • Meningococcal meningitis causes a polymorphonuclear leukocytosis in the cerebrospinal fluid, which can be evaluated using lumbar puncture.
  • In meningococcemia, Gram stain results of the cerebrospinal fluid are often negative.
  • Detection of N meningitidis capsular polysaccharide antigen in cerebrospinal fluid and urine with rapid serologic tests based on latex particle agglutination is commercially available.
• Skin scrapings
• • In an effort to obtain a more rapid diagnosis, several studies have concentrated on the identification of meningococci from skin specimens.
  • Up to 50-80% of rigorous skin scrapings, lesional aspirates, or punch biopsy samples from bullous or pustular lesions reveal gram-negative N meningitidis with Gram staining or Brown-Hopp–modified Gram stain; however, these results must be interpreted with caution because many gram-negative commensals are possible on the skin.

Histologic Findings

Cutaneous petechiae and purpura correspond to thrombi in the dermal vessels composed of neutrophils, platelets, and fibrin. Acute vasculitis with neutrophils and nuclear dust present within and around vessels leads to hemorrhage into the surrounding tissue. Meningococci can often be seen in the luminal thrombi and vessel walls. Intraepidermal and subepidermal neutrophilic pustules also may be present.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• The most important measure in treating meningococcemia is early detection and rapid administration of antibiotics. Penicillin G is the antibiotic of choice for susceptible isolates. A third-generation cephalosporin (eg, cefotaxime, ceftriaxone) can be used initially in septic patients while the diagnosis is being confirmed or in countries such as the United Kingdom or Spain, where penicillin-resistant strains of N meningitidis have been isolated.
• Intensive supportive care is required for patients with fulminant meningococcemia. Components of treatment include antibiotic therapy, ventilatory support, inotropic support, and intravenous fluids. Central venous access facilitates the administration of massive amounts of volume expanders and inotropic medications needed for adequate tissue perfusion. If DIC is present, fresh frozen plasma may be indicated. Treatment is individualized depending on the severity of hemodynamic compromise of the patient.
• Many experimental and alternate therapies have been tried with varying success. Currently under study are treatments to inhibit inflammatory mediators (eg, monoclonal antibodies to endotoxin, tumor necrosis factor, interleukin 1, interleukin 6, and interferon-gamma). Anecdotal reports show removal of inflammatory mediators by dialysis may offer some benefit. Fibrinolytic treatment using recombinant tissue plasminogen activator or the administration of highly purified protein C concentrate may prove to be helpful adjuncts to conventional therapy to improve tissue perfusion in the presence of DIC.

Surgical Care

Patients who survive the initial acute phase of fulminant meningococcemia are at increased risk for serious complications as a result of poor tissue perfusion.

• Early in the course of tissue injury, conservative therapy is recommended until a distinct line of demarcation is apparent between viable and nonviable tissue.
• Once the patient is stable, debridement of all necrotic tissue is essential and may necessitate extensive removal of skin, subcutaneous tissue, and muscle.
• Large defects may be covered using microvascular free flaps or skin grafts.
• The use of artificial skin can spare the patient immediate use of autograft sites, which frequently are limited.
• Avoid amputation whenever useful function of a limb can be salvaged.
• Poor tissue perfusion may also lead to dental complications that require extensive extraction of severely affected teeth.

Consultations

• Infectious disease specialist - To assist in management and provide guidance in antimicrobial therapy
• Preventive medicine specialist - To evaluate the community risk associated with an index case and initiate reporting to local and regional health authorities if indicated

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to eradicate the microorganism, to reduce morbidity, and to prevent complications.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention

• Vaccines have been developed that consist of purified capsular polysaccharide.
• • The currently available quadrivalent vaccine contains polysaccharide from serogroups A, C, Y, and W-135. This vaccine is recommended for military personnel and patients younger than 2 years with terminal complement deficiencies or anatomic or functional asplenia. Since the start of vaccination against serogroup C, the prevalence of this disease has decreased.
  • The development of an effective serogroup B vaccine is ongoing. A vaccine that combines meningococcal serogroups B and C is under development.
  • Routine vaccination of civilians with the quadrivalent meningococcal vaccine is not recommended because of its relative ineffectiveness in children younger than 2 years and its relatively short duration of action (approximately 3 y).
• Antimicrobial chemoprophylaxis is recommended for close contacts of patients with meningococcal disease and is the primary means of prevention in the United States.
• • Close contacts include household members, day care center classmates, and anyone exposed to the patient's respiratory secretions.
  • Institute antimicrobial chemoprophylaxis as soon as possible because the rate of secondary disease is highest in the first few days after the onset of disease in the index case.
  • Current adult recommendations include rifampin at 600 mg orally twice daily for 2 days.
  • In addition to rifampin, other antimicrobial agents are effective in reducing nasopharyngeal colonization with N meningitidis.
  • • Ciprofloxacin and ofloxacin are effective single-dose oral substitutes.
    • Ceftriaxone is available for parenteral single-dose use in children and adults.
    • These medications achieve adequate concentrations in upper respiratory tract secretions and are reasonable alternatives to the multidose rifampin regimen for chemoprophylaxis.

Complications

• Complications of meningococcemia may occur at the time of acute disease or during the recovery phase.
• Meningococcal arthritis occurs with acute bacteremia in up to 10% of adult cases.
• Up to 5% of patients develop a nonpurulent pericarditis with substernal chest pain and dyspnea approximately 1 week after the onset of illness.
• Neurologic complications (including peripheral neuropathy) have also been documented.
• Long-term complications in patients who survive fulminant meningococcemia are related to permanent musculoskeletal sequelae.
• Amputation may be required for extensive tissue necrosis of the limbs.

Prognosis

• Several investigators have identified unfavorable prognostic features in patients with meningococcemia using clinical and laboratory parameters at the time of hospitalization.
• A mortality rate of 40-80% is associated with the acute onset of petechiae less than 12 hours before admission, shock, coma, high fever, low peripheral leukocyte count, thrombocytopenia, high serum antigen titer, absence of meningitis, metabolic acidosis, and DIC.
• Cases of fulminant meningococcemia can also be associated with the complication of massive adrenal hemorrhage (Waterhouse-Friderichsen syndrome). In these cases, the mortality rate is close to 100%.

Patient Education

• For excellent patient education resources, see eMedicine's Bacterial and Viral Infections Center. Also, see eMedicine's articles Meningitis in Adults and Meningitis in Children.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Special Concerns

• Chronic meningococcemia is a rare (<200 documented cases) clinical presentation of N meningitidis most often observed in adults.
• • Rare case reports associate chronic meningococcemia with the absence of a terminal component of complement. Clinically, it can be confused with the dermatitis-arthritis syndrome associated with subacute gonococcemia. The presentation is that of recurrent attacks of fever associated with migratory arthralgias, arthritis, and leukocytosis. These attacks may recur over a period of 6-8 months. Cutaneous manifestations are variable and include rose-colored macules and papules, indurated nodules, petechiae, purpura, or large hemorrhagic areas.
  • The diagnosis of chronic meningococcemia is confirmed with identification of N meningitidis from blood cultures. The blood culture should be performed during febrile episodes to ensure a correct diagnosis. Multiple cultures are often necessary to confirm bacteremia because of the high rate of false-negative test results.
  • Chronic meningococcemia differs histopathologically from acute meningococcemia in that no bacteria are present, thrombi do not occlude capillaries and venules, and endothelial swelling does not occur. The most common finding in a person with chronic meningococcemia is a leukocytoclastic angiitis.
  • The course of chronic meningococcemia is as variable as the cutaneous findings. Patients may recover spontaneously or progress to systemic complications such as meningitis. The prognosis for treated patients is excellent, with a cure rate of nearly 100% with appropriate antibiotic therapy. Penicillin G at 6-12 million U/d in divided doses for a minimum of 7 days is effective therapy.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Aaberge IS, Oster P, Helland OS, et al. Combined administration of meningococcal serogroup B outer membrane vesicle vaccine and conjugated serogroup C vaccine indicated for prevention of meningococcal disease is safe and immunogenic. Clin Diagn Lab Immunol. May 2005;12(5):599-605. [Medline].
• Aiuto LT, Barone SR, Cohen PS, Boxer RA. Recombinant tissue plasminogen activator restores perfusion in meningococcal purpura fulminans. Crit Care Med. Jun 1997;25(6):1079-82. [Medline].
• Besner GE, Klamar JE. Integra Artificial Skin as a useful adjunct in the treatment of purpura fulminans. J Burn Care Rehabil. Jul-Aug 1998;19(4):324-9. [Medline].
• Centers for Disease Control and Prevention. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. Jun 30 2000;49(RR-7):1-10. [Medline].
• Darmstadt GL. Acute infectious purpura fulminans: pathogenesis and medical management. Pediatr Dermatol. May-Jun 1998;15(3):169-83. [Medline].
• Endler G, Marculescu R, Starkl P, et al. Polymorphisms in the interleukin-1 gene cluster in children and young adults with systemic meningococcemia. Clin Chem. Mar 2006;52(3):511-4. [Medline].
• Faibis S, Widmer R, Sapir S, et al. Meningococcal septicaemia and dental complications: a literature review and two case reports. Int J Paediatr Dent. May 2005;15(3):213-9. [Medline].
• Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev. Jul 1991;4(3):359-95. [Medline].
• Hazelzet JA. Diagnosing meningococcemia as a cause of sepsis. Pediatr Crit Care Med. May 2005;6(3 Suppl):S50-4. [Medline].
• Herf C, Nichols J, Fruh S, et al. Meningococcal disease: recognition, treatment, and prevention. Nurse Pract. Aug 1998;23(8):30, 33-6, 39-40 passim. [Medline].
• Herrera R, Hobar PC, Ginsburg CM. Surgical intervention for the complications of meningococcal-induced purpura fulminans. Pediatr Infect Dis J. Aug 1994;13(8):734-7. [Medline].
• Ikeda C, Capozzi A. Management of skin loss in meningococcal infection. Ann Plast Surg. Oct 1987;19(4):375-7. [Medline].
• Jarva H, Ram S, Vogel U, et al. Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis. J Immunol. May 15 2005;174(10):6299-307. [Medline].
• Lynn WA, Cohen J. Adjunctive therapy for septic shock: a review of experimental approaches. Clin Infect Dis. Jan 1995;20(1):143-58. [Medline].
• Periappuram M, Taylor MR, Keane CT. Rapid detection of meningococci from petechiae in acute meningococcal infection. J Infect. Nov 1995;31(3):201-3. [Medline].
• Ploysangam T, Sheth AP. Chronic meningococcemia in childhood: case report and review of the literature. Pediatr Dermatol. Nov-Dec 1996;13(6):483-7. [Medline].
• Razminia M, Salem Y, Elbzour M, et al. Importance of early diagnosis and therapy of acute meningococcal myocarditis: a case report with review of literature. Am J Ther. May-Jun 2005;12(3):269-71. [Medline].
• Rivard GE, David M, Farrell C, Schwarz HP. Treatment of purpura fulminans in meningococcemia with protein C concentrate. J Pediatr. Apr 1995;126(4):646-52. [Medline].
• Salzman MB, Rubin LG. Meningococcemia. Infect Dis Clin North Am. Dec 1996;10(4):709-25. [Medline].
• Schaller RT Jr, Schaller JF. Surgical management of life-threatening and disfiguring sequelae of fulminant meningococcemia. Am J Surg. May 1986;151(5):553-6. [Medline].
• Tuncer AM, Gur I, Ertem U, et al. Once daily ceftriaxone for meningococcemia and meningococcal meningitis. Pediatr Infect Dis J. Oct 1988;7(10):711-3. [Medline].
• van Deuren M, van Dijke BJ, Koopman RJ, et al. Rapid diagnosis of acute meningococcal infections by needle aspiration or biopsy of skin lesions. BMJ. May 8 1993;306(6887):1229-32. [Medline].

Article Last Updated: Feb 21, 2007