eMedicine Specialties > Infectious Diseases > Bacterial Infections

Meningococcal Infections

Author: Darvin Scott Smith, MD, MSc, DTM&H,, Adjunct Assistant Professor, Department of Microbiology and Immunology, Stanford University; Chief of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, Kaiser Redwood City Hospital
Coauthor(s): Thomas A Hoffman, MD, Professor, Department of Internal Medicine, Division of Infectious Diseases, Jackson Memorial Hospital, University of Miami; Joanna L Chan, MD, Resident Physician, Department of Dermatology, University of Texas Southwestern Medical Center
Contributor Information and Disclosures

Updated: Mar 12, 2009

Introduction

Background

Meningococcal (Neisseria meningitidis) bloodstream infections (known as meningococcemia) can range in severity from a transient bacteremia that is relatively benign to an overwhelming infection that is rapidly fatal. Meningitis commonly occurs during the course of meningococcemia. In rare cases, N meningitidis organisms can spread hematogenously to other sites, such as the pericardium, the joints, and the eyes.

Pathophysiology

The human nasopharynx is the only known reservoir for N meningitidis. Meningococci spread from person to person by airborne droplets of infected nasopharyngeal secretions. Meningococcal organisms attach to mucosal surfaces, where they produce few symptoms. Concomitant viral respiratory infections, particularly those involving influenza viruses, appear to enhance the spread of meningococcal infection and the likelihood of nasopharyngeal carriage after exposure to meningococci.

Nasopharyngeal meningococcal infection is usually subclinical. Asymptomatic nasopharyngeal carriage of meningococci is transient and resolves within several weeks. In very rare cases, N meningitidis organisms invade the bloodstream and cause clinical disease. Clinical meningococcal disease can be arbitrarily classified into 3 general forms: (1) an uncomplicated bacteremic process, (2) a metastatic infection that commonly involves the meninges, or (3) an overwhelming systemic infection with circulatory collapse and evidence of disseminated intravascular coagulation (DIC).

The fundamental pathologic change in meningococcemia is widespread vascular injury characterized by endothelial necrosis, intraluminal thrombosis, and perivascular hemorrhage. Skin lesions usually contain numerous meningococci undergoing phagocytosis by neutrophils. Occlusive thrombi composed of platelets, red blood cells, and fibrin are most prominent in deep dermal vessels. Serous surfaces and other organs incur the same vascular injury, although N meningitidis bacteria are difficult to find in tissues other than the skin.

Patients with fulminant meningococcemia develop thrombosis and hemorrhage in the skin, the mucous membranes, the serosal surfaces, the adrenal sinusoids, and the renal glomeruli. Adrenal hemorrhage is rarely extensive. Thrombosis of the glomerular capillaries may cause renal cortical necrosis, the chief characteristic of the generalized Shwartzman reaction. Thrombi containing numerous leukocytes are occasionally found in the lungs, and extensive intra-alveolar hemorrhage can occur. Myocarditis has been observed in adults with fatal meningococcal infections.

Frequency

United States

During the past 6 decades, the occurrence of meningococcal disease has been mostly sporadic, and no widespread outbreaks have occurred. The prevalence has been approximately 1-2 cases per 100,000 population, although it has shown variation from year to year.

Limited outbreaks of meningococcal disease have occurred in some populations. Public health officials arbitrarily define an outbreak of meningococcal disease as the occurrence of 3 or more cases during a 3-month period, with a primary attack rate of at least 10 cases per 100,000 population, which is approximately 10 times greater than normal. Outbreaks may be restricted to a closed population or may involve a larger community. In a Los Angeles County outbreak of meningococcal disease, nearly one half of community residents with the disease had had contact with persons who had been incarcerated.¹

Recently, the incidence of meningococcal disease in adolescents and college-aged young adults appears to have increased. College students living in dormitories seemed to be the population at an increased risk (see Deterrence/Prevention).

Meningococcal disease is also a relatively common problem in military recruit populations.²

International

Meningococcal disease occurs sporadically or in episodic epidemics worldwide. Massive outbreaks of meningococcal disease have occurred in many parts of the world. Large-scale outbreaks have spread at cyclic intervals through Central African countries, with attack rates as high as 400-500 cases per 100,000 population, as shown in the image below.

Outbreaks of meningococcal disease have also occurred in Mecca, Saudi Arabia, and in visitors returning from that city.

Mortality/Morbidity

The case-fatality rate of meningococcal infections varies depending on the prevalence of disease, the clinical form of disease, and the socioeconomic conditions of the society in which the infections occur. In the United States, the case-fatality rate is approximately 10%.

• During endemic situations in industrialized countries, the case-fatality rate can be as low as 3% for meningitis and as high as 50% for fulminant meningococcemia. The mortality rate of meningococcal disease may be lower during epidemic situations because heightened diagnostic awareness may result in detection and treatment of greater numbers of cases before the disease progresses to a more lethal form.
• Fulminant meningococcemia carries the highest mortality rate; it can exceed 50% despite the use of appropriate antibiotic therapy. It can be as high as 70% in developing countries. Survivors of fulminant meningococcemia may have ischemic complications.
• Meningococcal meningitis without antibiotic therapy is uniformly fatal.

Race

One population-based study in the United States found that the incidence of meningococcal disease was significantly higher among African Americans (1.5 cases per 100,000 population) than among Anglo Americans (1.1 cases per 100,000 population). The relative risk (RR) was 1.4 (95% confidence interval [CI], 1.1-1.8).

Sex

Males accounted for 55% of all cases, with an incidence of 1.2 cases per 100,000 population, compared to 1 case per 100,000 population among females (RR, 1.3; 95% CI, 1.0-1.6).

Age

Age is a major determinant of susceptibility to meningococcal disease.

• The age-specific incidence of meningococcal disease is highest in young children, although maternal antibodies usually protect infants in the first few months of life. A multicenter study evaluating the serogroups in children with N meningitis infection found that meningococcal disease continues to result in substantial morbidity and mortality in children. The study found that, overall, 55 (44%) of isolates were serogroup B, 32 (26%) were serogroup C, and 27 (22%) were serogroup Y. All but one isolate (intermediate) were susceptible to penicillin. The overall mortality rate in this pediatric population was 8%.³
• A 1995 study in the United States found that the incidence of meningococcal disease among infants aged 1-23 months was 11.1 cases per 100,000 population. The age-specific rate was 1.5 per 100,000 population among individuals aged 2-29 year, 0.6 among individuals aged 30-50 years, and 1.3 among individuals aged 60 years and older.
  
  

  

  A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

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  A 9-month-old baby in septic shock with purpuric Neisseria meningitis skin lesions. Photo by D. Scott Smith, MD, taken at Stanford University Hospital.

• About one third of meningococcal disease cases occur in adults.

Clinical

History

• The clinical pattern of meningococcemia varies.
  • After a few days of upper respiratory symptoms, the temperature rises abruptly, often after a chill. Malaise, weakness, myalgias, headache, nausea, vomiting, and arthralgias are common presenting symptoms.
  • A skin rash, which is essential for recognizing meningococcemia, is the characteristic manifestation. The skin rash may advance from a few ill-defined lesions to a widespread petechial eruption within a few hours.
• Fulminant meningococcemia is the most serious form of meningococcal disease.
  • This form occurs in approximately 5-15% of cases of meningococcal disease.
  • It begins abruptly with a high fever, chills, myalgias, weakness, nausea, vomiting, and headache. Apprehension, restlessness, and, frequently, delirium occur within the next few hours.
  • The rash appears suddenly and is widespread, purpuric, and ecchymotic.
• In adults, bacterial meningitis has a characteristic clinical pattern, although the progression of symptoms varies somewhat. Symptoms of meningitis may accompany the petechial rash of meningococcemia and may produce the predominant features on presentation.
  • Bacterial meningitis is a febrile illness of short duration; the major symptoms include headache and a stiff neck. Lethargy or drowsiness is common. Confusion, agitated delirium, and stupor are rarer; however, coma is an ominous prognostic sign.
  • The clinical pattern of bacterial meningitis is often atypical in young children because headache and nuchal rigidity are frequently absent. Irritability, especially upon movement, is a common presenting manifestation of meningitis in a young child. Convulsions may signal the onset of meningitis at this age. Progression of the illness results in the development of lassitude and a more constant fever, often accompanied by abdominal discomfort. Projectile vomiting may occur.
• Chronic meningococcemia is a rare form of meningococcal disease. This is an intermittent bacteremic illness that lasts from at least one week to as long as several months.
  • The fever tends to be intermittent, with afebrile periods ranging from 2-10 days, during which the patient seems completely healthy. As the disease progresses, the febrile periods become more common, and the fever may become continuous.
  • Eventually, a skin eruption or some other manifestation of meningococcal disease appears during a febrile episode.

Physical

Petechiae are the most common skin lesions of meningococcemia, and they may be distributed sparsely over the body, as depicted in the image below.

Critically ill patients with sepsis may develop rapidly progressing petechiae, ecchymoses, and extensive palpable purpura or retiform purpura, accompanied by DIC and vascular collapse.

Ill-defined pink macules are noted in some cases. Maculopapular lesions also occur and are sometimes large and plaquelike with a central petechia. Rash may be missed early in an individual with dark skin.

The skin lesions tend to occur in crops on any part of the body, occasionally presenting on the conjunctivae and the mucous membranes. The face is usually spared, and involvement of the palms and the soles is less common.

Patients with acute meningococcemia usually present with moderate fever (average, 39.5°C) and no signs of shock.

Fulminant meningococcemia is associated with a purpuric eruption, as shown in the images below. Lesions are generally characterized by maplike purpuric or necrotic areas. Amputation may be required in severe cases.

• Hemorrhages may appear on the buccal mucosa and the conjunctivae.
• Less frequently, fulminant meningococcemia presents as purpura fulminans. In rare cases, no skin lesions develop.
• Symmetric peripheral gangrene has been described in this form.
• Signs of meningitis are typically absent. However, cyanosis, hypotension, and profound shock eventually appear.
• Patients with fulminant meningococcemia usually present with a high fever (average temperature, 40.6°C). The blood pressure is lowered, and pulmonary insufficiency develops within a few hours.
• Many patients with fulminant meningococcemia die despite appropriate antibiotic therapy and intensive care. Patients with fatal forms of fulminant meningococcemia are likely to die within 24-48 hours of presentation.

The characteristic physical examination findings of meningitis include pain and resistance to neck flexion. Other signs of meningeal irritation can also be elicited. Children with meningitis may have none of these findings.

• The Kernig sign is positive when the leg cannot be extended more than 135° on the thigh when flexed 90° at the hip.
• The Brudzinski sign is positive when neck flexion causes involuntary flexion of the thighs and the legs.
• Focal neurologic signs are uncommon presenting findings of bacterial meningitis. However, nuchal rigidity may not be elicited in patients who are comatose and who may have signs of focal or diffuse neurologic deficits.
• Papilledema is not a presenting feature of bacterial meningitis and suggests the presence of an accompanying process.
• A common presenting sign of meningococcal meningitis is a petechial rash.
• Most patients with meningitis are febrile, although the height of fever varies.

Causes

• N meningitidis is a gram-negative diplococcus that grows well on solid media supplemented with blood and incubated in a moist atmosphere enriched with carbon dioxide.
• Oxidase and catalase are biochemical markers for preliminary identification of N meningitidis. Sugar fermentations are required for final identification of the species. N meningitidis ferments glucose and maltose, not sucrose or lactose.
• Agglutination reactions with immune serum subdivide N meningitidis into serogroups A, B, C, W135, X, Y, and Z, depending on a group-specific capsular polysaccharide antigen.
  • Most strains that cause meningococcal disease have the polysaccharide antigen of groups A, B, or C.
  • Group Y and group W135 meningococci cause disease more commonly than groups X and Z.
  • Meningococcal strains that lack these group-specific antigens are believed to be nonpathogenic.
  • The cell wall of pathogenic meningococci contains a toxic lipopolysaccharide or endotoxin. Meningococcal endotoxin appears to be chemically identical to enteric bacilli endotoxin.
• Susceptibility to meningococcal disease has been linked with the absence of bactericidal antibody against pathogenic meningococci.
  • Immunoglobulin G (IgG) antibodies that have specificity for the meningococcal polysaccharides mediate bactericidal activity. Complement is needed for expression of this activity.
  • Asymptomatic nasopharyngeal carriage of meningococci induces a humoral antibody response, and most individuals acquire immunity to meningococcal disease by age 20 years.
  • Passively transferred maternal antibody provides temporary protection to infants for the first 3-6 months of life.
  • Colonization with nonpathogenic meningococci seems to induce cross-reacting protective antibodies. An episode of meningococcal disease confers group-specific immunity, but a second episode may be caused by another meningococcal serogroup.
  • Recurrent meningococcal disease has been linked to congenital complement deficiencies, which usually affect the terminal components of the complement cascade.
  • Hereditary properdin deficiency may also predispose to meningococcal disease.

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