eMedicine Specialties > Infectious Diseases > Bacterial Infections

Meningococcemia

Mahmud H Javid, MD, Chief, Section of Infectious Diseases, Shifa Hospital, Islamabad, Pakistan
Shadab Hussain Ahmed, MD, FACP, FIDSA, MACGS, AAHIVS, Associate Professor of Clinical Medicine, State University of New York at Stony Brook; Attending Physician, Division of Infectious Diseases, Director of HIV Prevention Services, Nassau University Medical Center

Updated: Feb 24, 2009

Introduction

Background

Meningococcemia is caused by Neisseria meningitidis, an encapsulated gram-negative diplococcus. Acquisition of N meningitidis can result in asymptomatic pharyngeal colonization or invasive disease. Meningococcemia is defined as dissemination of meningococci into the bloodstream and is a medical emergency, making early recognition of the disease essential.

Patients with acute meningococcal infection can present clinically with one of 3 syndromes: meningitis, meningitis with meningococcemia, or meningococcemia without obvious meningitis. Prior to the advent of antibiotics, almost all cases resulted in death or marked morbidity.

Pathophysiology

Humans are the only natural reservoir of meningococci and can transmit the organisms by aerosols or nasopharyngeal secretions. Meningococcal infection is preceded by nasopharyngeal colonization. Attachment to the nasopharyngeal epithelial cells is aided by meningococci-expressed pili, which bind to human cell surface protein CD 46. Meningococci then enter the bloodstream and spread to specific sites, such as the meninges or joints, or disseminate throughout the body. Five percent of individuals become long-term carriers, most of whom are asymptomatic. In outbreaks, the carriage rate can be as high as 35%. Intimate contacts of individuals with meningococcemia are 100-1000 times more likely than normal to acquire infection.

A study of 14,000 teenagers in the United Kingdom found that attendance at pubs or clubs, intimate kissing, and cigarette smoking were each independently and strongly associated with an increased risk of meningococcal carriage.¹

Meningococci have 3 important virulence factors, as follows:

• A polysaccharide capsule enables the organism to resist phagocytosis.
• A lipo-oligosaccharide endotoxin (LOS) can be shed in large amounts by a process called blebbing, causing fever, shock, and other pathophysiology. This is considered the principal factor that produces the high endotoxin levels in meningococcal sepsis. Meningococcal LOS interacts with human cells, producing proinflammatory cytokines and chemokines, including interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF). LOS is one of the important structures that mediate meningococcal attachment to and invasion into epithelial cells.²
• An immunoglobulin A1 protease cleaves lysosomal membrane glycoprotein-1 (LAMP1), helping the organism to survive intracellularly.

Individuals with immunity against meningococcal infections have bactericidal antibodies against cell wall antigens and capsular polysaccharide. A deficiency of circulating antimeningococcal antibodies is associated with disease.

Impairment of the protein C anticoagulation pathway leads to the development of purpura fulminans in meningococcemia.

Endotoxin, cytokines, and free radicals damage the vascular endothelium, producing platelet deposition and vasculitis.

Frequency

United States

The incidence of meningococcal disease in the United States is estimated to be 0.7-1.4 cases per 100,000 population. The case-fatality rate is approximately 10%. The incidence and case fatality rates have been relatively constant. While serogroups B and C are most common, an increase in serogroup Y disease was noted in the 1990s.

An outbreak of meningococcal disease is defined as 3 or more cases in a 3-month period or a primary attack rate of at least 10 cases per 100,000 population.

International

Serogroups A, B, and C account for most cases worldwide. Serogroups A and C predominate in Asia and Africa, and serogroups B and C predominate in Europe, North America, and South America.

In the United Kingdom, the number of cases of meningococcal disease and attributed deaths rose in 1995, due mainly to serogroup C disease. This declined when serogroup C conjugate vaccine was introduced in the national immunization program.³

For more than a century, serogroup A meningococcal disease has been endemic in the African Meningitis Belt, which extends from Ethiopia in eastern Africa to Senegal in West Africa.

Outbreaks of meningococcal disease occurred during the annual hajj (pilgrimage) in Saudi Arabia in 2000 and 2001 among pilgrims and household contacts.^4,5 Outbreaks have also occurred in Africa, parts of Asia, South America, and the former Soviet republics. Serogroup A is usually implicated in these epidemics. Outbreaks are also occasionally reported in the United States.

Up to 95% of patients with meningococcal disease have meningococcemia and/or meningitis. Up to 50% have meningococcemia without meningitis. Fulminant meningococcemia occurs in up to 20%. Nosocomial transmission to patient care personnel and laboratory staff is rare.

Mortality/Morbidity

• The mortality rate of fulminant infection remains high, with most deaths occurring within 48 hours.
• Half of all patients with shock who die do so within the first 12 hours of hospitalization.⁶
• In industrialized countries, the mortality rate can exceed 40%; in developing countries, it is higher and can approach 70%.

Race

In the United States, the incidence of meningococcal disease is higher in blacks and in lower socioeconomic groups.

Sex

Meningococcal disease is somewhat more prevalent in males (1.2 cases per 100,000) than in females (1 case per 100,000).

Age

• In epidemics of meningococcal disease, people of any age may be affected, with the case distribution shifted toward older individuals.
• Endemic meningococcal disease is most common in children aged 6-36 months. Children younger than 6 months are protected by maternal antibodies. In New York City, from 1989-2000, the overall incidence rates of meningococcal disease decreased. This was more evident in the younger age groups, and this increased the median age of patients from 15 years in 1989-1991 to 30 years in 1998-2000.⁷
• Occult meningococcemia is an uncommon form of infection that affects children aged 3-24 months.

Clinical

History

Persons with meningococcal disease may present with a nonspecific prodrome of cough, headache, and sore throat. This is followed by rapid onset of fever with chills, arthralgias, and myalgias. The potential rapidity of progression cannot be stressed enough.

• In fulminant meningococcemia, collapse occurs within a few hours, with rapid enlargement of petechiae and purpuric lesions.
• Meningitis that accompanies meningococcemia may result in headache, neck stiffness, lethargy, and drowsiness.
• Decreased mentation and coma may be present.
• Young children may present with sudden onset of fever and lethargy. They may also have vomiting and convulsions.
• In chronic meningococcemia (rare), painful skin lesions are present on the extremities, similar to those seen in gonococcemia, with migratory polyarthritis and tenosynovitis. Antibiotic treatment results in a prompt response.

Physical

Patients with meningococcal disease appear severely ill.

• Tachycardia and mild hypotension are present.
• Fever is moderate. High fever is present in fulminant meningococcemia.
• A petechial rash develops in 50-80% of patients and involves the axillae, flanks, wrists, and ankles. Petechiae are often located in the center of lighter-colored macules. Lesions commonly begin on the trunk and legs in areas where pressure is applied. They are discrete lesions 1-2 mm in diameter. Confluence of lesions results in hemorrhagic patches, often with central necrosis.
• In some cases, a transient maculopapular rash develops, usually lasting for less than 48 hours.⁸
• Congestive heart failure, gallops, and pulmonary edema may be present. Other evidence of end-organ damage may also rapidly appear.
• Patients with fulminant meningococcemia rapidly deteriorate clinically, with hypotension and respiratory failure.
• Pericarditis can occur during the acute disease or in the recovery period and is associated with serogroup C disease.

Causes

Meningococci (0.6 µm X 0.8 µm) are gram-negative single cocci or diplococci with flattened adjacent sides. Older cultures can vary considerably in size and shape. Serotyping is based on the polysaccharide capsule. The organisms grow at 35-37°C in a moist oxygen-reduced atmosphere containing 5-19% carbon dioxide on media that contains blood.

• Seroagglutination is used to segregate meningococci into 13 serogroups: A, B, C, D, X, Y, Z, E, W-135, H, I, K, and L. Ninety-eight percent of infections are caused by encapsulated serogroups A, B, C, Y, and W-135.
• Individuals with complement component deficiencies are at an increased risk for meningococcal infections.
• Recurrent meningococcemia has also been reported in patients with immunoglobulin G2 subclass deficiency.

Differential Diagnoses

Workup

Laboratory Studies

• Definitive diagnosis of meningococcal infection requires culture of meningococci from blood, spinal fluid, joint fluid, or, occasionally, from skin lesions.
  • The sensitivity of blood culture is 60%-80% in untreated patients.
  • Cerebrospinal fluid (CSF) culture yields a sensitivity of up to 70% in untreated patients.
• Polymorphonuclear leukocyte levels are usually elevated, but they may be within the reference range or low.
• Thrombocytopenia may be present.
• In meningitis, CSF pressures are elevated, with elevated protein levels and low glucose levels.
  • CSF Gram stain yields a sensitivity of approximately 50% in patients with meningococcal meningitis.
  • Detection of meningococcal capsular polysaccharide in CSF may be used for rapid diagnosis. It is sensitive for A and C polysaccharides.
• Gram-negative diplococci may be observed in punch biopsy and needle aspiration specimens of skin lesions or buffy coat preparations. Gram-negative diplococci may also be recovered from joint fluid. Findings on Gram stains of skin lesions remain positive for up to 2 days after the start of antibiotics and form a rapid means of diagnosis, including when meningitis is not present and when spinal fluid culture findings are negative owing to the administration of antibiotics.
• Polymerase chain reaction (PCR) is a rapid method for diagnosing CSF infection. It may not be available commercially in the United States but has been used extensively in the United Kingdom. PCR of spinal fluid yields a sensitivity and specificity of more than 90% in the diagnosis of meningococcal meningitis. It is useful when antibiotics have been administered and can be used to rapidly type strains in developing epidemics. Diagnosis and serogrouping of N meningitidis infection can also be performed on formalin-fixed tissue samples using immunohistochemical analysis and PCR.^9,10

Imaging Studies

• Chest radiography is useful to evaluate for pneumonia and acute respiratory distress syndrome.
• Echocardiography can be used to evaluate for myocardial dysfunction and pericarditis.

Procedures

• Lumbar puncture is used to test for meningitis.
  • Stain and culture of fluid
  • WBC count and differential
  • Total protein level
  • Glucose level

Staging

Evaluate for evidence of other end-organ damage (eg, kidney or hepatic failure) with appropriate blood tests.

Treatment

Medical Care

Hospitalization is required for severely ill patients with fever, headache, and petechial rash.

• Promptly begin antibiotic treatment.
• Suspect fulminant meningococcemia in patient with hypotension and severe coagulation abnormalities. In such cases, monitoring in an intensive care setting is required.
• Other than antimicrobial treatment, supportive measures may be needed to correct circulatory collapse.
• Any adrenal insufficiency requires corticosteroid replacement.

Surgical Care

• Arterial occlusion caused by intravascular clotting in the extremities may require amputation.
• Pericardiocentesis may be required if pericarditis is complicated by tamponade.

Consultations

• Consult an infectious diseases specialist.
• Consultation with a surgeon is needed in gangrene of the extremities.
• Consultation with a hematologist may be needed to manage coagulopathy.
• Consultation with a cardiologist may be needed upon evidence of heart failure or pericarditis.

Activity

Activity is determined by the severity of the presentation. In most severe cases, patients are bed bound.

Medication

Antimicrobial therapy is directed toward treatment of active infection or used prophylactically to protect those exposed to N meningitidis through close contact.

Drugs effective in treating active meningococcal infection include penicillin G, chloramphenicol in patients who are allergic to penicillin, and some cephalosporins (ie, cefotaxime, ceftriaxone, cefuroxime) used to treat pediatric patients. Meningococcal resistance to penicillins has occurred; the mechanism of resistance involves altered penicillin-binding proteins. Sulfonamides have a limited role in meningococcal infections because of the resistance of serogroups A, B, and C; these are not discussed further in this article. The duration of treatment is dictated by clinical response and manifestation of disease, although 10-14 days should be sufficient with a sensitive organism.

Individuals with at least 4 hours of close contact with an index patient during the week before onset of illness are at an increased risk of infection. Individuals at risk include housemates, daycare contacts, cellmates, or individuals exposed to infected nasopharyngeal secretions (eg, through kissing, mouth-to-mouth resuscitation, intubation, suctioning).

Rifampin and ciprofloxacin are commonly used for chemoprophylaxis. Other agents include ceftriaxone and azithromycin. A single dose of intramuscular ceftriaxone may be used in children or adults. Spiramycin is the primary prophylactic regimen used in many European countries. Vaccination with monovalent A; monovalent C; bivalent A-C; or quadrivalent A, C, Y, and W-135 vaccine should be adjunctive to antibiotic chemoprophylaxis in susceptible contacts in epidemics.

The Centers for Disease Control and Prevention (CDC) has issued new (2007) guidelines for the use of meningococcal vaccinations. In addition, in June 2007, the Advisory Committee on Immunization Practices (ACIP) revised its guidelines and advises routine immunization of individuals aged 11-18 years with the quadrivalent conjugate meningococcal vaccine (MCV4), which was first licensed in 2005 in the United States (Menactra, Sanofi Pasteur, Inc.)

Guillain-Barré syndrome has been associated with its use, and this is a relative contraindication.¹¹

The eradication of carriage is also indicated in the index case unless third-generation cephalosporins have been used.

A single intramuscular dose of an oily suspension of chloramphenicol has been shown to be as effective as 5 days of penicillin in persons with meningococcal meningitis, and this may be useful in resource-poor countries.

Antimicrobial agents

These agents are used to treat active meningococcal infection.

Penicillin G (Pfizerpen)

Treat suspected meningococcal disease with a high dose in the initial 48 h of therapy because meningitis is a likely complication.

Dosing

Adult

4 million U IV q4h initial

Pediatric

250,000 U/kg/d IV divided q4h

Interactions

Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in impaired renal function

Chloramphenicol (Chloromycetin)

Used in patients with penicillin allergy. Chloramphenicol binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria. Chloramphenicol-resistant strains are found in Southeast Asia but are rare in the United States.

Dosing

Adult

100 mg/kg/d IV divided q6h; not to exceed 4 g/d

Pediatric

50-100 mg/kg/d IV divided q6h

Interactions

Concurrent use with barbiturates may decrease chloramphenicol serum levels, while barbiturate levels may increase and cause toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum chloramphenicol levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; chloramphenicol levels may be increased or decreased

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (ie, aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum gram-negative activity. Lower efficacy against gram-positive organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.

Dosing

Adult

2 g IV q12h initial; 1 g IV q24h for infections other than meningitis

Pediatric

50 mg/kg IV q12h

Interactions

Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; caution with breastfeeding and penicillin allergy

Cefotaxime (Claforan)

Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms. Has been used successfully in pediatric meningococcal meningitis

Dosing

Adult

2 g IV q6h

Pediatric

50 mg/kg IV q6h

Interactions

Probenecid may increase cefotaxime levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe renal impairment; associated with severe colitis; caution in patients with penicillin allergy

Antimicrobial agents, chemoprophylaxis

These agents protect individuals who are at risk because of close contact with patients who have meningitis.

Rifampin (Rifadin, Rimactane)

Semisynthetic derivative of rifamycin B that inhibits bacterial and mycobacterial RNA synthesis by binding to beta-subunit of DNA-dependent RNA polymerase, thus inhibiting binding to DNA and blocking RNA transcription.

Dosing

Adult

600 mg PO bid for 2 d

Pediatric

<1 month: 5 mg/kg PO q12h for 2 d
>1 month: 10 mg/kg PO q12h for 2 d

Interactions

Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Obtain CBC counts and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur

Ciprofloxacin (Cipro)

Fluoroquinolone. Inhibits bacterial DNA synthesis and, consequently, growth.

Dosing

Adult

500 mg PO single dose prophylaxis

Pediatric

Not recommended

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Seizures; adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum gram-negative activity. Lower efficacy against gram-positive organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins. Has successfully treated pediatric meningococcal meningitis. Useful in special circumstances (ie, relatively penicillin-resistant organisms, hypersensitivity reactions to penicillin or chloramphenicol).

Dosing

Adult

250 mg IM single dose prophylaxis

Pediatric

<15 years: 125 mg IM single dose
>15 years: Administer as in adults

Interactions

Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; caution in breastfeeding and in penicillin allergy

Azithromycin (Zithromax)

Semisynthetic antibiotic structurally similar to erythromycin. Inhibits protein synthesis in bacterial cells by binding to 50S subunit of bacterial ribosomes.

Dosing

Adult

500 mg PO single dose prophylaxis

Pediatric

Not established

Interactions

May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine

Contraindications

Documented hypersensitivity; hepatic impairment; coadministration with pimozide

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution with impaired hepatic function and prolonged QT intervals; caution in patients who are hospitalized, geriatric, or debilitated

Spiramycin (Rovamycine)

Macrolide antibiotic with antimicrobial activity similar to erythromycin and clindamycin. Not commercially available in the United States.

Dosing

Adult

500 mg PO q6h for 5 d

Pediatric

10 mg/kg PO q6h for 5 d

Interactions

May potentiate effects of corticosteroids, digoxin, antihistamines, theophylline, and carbamazepine; may decrease effectiveness of PO contraceptives

Contraindications

Documented hypersensitivity (including hypersensitivity to related medications, eg, erythromycin, azithromycin, clarithromycin, troleandomycin)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in liver disease or bile duct obstruction; associated with rash, itching, bleeding, bloody stools, chest pain, fever, GI distress, and jaundice

Vaccines

These agents may be used to prevent and control outbreaks of serogroup C meningococcal disease.

Meningococcal polysaccharide (Menactra A, C, Y, W-135 diphtheria toxoid conjugate vaccine)

Diphtheria toxoid conjugate vaccine induces the production of bactericidal antibodies specific to capsular polysaccharides of serogroups A, C, Y, and W-135.

Dosing

Adult

0.5 mL IM once, preferably in deltoid region

Pediatric

Not established

Interactions

Immunosuppressive therapies, including irradiation, antimetabolites, cytotoxic drugs, alkylating agents and corticosteroids may reduce immune response to vaccines

Contraindications

Documented hypersensitivity; during course of any acute illness; Guillain-Barré syndrome (GBS) reported following administration of vaccine; persons previously diagnosed with GBS should not receive Menactra vaccine

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

If vaccine administered in persons receiving immunosuppressive therapy, expected immune response may not be obtained; obtain previous immunization history of vaccinee

Meningococcal vaccine (Menomune A/C/Y/W-135)

Quadrivalent vaccine for meningitis prophylaxis. Considered an adjunct to antibiotic chemoprophylaxis.

Dosing

Adult

0.5 mL SC once

Pediatric

<2 years: Do not administer
>2 years: Administer as in adults

Interactions

Immunosuppressive therapies, including irradiation, antimetabolites, cytotoxic drugs, alkylating agents and corticosteroids may reduce immune response to vaccines

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

If vaccine administered in persons receiving immunosuppressive therapy, expected immune response may not be obtained; obtain previous immunization history of vaccinee; caution in acute illness, asplenic patients, and pregnancy

Follow-up

Further Inpatient Care

• Patients with meningococcal disease should complete a course of antimicrobial therapy.
• Manage any complications appropriately.
• Discontinue respiratory isolation precautions after 24 hours of antibiotics.
• Supportive care may be needed, including maintenance of fluid and electrolyte balance and vasoactive drugs in shock (eg, dopamine).
• Monitor blood pressure, urine output, and cardiac function.
• Closely monitor platelets, fibrin, and fibrin degradation products.
• Some studies have shown inconclusive benefits with the use of low-dose steroids.
• No proof shows that unconventional treatments have a significant impact on outcome in meningococcemia.
• Currently, early recognition and appropriate treatment seem to be the optimal methods of improving outcome. However, a bactericidal/permeability-increasing (BPI) protein, a natural protein stored within the neutrophil granules that binds to and neutralizes the effects of endotoxin in vitro, in laboratory animals, and in humans, has shown some promise in clinical trials in children with severe meningococcal sepsis.
• Activated protein C (drotrecogin alfa [Xigris]) may be used for the treatment of severe sepsis in the absence of bleeding.
• Make sure all significant contacts of the patient have been evaluated for prophylaxis, as appropriate.

Further Outpatient Care

• Observe for any late neurologic sequelae.
• Pericarditis can occur while patients are recuperating from meningococcemia. Consider pericarditis in patients with fever and shortness of breath upon minimal exertion during the recovery period.
• Late skeletal deformities are rare, but epiphyseal avascular necrosis and epiphyseal-metaphyseal defects have been described. These usually occur in the lower extremities and result in angular deformity and inequality of leg length.

Transfer

• Once the patient is stabilized, attempt transfer to a tertiary care center because meningococcal sepsis frequently produces multisystem organ dysfunction.

Deterrence/Prevention

• Meningococcal polysaccharide vaccine is used for immunization in individuals older than 2 years. The CDC has issued new (2007) guidelines for the use of meningococcal vaccinations. The tetravalent vaccine contains A, C, Y, and W135 polysaccharides. It is safe and effective. It is useful in aborting outbreaks caused by serogroups represented in the vaccine and therefore should be used in their control. Administer in the following groups:
  • Immunization of military recruits
  • Routine immunization of travelers to areas where epidemics occur (eg, as per Saudi requirements, individuals traveling for the hajj pilgrimage)
  • Immunization of individuals with complement deficiencies or asplenia
• To decrease the risk of infection in the clinical setting, staff caring for patients with known or suspected meningococcal infections should wear masks in addition to standard precautions.
• Antibiotic prophylaxis may be needed if intensive direct contact with patients has occurred in the absence of appropriate precautions.
  • Prophylaxis aims to produce long-term (ie, 3-4 wk) eradication of meningococci from the nasopharynx using short-term antibiotics.
  • Treatment must be initiated immediately if prophylaxis is deemed necessary. The tetravalent vaccine must be administered to all intimate contacts of the index patient.

Complications

• Disseminated intravascular coagulation
• Vasomotor collapse and shock
• Adrenal hemorrhage and insufficiency
• Meningitis
• Cranial nerve dysfunction, particularly involving the sixth, seventh, and eighth cranial nerves
• Seizures or deafness in the acute stages of meningitis
• Postmeningitic epilepsy (rare)
• Coma
• Thrombocytopenia
• Septic arthritis
• Herpes labialis (5-20% of patients with meningococcal disease)
• Immune complex arthritis involving multiple joints
• Pericarditis due to immunologic reaction or toxin
• Tamponade due to pericarditis
• Bacterial endocarditis
• Myocarditis
• Gangrene
• Urethritis and endometritis
• Osteomyelitis
• Purulent conjunctivitis and sinusitis

Prognosis

• Patients with terminal complement component deficiency have a more favorable prognosis.
• A fatal outcome is associated with properdin deficiencies.
• Coagulopathy with partial thromboplastin time greater than 50 seconds or fibrinogen concentration less than 150 µg/dL indicates a poor prognosis.

Miscellaneous

Medicolegal Pitfalls

• In nonoutbreak situations, health care workers who are asymptomatic carriers of N meningitidis do not need to be identified, treated, or removed from patient care.
• Make sure that the local department of health is notified of suspected and/or proven cases of meningococcal infection to assist in evaluation of close contacts and prophylaxis.
• Watch for pericarditis and tamponade in the recovery period.

Special Concerns

• Chemoprophylaxis should be administered to intimate household, daycare center, and nursery school contacts of sporadic cases. Vaccinate household and other intimate contacts.
• The safety of the meningococcal polysaccharide vaccine in pregnant women has not been evaluated, and it should be avoided unless the risk of infection is high. The vaccine is also not routinely indicated for health care workers in the United States. The vaccine, similar to other polysaccharide vaccines, is not immunogenic in children younger than 2 years because of unknown reasons.

Multimedia

Media file 1: Dorsum of the hand showing a petechial rash. Courtesy of Professor Chien Liu.

Media file 2: Petechial lesions on the palm. Courtesy of Professor Chien Liu.

Media file 3: Petechial rash on lower extremities. Courtesy of Professor Chien Liu.

Media file 4: Conjunctival petechiae. Courtesy of Professor Chien Liu.

Media file 5: Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.

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Keywords

meningococcemia, Waterhouse-Friderichsen syndrome, Neisseria meningitidis infection, N meningitidis, meningitis with meningococcemia, acute meningococcal infection, meningitis, meningococci, fulminant meningococcemia, meningococci A, meningococci B, meningococci C, meningococci Y, meningococci W-135, immunoglobulin G2 subclass deficiency, purpura fulminans, meningococcal disease, occult meningococcemia, chronic meningococcemia, meningococcal sepsis

Contributor Information and Disclosures

Author

Mahmud H Javid, MD, Chief, Section of Infectious Diseases, Shifa Hospital, Islamabad, Pakistan
Mahmud H Javid, MD is a member of the following medical societies: Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Shadab Hussain Ahmed, MD, FACP, FIDSA, MACGS, AAHIVS, Associate Professor of Clinical Medicine, State University of New York at Stony Brook; Attending Physician, Division of Infectious Diseases, Director of HIV Prevention Services, Nassau University Medical Center
Shadab Hussain Ahmed, MD, FACP, FIDSA, MACGS, AAHIVS is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and International AIDS Society
Disclosure: Nothing to disclose.

Medical Editor

Mary Nettleman, MD, MS, Chair, Department of Medicine, Michigan State University
Mary Nettleman, MD, MS is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine
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Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
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Managing Editor

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, New Island Hospital
Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
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