From July to August 1995, there were 4 cases of laboratory-confirmed Neisseria meningitidis and 1 additional probable case reported in Miami-Dade County, Florida. Cases developed in individuals staying at 2 hotels. The index case developed fever, and 2 other children who had played with the index case developed symptoms. One of these children died. N meningitidis type B serogroup was isolated from blood cultures taken from the child who died. N meningitidis was noted on gram stain of the CSF of the child who did not die. Two additional cases occurred 5 weeks later. A 17-year-old had provided child care at one of the hotels, and a child who the 17-year-old had cared for developed the disease. Chemoprophylaxis was offered to employees and guests at the 2 hotels as well as to the families of the last 2 cases.^[30]

Most cases of meningococcal disease are sporadic.^[31] However, the number of outbreaks increased in the 1990s. Seventy-six outbreaks were reported in the United States from July 1994 to June 2002, with 48 caused by serogroup C, 19 by serogroup B, and 9 by serogroup Y. Fifty-three percent or 26 were community-based outbreaks, whereas the rest were organization-based -- 13 (25%) in colleges, 19 (38%) in schools, and 9 (18%) in nursing homes.^[31,32]

Incidence

The incidence in the United States is 0.5-1.5/100,000 or an estimated 1400-2800 cases annually, with infants having the highest incidence.^[32] There is a variation in incidence with peaks in 10- to 15-year cycles. The most recent peak was in the 1990s. From 1991 to 2002, infants younger than age 1 had the highest rate of meningococcal disease at 9.2/100,000 followed by 11- to 19-year-olds at 1.2/100,000. Sixty-two percent of meningococcal disease occurred in ages ≥11.^[33] The majority of cases occur from winter to early spring, although meningococcal disease can occur year-round.^[34,35] The case-fatality rate equals 10% to 14% (mmw54 RR-7), but the most deadly is meningococcemia without meningitis with a case-fatality rate of 40%.^[32,34,35]

The exposure factors for N meningitidis infection include the following:^{[31-32, 34]}

1. Concomitant upper respiratory infections;
   
   
2. Crowding;
   
   
3. Climate;
   
   
4. Low socioeconomic status;
   
   
5. Bar patronage;
   
   
6. College students living on campus;
   
   
7. Microbiologists working with the pathogen;
   
   
8. Travelers to areas of high endemicity;
   
   
9. Military recruits; and
   
   
10. Active and passive smoking as well as alcohol use.

The host factors for N meningitidis infection include the following:^{[31-32, 34]}

• Race/ethnicity -- higher risk for African Americans;
  
  
• Chronic disease -- antibody deficiency syndromes, malignancies, chemotherapy, immunodeficiency, HIV infection, functional asplenia, congestive heart failure, diabetes mellitus, and organ transplantation;
  
  
• Male gender < 45 years; and
  
  
• Female gender > 45 years.

Postinfection sequelae are common in survivors at a rate of 11% to 19%. These include neurologic disability, amputation, and hearing loss.^[32,34]

Pathogenic strains have a polysaccharide capsule, of which 5 serogroups (A, B, C, W-135, and Y) cause invasive disease.^[33,34] Outbreaks due to serotype A are rare in the United States, but occur in 8- to 10-year cycles in the meningitis belt in sub-Saharan Africa. Serotype B is common in the United States and responsible for 50% of invasive infections in infants and 33% of meningococcal infections in other age groups in the United States.^[33,34,36] Serotype C causes 33% of cases in the United States with occasional outbreaks in Africa. It is endemic in North America and Europe.^[36] Serotype W-135 is rare in the United States. It was responsible for the outbreak in Saudi Arabia during the annual Hajj pilgrimage in 2000. Serotype Y also has caused numerous cases in the United States, 33% since the 1990s, and is associated with pneumonia and common in the elderly.^[33,35,36]

Asymptomatic nasopharyngeal carriage can be brief, intermittent, or long term. It is highest in adolescents and young adults, and produces an antibody response leading to immunity against that strain.^[33] Invasive disease typically occurs 2 weeks after acquiring a new strain.^[31]

Pathogenesis

N meningitidis is a gram-negative aerobic diplococcus that is only pathologic in humans.^[32-35] Transmission is by direct contact with large droplet respiratory secretions.^[31,32]

Clinical Manifestations

The incubation period is 3-4 days (range, 2-10 days).^[33,37] Meningitis symptoms are present in 50% of patients. In infants, symptoms may be nonspecific. Meningococcemia presents with fever, petechial or purpuric rash, and can rapidly progress to hypotension, adrenal hemorrhage, and multiorgan failure (Table 8).^[35]

Table 8. Clinical Manifestations of Neisseria meningitidis*

*1992-1996 data US Centers for Disease Control and Prevention (CDC)
From: Meningococcal disease. In: Epidemiology and Prevention of Vaccine Preventable Diseases: The Pink Book. 10th ed. Atlanta: CDC; 2007:271-282. Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/mening.pdf Accessed October 31, 2007.

Diagnosis

Diagnosis requires the presence of N meningitidis in sterile body fluid or bacterial DNA by PCR.^[33,34] Blood cultures are positive in 75% of individuals with meningitis, and gram stain of CSF may show gram-negative diplococci.^[33,34] Polysaccharide antigen detection kits are available, but these have high false positives for serogroup B infections.^[33-35]

Treatment

Treatment is supportive, including circulatory and ventilator support as warranted. Prompt administration of broad-spectrum antibiotics is the mainstay of treatment after specimen collection. Penicillin alone can be used after confirmation of the diagnosis, as resistance studies have demonstrated that there are few penicillin-resistant strains in the United States.^[33-35] Complications include septic shock, ARDS, and disseminated intravascular coagulation (DIC). Treatment with activated protein C may be beneficial.^[33] In a Cochrane review of the use of steroids in patients with bacterial meningitis, the evidence demonstrated that patients who received steroids had decreased mortality, hearing loss, and other neurologic sequelae. Patients should receive a loading dose of 0.6 mg/kg at the same time or before giving antibiotics.^[37] Administration of steroids remains controversial.

Prevention

There are 2 vaccines licensed for use in the United States. See Table 9 for vaccine recommendations. MPSV4 (Menomune, Sanofi Pasteur) is an A/C/W-135/Y polysaccharide vaccine. Efficacy is present for all 4 components. A study demonstrated short-term efficacy for the C component in military recruits of 89%, and prevention of disease from serogroup C during an outbreak in Texas was 85% for 2- to 29-year-olds. Duration of protection is unclear with detection of antibody levels in adults after 10 years, although clinical protection decreased over time.^[32] Serogroup A caused antibody responses for age 3 months or older, but was not as effective as that achieved at age 4-5 years. Serogroup C caused a poor antibody response in age ≤18-24 months. However, the vaccine efficacy for these 2 serogroups is ≥85% for school-aged children and adults. Serogroups Y and W-135 are immunogenic for age >2 years.^[32]

Table 9. Recommended Vaccine Schedule for Neisseria meningitidis

SQ = subcutaneously; IM = intramuscularly
*Menomune (Sanofi Pasteur, Swiftwater, Pennsylvania)
^†Menactra (Sanofi Pasteur)
^‡MCV4 is preferred; MSPV4 is acceptable. Revaccination may be considered after 5 years with 1 dose of MCV4 if previously vaccinated with MSPV4 and continued high risk.
^§IM deltoid muscle with needle length appropriate for size (minimum, 1 in)
From: Prevention and control of meningococcal disease -- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005;54:1-21. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5407a1.htm Accessed May 6, 2007.
From: US Centers for Disease Control and Prevention (CDC). Meningococcal disease. In: Epidemiology and Prevention of Vaccine Preventable Diseases: The Pink Book. 10th ed. Atlanta: CDC; 2007:271-282. Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/mening.pdf Accessed October 31, 2007.

Adverse reactions to MPSV4 vaccine consist of pain and redness at the injection site and are common, but mild and last 1-2 days.^[32] Fever occurs in 5% of recipients, more commonly in infants, and severe adverse events are rare with a systemic allergic response rate of 1 case/million and anaphylaxis at < 1 case/million. Neurologic reactions, such as seizures and paresthesias, have occurred infrequently.^[32]

In the United States in 2005, a new quadrivalent meningococcal conjugate vaccine MCV4 (Menactra, Sanofi Pasteur) was licensed for 11- to 55-year-olds. Vaccine efficacy trials have not been completed, although the rise in titers was >98% for all serogroups in vaccinees 11-18 years and >97% in vaccinees 18-55 years, and persisted in those age 14-21 years when tested 3 years later. Both vaccines may be used to control outbreaks.^[32]

Three serogroup C conjugate vaccines are licensed for use in the United Kingdom, Europe, Australia, and Canada. In the United Kingdom these are Meningtec (Wyeth-Lederle Vaccines and Pediatrics, Pearl River, New York), Menjugate (Chiron Vaccines, Siena, Italy), and NeisVac (Baxter Hyland Immuno, Beltsville, Maryland).^[32,33]

There are no licensed serogroup B vaccines available in the United States. Endemic serogroup B outbreaks are caused by divergent strains requiring a polyvalent vaccine.^[33] Several B vaccines have been developed with only modest success in immunogenicity.^[31,33]

Contraindications to the vaccines are hypersensitivity reactions to any of the vaccine components. Minor illness, breastfeeding, and pregnancy are not contraindications, and immunocompromised individuals may receive the vaccine. No safety data are available for MPSV4 and MCV4.^[34]

Household contacts have a case rate of 0.4%, and chemoprophylaxis should be given to prevent secondary disease. Chemoprophylaxis should be given to household members, day care contacts, and anyone with direct contact with secretions.^[34] Drugs used for chemoprophylaxis reduce the nasal carriage rate 90% to 95%. These drugs should be given as soon as possible after the diagnosis of the index case and are ineffective after 14 days (Table 10).^[31,32] Chemoprophylaxis should be given to those who have previously received meningococcal vaccine because vaccines are not 100% protective and immunity decreases over time.^[31]

Table 10. Schedule for Chemoprophylaxis Against Meningococcal Disease

IM = intramuscularly
*Not recommended for pregnant women because it is teratogenic in laboratory animals. Because the reliability of oral contraceptives may be affected by rifampin therapy, consideration should be given to using alternative contraceptive measures while rifampin is being administered.
^†Not usually recommended for persons aged <18 years or for pregnant or lactating women because it causes cartilage damage in immature laboratory animals. Can be used for chemoprophylaxis of children when no acceptable alternative therapy is available. (Source: Burstein G, Berman S, Blumer J, Moran J. Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: does the benefit outweigh the risk? Clin Infect Dis. 2002;35[suppl2]:S191-199).
From: Gardner P. Prevention of meningococcal disease. N Engl J Med. 2006;355:1466-1473.
From: Prevention and control of meningococcal disease -- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005;54:1-21. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5407a1.htm Accessed May 6, 2007.