Neisseria meningitidis infects only humans; it causes 1,400 to 2,800 cases of invasive disease in the United States each year, with an annual incidence of approximately one case per 100,000 persons.^1,2 N. meningitidis is the most common cause of bacterial meningitis in children and young adults in the United States and the second most common cause of community-acquired meningitis in adults.³ Death occurs in 10 to 14 percent of patients despite treatment, and sequelae such as limb loss, neurologic disabilities, and hearing loss occur in another 11 to 19 percent.^1,2 New recommendations regarding prevention and chemoprophylaxis for meningococcal disease are emerging, and a tetravalent conjugate vaccine was recently approved.

Transmission

N. meningitidis is a gram-negative diplococcus that colonizes the upper respiratory tract of 10 percent or more of humans and is transmitted from person to person by aerosol droplets or contact with respiratory tract secretions (e.g., by kissing, sharing drinking glasses, mouth-to-mouth resuscitation, or intubation management).⁴ Less than 2 percent of young children are asymptomatic carriers of N. meningitidis,⁵ and children younger than two years have the highest rate of disease.¹ However, more than 60 percent of meningococcal cases in the United States occur in persons 11 years or older.¹ Most cases of meningococcal disease are sporadic and are not linked to outbreaks; however, outbreaks have occurred in communities and secondary schools.^6,7 The disease also has occurred in travelers returning from Mecca, Saudi Arabia;⁸ in microbiology laboratory workers;⁹ and in persons who had been on a long-distance flight.¹⁰

Changing Epidemiology

The 13 capsular serogroups of N. meningitidis shift over time, geographic location, and age group. Serogroups A, B, C, W-135, and Y cause almost all cases of human disease.⁴ Serogroup A disease is rare in the United States, although it is the most common cause of meningococcal infection in sub-Saharan Africa.² Serogroup B is the most common cause of sporadic disease in some European countries, and has caused outbreaks in Canada and the Pacific Northwest.⁴ In the United States, serogroup B accounts for more than one half of meningococcal cases in infants younger than one year.^1,2,11 Serogroup Y caused only 2 percent of disease from 1989 to 1991, but accounted for 37 percent of cases from 1997 to 2002.¹ Serogroup Y causes a higher proportion of pneumonia than serogroups B and C (14 versus 2 percent). Serogroup Y also causes a higher percentage of meningococcal disease than other serogroups in blacks (50 versus 23 percent)¹² and in patients 65 years or older.¹¹ The median age of female patients with serogroup Y disease (42 years) is significantly higher than male patients with the disease (18 years).¹²

An outbreak is defined as three or more cases of meningococcal disease in less than three months occurring among persons in an organization or community who are not close contacts, and with a primary disease attack rate of at least 10 per 100,000 persons.¹ Outbreaks account for 2 to 3 percent of meningococcal disease.¹³ Serogroup C caused 26 of 42 outbreaks reported to state health departments from 1994 to 1997.¹⁴ During the 1990s, serogroup C also was associated with 47 percent of cases of meningococcal disease in persons 15 to 24 years of age in Maryland, whereas serogroups Y, B, and W-135 accounted for 31, 12, and 5 percent of cases, respectively.¹⁵ In the same study,¹⁵ serogroups C, Y, and B accounted for 57, 29, and 14 percent, respectively, of the 14 of 16 fatalities in which the serogroup was known.

Antimicrobial Chemoprophylaxis

Close contacts of patients with invasive meningococcal disease should receive antimicrobial chemoprophylaxis, regardless of whether the disease is sporadic or occurs in an outbreak setting.¹ Household contacts have a 500 to 800 times greater rate of disease and should be given prophylaxis, ideally within 24 hours after identification of the index patient.¹ Child care center contacts and anyone exposed to the patient’s oral secretions also should be given chemoprophylaxis (Table 1). ¹ Travelers seated next to an indexz patient on a flight lasting eight hours or more or those who had direct contact with an index patient’s respiratory secretions also should receive prophylaxis.¹ Because penicillin does not eradicate nasopharyngeal carriage, patients with invasive meningococcal disease who are treated with penicillin also should receive prophylaxis before hospital discharge.¹⁶

High-Risk Groups

A study¹⁷ of meningococcal disease in Maryland from 1992 to 1997 found that college students residing on campus had at least a three times greater relative risk for contracting meningococcal infection than students living off campus. A subsequent 1998 to 1999 nationwide survey¹³ of state health departments and college health centers found that the incidence of meningococcal disease for freshman living in dormitories was 5.1 per 100,000, compared with 0.7 per 100,000 for all undergraduates combined and 1.4 per 100,000 18- to 23-year-old patients in the general population. Serogroups C (48 percent), B (28 percent), Y (19 percent), and W-135 (1 percent) were responsible for the infections.¹³

Dormitory or barracks-style living brings persons together from different geographic areas with diverse strains of meningococci, some highly virulent. A British university study¹⁸ found that the carriage rates for meningococci increased rapidly among students living in dormitories (from 6.9 percent on day 1 to 23.4 percent on day 4). Average carriage rates increased from 14 percent in October to 34 percent by December.¹⁸ Male sex, smoking, visits to bars in dormitories and night-clubs, intimate kissing, and coeducational halls also were identified as risk factors for acquisition of meningococci.¹⁸ Other potential risk factors for meningococcal disease among students include white race, use of radiator heat, and recent upper respiratory infection.^17,19

Approximately 70 to 80 percent of the serogroups most likely to cause meningococcal disease in adolescents and young adults are potentially preventable by the tetravalent meningococcal vaccine. The majority of U.S. states mandate education about meningococcal disease and vaccines for students attending public (and private, in some states) colleges and universities or for all full-time students residing on campus.^1,20

Meningococcal Vaccines

Meningococcal vaccines can be polysaccharide or conjugated. Polysaccharide vaccines are T-cell independent and stimulate mature B lympho­cytes that produce antibodies but not immunologic memory. Conjugated vaccines covalently link the polysaccharide to a carrier protein, making them T-cell dependent and capable of stimulating immunologic memory that results in a greater and longer lasting immunity. Characteristics of the two types of vaccines are summarized in Table 2.^4,21,22

TETRAVALENT MENINGOCOCCAL POLYSACCHARIDE VACCINE

The tetravalent meningococcal polysaccharide vaccine (MPSV4 [Menomune]) contains polysaccharide antigens to meningococcal groups A, C, Y, and W-135. It is T-cell independent and not effective in children younger than two years but has effectiveness as high as 85 percent for serogroups A and C in school-age children and in adults.¹ Immunity decreases about three years after initial administration. This is measured by declining antibody levels to groups A and C, especially in children younger than five years.²³ The serogroup B antigen is not contained in the vaccine because its capsular polysaccharide is poorly immunogenic in humans,¹⁶ and serogroup B anticapsular antibodies have poor complement bactericidal activity.⁴ The capsular polysaccharide of serogroup B also has structural homology to human embryonic neural tissue.²⁴ Consequently, MPSV4 does not confer protection against serogroup B disease, which is responsible for about 30 percent of all invasive meningococcal disease in the United States.¹

A single immunizing dose is 0.5 mL given subcutaneously. The multidose formulation of the vaccine contains thimerosal and should not be given to anyone sensitive to this or any other vaccine constituent.²³ Pain, tenderness, and redness at the injection site are the most common local reactions; fever, malaise, and headache occur in a small percentage of patients.²³ Severe adverse events including allergic reactions, seizures, and paresthesias are rare, occurring in fewer than 0.1 out of 100,000 doses.¹⁴

MENINGOCOCCAL C CONJUGATED VACCINES

Meningococcal conjugate vaccines containing serogroup C or serogroups C and A are safe and stimulate immunologic memory, although they are not available in the United States.^25–27 In November 1999, the United Kingdom began an immunization program using meningococcal serogroup C conjugate (MCC) vaccine, resulting in a 76 percent reduction of group C cases in adolescents between January 1 and September 30, 2000.²⁸ Vaccine effectiveness was estimated at 97 percent for adolescents and 92 percent overall for toddlers and adolescents. ²⁸A four-year follow-up study²⁹ demonstrated vaccine effectiveness of greater than 82 percent in all children who had received MCC vaccines in the catch-up program at five months to 18 years of age. Vaccination was 66 percent effective in infants vaccinated at two to four months of age, but immunity waned after one year.²⁹By November 2000, more then 70 percent of persons younger than 18 years in the United Kingdom had been immunized against meningococcal serogroup C.²¹ Oropharyngeal samples obtained from students 15 to 17 years of age demonstrated a 66 percent decrease in carriage of serogroup C meningococci from 1999 to 2000, but there was no significant change in carriage of serogroups B, Y, and W-135.²¹ Another study²² subsequently estimated an overall 67 percent reduction in the rate of confirmed meningococcal serogroup C disease in unvaccinated children and estimated vaccine effectiveness at 96 percent. Although the confidence intervals for the younger age groups were relatively wide, this study supports the development of herd immunity with the MCC vaccine.²²

TETRAVALENT MENINGOCOCCAL CONJUGATE VACCINE

A meningococcal vaccine containing polysaccharide serogroups A, C, Y, W-135 conjugated to diphtheria toxoid (MCV4 [Menactra]) has been approved by the U.S. Food and Drug Administration for active immunization of adolescents and adults 11 to 55 years of age.³⁰ A small study³¹ of this vaccine demonstrated it to be immunogenic in adults and acceptably tolerated. A study³² comparing vaccine doses of 1, 4, and 10 mcg for each of the four polysaccharide serogroups conjugated to diphtheria toxoid found it to be modestly immunogenic in infants, with 47 to 83 percent experiencing some redness, induration, or pain at the injection site after one or more primary series doses. There was no increase in local reaction rates with increasing numbers of primary doses, and most reactions were mild or moderate.³² Studies by the manufacturer indicate that the most commonly reported adverse reactions with MCV4 in adolescents (11 to 18 years of age) and adults (18 to 55 years of age) were local pain, headache, and fatigue.³³ Local reactions other than redness in adults were more common in MCV4 recipients than MPSV4 recipients, but most reactions were mild.³³

A recent U.S. study³⁴ compared MCV4 with MPSV4 in two- to 10-year-old children. The MCV4 had a similar safety profile and produced a higher and more persistent serum bactericidal antibody response against serogroups A, C, Y, and W-135 than did MPSV4.³⁴ Protective antibody levels usually are obtained seven to 10 days after vaccination.¹ Table 3^23,33 compares the composition and administration of MPSV4 and MCV4.

Indications

Table 4^1,35 summarizes the 2005 recommendations from the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC).¹ It is recommended that MCV4 be given at the 11- to 12-year-old preadolescent visit, to adolescents entering high school, and to college freshman living in dormitories.¹ Although recommendations for catch-up vaccinations have not been made, it is the goal by 2008 that all adolescents will be vaccinated with MCV4 beginning at 11 years of age.¹

Cost-Effectiveness

A recent study³⁶ analyzed the cost-effectiveness of immunizing different age groups in the United States with MCV4. Comparisons were made among immunizing infants at two, four, and six months of age; toddlers at one year of age; and preadolescents with one dose at 11 years of age. The last strategy was projected to prevent 270 cases and 36 deaths over 22 years at a cost of $633,000 per meningococcal case prevented and $121,000 per life-year saved.^35,36 However, the devastation of the disease and the anxiety that often accompanies the presence of the disease in the community are thought to justify the cost of prevention.