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Am Fam Physician. 2005;72(10):2049-2056

See editorial on page 1978.

Author disclosure: Dr. Kimmel serves as a speaker and consultant for Sanofi-Pasteur and is on the Family Medicine Immunization Advisory Board for Merck, Inc.

Invasive disease caused by Neisseria meningitidis has an average annual incidence of one case per 100,000 in the United States. The disease can be rapidly fatal or result in severe neurologic and vascular sequelae despite antibiotic therapy. Antibiotic chemoprophylaxis with rifampin, ciprofloxacin, or ceftriaxone is required for household and other close contacts. Although the majority of cases of meningococcal disease are sporadic, outbreaks can occur, and vaccination of the affected population often is necessary. Serogroup B accounts for the highest incidence of disease in young infants but is not contained in any vaccine licensed in the United States. Adolescents and young adults 15 to 24 years of age have a higher incidence of disease and a higher fatality rate than other populations. Because 70 to 80 percent of these infections in the United States are caused by meningococcal serogroups C, Y, and W-135, which are contained in the tetravalent meningococcal vaccines, they are potentially preventable. The U.S. Food and Drug Administration recently approved a meningococcal conjugate vaccine containing serogroups A, C, Y, and W-135. This T-cell–dependent vaccine induces bactericidal antibody production and promotes immunologic memory that should result in a longer duration of immunity. The Advisory Committee on Immunization Practices recommends that this vaccine be given to 11- and 12-year-old adolescents, to adolescents entering high school, and to college freshmen living in dormitories. The vaccine also may be given to persons 11 to 55 years of age who belong to certain high-risk groups.

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.

Clinical recommendationsEvidence ratingReferencesComments
Prescribe antimicrobial chemoprophylaxis to household and other close contacts of patients with meningococcal disease.B1 Based on consistent data from observational studies
For meningococcal outbreaks caused by serogroups A, C, W-135, and Y, use MCV4 or MPSV4.B1 Based on consistent data from observational studies
Children 11 to 12 years of age, adolescents entering high school, and college freshmen living in dormitories should receive MCV4 routinely.B1, 35 Based on consistent data from observational studies
Military recruits, asplenic persons, and travelers to high-risk areas should receive MCV4.C1, 35


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

AntibioticAge rangeDosage and routeDuration
Rifampin* (Rifadin)Children younger than one month5 mg per kg orally every 12 hours2 days
Children older than one month10 mg per kg (up to 600 mg) orally every 12 hours2 days
Adults600 mg orally every 12 hours2 days
Ciprofloxacin† (Cipro)Adults500 mg orallySingle dose
Ceftriaxone (Rocephin)Patients younger than 15 years125 mg intramuscularlySingle dose
Patients 15 years and older250 mg intramuscularlySingle dose

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

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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 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.2527 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


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 323,33 compares the composition and administration of MPSV4 and MCV4.

MPSV4 (Menomune)MCV4 (Menactra)
Antigenic components A, C, Y, W-135 purified polysaccharides50 mcg each polysaccharide4 mcg each polysaccharide conjugated to 48 mcg diphtheria toxoid protein carrier
Preservative or adjuvantThimerosal 1:10,000 added as preservative to diluent in multidose vial; single dose is preservative-free.None; only single-dose vials
Dosage and administration0.5 mL subcutaneously0.5 mL intramuscularly
StorageBetween 2ºC and 8ºC (35ºF and 46ºF)23 Between 2ºC and 8ºC33


Table 41,35 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

Population classificationApproximate agePreferred vaccine type
Routine vaccination
Adolescents at routine checkup11 to 12 yearsMCV4 (Menactra)
Adolescents (who have not previously received MCV4) before high school entry15 yearsMCV4
Patients at increased risk for meningococcal disease
College freshmen living in dormitories17 to 24 yearsMCV4 (MPSV4 [Menomune] acceptable)
Military recruits18 years or olderMCV4 (MPSV4 acceptable)
Microbiologists routinely exposed to Neisseria meningitidisAdultMCV4 (MPSV4 acceptable)
Persons with anatomic or functional asplenia or terminal complement deficienciesTwo to 10 years of age or older than 55 yearsMPSV4
11 to 55 years of ageMCV4
Travelers to countries where N. meningitidis is hyperendemic or epidemic, especially sub-Saharan Africa or Saudi ArabiaTwo to 10 years of age or older than 55 yearsMPSV4
11 to 55 years of ageMCV4
Patients with HIV*11 years35 or older (elective)MCV4 or MPSV4


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.


The Vaccine Adverse Event Reporting System has received notification of five cases of Guillain-Barré syndrome (GBS) that have occurred in individuals 17 to 18 years of age within 14 to 31 days of receiving MCV4. The CDC states that there is not sufficient evidence at this time to determine a causal relationship between GBS and MCV4, and no changes have been made to current recommendations. However, it may be reasonable to withhold the vaccine in low-risk individuals who have a history of GBS. The CDC recommends that adolescents and their parents or guardians be informed of this ongoing investigation as part of the consent process for vaccination with MCV4.

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