Meningococcal disease is an acute, potentially severe illness caused
by the bacteria Neisseria meningitidis. Illness believed to be
meningococcal disease was first reported in the sixteenth century.
The first definitive description of the disease was by Vieusseux in
Switzerland in 1805. The bacteria was first identified in the spinal
fluid of patients by Weichselbaum in 1887.
Neisseria meningitidis is a leading cause of bacterial meningitis and
sepsis in the United States. It can also cause focal disease, such as
pneumonia and arthritis. N. meningitidis is also a cause of epidemics
of meningitis and bacteremia in sub-Saharan Africa.The
World Health Organization estimated meningococcal disease was
the cause of 171,000 deaths worldwide in 2000.
The first monovalent (group C) polysaccharide vaccine was
licensed in the U.S. in 1974. The current quadrivalent vaccine was
licensed in 1978. Meningococcal conjugate vaccine is licensed in
Europe, and has had a major impact on the incidence of type C
meningococcal disease in the United Kingdom. A meningococcal
conjugate vaccine may be available in the United States in the
future.

NEISSERIA MENINGITIDIS
Neisseria meningitidis, or meningococcus, is an aerobic gram-negative
diplococcus, closely related to Neisseria gonorrhea, and to several
nonpathogenic Neisseria species, such as N. lactamica. The organism
has both an inner (cytoplasmic) and outer membrane, separated
by a cell wall. The outer membrane contains several protein
structures which enable the bacteria to interact with the host cells,
as well as other functions.
The outer membrane is surrounded by a polysaccharide capsule
that is necessary for pathogenicity because it helps the bacteria
resist phagocytosis and complement-mediated lysis. The outer
membrane proteins and the capsular polysaccharide comprise the
main surface antigens of the organism.
Meningococci are classified using serological methods based on the
structure of the polysaccharide capsule. Thirteen antigenically and
chemically distinct polysaccharide capsules have been described.
Some strains, often those found to cause asymptomatic nasopharyngeal
carriage, are not groupable, and do not have a capsule.
Almost all invasive disease is caused by one of five serogroups: A,
B, C,Y, and W-135. The relative importance of each serogroup
depends on geographic location, as well as other factors, such as
age. For instance, serogroup A is a major cause of disease in sub-
Saharan Africa, but is rarely isolated in the United States.
Meningococci are further classified on the basis of certain outer
membrane proteins. Molecular subtyping using specialized laboratory
techniques (e.g., pulsed-field electrophoresis) can provide useful
epidemiologic information.
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PATHOGENESIS
Meningococci are transmitted by droplet aerosol or secretions from
the nasopharynx of colonized persons. The bacteria attach to and
multiply on the mucosal cells of the nasopharynx. In a small proportion
(<1%) of colonized persons the organism penetrates the
mucosal cells and enters the bloodstream. The bacteria spread by
way of the blood to many organs. In about 50% of bacteremic persons
the organism crosses the blood-brain barrier into the cerebrospinal
fluid and causes purulent meningitis. An antecedent
URI may be a contributing factor.

CLINICAL FEATURES
The incubation period of meningococcal disease is 3-4 days, with
a range of 2-10 days.
Meningitis is the most common presentation of invasive meningococcal
disease and results from hematogenous dissemination of the
organism. Meningeal infection is similar to other forms of acute
purulent meningitis, with sudden onset of fever, headache, and stiff
neck, often accompanied by other symptoms, such as nausea, vomiting,
photophobia (eye sensitivity to light), and altered mental status.
Meningococci can be isolated from the blood in up to 75% of
persons with meningitis.
Meningococcal sepsis (bloodstream infection or meningococcemia)
occurs without meningitis in 5%-20% of invasive meningococcal
infections. This condition is characterized by abrupt onset of
fever and a petechial or purpuric rash, often associated with
hypotension, shock, acute adrenal hemorrhage, and multiorgan
failure.
Less common presentations of meningococcal disease include
pneumonia (5%-15% of cases), arthritis (2%), otitis media (1%),
and epiglottitis (<1%).
The case fatality rate of invasive meningococcal disease is 9%-
12%, even with appropriate antibiotic therapy. The fatality rate of
meningococcemia is up to 40%. Up to 20% of survivors have permanent
sequelae, such as hearing loss, neurologic damage, or loss
of a limb.

LABORATORY DIAGNOSIS
Invasive meningococcal disease is typically diagnosed by isolation
of N. meningitidis from a normally sterile site. However, sensitivity
of bacterial culture may be low, particularly when performed after
initiation of antibiotic therapy. A Gram stain of cerebrospinal fluid
showing gram negative diplococci strongly suggests meningococcal
meningitis.
Kits to detect polysaccharide antigen in cerebrospinal fluid are
rapid and specific but false negative results are common, particularly
in serogroup B disease. Antigen tests of urine or serum are
unreliable.
Serologic testing (e.g., enzyme immunoassay) for antibodies to
polysaccharide may be used as part of the evaluation if meningococcal
disease is suspected but should not be used to establish the
diagnosis.

MEDICAL MANAGEMENT
The clinical presentation of meningococcal meningitis is similar to
other forms of bacterial meningitis. Consequently, empiric therapy
with broad spectrum antibiotics (e.g., third generation
cephalosporin, vancomycin) should be started promptly after
appropriate cultures have been obtained.
Many antibiotics are effective for N. meningitidis infection, including
penicillin. Few penicillin-resistant strains of meningococcus
have been reported in the United States. Once N. meningitidis
infection has been confirmed, penicillin alone is recommended.

EPIDEMIOLOGY
OCCURRENCE
Meningococcal disease occurs worldwide in both endemic and epidemic
form.

RESERVOIR
Humans are the only natural reservoir of meningococcus. Up to
10% of adolescents and adults are asymptomatic transient carriers
of N. meningitidis, most of which are not pathogenic (i.e, strains
that are not groupable).

TRANSMISSION
Primary mode is by respiratory droplet spread or by direct contact.

TEMPORAL PATTERN
Meningococcal disease occurs throughout the year, However, the
incidence is highest in the late winter and early spring.

COMMUNICABILITY
The communicability of N. meningitidis is generally limited. In
studies of households in which a case of meningococcal disease has
occurred, only 3%-4% of households had secondary cases. Most
households had only one secondary case. Estimates of the risk of
secondary transmission are generally 2-4 per 1000 household
members at risk. However, this risk is 500-800 times that of the
general population.

SECULAR TRENDS IN THE UNITED STATES
Approximately 2,500 to 3,000 cases of meningococcal disease are
reported each year in the United States (0.8-1.3 cases per 100,000
population). In 2002, an estimated 150 deaths due to meningococcal
disease occurred in the United States. Infants <12 months of
age have the highest rates of disease. Incidence of disease
declines in early childhood, increases during adolescence and early
adulthood, then declines among older adults. Although incidence is
relatively low, more cases occur in persons 23-64 years of age than
in any other age group. The proportion of cases among adolescents
and young adults has increased in recent years. During 1992-1998,
28% of reported cases were 12-29 years of age.
The proportion of disease caused by different serogroups has
changed during the last 15 years. From 1988 to 1991, most cases
of meningococcal disease in the United States were due to either
serogroup C or B, and serogroup Y accounted for only 2% of
cases. However, in 1996-2001, serogroup Y accounted for 21% of
cases, with serogroups B and C accounting for 31% and 42%,
respectively. Nongroupable strains accounted for 5% of cases.The
proportion of cases caused by each serogroup varies by age group.
In 2001, 65% of cases among infants aged <1 year were caused by
serogroup B, for which no vaccine is available in the United States.
Among persons 18-34 years of age, 41% of cases were due to
serogroup B, and 25% and 14% were due to serogroups C or Y,
respectively.
Risk factors for the development of meningococcal disease
include deficiencies in the terminal common complement pathway
and functional or anatomic asplenia. Persons with HIV infection
are probably at increased risk for meningococcal disease. Certain
genetic factors (such as polymorphisms in the genes for mannosebinding
lectin and tumor necrosis factor) may also be risk factors.
Family members of a person with meningococcal disease are at
increased risk. Antecedent viral infection, household crowding, and
both active and passive smoking also are associated with increased
risk for meningococcal disease. In the United States, blacks and
persons of low socioeconomic status have been consistently at
higher risk for meningococcal disease. However, race and low
socioeconomic status are likely markers for differences in factors
such as household crowding, rather than risk factors. During outbreaks,
bar or nightclub patronage and alcohol use have also been
associated with higher risk for disease.
Cases of invasive meningococcal disease, including at least 2 fatal
cases, have been reported among microbiologists. Cases have
occurred among persons who work with N. meningitidis isolates
rather than patient specimens.
Recent studies have shown that college freshmen living in dormitories
are at modestly increased risk of meningococcal disease.
However, U.S. college students are not at higher risk for meningococcal
disease than other people of similar age.
In the United States, meningococcal outbreaks account for <5%
of reported cases (95%-97% of cases are sporadic). However, since
1991, the frequency of localized outbreaks has increased. Most of
these outbreaks have been caused by serogroup C. Since 1997,
localized outbreaks caused by serogroup Y and B organisms have
also been reported. See
http://www.cdc.gov/mmwr/PDF/rr/rr4605.pdf for additional information
on the evaluation and management of meningococcal outbreaks.
Large outbreaks of serogroup A meningococcal disease occur in
the African "meningitis belt", an area that extends from Ethiopia to
Senegal. Rates of endemic meningococcal disease in this area are
several times higher than in industrialized countries. In addition,
outbreaks occur every 8-12 years with attack rates of 500-1000
cases per 100,000 population.

MENINGOCOCCAL POLYSACCHARIDE VACCINE
CHARACTERISTICS
The first meningococcal polysaccharide vaccine (MPV) was
licensed in the United States in 1974. The current quadrivalent A,
C,Y,W-135 polysaccharide vaccine (Menomune, manufactured by
Aventis Pasteur) was licensed in 1978, and is the only formulation
currently available in the United States. Each dose consists of 50
µg of each of the four purified bacterial capsular polysaccharides.
The vaccine contains lactose as a stabilizer.
The vaccine is available in single-dose and 10-dose vials. Fifty-dose
vials are no longer available. Diluent for the single dose vial is sterile
water without preservative. Diluent for the 10-dose vial is sterile
water with thimerosal added as a preservative. After reconstitution
the vaccine is a clear colorless liquid.
No vaccine is available in the United States for serogroup B.

IMMUNOGENICITY AND VACCINE EFFICACY
The characteristics of MPV are similar to other polysaccharide
vaccines (e.g., pneumococcal polysaccharide). The vaccine is not
effective among children younger than 18 months of age.The
response to the vaccine is typical of a T-independent antigen, with
an age-dependent response, and poor immunogenicity in children
<2 years of age. In addition, no boost in antibody titer occurs with
repeated doses, the antibody which is produced is relatively lowaffinity
IgM, and "switching" from IgM to IgG production is poor.
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A protective level of antibody is usually achieved within 7-10 days
of vaccination. Among infants and children <5 years of age, measurable
levels of antibodies against serogroup A and C polysaccharides
decrease substantially during the first 3 years following a single
dose of vaccine. In healthy adults, antibody levels also decrease,
but antibodies are detectable as long as 10 years after vaccination.
Although vaccine-induced protection likely persists in school-aged
children and adults for at least 3 years, the efficacy of the group A
vaccine in children <5 years of age may decrease markedly within
this period. In one study, efficacy declined from >90% to <10%
three years after vaccination among children who were aged <4
years when vaccinated. Efficacy was 67% among children who
were >4 years of age at vaccination.

VACCINATION SCHEDULE AND USE
For both children and adults, MPV is administered subcutaneously
as a single 0.5 mL dose. The vaccine can be administered
at the same time as other vaccines but should be given at a
different anatomic site.
Routine vaccination of civilians with MPV is not recommended
because of its relative ineffectiveness in children <2 years
of age (the age group with the highest risk for sporadic disease)
and because of its relatively short duration of protection.
Vaccination with MPV is recommended for certain high-risk
groups, including persons who have terminal complement component
deficiencies and those who have functional or anatomic
asplenia. Research, industrial, and clinical laboratory personnel
who are exposed routinely to N. meningitidis in solutions that
may be aerosolized also should be considered for vaccination.
Laboratory workers should also follow appropriate laboratory precautions
(biosafety level 2), particularly when working with isolates.
Vaccination with MPV may benefit travelers to and U.S. citizens
residing in countries in which N. meningitidis is hyperendemic
or epidemic, particularly if contact with the local population
will be prolonged. Recurrent epidemics of meningococcal
disease occur in the sub-Saharan Africa "meningitis belt,"
(Ethiopia in the east to Senegal in the west). Epidemics in the
meningitis belt usually occur during the dry season (i.e., from
December to June). As a result, vaccination is recommended for
travelers visiting the region during this time. Information concerning
geographic areas for which vaccination is recommended can be
obtained from the CDC Travelers Health website at
http://www.cdc.gov/travel/.
Meningococcal polysaccharide vaccine is recommended for use in
control of meningococcal outbreaks. An outbreak is defined by
the occurrence of three or more confirmed or probable cases of
meningococcal disease during a period of <3 months, with a
resulting primary attack rate of >10 cases per 100,000 population.
For calculation of this threshold, population-based rates are used
and not age-specific attack rates, as have been calculated for college
students. These recommendations are based on experience
with serogroup C meningococcal outbreaks, but these principles
may be applicable to outbreaks caused by the other vaccine-preventable
meningococcal serogroups.
College freshmen, particularly those living in dormitories or residence
halls, are at modestly increased risk for meningococcal disease
compared with persons the same age who are not attending
college. However, ACIP does not recommend routine MPV
vaccination of all college students, freshmen college students, or
students who reside in dormitories. ACIP recommends that
providers of medical care to incoming and current college freshmen,
particularly those who plan to or already live in dormitories
and residence halls, should, during routine medical care, inform
these students and their parents about meningococcal disease and
the benefits of vaccination. ACIP does not recommend that the
level of increased risk among freshmen warrants any specific
changes in living situations for freshmen. College freshmen who
want to reduce their risk for meningococcal disease should either be
administered vaccine by the provider or directed to a site where
vaccine is available. Refer to the ACIP statement on this topic at
http://www.cdc.gov/mmwr/PDF/rr/rr4907.pdf for more information.

REVACCINATION
Revaccination may be indicated for persons at high risk for infection
(e.g., persons residing in areas in which disease is epidemic),
particularly for children who were first vaccinated when they were
<4 years of age. Such children should be considered for revaccination
after 2-3 years if they remain at high risk. Although the need
for revaccination of older children and adults has not been determined,
antibody levels rapidly decline in 2-3 years, and if indications
still exist for vaccination, revaccination may be considered 3-
5 years after receipt of the first dose.
Continued attendance of college, or continued residence in a college
dormitory is not an indication for revaccination in the absence
of another indication (such as asplenia).

ADVERSE REACTIONS FOLLOWING VACCINATION
Adverse reactions to MPV are generally mild. The most frequent
are local reactions, such as pain and redness at the injection site.
These reactions last for 1-2 days, and occur in 5%-10% of recipients.
Systemic reactions, such as headache and malaise are reported
in 2%-5% of recipients, and low grade fever occurs in up to 3%
of vaccinees. Severe reactions to polysaccharide meningococcal
vaccine are uncommon.
All serious adverse events that occur after receipt of any vaccine
should be reported to the Vaccine Adverse Events Reporting
System (VAERS). See the VAERS website at http://www.vaers.org
for information on reporting.

CONTRAINDICATIONS AND PRECAUTIONS TO
VACCINATION
A severe allergic (anaphylactic) reaction to a vaccine component
or following a prior dose of meningococcal polysaccharide
vaccine is a contraindication to receipt of further doses. A moderate
or severe acute illness is reason to defer routine vaccination,
but a minor illness is not. Pregnancy, breastfeeding, and immunosuppression
are not contraindications to vaccination.

VACCINE STORAGE AND HANDLING
MPV should be shipped in insulated containers to prevent exposure
to freezing temperature.Vaccine should be stored at refrigerator
temperature (2-8 degrees  centigrade [35-46 degrees  Fahrenheit]). The vaccine
must not be exposed to freezing temperature.
Single dose vials of MPV must be used within 30 minutes of
reconstitution. Multidose vials must be discarded 35 days after
reconstitution.

SURVEILLANCE AND REPORTING OF
MENINGOCOCCAL DISEASE
Invasive meningococcal disease is a reportable condition in most
states. All healthcare workers should report any case of invasive
meningococcal disease to local and state health departments.

ANTIMICROBIAL CHEMOPROPHYLAXIS
In the United States, the primary means for prevention of sporadic
meningococcal disease is antimicrobial chemoprophylaxis of close
contacts of infected persons. Close contacts include household
members, daycare center contacts, and anyone directly exposed to
the patient's oral secretions (e.g., through kissing, mouth-to-mouth
resuscitation, endotracheal intubation, or endotracheal tube management).
Because the rate of secondary disease for close contacts
is highest during the first few days after onset of disease in the
index patient, antimicrobial chemoprophylaxis should be administered
as soon as possible - ideally within 24 hours after identification
of the index patient. Chemoprophylaxis administered >14
days after onset of illness in the index patient is probably of limited
or no value. Oropharyngeal or nasopharyngeal cultures are not
helpful in determining the need for chemoprophylaxis and may
unnecessarily delay institution of this preventive measure.
Rifampin, ciprofloxacin, and ceftriaxone are all 90%-95% effective
in reducing nasopharyngeal carriage of N. meningitidis and are all
acceptable alternatives for chemoprophylaxis. Systemic antimicrobial
therapy of meningococcal disease with agents other than ceftriaxone
or other third-generation cephalosporins may not reliably
eradicate nasopharyngeal carriage of N. meningitidis. If other agents
have been used for treatment, the index patient should receive
chemoprophylactic antibiotics for eradication of nasopharyngeal
carriage before being discharged from the hospital. Information on
dosage, duration, and route of administration are available in the
meningococcal vaccine ACIP statement at
www.cdc.gov/mmwr/PDF/rr/rr4907.pdf.

SELECTED REFERENCES
Active Bacterial Core Surveillance (ABCs) 2001 provisional
meningococcal surveillance report. Available at
http://www.cdc.gov/ncidod/dbmd/abcs/. Accessed December 30,
2003.
American Academy of Pediatrics. Meningococcal Disease. In:
Pickering L ed. Red Book: 2003 Report of the Committee on Infectious
Diseases. 26th ed. Elk Grove Village, IL: American Academy of
Pediatrics, 2003: 430-6.
Baltimore RS. Meningococcal infections. In: Evans AS and
Brachman PS, eds. Bacterial infections of humans. Epidemiology and
control. 3rd ed. New York, NY: Plenum Medical Book Company;
1998: 459-79.
CDC. Prevention and control of meningococcal disease and
meningococcal disease and college students. Recommendations of
the Advisory Committee on Immunization Practices (ACIP).
MMWR 2000;49(RR-7):1-22.
CDC. Laboratory-acquired meningococcal disease - United States,
2000. MMWR 2002;51:141-4.
Granoff DM, Feavers IM, Borrow R. Meningococcal vaccine. In:
Plotkin SA and Orenstein WA, eds. Vaccines. 4th ed. Philadelphia,
PA: Saunders; 2003: 959-87.
Harrison LH, Pass MA, Mendelsohn AB, et al. Invasive meningococcal
disease in adolescents and young adults. J Am Med Assoc
2001;286(6):694-9.
Jodar L, Feavers IM, Salisbury D, Granoff DM. Development of
vaccines against meningococcal disease. Lancet
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Morley SL, Pollard AJ.Vaccine prevention of meningococcal disease,
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Rosenstein NE, Perkins BA, Stephens DS, et al. Meningococcal
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Van Deuren M, Brandtzaeg,Van der Meer JWM. Update on
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