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Bruce MG, Rosenstein NE, Capparella JM, Shutt KA, Perkins BA, Collins M. Risk Factors for Meningococcal Disease in College Students. JAMA. 2001;286(6):688–693. doi:10.1001/jama.286.6.688
Author Affiliations: Meningitis and Special Pathogens Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Ga (Drs Bruce, Rosenstein, and Perkins and Ms Shutt); American College Health Association, Baltimore, Md (Ms Capparella); and Student Health Services, University of Pennsylvania, Philadelphia (Dr Collins).
Context Elevated rates of meningococcal disease were noted among 18- to 22-year-olds
in the mid-1990s. However, national data on rates of meningococcal disease
in US college students were not collected until 1998.
Objectives To determine rates of meningococcal disease in US college students and
to identify risk factors for meningococcal disease in this population.
Design, Setting, and Patients Prospective surveillance study with nested case-control study of US
college students with meningococcal infection from September 1, 1998, to August
31, 1999. Fifty state health departments and 231 college health centers participated.
Main Outcome Measures Incidence of and risk factors for meningococcal disease in US college
Results Ninety-six cases of meningococcal disease were identified. The incidence
rate for undergraduates was 0.7 per 100 000 persons vs 1.4 per 100 000
for the general population of 18- to 23-year-old nonstudents (P<.001). Freshmen living in dormitories had the highest incidence
rate at 5.1 per 100 000. Of the 79 case-patients for whom information
was available, 54 (68%) had illness due to vaccine-preventable meningococcal
serogroups. On multivariable analysis of case-control study data, freshmen
who lived in dormitories had an elevated risk of meningococcal disease (matched
odds ratio, 3.6; 95% confidence interval, 1.6-8.5; P
= .003) compared with other college students.
Conclusions Freshmen who live in dormitories have an independent, elevated risk
of meningococcal disease compared with other college students. Use of the
currently available quadrivalent polysaccharide vaccine among college students
could substantially decrease their risk of meningococcal disease.
Neisseria meningitidis causes an estimated
2400 cases of invasive meningococcal disease annually in the United States
with a case fatality rate of 10% to 15%.1 Meningococcal
disease has traditionally been considered a disease of children; however,
it is now a leading cause of both meningitis and sepsis in young adults.2 Since 1990, the number of meningococcal disease outbreaks
has increased including on college campuses3
but outbreaks represent only 2% to 3% of overall meningococcal disease.4 Over the past 10 years, rates of meningococcal disease
among adolescents and young adults have increased5
while rates among college students were not available.
In September 1997, the American College Health Association (ACHA) issued
a statement recommending that "college students consider vaccination against
potentially fatal meningococcal disease" with the currently available quadrivalent
meningococcal polysaccharide vaccine (serogroups A, C, Y, and W-135).6 This led many colleges and parents to advocate increased
use of vaccine for college students. At that time, the risk of meningococcal
disease in college students was not well understood, and guidelines from the
Advisory Committee on Immunization Practices (ACIP) and the American Academy
of Pediatrics (AAP) recommended the use of meningococcal vaccine for control
of outbreaks but did not recommend routine use of meningococcal vaccine in
civilians because of its relative ineffectiveness in children 2 years or younger,
among whom risk of endemic disease is highest, and the relatively short duration
In 1998, the Centers for Disease Control and Prevention (CDC), in conjunction
with the Council of State and Territorial Epidemiologists (CSTE) and ACHA,
began nationwide surveillance for meningococcal disease in college students
and initiated a case-control study to determine both incidence and risk factors
for meningococcal disease in US college students. These studies, along with
other recently published data,9-11
have been used by both ACIP and AAP as the basis for new recommendations.12,13
In collaboration with CSTE, surveillance for meningococcal disease in
college students was conducted in all 50 states from September 1, 1998, through
September 1, 2000. A US college student case was defined as having clinically
compatible disease with isolation of N meningitidis
from a normally sterile site, a positive meningococcal antigen test in cerebrospinal
fluid, or clinical purpura fulminans in the absence of a positive blood culture
in an undergraduate or graduate student attending a 2-year, 4-year, or vocational
college or university in the United States. Surveillance continued through
September 1, 2000, but only patients meeting the above case definition identified
between September 1, 1998, and August 31, 1999, are reported in this analysis.
State health department surveillance officers were prospectively asked
to review all meningococcal disease cases occurring in persons 17 to 30 years
of age to determine whether the patient was a college student. A brief supplemental
case report form with information on class level, type of housing, and method
of diagnosis was forwarded to the CDC for all college student cases along
with the routine surveillance form used by the state health department. In
addition to state health departments, 231 college health centers within the
ACHA network also conducted prospective and retrospective surveillance. After
identifying a case at a student health center, case managers notified both
the state health department and the ACHA study coordinator to whom they sent
a case report form containing demographic and clinical information. Information
from state health departments and college health centers was transferred onto
a standardized form and entered into an Epi-Info (version 6.04, CDC, Atlanta,
Numerator data for 18- to 23-year-old nonstudents were obtained from
the National Electronic Telecommunications System for Surveillance (NETSS),
the system whereby meningococcal disease cases are reported to the CDC. The
NETSS case definition is identical to the case definition stated above. The
number of cases in 18- to 23-year-old nonstudents was determined by taking
the number of cases in all people 18 to 23 years of age reported in NETSS
and subtracting the number of 18- to 23-year-old college student cases reported
through our enhanced surveillance.
Multiple sources were used to determine population denominators. Census
data from 1998 were used to estimate the US population of 18- to 23-year-olds.14 Data from the National Center for Education Statistics
(NCES) at the US Department of Education15
from 1996 to 1997 were used to determine the college student population. Both
US Census data and the NCES data were used to determine the population of
18- to 23-year-old nonstudents.14,15
Undergraduate students were categorized as first-time freshmen (2 285 001)
or non–first-time freshmen (12 612 267). In this article,
the term "freshmen" will refer to first-time freshmen, defined as students
who have completed high school and are entering college for the first time.
Data from the 1995 National College Health Risk Behavior Survey16
and the Higher Education Research Institute at the University of California,
Los Angeles,17 were used to estimate the number
of students living in dormitories. We did not define the variables "dormitory,"
"fraternity," or "sorority," but instead relied on how they were defined by
the given college or university. These 3 variables were mutually exclusive.
We performed a matched case-control study to examine risk factors for
meningococcal disease among college students. For the case-control study,
an eligible case-patient was defined as a student with clinically compatible
disease and a positive diagnostic test result between September 1, 1998, and
April 30, 1999.
An eligible control was defined as a student enrolled at a US college
between September 1998 and April 1999 without history of prior meningococcal
vaccination. Three controls were matched to each case-patient by college,
sex, and undergraduate vs graduate status. Upon identification of a college
student case, the study coordinator in conjunction with both the student health
service representative and the school database manager generated a list of
all currently enrolled students at the institution. Controls were then randomly
selected for each case.
Interviews occurred within 2 weeks of receiving a case report, which
occurred a mean of 62 days after diagnosis. After obtaining informed consent,
we interviewed each case-patient and control (or surrogate for case-patients
who had died) by telephone using a standardized questionnaire. The questionnaire
was pretested and took 15 to 20 minutes to complete. Data collected included
basic demographics: class level, housing, active and passive smoking, recreational
drug and alcohol use, medical history, and exposure to large groups of people.
As a reference period, we asked about the month preceding the onset of illness
for case-patients and about the same calendar month in the matched controls.
Telephone interviews were conducted by the project coordinator and staff.
The telephone was allowed to ring 10 times before the control patient was
considered unavailable. A minimum of 5 attempts were made at different times
of the day to contact each potential control over a period of 2 weeks including
at least 1 weekend call.
The study was approved by the institutional review board (IRB) (or its
equivalent) at the University of Pennsylvania, each participating college,
and the CDC.
Univariate matched odds ratios were calculated using SAS (version 6.12,
SAS Institute, Cary, NC). Conditional logistic regression was performed using
the SAS procedure PHREG to determine independent risk factors for disease.
Multivariable models included variables found to be significant in previous
studies as well as those that were univariately significant in the present
study. Several different multivariable models were created; for simplicity
a model without an interaction term is presented in detail but we also refer
to one with an interaction term to further explain the data.
Among college students in the United States, 96 cases of meningococcal
disease were identified between September 1, 1998, and August 31, 1999. Fifty
(52%) patients were male and 46 (48%) were female with a median age of 19
years (range, 18-37 years). Eighty-six (90%) students were white, 3 (3%) students
were black, 2 (2%) were Asian, 1 (1%) was of other race, and 4 (4%) were unknown.
One student was of Hispanic ethnicity. Two (2%) cases were outbreak-related.
Eighty-six (90%) students attended 4-year institutions and 86 (90%) were full-time
students. Ninety (97%) were hospitalized and 8 (9%) died. Of the 96 cases,
91 (95%) were confirmed by culture from a sterile site, 3 (3%) by a positive
latex agglutination test result, and 2 (2%) patients had clinical purpura
fulminans without a positive culture or latex agglutination test result. Of
the 91 isolates available for testing, 46 (51%) were obtained from blood,
44 (48%) from cerebrospinal fluid, and 1 (1%) from synovial fluid. Fifty-two
(54%) students were diagnosed with a clinical syndrome consistent with meningitis.
Of the 79 isolates for which serogroup information was available, 38 (48%)
were serogroup C, 22 (28%) were serogroup B, 15 (19%) were serogroup Y, 1
(1%) was serogroup W-135, and 3 (4%) were nongroupable. Thus, 54 (68%) had
illness due to vaccine-preventable serogroups. Forty-four cases (46%) occurred
in the winter months from December through March, and rates were highest in
the northern and southeastern regions of the United States.
For the 1-year period from September 1, 1998, through August 31, 1999,
the incidence of meningococcal disease among US undergraduates was 0.7 per
100 000 (Table 1), significantly
lower than the rate of 1.4 per 100 000 for the general population of
18- to 23-year-old nonstudents (P<.001).12 Rates were higher among freshmen and among students
living in dormitories. Freshmen students living in dormitories had the highest
incidence of disease at 5.1 per 100 000 (95% confidence interval [CI],
3.4-7.2). Rates of disease were higher among whites than blacks (P = .005).
Of the 82 college students with meningococcal disease onset between
September 1, 1998, and April 30, 1999, 75 cases were reported to CDC by May
7, 1999, and of those cases, 50 (67%) were enrolled in the case-control study.
Of the 25 cases not included in the case-control study, most were excluded
because of late reporting or lack of IRB approval from the school. Twenty-three
(46%) were male and 27 (54%) were female with a median age of 19 years (range,
18-24 years). None were of black race. Forty-eight students (96%) attended
4-year institutions and 47 (94%) were full-time students. Forty-nine students
(98%) were hospitalized and 4 (8%) died. Of the 42 isolates for which serogroup
information was available, 23 (55%) were serogroup C, 10 (24%) were serogroup
B, and 9 (21%) were serogroup Y. No students had been vaccinated prior to
Of the 276 potential controls called, 148 (54%) were enrolled in the
study. Of the 128 students who elected not to participate as controls in the
study, 60% reported that they did not wish to spend the time required to complete
the questionnaire, 20% did not call back once initial contact was made and
an interview time was set up, 15% declined participation due to lack of interest
in the study, and 5% hung up. Two controls were previously vaccinated and
were excluded from further analysis.
Enrolled case-patients were similar to nonenrolled patients in age,
sex, race, serogroup, hospitalization, class level, and type of school. Case-patients
enrolled in the study were more likely than nonenrolled patients to live in
dormitories (66% vs 33%, P = .001) and to have been
enrolled at a 4-year school (96% vs 83%, P = .03).
Use of matched case-control methodology should adjust for any enrollment bias
toward students living in dormitories.
In a univariate matched analysis, case-patients did not differ significantly
from controls by age, sex, undergraduate vs graduate status, or maternal education.
Case-patients, however, were more likely than controls to be freshmen (P = .001), to live in a dormitory (P = .008), and to be freshmen living in a dormitory (P = .001). Case-patients were also more likely than controls to be
of white race and to have had an upper respiratory tract infection in the
month preceding the onset of meningococcal disease (Table 2). Attending 1 or more movies in the month before illness
onset was protective; however, movie attendance was inversely correlated with
smoking, bar patronage, and alcohol consumption (data not shown). Crowding
(defined as ≥2 people per bedroom), active and passive smoking, and low
socioeconomic status (≤ $30 000 per year in household income, which
includes parents and student) were not significantly associated with disease.
In a multivariable analysis (Table
3), freshmen living in dormitories were at highest risk for meningococcal
disease. Other risk factors for meningococcal disease were white race, radiator
heat, and a history of upper respiratory tract infection in the month preceding
the onset of illness, whereas movie attendance remained protective. Use of
radiator heat was positively correlated with living in a dormitory and being
a freshman. No significant interactions were found among the variables included
in the multivariable model. The multivariable model was examined for multicollinearity
and no single or combination of variables was found to be correlated with
other factors in the model.
We created a separate multivariable model including radiator heat, white
race, upper respiratory tract infection, movie attendance, freshmen, dormitory
status, and an interaction term for freshmen and dormitory status. In this
model, among freshmen, dormitory residents were at increased risk for meningococcal
disease (P = .06) and among dormitory residents,
freshmen were at increased risk (P = .07).
This study suggests that freshmen living in dormitories have a moderately
increased risk of disease, but US college students as a group are at no greater
overall risk for meningococcal disease than nonstudents in similar age groups.
The reason college students overall are not at increased risk is unclear and
additional studies are needed.
Our findings are consistent with the experience in the military18 and our understanding of risk factors for meningococcal
disease. Because of the close quarters in which they live, freshmen in dormitories
may be exposed to N meningitidis more frequently
than other college students. The exposed freshmen who become asymptomatic
transient carriers would develop protective immunity leading to lower rates
in subsequent years. The higher incidence of disease in freshmen in dormitories
suggests that the college setting may be similar to the military setting where,
prior to routine vaccination in 1971, the overall rate of meningococcal disease
among all active duty members was 25 per 100 000 person-years (LTC Frederick
Erdtmann, MC, USA, Office of the Surgeon General, US Army, written communication,
1981) and rates were highest among military recruits.18,19
While rates are elevated among freshmen students living in dormitories, they
are not as high as rates among military recruits living in barracks. One possible
explanation for this difference is that crowding among freshmen in college
dormitories may not reach levels comparable to those of new military recruits
in barracks. We evaluated the number of people sharing a room in a college
dormitory but did not have more exact measures of crowding, such as distance
between beds, which was shown in one military study to be associated with
rates of meningococcal carriage.20 While crowding
is one possible explanation, insufficient data are available to suggest that
changes in living conditions would decrease risk among college students.
In addition, the majority of cases among military recruits occurred
shortly after reporting to basic training whereas cases among college students
are highest in the winter months, similar to the overall seasonality of meningococcal
disease in the United States. These data suggest that while there are similarities
between college students and military recruits, risk factors between the groups
Other studies have examined risk factors for meningococcal disease;
however, this is the first case-control study to our knowledge that addresses
the risk factors for this disease among college students throughout the United
States. Previously identified risk factors for meningococcal disease include
underlying immune deficiency,21,22
recent upper respiratory tract infection,23-26
low socioeconomic status,27-29
household and institutional crowding,27,30-32
tobacco smoke exposure,27-35
bar and nightclub patronage,33,34
and black race.1,36 Aside from
implicating freshmen living in dormitories, our study found that students
with prior upper respiratory tract infections, students exposed to radiator
heat, and white students were at higher risk for disease, while students who
attended movies were at lower risk. Tobacco smoke exposure, alcohol consumption,
low socioeconomic status, and crowding were not implicated. Exposure to tobacco
smoke may not have been associated with meningococcal disease in this population
because of the low proportion of people exposed. Only 7 case-patients (14%)
and 15 controls (10%) reported smoking, and both case-patients and controls
reported infrequent exposure to passive smoke. However, of the 19 case-patients
and 36 controls who reported frequenting bars or parties, which are often
associated with passive smoke exposure, only 11 (58%) case-patients and 20
(56%) controls reported exposure to passive smoke, suggesting that underreporting
may have led us to underestimate the risk.
Recent upper respiratory tract infection was also independently associated
with meningococcal disease and was common in this population through the entire
school year (data not shown), suggesting that multiple etiologies could be
responsible and that prevention would be difficult. Alcohol has been reported
as a risk factor for meningococcal disease in several outbreaks33,34,37;
our finding of alcohol consumption as a risk factor on univariate analysis,
but not in the multivariable analysis, suggests that it may be a marker for
other high-risk behaviors such as active and passive smoking. Likewise, movie
attendance and radiator heat are probable markers for other exposures or behaviors.
The data from our study are consistent with 2 other recent US studies
that found no significant increased risk of meningococcal disease in college
students but found that subgroups of college students were at higher risk9,10; however, these previous studies have
important limitations. A survey published in 1988 found a low overall incidence
of meningococcal disease among college students, but higher rates of disease
in students living in dormitories compared with students living in other types
of residences.10 However, responses were available
from only 38% of the 1900 universities to which surveys were sent and the
study design did not allow separate evaluation of the risk among freshmen.
A study from Maryland found that from 1992 to 1997 on-campus residents (defined
as students living in a dormitory or apartment located on campus) were at
higher risk of meningococcal disease. However, the number of cases detected
was small and the data from Maryland may not be representative of the entire
country.9 Consistent with this, although only
a single year of national data is available, in our study the incidence of
meningococcal disease in college students varied by geographic region with
the highest rates in the southeast, northeast, and north central regions.
A recent study from the United Kingdom where rates of serogroup C meningococcal
disease are higher than in the United States found that unlike those in the
United States, college students in the United Kingdom were at higher risk
than other 18- to 23-year-olds.11 This increased
risk along with the overall higher rates of meningococcal disease in the United
Kingdom led the National Health Service to begin routine vaccination of college
students with a serogroup C polysaccharide vaccine.38
Similar to the US studies, UK students living in catered halls (equivalent
of US dormitories) were at higher risk.11 In
our case-control study, 85% of freshmen lived in dormitories, making it difficult
to disentangle these 2 risk factors.
The 96 cases of meningococcal disease in college students detected between
September 1998 and August 1999 represent approximately 3% of the total number
of cases that occur each year in the United States (NETSS data). Of these
96 cases, 30 (31%) occurred among freshmen in dormitories. Immunization with
the currently available quadrivalent meningococcal polysaccharide vaccine
would decrease the risk for meningococcal disease in college students who
choose to be vaccinated, but would not eliminate risk because the vaccine
confers no protection against the 28% of cases that were serogroup B and its
efficacy against serogroups A, C, Y, and W-135 is 85% to 95%.7
Our study is important because it identified a relatively small group
of college students at a higher risk for meningococcal disease who are easily
accessible and could be targeted for immunization. Both ACIP and AAP used
these data and other recently published studies9-11
as a basis for new recommendations.12,13
In addition, they considered data on cost-effectiveness that showed from a
societal perspective vaccination of college freshmen is unlikely to be cost
saving; however, cost-effectiveness analysis does not take into consideration
disruption of campus life, public anxiety, and private tragedy resulting from
a case of severe meningococcal disease (R. Douglas Scott II, PhD, unpublished
data, 2000). The ACIP and AAP recommended educating college freshmen, especially
those who live in dormitories, and their parents about the risk of meningococcal
disease and the availability of a safe and effective vaccine that could decrease
their risk; they further recommended increasing access to the vaccine for
Meningococcal conjugate vaccines are currently under development and
will be available within 2 to 3 years in the United States. These vaccines,
similar to Haemophilus influenzae type b vaccine
and pneumococcal conjugate vaccines,39,40
are expected to provide long-lasting immunity in infants and adults and possibly
confer herd immunity. During this interim 2- to 3-year period, widespread
use of the currently available quadrivalent polysaccharide vaccine among college
freshmen could substantially decrease their risk of meningococcal disease.
When conjugate vaccines become available, further evaluation will need to
be performed to assess the use of conjugate vaccines among college students
compared with less expensive polysaccharide vaccines.