Harrison LH, Pass MA, Mendelsohn AB, Egri M, Rosenstein NE, Bustamante A, Razeq J, Roche JC. Invasive Meningococcal Disease in Adolescents and Young Adults. JAMA. 2001;286(6):694-699. doi:10.1001/jama.286.6.694
Author Affiliations: Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Md (Dr Harrison and Mss Pass and Bustamante); Infectious Diseases Epidemiology Research Unit, University of Pittsburgh Graduate School of Public Health and School of Medicine (Drs Harrison and Egri) and Department of Epidemiology, University of Pittsburgh; Graduate School of Public Health (Dr Mendelsohn), Pittsburgh, Pa; Meningitis and Special Pathogens Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Rosenstein); Laboratories Administration (Dr Razeq) and Epidemiology and Disease Control Program (Dr Roche), Maryland Department of Health and Mental Hygiene, Baltimore.Dr Egri is now with the Department of Public Health, Inonu University School of Medicine, Malatya, Turkey.
Context Incidence of invasive meningococcal disease has increased recently in
persons aged 15 through 24 years.
Objective To characterize meningococcal infection in adolescents and young adults
in Maryland during the 1990s.
Design and Setting Population-based surveillance study for meningococcal disease from January
1, 1990, through December 31, 1999, in Maryland.
Patients Maryland residents diagnosed as having invasive meningococcal disease.
Main Outcome Measure Invasive meningococcal infection.
Results Of 295 total cases, 71 (24.1%) occurred among persons aged 15 through
24 years. Sixteen (22.5%) of these cases were fatal. The annual incidence
rate increased from 0.9 to 2.1 cases per 100 000 among 15 through 24
year olds (P = .01). The proportion of all disease
increased from 16.0% to 28.9% (P = .03). The incidence
and proportion of cases subsequently decreased to 1.0 and 16.4% in 1998 through
1999, respectively. Infection in 15 through 24 year olds was more likely to
be fatal than infection in those younger than age 15 years (22.5% vs 4.6%; P = .001). Infection in 15 through 24 year olds, compared
with those aged 25 years or older, was more likely to be associated with male
sex (66.2% vs 34.8%; P<.001) and serogroup C infection
(46.9% vs 20.2%; P<.001), respectively. Infections
were potentially preventable with the licensed meningococcal vaccine in 82.8%
of 15 through 24 year olds, 68.1% of those younger than 15 years, and 76.8%
of adults aged 25 years or older.
Conclusions Incidence of meningococcal infection in 15 through 24 year olds in Maryland
increased and then declined during the 1990s. Infection in this age group
was associated with an unusually high case-fatality ratio, and the vast majority
of cases were potentially vaccine preventable.
Neisseria meningitidis is a leading cause of
meningitis and other serious infections in the United States and throughout
the world.1,2 In recent years,
the overall annual incidence of meningococcal infection in the United States
has ranged from 0.8 to 1.0 per 100 000 population, with infants having
the highest risk.3 Adolescents and young adults
have generally had a low risk of invasive meningococcal infection.3,4
During the 1990s, the number of meningococcal outbreaks increased in
the community and on college campuses.5- 9
Several recent studies identified subgroups of college students that were
at increased risk of meningococcal infection, such as freshmen living on-campus.9- 11 This finding led to
recent national recommendations about the use of meningococcal vaccine among
However, the incidence of meningococcal infection has increased overall
in persons aged 15 through 24 years, including persons of high school age.9 The features of meningococcal infection in 15 through
24 year olds during the period of this increase have not been well characterized.
This is an important public health issue because of the devastating nature
of meningococcal infection and because many of these cases are potentially
vaccine preventable. The purpose of this study was to characterize the problem
of meningococcal infection in adolescents and young adults in an entire state
during the 1990s.
This study was approved by institutional review boards of the Johns
Hopkins University and Maryland Department of Health and Mental Hygiene. Active
surveillance for invasive meningococcal infection was initiated in Maryland
on November 1, 1991, as part of the Maryland Bacterial Invasive Disease Surveillance
(BIDS) project.9,13 BIDS is the
Active Bacterial Core Surveillance (ABCs) component of the Emerging Infections
Program Network that is funded by the Centers for Disease Control and Prevention
(further information is available at http://www.cdc.gov/ncidod/dbmd/abcs). The case definition is the isolation of N meningitidis from a normally sterile body fluid from a Maryland resident of any
age. All acute care hospitals in Maryland participate, as do large hospitals
in Washington, DC, where Maryland residents frequently seek medical care.
Nonhospital microbiology laboratories that receive blood cultures are also
included. For eligible cases, the hospital infection control professional
completes a case report form, which includes demographic and brief clinical
information, and the laboratory submits the bacterial isolate for species
confirmation and further testing. Microbiology laboratory audits to identify
unreported cases are performed by reviewing the laboratory records.
For this study, case report form data were supplemented with reviews
of the medical and health department records, using a standardized chart abstraction
form. For clinical variables of disease severity, the most abnormal observation
during the first 3 days of the hospital stay was recorded.
For most of the analyses in this study, we used BIDS data for 1992 (the
first full calendar year of the BIDS project) through 1999. For trends analysis,
we included passive Maryland Department of Health and Mental Hygiene surveillance
data for the years 1990 through 1991 because, based on previous studies, there
was evidence that the increase in meningococcal infection in adolescents and
young adults began around this time.3,8,9
Combining the passive and active surveillance data was justified because there
were features of meningococcal infection surveillance in Maryland that made
substantial underreporting unlikely. These included the legal requirement
that both health care providers and microbiology laboratories report cases
(ie, dual reporting), that providers were given an incentive to report because
of the assistance provided by health authorities in administering chemoprophylaxis
to prevent secondary cases and because of the frequent reporting of meningococcal
cases in the local media. Seventy-five cases were reported during the 1990
through 1991 passive surveillance years vs 72 cases in the years 1992 through
1993, suggesting that passive reporting in Maryland was reasonably complete.
In addition to analyzing trends in meningococcal incidence, we examined trends
in the proportion of all meningococcal disease that occurred among persons
aged 15 through 24 years because it is unlikely that this proportion would
be influenced by incomplete reporting, if it occurred, in passive surveillance.
The cases obtained through the passive surveillance system were excluded from
all other analyses because the meningococcal isolates were not available for
Species identification and serogrouping were performed using standard
Population estimates based on the 1990 census for the years 1990 through
1996 were obtained from the Centers for Disease Control and Prevention Wonder
database (available at http://wonder.cdc.gov) and for the years
1997 through 1999 were obtained from the US Census Bureau. A Washington, DC,
suburb was defined as the Maryland counties of Prince Georges and Montgomery.
A vaccine serogroup was defined as a serogroup included in the licensed serogroup
A, C, W-135, and Y polysaccharide vaccine.15
Meningitis was defined as either a physician diagnosis of meningitis and/or
a white cell count of higher than 50 × 103/µL in the
cerebrospinal fluid. Shock was defined as having either a systolic or a diastolic
blood pressure of lower than 90 mm Hg or 60 mm Hg, respectively, for those
aged 13 years or older, lower than 80 mm Hg or 50 mm Hg for ages 6 through
12 years, and lower than 70 mm Hg or 40 mm Hg from birth through age 5 years.
Meningococcemia without meningitis, included because of evidence that meningococcemia
alone has a worse prognosis than meningitis with or without meningococcemia,4 was defined as the presence of ecchymoses and/or petechiae,
shock, and/or a physician diagnosis of purpura fulminans, and the absence
Incidence rates were based on Maryland census data for each year of
the study. The 2-sided Fisher exact test was used for the analysis of dichotomous
variables. Trends in meningococcal incidence and the proportion of all cases
among 15 through 24 year olds were analyzed by the χ2 test
for trend. SAS version 6.12 (SAS Institute, Cary, NC) was used for the logistic
regression analyses to identify demographic and vaccine-related factors, which
could be used to distinguish patients aged 15 through 24 years from those
in other age groups. Models were constructed using stepwise model-building
procedures with only demographic and vaccine-related variables that were associated
with having a 15 through 24-year-old case in univariate analysis being eligible
for entry. Entry and stay criteria for the models were set at a significance
level of .10. Another pair of stepwise models was constructed to determine
whether having a 15 through 24-year-old case was independently associated
A total of 295 meningococcal cases of all ages were identified during
the years 1992 through 1999. An additional 75 cases of all ages were identified
through the passive surveillance during the years 1990 through 1991. Of the
295 cases identified through active surveillance, the N
meningitidis isolates were available for serogrouping for 257 cases
(87.1%) and the medical and/or health department records for 272 cases (92.2%).
One hundred nine cases (36.9%) were younger than 15 years, 71 (24.1%) were
aged 15 through 24 years, and 115 (39.0%) were 25 years or older. The median
age among those younger than 15 years was 12 months, 18 years among cases
aged 15 through 24 years, and 51 years among those 25 years or older. Among
those aged 15 through 24 years, 21 were high school and 21 were college students.
There were 2 small meningococcal clusters during the study period: 2 serogroup
C cases on a college campus in 1997 and a party-associated cluster of 3 cases
among adults (ages 18, 20, and 21 years) in 19999,16;
both outbreaks were caused by identical serogroup C strains.
The average annual meningococcal incidence from 1992 through 1999 was
0.73 per 100 000 population and varied considerably by age (Figure 1). The annual incidences in those
aged 15 through 19 years and in those aged 20 through 24 years were 1.8 and
1.0 per 100 000, respectively. The highest incidence in 15 through 24
year olds occurred during the years 1996 through 1997, when it was 2.1 (Figure 2). During this period, the incidence
was 2.6 in 15 through 19 year olds and 1.5 in 20 through 24 year olds. When
analyzed by each year of age, the highest rates were among 17 and 18 year
olds, with annual incidences of 2.8 and 3.0, respectively.
From 1990 to 1997, the annual incidence in persons aged 15 through 24
years increased from 0.9 to 2.1 cases per 100 000 (P = .01, χ2 for trend) (Figure 2). Likewise, the proportion of all disease that occurred
in this age group increased from 16.0% to 28.9% (P
= .03, χ2 for trend). The incidence and proportion of cases
subsequently decreased to 1.0 per 100 000 and to 16.4% in the years 1998
through 1999 essentially to what they were in the years 1990 through 1991.
During the period 1990 through 1999 the overall annual incidence varied from
a low of 0.6 in the years 1994 through 1995 to a high of 0.9 in the years
1996 through 1997. The annual incidence in children younger than age 15 years
declined from 2.2 to 1.2 (P = .01, χ2
for trend), mostly due to a decline among children younger than 5 years, and
the annual incidence in adults aged 25 years or older increased from 0.3 to
0.5 (P = .03, χ2 for trend).
Compared with those younger than 15 years, 15 through 24 year olds were
more likely to live in a suburb of Washington, DC, to have ecchymoses, meningococcemia
without meningitis, shock, coma, thrombocytopenia, an elevated serum creatinine
level, a fatal outcome, and infection caused by a vaccine serogroup strain
(Table 1). Compared with those
25 years or older, 15 through 24 year olds were more likely to be male; be
a smoker; have meningitis, ecchymoses, shock, and serogroup C infection; and
less likely to have a chronic medical condition. Of those aged 15 through
24 years, 22.5% died vs 4.6% of those younger than 15 years and 16.5% of those
25 years or older. Among those younger than 15 years, the case fatality ratio
was 3.8% (3 of 79) for children younger than 5 years and 11.8% (2 of 17) for
children aged 5 through 9 years.
In the logistic regression analysis, fatal infection was associated
with being aged 15 through 24 years vs being younger than 15 years (odds ratio
[OR], 5.2; 95% confidence interval [CI], 1.8-15.6; P
= .003). Infected individuals from a Washington, DC, suburb had a higher odds
of being aged 15 through 24 years old vs being younger than 15 years (OR,
2.3; 95% CI, 1.1-5.1; P = .03). Males (OR, 4.3; 95%
CI, 2.1-8.8; P<.001) and those with serogroup
C infection (OR, 3.9; 95% CI, 1.9-8.4; P<.001)
were at higher odds of being aged 15 through 24 years than being aged 25 years
or older. In the separate logistic regression analysis using death as the
outcome, being aged 15 through 24 years was associated with a fatal outcome
compared with being younger than age 15 years (OR, 6.1; P = .002) but not when compared with patients 25 years or older (OR,
1.2; P = .70).
There were 3 (2.9%), 5 (7.2%), and 56 (50.0%) patients with chronic
conditions among the persons younger than 15 years, aged 15 through 24 years,
and 25 years or older, respectively. Among the children younger than 15 years,
2 had human immunodeficiency virus infection and 1 was receiving short-term
steroid therapy at the time of the onset of meningococcal infection. Among
the 15 through 24 year olds, 1 abused alcohol and 1 each had diabetes mellitus,
ulcerative colitis, and a cerebrospinal fluid leak. Among the patients 25
years or older, the most common chronic medical conditions were diabetes mellitus
(17 patients), malignancy (11 patients), alcohol abuse and HIV/AIDS (7 patients
each), congestive heart failure (6 patients), and organ transplantation (3
patients). Many patients 25 years or older had more than 1 chronic condition.
Among the fatal cases of those aged 15 through 24 years, there were
2 deaths each in 1992 and 1993, 1 in 1994 and 1996, 3 each in 1995 and 1997,
and 4 in 1999. Three (18.8%) lived in Baltimore County, 5 (31.3%) lived in
a Washington, DC, suburb, and 8 (50.0%) lived in other Maryland counties.
Ten (62.5%) fatal cases were male, and 9 (56.3%) were white. Of the 14 fatal
cases for which serogroup was known, 8 (57.1%) were serogroup C, 4 (28.6%)
serogroup Y, and 2 (14.3%) serogroup B. There were no significant differences
in case fatality by year.
In the 55 survivors aged 15 through 24 years, long-term sequelae included
1 survivor with bilateral below-the-knee amputation and 1 with hearing loss;
in the 104 survivors younger than 15 years, they included 1 survivor with
bilateral below-the-knee amputation, 1 with above-the-knee amputation, and
9 with hearing loss; and in the 96 survivors aged 25 years or older, they
included 1 survivor with multiple toe amputations and 3 with hearing loss.
In those aged 15 through 24 years, 46.9% had serogroup C, 31.3% had
serogroup Y, 12.5% had the serogroup B, and 4.7% had serogroup W-135 strains.
In analyzing infections by group, 82.8% of those aged 15 through 24 years
had infections that were potentially vaccine preventable compared with 68.1%
of children younger than 15 years and compared with 76.8% of those aged 25
years or older (P = .04, comparing 15 through 24
year olds vs <15 years). Among 15 through 24 year olds, the proportion
of infections caused by the serogroup C and Y strains tended to increase and
decrease, respectively, during the 1990s. Neither of these trends was statistically
significant (Figure 3). The increase
in the proportion of infections caused by serogroup C continued even during
the years 1998 through 1999, when the overall incidence rate fell. Serogroup
Y accounted for half of cases during the years 1992 through 1993 but only
16.7% of infections in the years 1998 through 1999. Serogroups B and W-135
accounted for a relatively small proportion of disease in this age group.
We found that the incidence of meningococcal infection in Maryland increased
substantially among 15 through 24 year olds during the 1990s. During the period
of 1994 through 1997, 15 through 24 year olds accounted for nearly 30% of
all meningococcal infections. The emergence of meningococcal infection in
this age group was not unique to Maryland. Similar increases were found in
Oregon and other states.8,17 Interestingly,
the incidence dropped precipitously and returned to baseline during the last
2 years of the study. This downward trend has recently been noted elsewhere,
albeit to a lesser extent. In several other ABCs sites, the incidence of meningococcal
infection in those aged 15 through 24 years was 0.72 per 100 000 in 1992,
peaked at 2.04 in 1996, and declined to 1.63 in 1999 (Kathleen Shutt, MS,
written communication, September 15, 2000).
We identified epidemiologic and clinical features of meningococcal infection
in 15 through 24 year olds that distinguished this group from meningococcal
infection occurring at other ages. The most striking finding was that nearly
a quarter of meningococcal infections in 15 through 24 year olds was fatal.
This was unexpected because the case fatality caused by meningococcal infection
in this age group typically is low; the highest case fatality tends to be
among neonates and elderly persons.4,18
The high case fatality in this group was particularly surprising because the
vast majority of these 15 through 24 year olds were previously healthy; whereas,
half of the those aged 25 years or older had chronic medical conditions that
would be expected on average to lead to a less favorable outcome. In a study
of 44 cases of meningococcal infection among adults (including elderly persons)
in Atlanta, Ga, from 1988 through 1993, 3 (8%) of cases were fatal.19 In a study of cases that occurred in Spain from 1987
through 1992, the case fatality rates among patients aged 15 through 19 and
20 through 29 years were 1.4% and 3.8%, respectively.20
Among children younger than 15 years in that study, the case fatality was
between 2.7% and 6.1%, similar to fatality rates in Maryland, indicating that
the association between death and being aged 15 through 24 years old was not
due to a spuriously low case fatality among Maryland children younger than
15 years. The mechanism of the high case fatality is not known but the clinical
data suggest that the increased mortality was because of a high frequency
of the syndrome of meningococcemia.
The factors responsible for the increased incidence of meningococcal
infection in 15 through 24 year olds and the subsequent decline are not known.
The increase in Oregon was found to be caused largely by a serogroup B clone.17,21 Although the increased incidence
in Maryland was caused mainly by 2 different serogroups, most serogroup C
disease from diverse regions of the United States has been found to belong
to the electrophoretic type 37.8 Similarly,
serogroup Y infection in the United States is fairly clonal, with the majority
of strains belonging to electrophoretic types 501/508 or 516. If these or
other clonal groups had been recently introduced into Maryland and were antigenically
new to adolescents and young adults, this could provide a partial explanation
for the observed increase. Ongoing studies will characterize the molecular
epidemiology of meningococcal infection in Maryland and correlate the findings
with the changing incidence of infection in 15 through 24 year olds.
Cigarette smoking is a known risk factor for meningococcal infection
and other invasive bacterial diseases and was reported for nearly half of
the 15 through 24-year-old cases in our study.22- 26
Although what role smoking played, if any, in the increase in meningococcal
incidence in 15 through 24 year olds is not known, national trends in youth
smoking mirrored trends in meningococcal incidence during the 1990s.27- 29 For example, the
prevalence of cigarette smoking in the previous 30 days among 12th grade high
school students was 28.3% in 1991, peaked at 36.5% in 1997, and decreased
to 34.6% in 1999.28 If smoking is in fact causally
associated with meningococcal infection, then, by definition, changes in smoking
prevalence would lead to changes in meningococcal incidence. That the decline
in meningococcal incidence in Maryland was of larger magnitude than the decline
in smoking prevalence, however, suggests that smoking is not responsible for
all of the changes in meningococcal incidence in 15 through 24 year olds.
The prevalence of binge drinking, also associated with meningococcal infection,
also seems to have increased slightly during the 1990s and then decreased
by 1999.30,31 We suspect that
the changes in meningococcal incidence we observed were due to a combination
of changes in population immunity to circulating strains and changes in behavioral
What are the implications of this study for the prevention of meningococcal
infection? Vaccine prevention in 15 through 24 year olds is attractive for
several reasons. First, more than 80% of infections in our study were caused
by serogroups that are included in the vaccine that is licensed in the United
States.15 Second, vaccine efficacy in adolescents
and young adults is high.32- 34
Third, there is evidence that transmission of N meningitidis frequently occurs from young adults to children, suggesting that a
vaccine that afforded herd immunity through a reduction in nasopharyngeal
carriage could potentially lead to reduced transmission to susceptible children.35,36 Fourth, a relatively large proportion
of all meningococcal infections in Maryland occurred in this age group. However,
the relatively small number of cases, potential logistical difficulties in
immunizing adolescents and young adults, questions about the cost-effectiveness
of meningococcal vaccines,11 and the decline
in incidence in the years 1998 through 1999 and elsewhere must also be considered.
In any case, these data and continued surveillance for meningococcal infection
will be useful in deciding whether vaccination is appropriate for this age
There are several limitations of this study. The requirement for the
isolation of N meningitidis in culture led to an
underestimation of the burden of meningococcal infection in all age groups
in our study.37 Since we did not follow up
cases prospectively after discharge from the hospital, we likely also underestimated
the frequency of certain sequelae, such as hearing loss. Finally, the study
design we used did not allow us to directly assess the contribution of smoking
and other behavioral risk factors to the changing epidemiology of meningococcal
infection in Maryland.
In summary, the incidence of meningococcal infection in Maryland residents
aged 15 through 24 years increased during the 1990s but subsequently decreased.
During some years, persons aged 15 through 24 years accounted for nearly 30%
of all meningococcal infections in Maryland. Infection in this age group was
associated with an unexpectedly high case fatality. The majority of infections
were vaccine preventable. This study underscores how the epidemiology of meningococcal
infection continuously changes and the need to monitor disease patterns with
active, laboratory-based surveillance. Surveillance will provide crucial information
for the development of optimal immunization strategies, once improved meningococcal
vaccines become available.