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Neisseria meningitidis : Epidemiological Study and Modeling on a Student Population LILLIAN S. WALDBESER*, MUFID ABUDIAB § and SOPHIA OMMANI* *Department of Physical and Life Sciences, § Department of Mathematics and Statistics Texas A&M University-Corpus Christi 6300 Ocean Drive, Unit 5802, Corpus Christi, Texas 78412-5802 USA E-mail: [email protected] http://falcon.tamucc.edu/~waldbese/ Abstract: - Neisseria Meningitidis (meningococcus) causes a variety of clinical syndromes ranging from meningitis to severe septicemia in children and young adults. All recent studies have shown that freshman living in dormitories have higher risk of developing meningococcal infections as non-resident students. In this paper, we report the findings in approximately 100 freshman students who were tested for carriage of the organism. It was found that smoking and socializing did not contribute to the increase. The data showed correlations between lowered immunity (associated stress and upper respiratory infections) with increase in meningococcal carriage. Statistical analysis and mathematical modeling tools were employed to picture and quantify the correlation between the above risk factor and the development of meningococcal infections. Key words: - Neisseria meningitidis, meningococcus, carriage, stress, immunity, epidemiology, mathematical modeling. 1. Introduction Neisseria meningitidis colonizes the oro- nasopharynx and spreads from person to person via respiratory droplets. The organism may remain in the upper respiratory tract without causing disease, or it may become invasive, giving rise to meningitis and septicemia. The incidence of meningococcal infection is low. In the United States, there were 0.8-1 per 100,000 population [1], and 10 to 25 cases per 100,000 persons in the developing countries [2]. The rapid onset of the disease, the fulminant course of the infection in some individuals, and the high mortality rate in the absence of immediate antimicrobial treatment, are the reasons for the profound impact of this infection. There are about 3000 cases of meningococcal infection in the United States each year. The mortality rate is 13% and about 15% of survivors develop permanent hearing loss or other neurological damage [3]. The course of this disease is intensely rapid. From the onset of symptoms to death, the time period is approximately 24 hours if not treated. In non epidemic periods, meningococcus is present in 5-10 % of the population in asymptomatic carriers in the United States [4]. The endemic form has an incidence of 1 to 5 cases per 100,000 population annually, while in epidemics the incidence is 500 cases per 100,00 [5]. While the overall meningococcal rates are low, they have been rising among young adults – from 1 to more than 2 per 100,000 people (ages 15-24) since 1991. Health centers started keeping statistics on college students in 1998, outbreaks seem to have been rising in this group as well. All recent studies have shown that freshman living in dormitories have seven times as much risk of developing meningococcal infections as college students overall [6]. 2. Objective This study was to determine the risk factors for meningococcal disease. Recent studies indicated Proceedings of the 2006 WSEAS Int. Conf. on Cellular & Molecular Biology, Biophysics & Bioengineering, Athens, Greece, July 14-16, 2006 (pp74-79)

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Page 1: Neisseria meningitidis : Epidemiological Study and Modeling ...wseas.us/e-library/conferences/2006athensbio/papers/536...Neisseria meningitidis : Epidemiological Study and Modeling

Neisseria meningitidis : Epidemiological Study

and Modeling on a Student Population

LILLIAN S. WALDBESER*, MUFID ABUDIAB§ and SOPHIA OMMANI*

*Department of Physical and Life Sciences, §Department of Mathematics and Statistics

Texas A&M University-Corpus Christi

6300 Ocean Drive, Unit 5802, Corpus Christi, Texas 78412-5802

USA

E-mail: [email protected] http://falcon.tamucc.edu/~waldbese/

Abstract: - Neisseria Meningitidis (meningococcus) causes a variety of clinical syndromes ranging from

meningitis to severe septicemia in children and young adults. All recent studies have shown that freshman living in

dormitories have higher risk of developing meningococcal infections as non-resident students. In this paper, we

report the findings in approximately 100 freshman students who were tested for carriage of the organism. It was

found that smoking and socializing did not contribute to the increase. The data showed correlations between

lowered immunity (associated stress and upper respiratory infections) with increase in meningococcal carriage.

Statistical analysis and mathematical modeling tools were employed to picture and quantify the correlation between

the above risk factor and the development of meningococcal infections.

Key words: - Neisseria meningitidis, meningococcus, carriage, stress, immunity, epidemiology, mathematical

modeling.

1. Introduction Neisseria meningitidis colonizes the oro-

nasopharynx and spreads from person to person

via respiratory droplets. The organism may

remain in the upper respiratory tract without

causing disease, or it may become invasive,

giving rise to meningitis and septicemia. The

incidence of meningococcal infection is low. In

the United States, there were 0.8-1 per 100,000

population [1], and 10 to 25 cases per 100,000

persons in the developing countries [2]. The

rapid onset of the disease, the fulminant course

of the infection in some individuals, and the high

mortality rate in the absence of immediate

antimicrobial treatment, are the reasons for the

profound impact of this infection. There are

about 3000 cases of meningococcal infection in

the United States each year. The mortality rate is

13% and about 15% of survivors develop

permanent hearing loss or other neurological

damage [3]. The course of this disease is

intensely rapid. From the onset of symptoms to

death, the time period is approximately 24 hours

if not treated.

In non epidemic periods, meningococcus is

present in 5-10 % of the population in

asymptomatic carriers in the United States [4].

The endemic form has an incidence of 1 to 5

cases per 100,000 population annually, while in

epidemics the incidence is 500 cases per 100,00

[5]. While the overall meningococcal rates are

low, they have been rising among young adults –

from 1 to more than 2 per 100,000 people (ages

15-24) since 1991. Health centers started

keeping statistics on college students in 1998,

outbreaks seem to have been rising in this group

as well. All recent studies have shown that

freshman living in dormitories have seven times

as much risk of developing meningococcal

infections as college students overall [6].

2. Objective This study was to determine the risk factors for

meningococcal disease. Recent studies indicated

Proceedings of the 2006 WSEAS Int. Conf. on Cellular & Molecular Biology, Biophysics & Bioengineering, Athens, Greece, July 14-16, 2006 (pp74-79)

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cigarette smoking and bar patronage are risk

factors for meningococcal infection [7 and 8].

Upper respiratory infections have also been

reported as a risk factor [9 and 10]. Since there is

a direct relationship between the carrier state and

the acquisition of the disease, this study was to

determine which risk factors are associated with

the carrier state.

3. Design and Methods The study group consisted of approximately 100

freshmen at Texas A&M University-Corpus

Christi. The students were given a questionnaire

to complete, and posterior nasal swabs were

obtained for identification of the presence of

Neisseria meningitidis. The questionnaire

contained questions on place of residence, active

and passive smoking, visits to bars and night

clubs, and recent symptoms of upper respiratory

tract infection. Posterior nasal swabs were done

at three different times throughout the semester.

The first was at the beginning of the semester;

the second at the week before midterms, and the

third during the week of finals. The swab

samples were immediately plated onto selective

medium for Neisseria. Gram stain was

performed on bacteria cultures. If gram negative

diplococci were seen under the microscope,

sugar utilization tests were performed to confirm

that the organisms isolated were Neisseria

meningitidis.

4. Results Data from our study was analyzed using

descriptive statistical tools to view the impact of

smoking (Graph 1), socialization (Graph 2),

living on campus (Graph 3), and low immunity

which includes feeling stressed and recent

influenza or viral upper respiratory infections

(Graph 4), on the percentage of students

colonized with Neisseria meningitidis.

Graph1: Correlation between Smooking and Incidence

of Colonization of Neisseria Meningitidis

0

5

10

15

20

25

30

1 2 3

Different Trials

# of Smokers vs % of

Colonization

# of Smokers

% of Colonization

Proceedings of the 2006 WSEAS Int. Conf. on Cellular & Molecular Biology, Biophysics & Bioengineering, Athens, Greece, July 14-16, 2006 (pp74-79)

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Graph2: Correlation between Socialization and

Incidence of Colonization of Neisseria Meningitidis

0

10

20

30

40

50

60

70

1 2 3

Different Trials

# of students who

Socialized

vs % of Colonization

# of Students who Socialize

% of Colonization

Graph3: Correlation between Living on Campus and

Incidence of Colonization of Neisseria Meningitidis

0

10

20

30

40

50

60

1 2 3

Different Trials

# of students who

lived on campus vs %

of Colonization

# of Students who Lived on

campus% of Colonization

Graph4: Correlation between Immune System

Levels and Incidence of Colonization of Neisseria

Meningitidis

0

20

40

60

80

100

1 2 3

Different Trials

# of students with

reportedly low

Immune System vs

% of Colonization

# of Students with reportedly low

Immune system% of Colonization

Proceedings of the 2006 WSEAS Int. Conf. on Cellular & Molecular Biology, Biophysics & Bioengineering, Athens, Greece, July 14-16, 2006 (pp74-79)

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Mathematical Models Mathematical modeling is a safe, economic and

effective way of studying the parameters that

control the dynamics of a biological structure.

Furthermore, it is a process that can be employed

to provide a rigorous, systematic, and

quantitative linkage between a biological

phenomena and its environment. Based on the

above descriptive statistical analysis, we use the

simplest mathematical modeling tool, Trend

Line, in order to find the best fit to our data.

The only factor that had a direct relationship

with carriage was the immune status of the

students (Graph 5).

For future prediction of colonization percentage

of Neisseria meningitidis, we could use the

model 20.0055 0.4431 18.333 y x x= − + where x

is number of students with low immunity and y

is percentage of students colonized by Neisseria

meningitidis.

Graph 5:# of students with low immune system vs % of

colonization

y = 0.0055x2 - 0.4431x + 18.333

R2 = 1

0

5

10

15

20

25

0 10 20 30 40 50 60 70 80 90

# of students with low immune system

% of colonization

Proceedings of the 2006 WSEAS Int. Conf. on Cellular & Molecular Biology, Biophysics & Bioengineering, Athens, Greece, July 14-16, 2006 (pp74-79)

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5. Conclusion Our data show that meningococcal carriage

increased from 10% at the beginning of the

semester to 15% at midterm, and 20% at the end

of the semester. At first glance, there seemed to

be no correlations between smoking and carrier

status. However, the number of student smokers

remained the same, but the number of carriers

climbed steadily. It is therefore possible that

smoking may contribute to susceptibility to

Neisseria Meningitidis infection and increase in

the number of carriers. There was no direct

relationship between students who frequently

visited bars and night clubs (“socialization”) and

the carrier status. In fact, at the end of the

semester, the number of students frequenting

bars and night clubs decreased, whereas the

number of meningococci carriers increased.

Living on campus cannot be ruled out as a risk

factor. The number of students living on campus

varied insignificantly, but the number of carriers

continued to rise as the semester progressed. It

is possible that living on campus increased the

students’ susceptibility to infection, and hence

the numbers of carriers were higher. Subsequent

studies should separate the living on campus

group from the off campus group. The only

factor that had a direct relationship with carriage

was the immune status of the students. The

immune status of the students was based on the

stress level and recent upper respiratory

infections, such as influenza and the common

cold. As the number of students was classified as

being in the “low immunity” category, increased

from 30 at the beginning of the semester to 84 at

the end of the semester, the carrier number

increased concomitantly from 10% at the

beginning of the semester to 20% at the end of

the semester. The correlation between low

immunity and increased carriage was

substantiated by the mathematical model in

Graph 5. In summary, there is no correlation

between the amount of socialization and carrier

status. Smoking and on campus living, may

possibly contribute to susceptibility to

meningococcal infections and increase in the

number of asymptomatic carriers. The data

demonstrated that stress and upper respiratory

infections (categorized as "low immunity") are

directly related to increased meningococcal

carriage. It is most likely that stress and viral

infections result in lowered immune status,

rendering the individuals more susceptible to

Neisseria Meningitidis infections.

In view of the fact that a rigorous academic

schedule can be very stressful for many students,

it would be advisable for universities to provide

information on meningococcal infection, and

the benefits of vaccination. A tetravalent

serogroup A/C/Y/W-135 polysaccharide vaccine

is available in the United States. A

polysaccharide vaccine for serogroup B is not

available because serogroup B polysaccharide is

poorly immunogenic in humans. Currently,

development of non-polysaccharide-based

vaccine is in progress (11). Immunization has

been reported to be successful in controlling

meningococcal infections in the military (12).

References:

[1] Harrison, LH, Preventing meningococcal

infection in college students, Clinical Infectious

Diseases, Vol. 30, 2000, pp. 648-51.

[2] Schwartz B, Moore PS, and Broome CV, global

epidemiology of meningococcal disease, Clin.

Microbiol. Rev.Vol. 2 (suppl), 1989, pp. S118-

S124.

[3] Kirsch, EA, Barton, RP, Kitcahen L, Giroir BP,

Pathophysiology, treatment and outcome of

meningococcemia: a review and recent

experience, Pediatr. Infect. Dis. J., Vol. 15, 1996,

pp. 067-079.

[4] Wenger JD, and Broome CV, Bacterial

Meningitis: epidemiology, in Kass E, Weller

TH, Wolff SM, and Tyrrell DAJ (ed.), Infections

of the Central Nervous System, B.C. Decker,

Inc., Philadelphia, 1991, pp. 1-15.

[5] Lifely MR, Moreno C, and Lindon JC, An

integrated molecular and immunological

approach towards a Meingococcal group B

vaccine, Vaccine Vol. 5, 1987, pp. 11-25.

[6] Bruce MG, Rosenstein NE, Capparella JM, et al.,

Risk factors for meningococcal disease in 2001,

pp. 677-687.

Proceedings of the 2006 WSEAS Int. Conf. on Cellular & Molecular Biology, Biophysics & Bioengineering, Athens, Greece, July 14-16, 2006 (pp74-79)

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[7] Imrey PB, Jackson LA, Ludwinski PH, et al.,

Outbreak if serogroup C meningococcal disease

associated with campus bar patronage, Am. J.

Epidemiol., Vol. 143, 1996, pp. 624-30.

[8] Fischer M, Hedberg K, Cardosi P, et al., Tobacco

smoke as a risk factor for meningococcal disease,

Pediatr. Infect. Dis. J., Vol. 16, 1997, pp. 979-

983.

[9] Olcen P, Kjellander J, Danielsson D, and

Lindquist BL, Epidemiology of Neisseria

meningitidis; prevalence and symptoms from the

upper respiratory tract in family members to

patients with menigococcal disease, Scand. J.

Infect. Dis., Vol. 13, No. 2, 1981, pp. 105-109.

[10]Harrison LH, Armstrong CW, Jenkins SR, et al.,

A cluster of meningococcal disease on a school

bus following epidemic influenza, JAMA, Vol.

151, No. 5, 1991, pp. 1005-1009.

[11] Lepow ML, Perkins BA, Hughes PA, et

al., Meningococcal vaccines. In Plotkin SA,

Orenstein WA eds. Vaccines. 3rd ed.

Philadelphia: WB Saunders, 1999:711-727.

[12] Anonymous. Meningoccocal disease among

soldiers, US Army, 1964-1998. Med.

Surveillance Monthly Rep. 2000; 6:2-3.

Proceedings of the 2006 WSEAS Int. Conf. on Cellular & Molecular Biology, Biophysics & Bioengineering, Athens, Greece, July 14-16, 2006 (pp74-79)