Transcript No Slide Title

Neisseria
meningitidis
Meningococcal Disease
MKT4734
1/1/99
1
Etiology




Neisseria meningitidis
Gram negative diplococcus with polysaccharide
capsule
13 serogroups classed by capsular specificity
(A/B/C/Y/W-135 & others)
T-independent capsular antigen (no memory
response)
Other classifications - outer membrane proteins
& lipopolysaccharide (LPS)
1. Apicella MA, Chapter 189: Neisseria meningitidis. In: Principles and Practice of Infectious Diseases, 4th ed. Eds. Mandell GL, et al. Churchill Livingstone,
New York, 1995, 1896-1898
2
Etiology
Antigens & Virulence
Factors
Porin*
(PorA or
PorB)
Opacity*
Associated
Protein
Polysaccharide
Capsule
(Opa)
Pili
* outer membrane proteins
LPS
10. Poolman JT, Development of a
meningococcal vaccine, Infectious Agents
and Disease, 4:1, 1995, 21
3
Epidemiology


Incubation - 2 to 10 days; often 3 to 4
Transmission2 »
»


Neisseria meningitidis
2
respiratory route
direct contact
Reservoir - humans only10
Carrier prevalence - 5% to 10%10, 14
2. WHO Information Fact Sheets, Meningococcal meningitis-Update: http://www.who.int/inf-fs/en/fact105.html
10. Poolman JT, Development of a meningococcal vaccine, Infectious Agents and Disease, 4:1, 1995, 13
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33
4
Epidemiology

Global Epidemiology
Group A epidemics:
Senegal, Gambia, GuineaBissau, Guinea, Sierra
Leone, Ivory Coast, Burkina
Faso, Ghana, Togo, Benin,
Nigeria, Cameroon, Chad,
Niger, Mali, Cen. African
Republic, Sudan, Uganda,
Kenya, Ethiopia
4. CDC, Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and management
of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 4
5
Epidemiology


Meningitis belt - peaks in dry season
Epidemics occasionally occur in:
»
»
»

Global Epidemiology
Saudi Arabia
Kenya & Tanzania
Burundi & Mongolia
CDC travelers information (404) 332-4559
4. CDC, Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and
management of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 4
6
Epidemiology
U. S. Epidemiology
Serogroup Distribution - 1989-1991

2100 - 3500 cases (1981-1996)
and 200 - 290 deaths (198623
1995) annually

Highest total disease incidence in
4
children 3 to 12 mos. of age

Leading cause of bacterial
5
meningitis in ages 2 to 18 yrs.

4
Peaks late winter/early spring
Y
5%
C
45%
Others
4%
B
46%
4.
CDC, Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and management of
suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 1
5. Schuchat A, et al, Bacterial meningitis in the United States in 1995, The New England Journal of Medicine, 337:1997, 970
23. CDC. Summary of notifiable diseases, United States, MMWR 45:53, 1996,74, 76, 80
7
Epidemiology
U.S. Total Disease Incidence
< 5 to > 59 yrs. - 1989 -1991
U.S. Incidence of M eningococcal Disease < 5 to > 59 Years 1989-1991
9
8
7
6
5
4
3
2
1
0
>59
55 - 59
50 - 54
45 - 49
35 - 39
30 - 34
25 - 29
20 - 24
10 - 15
5 - 10
<5
Age (years)
4. CDC, Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and management
of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 2, with actual data
points supplied by CDC
8
U.S. Total Disease Incidence
< 1 to 23 mos. - 1989 -1991
Epidemiology
U.S. Incidence of Meningococcal Disease < 1 to 23 Months 1989-1991
30
Incidence
(cases/100,000)
25
20
15
10
5
0
<1
1-4
4-8
8-12
Age (months)
12-16
16-19
20-23
4. CDC, Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and management of
suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 2, with actual data points
supplied by CDC
9
Bacterial Meningitis Incidence
Major Causes
Epidemiology
Bacterial Meningitis Incidence - 1995
140
7
< 1 month
of age
120
6
Cases/100,000
Cases/100,000
100
80
60
> 1 month of
age
Streptococcus
pneumoniae
5
Neisseria
meningitidis
4
Group B
Streptococcus
3
Listeria
monocytogenes
40
2
20
1
0
0
< 1 month
Haemophilus
influenzae
1 - 23 mos
2 - 29 yrs
30 - 59 yrs
> 60 yrs
Age (months)
5. Schuchat A, et al, Bacterial meningitis in the United States in 1995, The New England Journal of Medicine, 337:1997, 972
10
Epidemiology

Meningococcal Disease
United States
Case-fatality rate
4
»
»
»
»
13% for meningitic disease (isolated in CSF)
4
11.5% when isolated from blood
case-fatality rate even higher with severe
meningococcemia1
case-fatality rate consistent in spite of antibiotic
use4
1. Apicella MA, Chapter 189: Neisseria meningitidis. In: Principles and Practice of Infectious Diseases, 4th ed. Eds. Mandell GL, et al. Churchill
Livingstone, New York, 1995, 1899
4. CDC, Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and
management of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 1
11
Epidemiology
U.S.A.- Changing Serogroup
Prevalence - 1990’s

Group C common cause of outbreaks since
6
early 1990’s

Group Y disease also increasing4

Overall invasive disease incidence constant
1.3/100,000 (since 1986)5

Meningitis incidence decreased 0.9 to
0.6/100,000 (since 1986)5
4. CDC, Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and management of
suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 1
5. Schuchat A, et al, Bacterial meningitis in the United States in 1995, The New England Journal of Medicine, 337, 1997, 972
6. CDC, Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks: recommendations of the
Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 13
12
Serogroup C Outbreaks United States - 1980 - 1993
Epidemiology

21 outbreaks
6
8
»
»
»



8 school outbreaks
8
3 institutional outbreaks
8
10 community outbreaks (no known contact)
Affect school-aged children & young adults
High frequency and severity of sequelae17
Most attack rates > 10 cases/100,000
6
(20 X higher than endemic rate)
8
6. CDC, Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks: recommendations of the
Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 13
8. Jackson LA, et al, Serogroup C meningococcal outbreaks in the United States, an emerging threat, JAMA, 273:5, 1995, 384, 386
17. Erickson L, et al, Complications and sequelae of meningococcal disease in Quebec, Canada, 1990-1994, Clin Infect Dis, 26, 1998, 1163
13
Epidemiology



Serogroup Y Disease United States
Increasing
proportion of
disease since 19917
More frequently
associated with
meningococcal
7
pneumonia
Median age 21.8
yrs.7
Changes in Serogroup Y Distribution
1978 - 1996 7, 9
35%
33%
30%
25%
21%
20%
15%
10%
7%
5%
2%
0%
1978-1981
1989-1991
1995
1995-1996
7. CDC, Serogroup Y meningococcal disease - Illinois, Connecticut, and selected areas, United States, 1989-1996, MMWR, 45:46, 1996, 1010-1013
9. Quick uptakes . . . meningitis patterns shift, JAMA, 279:16, 1998, 1249
14
Clinical Syndromes
19955
Epidemiology
Me ningitis
48%
Bacteremic
pneumonia
3%
Other
1%
Bacteremia
48%
5. Schuchat A, et al, Bacterial meningitis in the United States in 1995, The New England Journal of Medicine, 337, 1997, 973
15
Epidemiology





4.
Risk Groups
Persons with terminal complement deficiencies
Persons with anatomic or functional asplenia
Persons with immunosuppression
Industrial or laboratory personnel routinely
exposed to organism
Residents or travelers to hyperendemic or
epidemic areas
CDC, Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and management of
suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 3 & 4
16
Pathogenesis
Stages of Pathogenesis
11
Organism Enters Nose or Mouth
Mucosal Barrier Cleared
11
Intravascular Space Invaded
11
12
Host Response
(Cytokines, PAF*, Arachidonic Metabolites)
*
Platelet activation factor
11. Quagliarello V, et al, Bacterial meningitis: pathogenesis, pathophysiology, and progress, The New England Journal of Medicine, 327:12, 1992, 865
12. Saez-Llorens X, et al, Molecular pathophysiology of bacterial meningitis: current concepts and therapeutic implications, The Journal of Pediatrics, 116:5, 1990,
672, 673, 675, 677
17
Pathogenesis
Disease Manifested
12
Host Response
Blood Brain Barrier
1,12
Breached 13,26
Effective Immune
1,13,
Response 26
Bacteremia
without
Sepsis
Vascular Damage, DIC*,
1,12
Tissue Damage, Shock 13,26
* Disseminated Intravascular Coagulation
Meningococcemia
without Meningitis
Meningitis with or
without
Meningococcemia
1. Apicella MA, Chapter 189: Neisseria meningitidis. In: Principles and Practice of Infectious Diseases, 4th ed. Eds. Mandell GL, et al. Churchill Livingstone, New
York, 1995, 1900 12. Saez-Llorens X, et al, Molecular pathophysiology of bacterial meningitis: current concepts and therapeutic implications, The Journal of
Pediatrics, 116:5, 1990, 672, 673, 675-677 13. Young LS, Chapter 56: Sepsis syndrome. In: Principles and Practice of Infectious Diseases, 4th ed., Eds. Mandell GL,
et al. Churchill Livingstone, New York, 1995, 690-705 26. Glode MP, Smith AL, Meningococcal disease. In: Textbook of Pediatric Infectious Diseases. Eds. Feigin
RD, et al. W. B. Saunders Company, Phila., 1981, 916 - 928
18
Clinical
Manifestations





Meningococcemia
without Meningitis
Malaise, weakness, nausea, myalgia,
arthralgia15
Significant fever & chills15
Macular, erythematous rash usually on
15
extremities
Petechiae/purpura on extremities14,15
Hypotension14
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33
15. Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 2
19
Clinical
Manifestations



Meningococcemia
without Meningitis
(cont’d.)
Disseminated intravascular coagulation
(DIC)14
Multiorgan failure14
Laboratory abnormalities15
»
»
»
»
leukocytosis with left shift
leukopenia
coagulopathy
blood positive for N. meningitidis
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33
15. Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 2
20
Clinical
Manifestations






Meningococcemia
Complications
Waterhouse-Friderichsen syndrome (10%)
Pneumonia1
Endocarditis, myocarditis, pericarditis15
Pleurisy15
Peritonitis15
Arthritis15
15
1.
Apicella MA, Chapter 189: Neisseria meningitidis. In: Principles and Practice of Infectious Diseases, 4th ed. Eds. Mandell GL, et al. Churchill Livingstone, New
York, 1995, 1902
15. Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 2
21
Clinical
Manifestations







Expressions of WaterhouseFriderichsen Syndrome
Fulminant septicemia
Shock
Purpura fulminans
DIC
Congestive heart failure
Bilateral adrenal hemorrhage
Progressive, irreversible collapse
15. Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 2
25. DeLellis RA, Chapter 26: The endocrine system. In: Robbins Pathologic Basis of Disease 4th ed. Eds. Cotran RS, et al. W. B. Saunders Company, Phila., 1989,
1253
22
Clinical
Manifestations




Meningitis with/without
Meningococcemia
Fever
Headache
Nuchal rigidity
CSF
»
»
»
»
> WBCs
< glucose
> Protein levels
+ for N. meningitidis
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33
23
Clinical
Manifestations

Meningitis with/without
Meningococcemia
Outcomes
»
»
Death
Long-term neurologic sequelae
–
–
–
deafness
cranial nerve palsy
retardation
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33
24
Clinical
Manifestations
Pathogenesis - Meningitis
Skull
Dura mater
Brain
Capillary in arachnoid
Space
25
Clinical
Manifestations
Pathogenesis - Meningitis
Blood Brain Barrier
(Tight Junctions)
Meningococci
26
Clinical
Manifestations
Pathogenesis - Meningitis
4. Neutrophils summoned;
attach to endothelium
1. Meningococci
release endotoxins
2. Cytokines
summoned;
endothelial cell
inflamed
5. Neutrophils enter brain;
3. Blood Brain
secrete inflammatory factors;
Barrier disrupted
further BBB disruption
11. Quagliarello V, et al, Bacterial meningitis: pathogenesis, pathophysiology, and progress, N Eng Jour Med, 327:12, 1992, 866-868
12. Saez-Llorens X, et al, Molecular pathophysiology of bacterial meningitis: current concepts and therapeutic implications, Journ Pediatrics, 116:5, 1990, 672, 673,
673-678
27
Diagnosis







Diagnostic Features
(Adults & Children)
Upper respiratory symptoms
Headache
Petechiae/purpura (significant finding)
Fever
Extreme vomiting
Photophobia
Nuchal rigidity
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33
28
Diagnosis









Diagnostic Features
(Infants)
Irritability
Full fontanel
Poor feeding
Elevated or subnormal temperature
Vomiting
Lethargy
Altered consciousness levels
Increased intracranial pressure (ICP)
Kernig’s & Brudzinski’s signs present
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33
29
Diagnosis

Confirmed case
»

isolation N. meningitidis from blood, CSF, petechiae or
purpuric lesions, synovial fluid, pleural fluid, pericardial
fluid
Presumptive case
»

Case Definitions
Gram negative diplococci in any of above normally
sterile fluids
Probable case
»
+ antigen test for organism in blood or CSF with illness
profile for meningococcal disease
3. American Academy of Pediatrics, Meningococcal disease prevention and control strategies for practice-based physicians, Pediatrics, 97:3, 1996, 405
30
Diagnosis

Laboratory Findings
Meningococcemia
15
»
»
»
»
»
»
»
isolation of N. meningitidis
14, 15
left shift leukocytosis
14
leukopenia (overwhelming disease)
15
coagulopathy
metabolic acidosis14
14
proteinuria
14, 15
increased urine specific gravity
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 34
15. Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 2
31
Diagnosis

Laboratory Findings
Meningitis - CSF
»
+ for N. meningitidis
–
»
»
»
Normal in early or overwhelming infection
WBCs - >90% segmented neutrophils
> protein levels
< glucose levels (< 60 mg/dL)
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 34
32
Treatment

Definitions
Primary case - occurs in the absence of previously
known close contact with another case

Secondary case - occurs among close contacts of
a primary case > 24 hours after onset of illness in
primary case

Coprimary case - two or more cases occur among
group of close contacts with illness onsets separated
by < 24 hours
6. CDC, Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks:
recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 15
33
Treatment

Treatment - Primary Cases
Appropriate antibiotics
»
»
»
»
Penicillin G1,14
Cefotaxime1
Ceftriaxone1,14
Chloramphenicol (for penicillin-resistant)14
1.
Apicella MA, Chapter 189: Neisseria meningitidis. In: Principles and Practice of Infectious Diseases, 4th ed. Eds. Mandell GL, et al. Churchill
Livingstone, New York, 1995, 1903
14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 36
34
Control

Close contacts »
»
»

Definitions
household members
day care center contacts
persons directly exposed to the patient’s oral secretions
(e.g. through mouth-to-mouth resuscitation or kissing)
Organization-based outbreak »
»
»
three or more confirmed or probable cases during period
< 3 mos. in persons with common affiliation, but no close
contact
primary disease attack rate of >10 cases/100,000
includes schools, universities, correctional facilities
6. CDC, Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks:
recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 15
35
Control

Community-based outbreak »
»
»

Definitions
three or more confirmed or probable cases during period
< 3 months among residents in same area with no close
contact and not sharing common affiliation
primary attack rate of >10 cases/100,000
includes towns, cities, counties
Population at risk - group of persons, who, in addition to
close contacts, are considered to be at increased risk for
disease, when compared with historical patterns of disease risk
in the same population
6. CDC, Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks:
recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 15, 16
36
Control





Ten Steps to Control
Establish diagnosis
Administer chemoprophylaxis to contacts
Enhance surveillance, save isolates, review
historical data
Investigate links between cases
Consider subtyping
6. CDC, Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks:
recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 20
37
Control






Ten Steps to Control
Exclude secondary & co-primary cases
Determine if suspected outbreak is organizationor community-based
Define population at risk and determine size
Calculate attack rate
Select target group for vaccination
Refer to MMWR reference below for information
6. CDC, Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks:
recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 13-22
38
Control



4.
Chemoprophylaxis Contact Cases
Rifampin
Ciprofloxacin
Ceftriaxone
CDC, Control and prevention of meningococcal disease and control and prevention of serogroup C meningococcal disease: evaluation and
management of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR, 46:RR-5, 1997, 6
39
Vaccination


Menomune® A/C/Y/W-135
Meningococcal Polysaccharide Vaccine, Groups A, C,
Y and W-135 Combined16
Dose 0.5 ml, subcutaneously16

Protective antibody levels may be achieved 7 to 10
days post-vaccination16

Revaccination may be indicated for persons
remaining at high risk16

Refractoriness to group C polysaccharide may limit
secondary response24
16. Pasteur Mérieux Connaught Meningococcal Polysaccharide Vaccine Groups A, C, Y and
W-135 Combined, Menomune ® - A/C/Y/W-135 package insert, June 1998, Copy serial
2494
24. Granoff DM, et al, Induction of immunologic refractoriness in adults by meningococcal
C polysaccharide vaccination, J Infec Dis, 178:1998, 874
40
Vaccination
Indications

Active immunization against serogroups
A, C, Y, W-135

May be used to prevent & control outbreaks of
serogroup C

Does not protect against other serogroups or
etiologic agents

Not for < 2 years of age except as short-term
protection of infants >3 mos. against group A
16. Pasteur Mérieux Connaught Meningococcal Polysaccharide Vaccine Groups A, C, Y and W-135 Combined, Menomune ® - A/C/Y/W-135 package insert,
June 1998, Copy serial 2494
41
Vaccination

Efficacy
Group A & C - 85% to 100% in children
> 4 yrs. & adults
Group A/C/Y/W-135 - 85% in 2 to 29 yr. olds
in controlling group C outbreaks
Group A/C/Y/W-135 - 93% in preschoolers
2 to 5 yrs. in controlling group C outbreaks
Group A/C/Y/W-135 - > 4-fold increase
increased bactericidal antibody; 90% subjects16
16

18

18

16. Pasteur Mérieux Connaught Meningococcal Polysaccharide Vaccine Groups A, C, Y and W-135 Combined, Menomune ® - A/C/Y/W-135 package insert, June
1998, Copy serial 2494
18. Rosenstein N, et al, Efficacy of meningococcal vaccine and barriers to vaccination, JAMA, 279:6, 1998, 435, 437
42
Vaccination

Vaccine Use
Routine vaccination recommended for high risk
groups:
»
»
»
»
deficiencies in late complement components
(C3, C5-C9)
functional or actual asplenia
persons with laboratory or industrial exposure to
N. meningitidis aerosols
travelers to, and residents of, hyperendemic areas
such as sub-Saharan Africa
16. Pasteur Mérieux Connaught Meningococcal Polysaccharide Vaccine Groups A, C, Y and W-135 Combined, Menomune ® - A/C/Y/W-135 package insert, June
1998, Copy serial 2494
43
Vaccination

Vaccine Use
Consider vaccination for
»
»
college students to reduce risk as recommended by
the American College Health Association (ACHA)16
household or institutional contacts16
16. Pasteur Mérieux Connaught Meningococcal Polysaccharide Vaccine Groups A, C, Y and W-135 Combined, Menomune ® - A/C/Y/W-135 package insert, June 1998,
Copy serial 2494
44
Vaccination

Contraindications
»
»

defer during any acute illness
known sensitivity to thimerosal, or any other vaccine
component
Warnings
»
»
»

Contraindications, Warnings
contains latex rubber in stopper
expected response may not be obtained in
immunosuppressed persons
do not give concurrently with whole-cell pertussis or
whole-cell typhoid vaccines
As with any vaccine, vaccination does not protect
100% of all susceptible individuals
16. Pasteur Mérieux Connaught Meningococcal Polysaccharide Vaccine Groups A, C, Y and W-135 Combined, Menomune ® - A/C/Y/W-135 package insert, June
1998, Copy serial 2494
45
Vaccination

Precautions
Precautions
»
»
»
»
»
health care worker to assure safe and effective
use of vaccine
epinephrine (1:1000) to be immediately available
review patient’s history and current health
use separate, sterile syringe and needle for each
patient
avoid intradermal, intramuscular, intravenous
injections
16. Pasteur Mérieux Connaught Meningococcal Polysaccharide Vaccine Groups A, C, Y and W-135 Combined, Menomune ® - A/C/Y/W-135 package insert, June
1998, Copy serial 2494
46
Vaccination




Adverse Reactions
Mild, consisting mainly of pain & redness at
injection site for 1 to 2 days
Transient fever in < 2% of young children
No significant systemic reactions reported in
150 adults observed
Other reactions - mild to moderate
headaches, malaise, mild chills and fever
16. Pasteur Mérieux Connaught Meningococcal Polysaccharide Vaccine Groups A, C, Y and W-135 Combined, Menomune ® - A/C/Y/W-135 package insert, June
1998, Copy serial 2494
47
New
Developments

PCR (polymerase chain reaction) testing
peripheral blood (buffy coat) used in research
laboratories:19
»
»
»
»

PCR Testing
100% specificity
rapid & sensitive
sensitivity unaffected by antibiotic treatment
serotype can be identified
May also be used on normally sterile fluids
such as CSF
19. Newcombe J, et al, PCR of peripheral blood for diagnosis of meningococcal disease, Journal of Clinical Microbiology, 34:7, 1996, 1637
48
New
Developments

Treatments
Additional data required to establish efficacy of
dexamethasone therapy to control
inflammation
Rare, intermediate penicillin-resistant isolates
in Europe, South Africa, North Carolina
Chloramphenicol-resistant serogroup B strains
in Vietnam & France
20,21

20

22
20. Quagliarello VJ, Scheld WM, Treatment of bacterial meningitis, N Engl J Med, 336:10, 1997, 710, 713
21. Schaad UB, et al, Steroid therapy for bacterial meningitis, Clin Infect Dis, 20, 1995, 689
22. Galimand M, et al, High-level Chloramphenicol resistance in Neisseria meningitidis. N Engl J Med,339:13, 1998, 868
49
New
Developments




Vaccines in Development
Conjugate vaccines
Single strain, outer membrane protein (OMP)
vaccines
Recombinant multivalent serosubtype vaccines
Lipopolysaccharide (LPS) vaccines
10. Poolman JT, Development of a meningococcal vaccine, Infectious Agents and Disease, 4:1, 1995, 24
50