1

Meningococcal Disease

Neisseriameningitidis

MKT47341/1/99

2

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)

Etiology

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

3

Antigens & VirulenceFactors

Etiology

Pili

PolysaccharideCapsule

LPS

Opacity* Associated Protein (Opa)

* outer membrane proteins

10. Poolman JT, Development of a meningococcal vaccine, Infectious Agents and Disease, 4:1, 1995, 21

Porin*(PorA or PorB)

4

Neisseria meningitidis

Incubation - 2 to 10 days; often 3 to 42

Transmission2 -» respiratory route» direct contact

Reservoir - humans only10

Carrier prevalence - 5% to 10%10, 14

Epidemiology

2. WHO Information Fact Sheets, Meningococcal meningitis-Update: http://www.who.int/inf-fs/en/fact105.html10. Poolman JT, Development of a meningococcal vaccine, Infectious Agents and Disease, 4:1, 1995, 1314. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33

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Global Epidemiology Epidemiology

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

Senegal, Gambia, Guinea-Bissau, Guinea, Sierra Leone, Ivory Coast, Burkina Faso, Ghana, Togo, Benin, Nigeria, Cameroon, Chad, Niger, Mali, Cen. African Republic, Sudan, Uganda, Kenya, Ethiopia

Group A epidemics:

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Global Epidemiology

Meningitis belt - peaks in dry season Epidemics occasionally occur in:

» Saudi Arabia» Kenya & Tanzania» Burundi & Mongolia

CDC travelers information - (404) 332-4559

Epidemiology

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

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U. S. Epidemiology

2100 - 3500 cases (1981-1996) and 200 - 290 deaths (1986-1995) annually

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Highest total disease incidence in children 3 to 12 mos. of age

4

Leading cause of bacterial meningitis in ages 2 to 18 yrs.

5

Peaks late winter/early spring4

Epidemiology

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, 97023. CDC. Summary of notifiable diseases, United States, MMWR 45:53, 1996,74, 76, 80

B46%

Y5%

C45%

Others4%

Serogroup Distribution - 1989-1991

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U.S. Total Disease Incidence < 5 to > 59 yrs. - 1989 -1991Epidemiology

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

U.S. Incidence of Meningococcal Disease < 5 to > 59 Years 1989-1991

0

1

2

3

4

5

6

7

8

9

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e (

ca

se

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00

,00

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<5

5 - 1

0

10

- 15

15

- 20

20

- 24

25

- 29

30

- 34

35

- 39

40

- 44

45

- 49

50

- 54

55

- 59

>5

9

Age (years)

9

U.S. Total Disease Incidence < 1 to 23 mos. - 1989 -1991

Epidemiology

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

0

5

10

15

20

25

30

< 1 1-4 4-8 8-12 12-16 16-19 20-23Age (months)

Inci

den

ce

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00,0

00)

U.S. Incidence of Meningococcal Disease < 1 to 23 Months 1989-1991

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Bacterial Meningitis Incidence Major Causes

5. Schuchat A, et al, Bacterial meningitis in the United States in 1995, The New England Journal of Medicine, 337:1997, 972

Epidemiology

Bacterial Meningitis Incidence - 1995

0

1

2

3

4

5

6

7

1 - 23 mos 2 - 29 yrs 30 - 59 yrs > 60 yrs

Cas

es/1

00,0

00

Haemophilusinfluenzae

Streptococcuspneumoniae

Neisseriameningitidis

Group BStreptococcus

Listeriamonocytogenes

> 1 month of age

< 1 month0

20

40

60

80

100

120

140

Cas

es/1

00,0

00

< 1 month of age

Age (months)

11

Meningococcal Disease United States

Case-fatality rate» 13% for meningitic disease (isolated in CSF)

4

» 11.5% when isolated from blood4

» case-fatality rate even higher with severe meningococcemia1

» case-fatality rate consistent in spite of antibiotic use4

Epidemiology

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, 18994. 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

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U.S.A.- Changing Serogroup Prevalence - 1990’s

Group C common cause of outbreaks since early 1990’s6

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

Epidemiology

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

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Serogroup C Outbreaks - United States - 1980 - 1993

21 outbreaks6

» 8 school outbreaks8

» 3 institutional outbreaks8

» 10 community outbreaks (no known contact)8

Affect school-aged children & young adults 8

High frequency and severity of sequelae17

Most attack rates > 10 cases/100,000

(20 X higher than endemic rate)6

Epidemiology

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, 38617. Erickson L, et al, Complications and sequelae of meningococcal disease in Quebec, Canada, 1990-1994, Clin Infect Dis, 26, 1998, 1163

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Serogroup Y Disease - United States

Increasing proportion of disease since 19917

More frequently associated with meningococcal pneumonia7

Median age 21.8 yrs.7

Epidemiology

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

Changes in Serogroup Y Distribution 1978 - 1996 7, 9

33%

21%

2%

7%

0%

5%

10%

15%

20%

25%

30%

35%

1978-1981 1989-1991 1995 1995-1996

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Epidemiology Clinical Syndromes19955

5. Schuchat A, et al, Bacterial meningitis in the United States in 1995, The New England Journal of Medicine, 337, 1997, 973

Bacteremia48%Bacteremic

pneumonia3%

Meningitis48%

Other1%

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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

Epidemiology

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, 3 & 4

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Stages of Pathogenesis

Organism Enters Nose or Mouth11

Mucosal Barrier Cleared11

Intravascular Space Invaded11

11. Quagliarello V, et al, Bacterial meningitis: pathogenesis, pathophysiology, and progress, The New England Journal of Medicine, 327:12, 1992, 86512. 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

Pathogenesis

Host Response12

(Cytokines, PAF*, Arachidonic Metabolites)

* Platelet activation factor

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Disease ManifestedPathogenesis

Host Response12

Effective Immune Response

Blood Brain Barrier Breached

Vascular Damage, DIC*,Tissue Damage, Shock

Meningococcemia without Meningitis

Bacteremia withoutSepsis

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

1,13,

26

1,12

13,26

1,12

13,26

* Disseminated Intravascular Coagulation

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Meningococcemiawithout Meningitis

Malaise, weakness, nausea, myalgia, arthralgia15

Significant fever & chills15

Macular, erythematous rash usually on extremities15

Petechiae/purpura on extremities14,15

Hypotension14

Clinical Manifestations

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

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Meningococcemiawithout 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

Clinical Manifestations

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MeningococcemiaComplications

Waterhouse-Friderichsen syndrome (10%)15

Pneumonia1

Endocarditis, myocarditis, pericarditis15

Pleurisy15

Peritonitis15

Arthritis15

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

Clinical Manifestations

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Expressions of Waterhouse-Friderichsen Syndrome

Fulminant septicemia Shock Purpura fulminans DIC Congestive heart failure Bilateral adrenal hemorrhage Progressive, irreversible collapse15. Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 225. 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

Clinical Manifestations

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Meningitis with/withoutMeningococcemia

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

Clinical Manifestations

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Meningitis with/withoutMeningococcemia

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

Clinical Manifestations

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Pathogenesis - Meningitis

Skull

Brain Capillary in arachnoid Space

Clinical Manifestations

Dura mater

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Pathogenesis - Meningitis

Blood Brain Barrier(Tight Junctions)

Meningococci

Clinical Manifestations

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Pathogenesis - MeningitisClinical

Manifestations

1. Meningococci release endotoxins

2. Cytokines summoned; endothelial cell inflamed

4. Neutrophils summoned;attach to endothelium

3. Blood BrainBarrier disrupted

5. Neutrophils enter brain;secrete inflammatory factors;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

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Diagnostic Features(Adults & Children)

Upper respiratory symptoms Headache Petechiae/purpura (significant finding) Fever Extreme vomiting Photophobia Nuchal rigidity

Diagnosis

14. Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33

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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

Diagnosis

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Case Definitions

Confirmed case» isolation N. meningitidis from blood, CSF, petechiae or

purpuric lesions, synovial fluid, pleural fluid, pericardial fluid Presumptive case

» 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

Diagnosis

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Laboratory Findings

Meningococcemia» isolation of N. meningitidis

15

» left shift leukocytosis 14, 15

» leukopenia (overwhelming disease)14

» coagulopathy15

» metabolic acidosis14

» proteinuria14

» increased urine specific gravity14, 15

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

Diagnosis

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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

Diagnosis

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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

Treatment

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

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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

Treatment

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Definitions

Close contacts -» 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

Control

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

36

Definitions

Community-based outbreak - » 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

Control

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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

Control

38

Ten Steps to Control

Exclude secondary & co-primary cases Determine if suspected outbreak is organization-

or 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

Control

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Chemoprophylaxis -Contact Cases

Rifampin Ciprofloxacin Ceftriaxone

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, 6

Control

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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

Vaccination

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

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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

Vaccination

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Efficacy

Group A & C - 85% to 100% in children > 4 yrs. & adults16

Group A/C/Y/W-135 - 85% in 2 to 29 yr. olds in controlling group C outbreaks18

Group A/C/Y/W-135 - 93% in preschoolers 2 to 5 yrs. in controlling group C outbreaks18

Group A/C/Y/W-135 - > 4-fold increase increased bactericidal antibody; 90% subjects16

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

Vaccination

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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

Vaccination

44

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

Vaccination

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Contraindications, Warnings

Contraindications» defer during any acute illness» known sensitivity to thimerosal, or any other vaccine

component 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

Vaccination

46

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

Vaccination

47

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

Vaccination

48

PCR Testing

PCR (polymerase chain reaction) testing peripheral blood (buffy coat) used in research laboratories:19

» 100% specificity» rapid & sensitive» sensitivity unaffected by antibiotic treatment» serotype can be identified

May also be used on normally sterile fluids such as CSF

NewDevelopments

19. Newcombe J, et al, PCR of peripheral blood for diagnosis of meningococcal disease, Journal of Clinical Microbiology, 34:7, 1996, 1637

49

Treatments

Additional data required to establish efficacy of dexamethasone therapy to control inflammation20,21

Rare, intermediate penicillin-resistant isolates in Europe, South Africa, North Carolina20

Chloramphenicol-resistant serogroup B strains in Vietnam & France22

20. Quagliarello VJ, Scheld WM, Treatment of bacterial meningitis, N Engl J Med, 336:10, 1997, 710, 71321. Schaad UB, et al, Steroid therapy for bacterial meningitis, Clin Infect Dis, 20, 1995, 68922. Galimand M, et al, High-level Chloramphenicol resistance in Neisseria meningitidis. N Engl J Med,339:13, 1998, 868

NewDevelopments

50

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

NewDevelopments