Presentation is loading. Please wait.

Presentation is loading. Please wait.

1 Meningococcal Disease Neisseria meningitidis MKT4734 1/1/99.

Similar presentations


Presentation on theme: "1 Meningococcal Disease Neisseria meningitidis MKT4734 1/1/99."— Presentation transcript:

1 1 Meningococcal Disease Neisseria meningitidis MKT4734 1/1/99

2 2 Neisseria meningitidis l Gram negative diplococcus with polysaccharide capsule l 13 serogroups classed by capsular specificity (A/B/C/Y/W-135 & others) l T-independent capsular antigen (no memory response) l 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,

3 3 Antigens & Virulence Factors Etiology Pili Polysaccharide Capsule 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 4 Neisseria meningitidis l Incubation - 2 to 10 days; often 3 to 4 2 l Transmission 2 - » respiratory route » direct contact l Reservoir - humans only 10 l Carrier prevalence - 5% to 10% 10, 14 Epidemiology 2.WHO Information Fact Sheets, Meningococcal meningitis-Update: 10.Poolman JT, Development of a meningococcal vaccine, Infectious Agents and Disease, 4:1, 1995, Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33

5 5 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 l Group A epidemics:

6 6 Global Epidemiology l Meningitis belt - peaks in dry season l Epidemics occasionally occur in: » Saudi Arabia » Kenya & Tanzania » Burundi & Mongolia l CDC travelers information - (404) 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

7 7 U. S. Epidemiology l cases ( ) and deaths ( ) annually 23 l Highest total disease incidence in children 3 to 12 mos. of age 4 l Leading cause of bacterial meningitis in ages 2 to 18 yrs. 5 l Peaks late winter/early spring 4 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, CDC. Summary of notifiable diseases, United States, MMWR 45:53, 1996,74, 76, 80 Serogroup Distribution

8 8 U.S. Total Disease Incidence 59 yrs 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 Incidence (cases/100,000) < >59 Age (years)

9 9 U.S. Total Disease Incidence < 1 to 23 mos 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 Incidence (cases/100,000) U.S. Incidence of Meningococcal Disease < 1 to 23 Months

10 10 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 Age (months)

11 11 Meningococcal Disease United States l Case-fatality rate » 13% for meningitic disease (isolated in CSF) 4 » 11.5% when isolated from blood 4 » case-fatality rate even higher with severe meningococcemia 1 » case-fatality rate consistent in spite of antibiotic use 4 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, 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

12 12 U.S.A.- Changing Serogroup Prevalence ’s l Group C common cause of outbreaks since early 1990’s 6 l Group Y disease also increasing 4 l Overall invasive disease incidence constant 1.3/100,000 (since 1986) 5 l 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, 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

13 13 Serogroup C Outbreaks - United States l 21 outbreaks 6 » 8 school outbreaks 8 » 3 institutional outbreaks 8 » 10 community outbreaks (no known contact) 8 l Affect school-aged children & young adults 8 l High frequency and severity of sequelae 17 l 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, Erickson L, et al, Complications and sequelae of meningococcal disease in Quebec, Canada, , Clin Infect Dis, 26, 1998, 1163

14 14 Serogroup Y Disease - United States l Increasing proportion of disease since l More frequently associated with meningococcal pneumonia 7 l Median age 21.8 yrs. 7 Epidemiology 7.CDC, Serogroup Y meningococcal disease - Illinois, Connecticut, and selected areas, United States, , MMWR, 45:46, 1996, Quick uptakes... meningitis patterns shift, JAMA, 279:16, 1998, 1249

15 15 Epidemiology Clinical Syndromes Schuchat A, et al, Bacterial meningitis in the United States in 1995, The New England Journal of Medicine, 337, 1997, 973

16 16 Risk Groups l Persons with terminal complement deficiencies l Persons with anatomic or functional asplenia l Persons with immunosuppression l Industrial or laboratory personnel routinely exposed to organism l 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

17 17 Stages of Pathogenesis Organism Enters Nose or Mouth 11 Mucosal Barrier Cleared 11 Intravascular Space Invaded Quagliarello V, et al, Bacterial meningitis: pathogenesis, pathophysiology, and progress, The New England Journal of Medicine, 327:12, 1992, 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 Response 12 (Cytokines, PAF*, Arachidonic Metabolites) * Platelet activation factor

18 18 Disease Manifested Pathogenesis Host Response 12 Effective Immune Response Blood Brain Barrier Breached Vascular Damage, DIC *, Tissue Damage, Shock Meningococcemia without Meningitis Bacteremia without Sepsis 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, Saez-Llorens X, et al, Molecular pathophysiology of bacterial meningitis: current concepts and therapeutic implications, The Journal of Pediatrics, 116:5, 1990, 672, 673, 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, Glode MP, Smith AL, Meningococcal disease. In: Textbook of Pediatric Infectious Diseases. Eds. Feigin RD, et al. W. B. Saunders Company, Phila., 1981, ,13, 26 1,12 13,26 1,12 13,26 * Disseminated Intravascular Coagulation

19 19 Meningococcemia without Meningitis l Malaise, weakness, nausea, myalgia, arthralgia 15 l Significant fever & chills 15 l Macular, erythematous rash usually on extremities 15 l Petechiae/purpura on extremities 14,15 l Hypotension 14 Clinical Manifestations 14.Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 2

20 20 Meningococcemia without Meningitis (cont’d.) l Disseminated intravascular coagulation (DIC) 14 l Multiorgan failure 14 l Laboratory abnormalities 15 » 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, Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 2 Clinical Manifestations

21 21 Meningococcemia Complications l Waterhouse-Friderichsen syndrome (10%) 15 l Pneumonia 1 l Endocarditis, myocarditis, pericarditis 15 l Pleurisy 15 l Peritonitis 15 l Arthritis 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, Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 2 Clinical Manifestations

22 22 Expressions of Waterhouse- Friderichsen Syndrome l Fulminant septicemia l Shock l Purpura fulminans l DIC l Congestive heart failure l Bilateral adrenal hemorrhage l 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 Clinical Manifestations

23 23 Meningitis with/without Meningococcemia l Fever l Headache l Nuchal rigidity l 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

24 24 Meningitis with/without Meningococcemia l 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

25 25 Pathogenesis - Meningitis Skull Brain Capillary in arachnoid Space Clinical Manifestations Dura mater

26 26 Pathogenesis - Meningitis Blood Brain Barrier (Tight Junctions) Meningococci Clinical Manifestations

27 27 Pathogenesis - Meningitis Clinical Manifestations 1. Meningococci release endotoxins 2. Cytokines summoned; endothelial cell inflamed 4. Neutrophils summoned; attach to endothelium 3. Blood Brain Barrier 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, Saez-Llorens X, et al, Molecular pathophysiology of bacterial meningitis: current concepts and therapeutic implications, Journ Pediatrics, 116:5, 1990, 672, 673,

28 28 Diagnostic Features (Adults & Children) l Upper respiratory symptoms l Headache l Petechiae/purpura (significant finding) l Fever l Extreme vomiting l Photophobia l Nuchal rigidity Diagnosis 14.Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 33

29 29 Diagnostic Features (Infants) l Irritability l Full fontanel l Poor feeding l Elevated or subnormal temperature l Vomiting l Lethargy l Altered consciousness levels l Increased intracranial pressure (ICP) l 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

30 30 Case Definitions l Confirmed case » isolation N. meningitidis from blood, CSF, petechiae or purpuric lesions, synovial fluid, pleural fluid, pericardial fluid l Presumptive case » Gram negative diplococci in any of above normally sterile fluids l 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

31 31 Laboratory Findings l Meningococcemia » isolation of N. meningitidis 15 » left shift leukocytosis 14, 15 » leukopenia (overwhelming disease) 14 » coagulopathy 15 » metabolic acidosis 14 » proteinuria 14 » increased urine specific gravity 14, Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, Howe WB, Meningococcemia heading off a killer, The Physician and Sportsmedicine, 24:2, 1996, 2 Diagnosis

32 32 Laboratory Findings l 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

33 33 Definitions l Primary case - occurs in the absence of previously known close contact with another case l Secondary case - occurs among close contacts of a primary case > 24 hours after onset of illness in primary case l 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

34 34 Treatment - Primary Cases l Appropriate antibiotics » Penicillin G 1,14 » Cefotaxime 1 » Ceftriaxone 1,14 » 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, Herf C, et al, Meningococcal disease: recognition, treatment, and prevention, The Nurse Practitioner, 23:8, 1998, 36 Treatment

35 35 Definitions l 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) l 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 36 Definitions l 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 l 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

37 37 Ten Steps to Control l Establish diagnosis l Administer chemoprophylaxis to contacts l Enhance surveillance, save isolates, review historical data l Investigate links between cases l 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 38 Ten Steps to Control l Exclude secondary & co-primary cases l Determine if suspected outbreak is organization- or community-based l Define population at risk and determine size l Calculate attack rate l Select target group for vaccination l 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, Control

39 39 Chemoprophylaxis - Contact Cases l Rifampin l Ciprofloxacin l 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

40 40 Menomune ® - A/C/Y/W-135 l Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined 16 l Dose 0.5 ml, subcutaneously 16 l Protective antibody levels may be achieved 7 to 10 days post-vaccination 16 l Revaccination may be indicated for persons remaining at high risk 16 l Refractoriness to group C polysaccharide may limit secondary response 24 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 Granoff DM, et al, Induction of immunologic refractoriness in adults by meningococcal C polysaccharide vaccination, J Infec Dis, 178:1998, 874

41 41 Indications l Active immunization against serogroups A, C, Y, W-135 l May be used to prevent & control outbreaks of serogroup C l Does not protect against other serogroups or etiologic agents l Not for 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

42 42 Efficacy l Group A & C - 85% to 100% in children > 4 yrs. & adults 16 l Group A/C/Y/W % in 2 to 29 yr. olds in controlling group C outbreaks 18 l Group A/C/Y/W % in preschoolers 2 to 5 yrs. in controlling group C outbreaks 18 l Group A/C/Y/W > 4-fold increase increased bactericidal antibody; 90% subjects 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 Rosenstein N, et al, Efficacy of meningococcal vaccine and barriers to vaccination, JAMA, 279:6, 1998, 435, 437 Vaccination

43 43 Vaccine Use l 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 44 Vaccine Use l Consider vaccination for » college students to reduce risk as recommended by the American College Health Association (ACHA) 16 » household or institutional contacts 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

45 45 Contraindications, Warnings l Contraindications » defer during any acute illness » known sensitivity to thimerosal, or any other vaccine component l 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 l 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 46 Precautions l 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 47 Adverse Reactions l Mild, consisting mainly of pain & redness at injection site for 1 to 2 days l Transient fever in < 2% of young children l No significant systemic reactions reported in 150 adults observed l 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 48 PCR Testing l 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 l May also be used on normally sterile fluids such as CSF New Developments 19. Newcombe J, et al, PCR of peripheral blood for diagnosis of meningococcal disease, Journal of Clinical Microbiology, 34:7, 1996, 1637

49 49 Treatments l Additional data required to establish efficacy of dexamethasone therapy to control inflammation 20,21 l Rare, intermediate penicillin-resistant isolates in Europe, South Africa, North Carolina 20 l Chloramphenicol-resistant serogroup B strains in Vietnam & France Quagliarello VJ, Scheld WM, Treatment of bacterial meningitis, N Engl J Med, 336:10, 1997, 710, Schaad UB, et al, Steroid therapy for bacterial meningitis, Clin Infect Dis, 20, 1995, Galimand M, et al, High-level Chloramphenicol resistance in Neisseria meningitidis. N Engl J Med,339:13, 1998, 868 New Developments

50 50 Vaccines in Development l Conjugate vaccines l Single strain, outer membrane protein (OMP) vaccines l Recombinant multivalent serosubtype vaccines l Lipopolysaccharide (LPS) vaccines 10.Poolman JT, Development of a meningococcal vaccine, Infectious Agents and Disease, 4:1, 1995, 24 New Developments


Download ppt "1 Meningococcal Disease Neisseria meningitidis MKT4734 1/1/99."

Similar presentations


Ads by Google