1. 1 Helping to Protect Against Meningococcal Disease Diana Christensen MD Assistant Professor of Medicine Infectious Diseases Attending University of Louisville MKT25429

2. 2 Extending Our Heritage: Helping to Protect Against Meningococcal Disease MKT25429 Photo courtesy of Centers for Disease Control and Prevention (CDC).

3. 3 Table of Contents I. I. Neisseria meningitidis: “An important and devastating human pathogen” 1 II. II. Prevention of Meningococcal Disease III. III. ACIP a Recommendations for Use of Meningococcal Vaccines I. I. Vaccines a ACIP = Advisory Committee on Immunization Practices. Reference: 1. Stephens DS, et al. Lancet. 2007;369(9580):2196-2210.

4. 4 Neisseria meningitidis: “An important and devastating human pathogen” 1 Reference: 1. Stephens DS, et al. Lancet. 2007;369(9580):2196-2210. Photo reprinted with permission from Schoeller T, Schmutzhard E. N Engl J Med. 2001;344(18):1372. Copyright © 2001 Massachusetts Medical Society. All rights reserved. Although rare, N meningitidis is “a worldwide cause of epidemic meningitis and rapidly progressing fatal shock” 1

5. 5 Difficult to Diagnose, Rapidly Lethal 1 Reference: 1. Thompson MJ, et al. Lancet. 2006;367(9508):397-403. 12–15 hours Characteristic 15– ~24 hours Late 4–8 hours Nonspecific Typical time course of meningococcemia and meningitis Fever, irritability, nausea or vomiting, drowsiness, poor appetite, sore throat, coryza, general aches Hemorrhagic rash, neck pain, meningismus, photophobia Confusion or delirium, seizure, unconsciousness; possible death Hospital admission at median of ~19 hours Improved recognition of early symptoms of sepsis—leg pain, cold hands and feet, and abnormal skin color—might increase early identification of disease and shorten the time to hospital admission

6. 6 Historically, 800-2800 cases per year in the United States 1,2 – – Fewer in recent years: ~800-1200 per year during 2006-2010 1,2 – – More than 95% of cases are sporadic; fewer than 5% are related to outbreaks 1 Case-fatality rate of 9%-12% 1,3 – – Up to 40% for meningococcemia 1,3 Significant sequelae in 11%-19% of survivors 3 – – Amputation, hearing loss, neurologic or cognitive deficits References: 1. CDC. Meningococcal disease. In: Epidemiology and Prevention of Vaccine-preventable Diseases. (The Pink Book). Atkinson W, Wolfe S, Hamborsky J, eds. 12th ed. Washington, DC: Public Health Foundation, 2011:193-204. 2. CDC. MMWR. 2011;60(32):1088-1101. 3. Rosenstein N, et al. N Engl J Med. 2001;344(18):1378-1388. Meningococcal Disease: Significant Morbidity and Mortality

7. 7 Meningococcemia Petechial or purpuric rash Disseminated intravascular coagulation Hypotension Shock Multi-organ failure Common Clinical Presentations of Meningococcal Disease 1 Reference: 1. Rosenstein NE, et al. N Engl J Med. 2001;344(18):1378-1388. Meningitis Fever and headache (influenza-like symptoms) Stiff neck Nausea Altered mental status Seizures © www.meningitis-trust.org.

8. 8 Meningitis Spastic quadriplegia 5 Hearing loss 1-5 Cortical venous thrombophlebitis 4 Cerebral edema 4 Cranial nerve palsies 4 Mental retardation 4 Hemiparesis 4 Meningococcemia Limb loss from gangrene 1-3 Skin scars from necrosis 2,3 Renal failure 2 Septic arthritis 1,2,4 Pneumonia 1 Epiglottitis 1 Pericarditis 1,4 Serious Outcomes of Meningococcal Disease References: 1. Rosenstein NE, et al. N Engl J Med. 2001;344(18):1378-1388. 2. Erickson L, De Wals P. Clin Infect Dis. 1998;26(5):1159-1164. 3. Erickson LJ, et al. Clin Infect Dis. 2001;33(5):737-739. 4. Munford RS. Meningococcal infections. In: Braunwald E, et al, eds. Harrison’s Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill Professional;2001:927-931. 5. Fellick JM, et al. Arch Dis Child. 2001;85(1):6-11.

9. 9 Age-specific Fatalities From Meningococcal Disease References: 1. Hoyert DL, et al. Natl Vital Stat Rep. 2001;49(8):1-116. 2. Miniño AM, et al. Natl Vital Stat Rep. 2002;50(15):1-120. 3. Arias E, et al. Natl Vital Stat Rep. 2003;52(3):1-116. 4. Kochanek KD, et al. Natl Vital Stat Rep. 2004;53(5):1-116. 5. Hoyert DL, et al. Natl Vital Stat Rep. 2006;54(13):1-120. 6. Miniño AM, et al. Nat Vital Stat Rep. 2007;55(19):1-120. 7. Kung H-C, et al. Natl Vital Stat Rep. 2008;56(10):1-124. 8. Heron M, et al. Natl Vital Stat Rep. 2009;57(14):1-136. 9. Xu J, et al. Natl Vital Stat Rep. 2010;58(19):1-136. 10. Miniño AM, et al. Nat Vital Stat Rep. 2011;59(10):1-126. 11. Kochanek KD, et al. Nat Vital Stat Rep. 2011;60(3):1-166.. United States, 1999-2009 1-11

10. 10 Clinically Significant N meningitidis Serogroups 1 A Leading cause of epidemic meningitis worldwide Most prevalent serogroup in Africa and China Rare in Europe and the Americas B A major cause of endemic disease in Europe and the Americas No vaccine commercially available in US C A major cause of endemic disease in Europe, North America Multiple outbreaks in schools and/or community Y Associated with pneumonia Increasing problem in the United States, affecting all age groups W-135 Small percentage of infections worldwide Recent outbreaks associated with hajj pilgrims Serogroup Characteristics Reference: 1. Granoff DM, et al. Meningococcal vaccines. In: Plotkin SA, et al, eds. Vaccines. 5th ed. Philadelphia, PA: Saunders Elsevier, 2008:399-434.

11. 11 Annual US Deaths from Meningococcal Disease, 0-24 Years of Age, All Serogroups, 1998-2007 1 Reference: 1. Cohn AC, et al, CDC. Clin Infect Dis. 2010;50(2):184-191. Age Group (Years)

12. 12 Prevention of Meningococcal Disease

13. 13 Meningococcal Vaccines Currently Licensed in the United States Menactra vaccine 1 – – Licensed: 2005 – – Indicated for: Individuals 9 months-55 years of age Menveo ®a (Meningococcal [Groups A, C, Y and W-135] Oligosaccharide Diphtheria CRM 197 Conjugate Vaccine) 2 – – Licensed: 2010 – – Indicated for: Individuals 2-55 years of age Menomune-A/C/Y/W-135 3 – – Licensed: 1981 – – Indicated for: Individuals 2 years of age and older MenHibrix ®b (Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine) 4 – – Licensed: 2012 – – Indicated for: Individuals 6 weeks-18 months of age a Menveo is a registered trademark of Novartis AG. b MenHibrix is a registered trademark of GlaxoSmithKline. References: 1. Menactra vaccine [Prescribing Information]. Swiftwater, PA: Sanofi Pasteur Inc., 2011. 2. Menveo [Prescribing information]. Cambridge, MA: Novartis Vaccines and Diagnostics, Inc., 2011. 3. Menomune-A/C/Y/W-135 vaccine [Prescribing Information]. Swiftwater, PA: Sanofi Pasteur Inc., 2009. 4. MenHibrix [Prescribing Information]. Research Triangle Park, NC: GlaxoSmithKline, 2012.

14. 14 ACIP Recommendations for Use of Meningococcal Vaccines Note: Some of the ACIP recommendations for use of meningococcal vaccines are inconsistent with the currently labeled indications for meningococcal conjugate vaccines.

15. 15 ACIP Recommendations for Use of Meningococcal Conjugate Vaccine in Adolescents Routine vaccination with quadrivalent meningococcal conjugate vaccine is recommended at 11 or 12 years of age 1,2 A booster dose is recommended at 16 years of age 1,a – – For adolescents who received the first dose of meningococcal conjugate vaccine at 13-15 years of age, a single booster dose should be administered preferably at 16-18 years of age 1,a – – Persons who receive their first dose of meningococcal conjugate vaccine at or after 16 years of age do not need a booster dose 1,a Unvaccinated persons 11-18 years of age should be vaccinated at “the earliest possible health-care visit” 2 Routine vaccination of healthy persons not at increased risk for exposure to N meningitidis is not recommended after 21 years of age 1 References: 1. CDC. MMWR. 2011;60(3):72-76. 2. CDC. MMWR. 2007;56(31):794-795. a These recommendations are inconsistent with the currently labeled indications for meningococcal conjugate vaccines.

16. 16 ACIP Guidance on Meningococcal Vaccines and College Enrollment 1 Some schools, colleges, and universities require vaccination against meningococcal disease prior to enrollment Persons ≤21 years of age should have documentation of receipt of a dose of meningococcal conjugate vaccine not more than 5 years before enrollment If the primary dose was administered before the 16th birthday, a booster dose should be given prior to enrollment in college a – – Booster can be given at any time after the 16th birthday a – – Minimum interval between doses of meningococcal conjugate vaccine is 8 weeks a Reference: 1. CDC. MMWR. 2011;60(3):72-76. a These recommendations are inconsistent with the currently labeled indications for meningococcal conjugate vaccines.

17. 17 ACIP Recommendations: 2-Dose Primary Series for Certain Persons at High Risk 1,a Two doses of meningococcal conjugate vaccine, 2 months apart, are recommended as a primary series for: Persons 2-55 years of age with persistent complement component deficiencies or functional or anatomic asplenia – – Booster vaccination then needed every 5 years Persons infected with human immunodeficiency virus (HIV) – – For HIV-infected persons 11-18 years of age: Give booster at 16 years of age if primary dose is given at 11-12 years of ageGive booster at 16 years of age if primary dose is given at 11-12 years of age Give booster at 16-18 years of age if primary dose is given at 13-15 years of ageGive booster at 16-18 years of age if primary dose is given at 13-15 years of age No booster needed if primary dose is given at ≥16 years of ageNo booster needed if primary dose is given at ≥16 years of age Reference: 1. CDC. MMWR. 2011;60(3):72-76. a These recommendations are inconsistent with the currently labeled indications for meningococcal conjugate vaccines.

18. 18 ACIP Recommendations: Vaccination of Persons at “Prolonged Increased Risk” 1 Persons 2-55 years of age who are at prolonged increased risk for exposure to N meningitidis include: – – Travelers to or residents of countries where meningococcal disease is hyperendemic or epidemic – – Microbiologists who routinely work with N meningitidis These individuals should receive – – 1 primary dose of meningococcal conjugate vaccine – – Booster dose if the person remains at increased risk: a If 2-6 years of age at primary dose, give booster dose 3 years later If ≥7 years of age at primary dose, give booster dose 5 years later Reference: 1. CDC. MMWR. 2011;60(3):72-76. a These recommendations are inconsistent with the currently labeled indications for meningococcal conjugate vaccines.

19. 19 ACIP Recommendations for Use of Menactra Vaccine in Infants and Children 1,2 The ACIP recommends use of Menactra vaccine in infants and children 9 months through 23 months of age who are at high risk for meningococcal disease, including those who: a – – Have persistent complement component deficiencies (eg, C5-C9, properdin, factor H, or factor D) – – Are at risk during a community or institutional outbreak – – Are traveling to an area where meningococcal disease is epidemic or hyperendemic The recommendation is for 2 doses, given 3 months apart a Does not include infants and children 9 months through 23 months of age with functional or anatomic asplenia. References: 1. CDC. MMWR. 2011;60(40):1391-1392. 2. ACIP. Vaccines for Children Program Resolution. Vaccines to Prevent Meningococcal Disease. Adopted and effective October 24, 2012. http://www.cdc.gov/vaccines/ programs/vfc/downloads/resolutions/1012-2-mening-mcv.pdf. Accessed December 12, 2012.

20. 20 ACIP Recommendations for Use of Menactra Vaccine in Infants and Children 1,2 (cont) For infants and children who received the 2-dose series at 9-23 months of age and are at prolonged increased risk of meningococcal disease: – – A booster dose should be given 3 years after completing the primary series a – – After the initial booster, persons who remain in a group at increased risk for disease should continue to receive a booster at 5-year intervals a References: 1. CDC. MMWR. 2011;60(40):1391-1392. 2. ACIP. Vaccines for Children Program Resolution. Vaccines to Prevent Meningococcal Disease. Adopted and effective October 24, 2012. http://www.cdc.gov/ vaccines/programs/vfc/downloads/resolutions/1012-2-mening-mcv.pdf. Accessed December 12, 2012. a These recommendations are inconsistent with the currently labeled indications for meningococcal conjugate vaccines.

21. 21 Use of Meningococcal Conjugate and Polysaccharide Vaccines Meningococcal conjugate vaccine is preferred over polysaccharide vaccine in persons for whom conjugate vaccine is indicated 1 Polysaccharide vaccine is currently the only vaccine licensed for individuals >55 years of age 1 In outbreaks: 2 – – Either vaccine can be used – – Conjugate vaccine is preferred if the population targeted for vaccination includes age groups for which conjugate vaccine is licensed References: 1. CDC. Meningococcal vaccines: what you need to know, 10/14/11. http://www.cdc.gov/vaccines/pubs/vis/ #mening. Accessed July 2, 2012. 2. CDC. MMWR. 2005;54(RR-7):1-21.

22. 22 Menomune and Menactra Vaccines: 4 Decades of Meningococcal Disease Prevention Efforts

23. 23 Menomune Vaccine 1 Meningococcal Polysaccharide Vaccine Groups A, C, Y and W-135 Combined Menomune – A/C/Y/W-135 vaccine is indicated for active immunization for the prevention of invasive meningococcal disease caused by N meningitidis serogroups A, C, Y, and W-135 Menomune – A/C/Y/W-135 vaccine is approved for use in persons 2 years of age and older Standard of care in meningococcal vaccination for 25 years, 1981-2005 Distributed in: United States, Argentina, Australia, Botswana, Canada, Egypt, Indonesia, Kenya, Malaysia, Mexico, Namibia, New Zealand, Philippines, Singapore, South Africa, and Thailand Reference: 1. Menomune vaccine [Prescribing Information]. Swiftwater, PA: Sanofi Pasteur Inc., 2012.

24. 24 Important Safety Information for Menomune-A/C/Y/W-135 Vaccine (cont) Safety Information The most common local and systemic adverse reactions include injection site pain, redness, and swelling; headaches, malaise, and fever. Other adverse reactions may occur. Menomune-A/C/Y/W-135 vaccine is contraindicated in persons with known hypersensitivity to any components of the vaccine (including thimerosal). Menomune-A/C/Y/W-135 vaccine is available in single-dose vials. For individuals sensitive to thimerosal, use the single-dose vial reconstituted with the preservative-free diluent. Vaccination with Menomune-A/C/Y/W-135 vaccine may not protect all individuals. Before administering Menomune-A/C/Y/W-135, please see full Prescribing Information.

25. 25 Menactra Vaccine 1 Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine Menactra vaccine is indicated for active immunization to prevent invasive meningococcal disease caused by N meningitidis serogroups A, C, Y, and W-135 1 Approved for use in individuals 9 months through 55 years of age Does not prevent N meningitidis serogroup B disease Reference: 1. Menactra vaccine [Prescribing Information]. Swiftwater, PA: Sanofi Pasteur Inc., 2011.

26. 26 Important Safety Information for Menactra Vaccine (cont) Safety Information The most common local and systemic adverse reactions to Menactra vaccine include injection site pain, redness, and induration (all age groups); irritability, crying, drowsiness, loss of appetite, and diarrhea (infants and children); headache, fatigue, and malaise (adolescents and adults). Other adverse reactions may occur. Menactra vaccine is contraindicated in persons with known hypersensitivity to any component of the vaccine. Persons previously diagnosed with Guillain-Barré syndrome (GBS) may be at increased risk of GBS following receipt of Menactra vaccine. The decision to give Menactra vaccine should take into account the potential benefits and risks. GBS has been reported in temporal relationship following administration of Menactra vaccine. Vaccination with Menactra vaccine may not protect all individuals. Before administering Menactra vaccine, please see full Prescribing Information.

27. 27 Menactra Vaccine Summary Menactra vaccine represents the latest phase of a 40-year corporate commitment to meningococcal disease prevention 7 years of real-world experience with >45 million doses distributed 1 Demonstrated immunogenicity and safety in clinical trials involving >51,000 US persons across all age groups 2 Approved for use in infants, children, adolescents, and adults 9 months-55 years of age 3 References: 1. Sanofi Pasteur Inc. Data on file (Doses sold from 2005-2012). July 2012. MKT25499. 2. Sanofi Pasteur Inc. Data on file (Menactra Vaccine Clinical Development Overview), November 2012. MKT25824. 3. Menactra vaccine [Prescribing Information]. Swiftwater, PA: Sanofi Pasteur Inc., 2011.

28. 28 THANK YOU THANK YOU QUESTIONS? QUESTIONS?