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Update 2010: Vaccines: HZ, HPV, Pneumococcus

Update 2010: Vaccines: HZ, HPV, Pneumococcus. T. Mazzulli, MD, FRCPC, FACP Department of Microbiology Mount Sinai Hospital and University Health Network. Learning Objectives:.

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Update 2010: Vaccines: HZ, HPV, Pneumococcus

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  1. Update 2010:Vaccines: HZ, HPV, Pneumococcus T. Mazzulli, MD, FRCPC, FACP Department of Microbiology Mount Sinai Hospital and University Health Network

  2. Learning Objectives: • Realize that immunization against adult infectious diseases is one of the most successful interventions to protect the health of Canadians • Describe recent clinical updates and what’s new in routine adult immunizations: Zoster, HPV and Pneumococcus • Develop procedures to enhance immunization rates based on the most recent clinical guidelines in adult immunizations

  3. Immunization: • Saved more lives in Canada in the last 50 years than any other health intervention2 • Single most cost-effective health investment, making immunization a cornerstone of efforts to promote health2 Ten Great Public Health Achievements1900 - 19991 • Vaccination • Motor vehicle safety • Safer workplaces • Control of infectious diseases • Decline in deaths from coronary heart disease and stroke • Safer and healthier foods • Healthier mothers and babies • Family planning • Fluoridation of drinking water • Recognition of tobacco use as a health hazard • MMWR, December 24, 1999 • 2. Canadian Coalition for ImmunizationAwareness & Promotion. 2005

  4. Comparison of Maximum and Current Reported Morbidity:Vaccine-Preventable Diseases in the US

  5. Cost per Life Year Saved for Selected Vaccine Programs and Other Public Health Interventions Canadian Cost-Benefit of Adult Vaccination Adapted from 2006 Canadian Immunization Guide

  6. Burden of Vaccine Preventable Diseases • There are 200-300 vaccine preventable deaths in Children in the U.S. each year vs 50,000 Adult vaccine preventable deaths/year in the U.S.3 • Total economic burden of treating vaccine preventable diseases in adults in the US is greater than $10 billion/year1 1. Inf Disease Clinics of NA. 15(1):9-19, 2000 Mar 2. Poland 2005 Vaccine 23 p 2251-2255 3. Poland 2003 Am J Prev Med, 25(2): 144-50

  7. Comparison of Pediatric & Adult Immunization Coverage 1. CCDR: 32 (10 2006 Immunization coverage by age 2 for the five recommended vaccines in the Capital Health Region (Edmonton) 2. Canadian Adult National ImmunizationCoverage Survey 2006

  8. Adult Immunization: Routinely for All & Specific Groups Adult immunization programs present new and different challenges relative to childhood programs • Adult Immunization Schedule Classification: • Routinely for All2 • Specific Groups2 • Age1 • Occupation1 • Health Status1 • Behaviour (travel, sexual behaviour)1 1. Plotkins, S. et al, Immunization in the United States. Vaccines 2008:1479-1510 2. 2006 Canadian Immunization Guide

  9. Adult Immunization: Key Issues Immunosenescence: • Diminished immune response of both innate and adaptive immune systems • Decline in vaccine efficacy with age • Increasing morbidity & mortality from natural infection =>Increased burden as we age Kumar, R, et al, Expert Rev. Vaccines 2008 7(4) 467-479.

  10. What’s New in Immunization? • Herpes Zoster Vaccine • Human Papilloma Virus Vaccine • Pneumococcal Vaccine • Influenza Vaccine (2010/2011)

  11. VZV: Reactivation Posterior column spinal cord Dorsal root ganglion Site of VZV replication Arvin AM. Varicella-zoster virus. In: Knipe DM, Howley PM, eds. Fields Virology. 4th ed. Vol 2. New York, NY: Lippincott Williams & Wilkins; 2001:2731-67 Straus SE, Oxman MN. Varicella and herpes zoster. In: Freedberg IM, Eisen AZ, Wolff K, et al, eds. Fitzpatrick’s Dermatology in General Medicine. 5th ed. Vol 2. New York, NY: McGraw-Hill; 1999:2427-50

  12. Incidence of Zoster by Age The incidence of shingles increases significantly with age, with 67% of cases occurring in persons over 50 years of age. Johnson R. et al. JID 2007 11(Suppl 2) S43-48

  13. Herpes Zoster: Canadian Epidemiology • Estimated ~30% lifetime risk of one VZV reactivation1; ~50% if live to 80 years of age • Estimated 129,882 cases of Shingles per year1 • ~90% of cases occur in immunocompetent people; • 13% of zoster episodes will result in PHN (Defined as Pain >90 days after rash onset) • 17,108 episodes/year • ~2,000 hospital admissions and 20 deaths per yr Brisson M. et al. Human Vaccine 2008

  14. Prevalence of PHN and Duration of Pain Associated with PHN Increase with Age 100 >1 yr 6 - 12 mo 80 1 - 6 mo <1 mo 60 Percent of patients reporting pain 40 20 0 0-19 20-29 30-39 40-49 50-59 60-69 ≥79 Age (years) Kost R et al. N Engl J Med. 1996;355:32-42.

  15. Zoster vaccination Aging & Zoster Risk Varicella Exposure Silent reactivation? VZV T-cells Zoster Threshold Herpes Zoster Varicella Age Arvin A. Aging, Immunity, and the varicella-zoster virus. N Engl J Med 2005;352(22):2266-7. Arvin A, NEJM 352:2266, 2005

  16. The Shingles Prevention Study Design • Randomized Double-blind, placebo-controlled, multicenter trial • 1:1 Zoster Vaccine or placebo (Study Timeline: Nov-1998 to April 2004) • Enrolled 38,546 subjects  60 years of age • Age-stratified (60 to 69 years, 70 years) • Median of 3.12 years of surveillance for Herpes Zoster Oxman M et al. N Engl J Med. 2005;352:2271-2284.

  17. Shingles Prevention StudyVaccineEfficacy: HZ Incidence by age 14 Vaccine Placebo 12 10 Incidence of HZ 8 * 6 4 2 0 All 60-69 yr 70 yr *P <0.001 N=38,546 subjects  60 years of age Adapted from Oxman M et al. N Engl J Med. 2005;352:2271-2284.

  18. 2.5 Vaccine 2.0 Placebo 1.5 Incidence of PHN 1.0 0.5 0.0 All Subjects 60-69 yr 70 yr Shingles Prevention StudyVaccineEfficacy: PHN Incidence by age * *P <0.001 N=38,546 subjects  60 years of age Adapted from Oxman M et al. N Engl J Med. 2005;352:2271-2284.

  19. Safety of Herpes Zoster Vaccine:Serious Adverse Events Among All Subjects Simberkoff MS, et al. Ann Intern Med 2010May;152(9); Oxman, M, et al, Shingles Prevention Study. NEJM 2005

  20. Safety of Herpes Zoster Vaccine:Adverse events at the inoculation site Simberkoff MS, et al. Ann Intern Med 2010May;152(9); Oxman, M, et al, Shingles Prevention Study. NEJM 2005

  21. 22,439 pts aged 50 to 59 yrs 2.2 yrs follow-up Efficacy for prevention of HZ was 69.8% (95% CI: 54.1 to 80.6) Adverse events (AE): 72.8% vs 41.5% (injection site AE & headache) 0.6% vs 0.5% for serious AE at 42 days Zoster Vaccine in Patients 50 to 59 yrs Schmader K et al. Abstract 1380. IDSA. Vancouver, BC, October 2010

  22. Zoster Vaccine (Oka/Merck) STORE FROZEN - Average temperature of –15°C or colder until it is reconstituted for injection DISCARD RECONSTITUTED VACCINE IF NOT USED WITHIN 30 MINS Live, attenuated, Oka/Merck strain of Varicella-zoster Virus Single-dose of entire vial (approx. 0.65ml) S.Q. administration only Contains at least 14-fold more PFU of VZV Oka/Merck/ dose than the Varicella Vaccine

  23. National Advisory Committee on Immunization (NACI) Members: Dr. J. Langley (Chairperson), Dr. B.Warshawsky (Vice-Chairperson), Dr. S. Ismail (Executive Secretary), Ms. A. Hanrahan, Dr. K. Laupland, Dr. A. McGeer, Dr. S. McNeil, Dr. B. Seifert, Dr. D. Skowronski, Dr. B. Tan. Liaison Representatives: Dr. B. Bell (CDC), Dr P. Orr (AMMI Canada), Ms. S. Pelletier (CHICA), Ms. K. Pielak (CNCI), Dr. P. Plourde (CATMAT), Dr. S. Rechner (CFPC), Dr. M. Salvadori (CPS), Dr. D. Scheifele (CAIRE), Dr. N. Sicard (CPHA), Dr. V. Senikas (SOGC).

  24. Zoster Vaccine in Canada • Recommendations: • For prevention of HZ and its complications in persons >60 yrs without contraindications • May be used in patients aged 50 and older • No recommendation for those with a past episode of zoster • Should be given to patients irrespective of a prior history of chickenpox or documented prior varicella infection • Booster doses are not recommended for healthy pts • Individuals who indavertently receive systemic anti-viral therapy active against VZV within 2 days before and 14 days after vaccine may benefit from a second dose 42 days or later • May be given with influenza vaccine; Pneumovax and zoster vaccine should be given at least 4 weeks apart National Advisory Committee on Immunization (NACI). CCDR January 2010; vol. 36

  25. Zoster Vaccine in Canada National Advisory Committee on Immunization (NACI). CCDR January 2010; vol. 36 • Contraindications: • History of hypersensitivity to any component of the vaccine, including gelatin • History of anaphylactic/anaphylactoid reaction to neomycin (traces) • History of dermatitis due to neomycin is not a contraindication to receiving live virus vaccines • Primary and acquired immunodeficiency states • Immunosuppressive therapy including high-dose corticosteroids • Active untreated tuberculosis • Pregnancy

  26. HPV Vaccines

  27. Estimated HPV Contribution in Cancer Cervix > 99% Anus 84.2% Vagina 69.9% Penis 47.0% Vulva 40.4% Oropharynx 35.6% Oral cavity 23.5% 20 80 100 40 60 0 Percentage WHO Information Centre on HPV and Cervical Cancer. Available at: www.who.int/hpvcentre/statistics/en/.

  28. National Advisory Committee on Immunization (NACI) • Members: Dr. M. Naus (Chairperson), Dr. S. Deeks (Executive Secretary), Dr. S. Dobson, Dr. B. Duval, Dr. J. Embree, Ms. A. Hanrahan, Dr. J. Langley, Dr. K. Laupland, Dr. A. McGeer, Dr. S. McNeil, Dr. M.-N. Primeau, Dr. B. Tan, Dr. B.Warshawsky. Liaison Representatives: S. Callery (CHICA), Dr. J. Carsley (CPHA), E. Holmes (CNCI), Dr. B. Larke (CCMOH), Dr. B. Law (ACCA), Dr. D. Money (SOGC), Dr. P. Orr (AMMI Canada), Dr. S. Rechner (CFPC), Dr. M. Salvadori (CPS), Dr. J. Smith (CDC), Dr. J. Salzman (CATMAT), Dr. D. Scheifele (CAIRE).

  29. Recommended Use 15 February 2007Statement on human papillomavirus vaccine. Canada Communicable Disease Report. An Advisory Committee Statement (ACS). Can Commun Dis Rep. 2007;33(ACS-2):1-32.

  30. Canadian HPV Vaccine Public Programs Multiple Age Groups(Uptake %) • Quebec: Grade 4, Grade 9, and Girls < age 18 (84-87%) • British Columbia: Grade 6 and Grade 9. (66%) • Alberta: Grade 5 and Grade 9 (starting in 2009). • Saskatchewan: Grade 6 with a one year Grade 7 catch-up. • New Brunswick: Grade 7 with a one year Grade 8 catch-up. • Nova Scotia: Grade 7 with a one year Grade 10 catch-up (80%) • Newfoundland and Labrador: Grade 6 and Grade 9 (83%) • Yukon: Grade 5 with a catch-up in Grade 6 and 7 • One Age Group • Manitoba: Grade 6 • Ontario: Grade 8 (55%) • Prince Edward Island: Grade 6 (80%) One Age Group Yuk Multiple Age Groups NWT Nun No Public Announcement BC AB SK MB QC NF ON PEI NB NS February 2009

  31. HPV Vaccines – Available in Canada Quadrivalent vaccine: • Contains HPV Types 6, 18 (20 ug each), 11, 16 (40 ug each) • Adjuvant: 225 ug Aluminum hydroxyphosphate sulfate • Approved in Canada – May 2006 (initially for females 9 to 26 yrs of age; now expanded indications) • 3 i.m. Doses: 0, 2 (± 1 m), and 6 (± 2 m) m Bivalent Vaccine: • Contains HPV Types 16 and 18 (20 ug each) • Adjuvant: 500 ug Aluminum hydroxide, 50ug 3-deacylated monophosphoryl Lipid A • Approved in Canada – February 2010 for females from 10 to 25 yrs of age • 3 i.m. Doses: 0, 1 (up to 2.5 m) and 6 (between 5 and 9 m after 1st dose) m

  32. HPV2 and HPV4 – Efficacy L. Markowitz. CDC. Presented at ACIP Oct 2009

  33. HPV Vaccine: Expanding Indications • “Older” women >26 years of age • Males http://www.cdc.gov/vaccines/recs/acip/slides-oct09.htm

  34. Quadrivalent HPV Vaccine: Efficacy in Women Aged 24-45 Years: Future III Muñoz N, et al. Lancet 2009; 373:1949-57.

  35. HPV Vaccine in Men 1. Partridge JM, et al. J Infect Dis 2007;196:1128-36. 2.Saraiya M, et al. Cancer 2008;113 (10 Suppl):2837-40. 3. Guris D. 25th International Papillomavirus Conference, Malmo. May 2009. Abstract P-27.16 4. Giuliano A, Palefsky J. 25th International Papillomavirus Conference, Malmo. May 2009. Abstract O-01.07 5. Palefsky J, Giuliano A. 25th International Papillomavirus Conference, Malmo. May 2009. Abstract O-27.01 • The incidence of anogenital HPV infection in men is at least as high as in women.1 • 32% of all HPV-related cancers in the USA occur in men.2 • Quadrivalent HPV vaccine is immunogenic in males.3 • Preliminary data demonstrate efficacy of quadrivalent HPV vaccine versus infection and disease in both heterosexual4 and homosexual men.5

  36. Efficacy Against HPV 6/11/16/18 Related External Genital Lesions (EGL) in Men 16-26 yr Per-protocol population *Two cases related to HPV 6 alone, and one case related to HPV 6/11/35 n = number of subjects randomized who received at least one injection and have follow-up after month 7 PY = person years; PIN = penile/perianal/perineal intraepithelial neoplasia; case counting began after month 7. A. Giulano & J Palefsky. IPVC 2009; O-01.07

  37. Use of Quadrivalent HPV Vaccine in Males Health Canada: • Feb. 23rd, 2010 – Approved for use in males between 9 to 26 yrs for prevention of infection caused by HPV types 6, 11, 16 and 18 and genital warts caused by HPV types 6 and 11 http://www.cdc.gov/vaccines/recs/acip/slides-oct09.htm

  38. Adverse Events to the HPV Vaccines Comparative Trial (Bivalent & Quadrivalent Vaccines) (N=1106): • Local symptoms (pain, redness, swelling) & general symptoms (fatigue, myalgia): Bivalent > Quadrivalent • SAEs similar between both (~7% vs 6.2%) http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/ucm183835.htm; Einstein et al. Human Vaccines 2009

  39. Duration of Protective Efficacy • Both vaccines induce antibody titers substantially higher than after natural infection • Minimum protective antibody threshold not known • Different antibody assays used in clinical trials – can’t compare antibody titers between trials • WHO: • Protective efficacy of the 2 vaccines has been maintained throughout their respective observation periods: 6.4 years (bivalent) and 5 years (quadrivalent) http://www.who.int/wer/2009/wer8415.pdf

  40. 100% 100% 100% 99% 71% 68% 61% Seropositivity and Efficacy of quadrivalent vaccine against HPV 18 related CIN2/3 or AIS in Women 16–26 years Seropositivity to HPV 18 neutralising antibodies as measured by cLIA Efficacy against HPV 18-related CIN 2/3 or AIS *Seropositivity to HPV 18 neutralizing antibodies to a single neutralizing epitope measured by cLIA Joura E, et al. Vaccine 2008; 26(52)

  41. Demonstration of Immune Memory* with an Antigen Challenge at Month 60 Among Women 16-23 Years of Age (HPV 18) Anti-HPV GMT levels [log10 scale]) GARDASIL™ (n=82) 10,000 Placebo (Sero and PCR neg) (n=70) 1000 Immune memory demonstrated after immune challenge 100 10 0 2 3 7 12 18 24 30 36 54 6 61 60 60+1week Months Similar results seen with HPV 16, 6, and 11 *In participants naïve to the relevant HPV type from day 1 through month 60. 41 Adapted from Olsson S-E et al. Vaccine (2007), doi:10.1016/j.vaccine.2007.03.049.4

  42. Pneumococcal Vaccine

  43. Pneumococcal Disease Is the Leading Cause of Vaccine-preventable Deaths (WHO) Estimated number of deaths (WHO 2002) aPolio, diphtheria, yellow fever. WHO 2004 Global Immunization Data. http://www.who.int/immunization_monitoring/data/GlobalImmunizationData.pdf. Accessed June 7, 2009.

  44. Age-Specific Incidence of Invasive Pneumococcal Disease, Toronto, 1995

  45. Pneumococcal Vaccines Conjugate vaccine (PCV-7): Jan. 2005 provincial program in Ontario started No catch-up; start with birth cohort Covers >80% of serotypes from blood and CSF of children in the pre-vaccine era 75% decrease in IPD in children 23-valent Polysaccharide vaccine: Oct. 1996 provincial program for routine vaccination of all persons 65 yrs All persons  5 yrs who are at high risk for IPD including those 19 – 65 yrs with asthma3 Routine booster not recommended; consider once in high risk group after 5 years Covers 90% of serotypes from bacteremia and meningitis in adults Has not been shown to reduce the incidence of CAP but may be associated with a decrease risk of bacteremia and death as well as severity 1. 2006 Canadian Immunisation Guide 2. Canadian Adult National ImmunizationCoverage Survey 2006 3. Ann Intern Med. March 2009

  46. Newer Pneumococcal Conjugate Vaccine Pneumococcal 10 Conjugate Vaccine (Synflorix): Licensed in Canada in December 2008 for children 6 weeks up to 2 years of age Primary series: 4 i.m. doses (2, 4, 6, 12-15 months) Conjugated to Non-typeable H. influenzae (NTHi) protein D, Diphteria or tetanus toxid Pneumococcal 13 Conjugate Vaccine (Prevnar 13): Licensed in Canada in February 2010 for children 6 weeks through 5 yrs of age Primary series: 4 i.m. doses (2, 4, 6, 12-15 months) Previous PCV-7: 1 dose in 2nd year of life Conjugated to Diphtheria CRM197 protein Will be licensed for use in adults >55 yrs

  47. Pneumococcal Vaccines

  48. Primary Objective: To evaluate the association between pneumococcal vaccination and the risk of myocardial infarction Pneumococcal vaccination associated with a decrease of more than 50% in the rate of myocardial infarction 2 years after exposure to vaccine

  49. Influenza Vaccine

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