Presentation on theme: "Update 2010: Vaccines: HZ, HPV, Pneumococcus T. Mazzulli, MD, FRCPC, FACP Department of Microbiology Mount Sinai Hospital and University Health Network."— Presentation transcript:
Update 2010: Vaccines: HZ, HPV, Pneumococcus T. Mazzulli, MD, FRCPC, FACP Department of Microbiology Mount Sinai Hospital and University Health Network
Learning Objectives: 1. 1.Realize that immunization against adult infectious diseases is one of the most successful interventions to protect the health of Canadians 2. 2.Describe recent clinical updates and whats new in routine adult immunizations: Zoster, HPV and Pneumococcus 3. 3.Develop procedures to enhance immunization rates based on the most recent clinical guidelines in adult immunizations
Ten Great Public Health Achievements Vaccination 2. 2.Motor vehicle safety 3. 3.Safer workplaces 4. 4.Control of infectious diseases 5. 5.Decline in deaths from coronary heart disease and stroke 6. 6.Safer and healthier foods 7. 7.Healthier mothers and babies 8. 8.Family planning 9. 9.Fluoridation of drinking water Recognition of tobacco use as a health hazard 1.MMWR, December 24, Canadian Coalition for Immunization Awareness & Promotion Immunization: –Saved more lives in Canada in the last 50 years than any other health intervention 2 –Single most cost-effective health investment, making immunization a cornerstone of efforts to promote health 2 Immunization: –Saved more lives in Canada in the last 50 years than any other health intervention 2 –Single most cost-effective health investment, making immunization a cornerstone of efforts to promote health 2
Comparison of Maximum and Current Reported Morbidity: Vaccine-Preventable Diseases in the US DiseasePrevaccine Era* Year1999% Decrease Diphtheria206, Measles894, Mumps152, Pertussis265, , Polio (wild)21, Rubella57, Cong. Rubella synd. 20, Tetanus1, Invasive Hib disease 20, , Total1,639,0669,
Canadian Cost-Benefit of Adult Vaccination Cost per Life Year Saved for Selected Vaccine Programs and Other Public Health Interventions Cost per life year saved Vaccines Influenza for adults aged 65 years of age< 0 ($45 saved per $ spent) Pneumococcal polysaccharide for adults aged 65 years < 0 ($8 saved per $ spent) Other interventions Low cholesterol diet for men > 20 yo and cholesterol over 4.65 mmol/L (180 mg/dL) $360,000 Smoking cessation counseling$1,000-10,000 Annual screening for cervical cancer$40,000 Adapted from 2006 Canadian Immunization Guide
Burden of Vaccine Preventable Diseases There are 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/year 1 1. Inf Disease Clinics of NA. 15(1):9-19, 2000 Mar 2. Poland 2005 Vaccine 23 p Poland 2003 Am J Prev Med, 25(2):
Comparison of Pediatric & Adult Immunization Coverage Pediatric Uptake Rates 1 2 years of age n=4,988 Adult Uptake Rates y.o. Total n = 2,237 with CMC n= (n=287) DTaP or IPV n( %) 85.5% n=4,265 Influenza*37.3 %38.2%69.9% Hib n(%)85.8% n=4,278 Hepatitis A25.1%22.7%10.3% Meningococcoal Conjugate n(%) 94.2% n=4,701 Hepatitis B30.2%29.2%10.5% Pneumococcal Conjugate n(%) 83.8% n=4,181 Pertussis3.9%2.4%2.5% MMR n(%)93.0% n=4,641 Tetanus46.5%49.1%28.5% Varicella n(%)86.8% n=4,328 Pneumococcal*29.4% n= % n= % n= CCDR: 32 ( Immunization coverage by age 2 for the five recommended vaccines in the Capital Health Region (Edmonton) 2. Canadian Adult National Immunization Coverage Survey 2006
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 All 2 – –Specific Groups 2 Age 1 Occupation 1 Health Status 1 Behaviour (travel, sexual behaviour) 1 1. Plotkins, S. et al, Immunization in the United States. Vaccines 2008: Canadian Immunization Guide
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 (4)
Whats New in Immunization? Herpes Zoster Vaccine Human Papilloma Virus Vaccine Pneumococcal Vaccine Influenza Vaccine (2010/2011)
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. 4 th ed. Vol 2. New York, NY: Lippincott Williams & Wilkins; 2001: Straus SE, Oxman MN. Varicella and herpes zoster. In: Freedberg IM, Eisen AZ, Wolff K, et al, eds. Fitzpatricks Dermatology in General Medicine. 5 th ed. Vol 2. New York, NY: McGraw-Hill; 1999:
Incidence of Zoster by Age Johnson R. et al. JID (Suppl 2) S43-48 The incidence of shingles increases significantly with age, with 67% of cases occurring in persons over 50 years of age.
Herpes Zoster: Canadian Epidemiology Estimated ~30% lifetime risk of one VZV reactivation 1 ; ~50% if live to 80 years of age Estimated 129,882 cases of Shingles per year 1 – –~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
Kost R et al. N Engl J Med. 1996;355: Percent of patients reporting pain Age (years) >1 yr <1 mo mo mo Prevalence of PHN and Duration of Pain Associated with PHN Increase with Age
Arvin A, NEJM 352:2266, 2005 Varicella Exposure Silent reactivation? Zoster vaccination Zoster Threshold Varicella Herpes Zoster Age Aging & Zoster Risk VZV T-cells Arvin A. Aging, Immunity, and the varicella-zoster virus. N Engl J Med 2005;352(22):
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:
Shingles Prevention Study Vaccine Efficacy: HZ Incidence by age Efficacy (95% CI) 51.3% ( ) 63.9%37.6% All60-69 yr 70 yr Incidence of HZ Vaccine Placebo * Adapted from Oxman M et al. N Engl J Med. 2005;352: N=38,546 subjects 60 years of age * P <0.001
Shingles Prevention Study Vaccine Efficacy: PHN Incidence by age Efficacy (95% CI) 66.5% ( ) 65.7% ( ) 66.8% ( ) All Subjects60-69 yr 70 yr Incidence of PHN Vaccine Placebo * * P <0.001 N=38,546 subjects 60 years of age Adapted from Oxman M et al. N Engl J Med. 2005;352:
Safety of Herpes Zoster Vaccine: Serious Adverse Events Among All Subjects EventVaccine Group Placebo Group No. Subjects19,27019,276 Day of Vaccination. To End of Study Death218 (2.1%)246 (2.4%) Vaccine-related SAE2 (<0.1%)3 (<0.1%) Day of Vaccination. To Day 42 Death14 (0.1%)16 (0.1%) 1 SAEs255 (1.4%)254 (1.4%) Simberkoff MS, et al. Ann Intern Med 2010May;152(9); Oxman, M, et al, Shingles Prevention Study. NEJM 2005
Safety of Herpes Zoster Vaccine: Adverse events at the inoculation site Adverse events Zoster Vaccine N=3326 Placebo N=3249 >1 Inoculation-site adverse event48.2%16.6% Erythema35.8%6.9% Pain or Tenderness34.4%8.5% Swelling26.2%4.5% Pruritus7.1%1.0% Temperature 38.3 o C or higher0.8% Rash0.3%0.1% *p<0.001 Simberkoff MS, et al. Ann Intern Med 2010May;152(9); Oxman, M, et al, Shingles Prevention Study. NEJM 2005
Zoster Vaccine in Patients 50 to 59 yrs 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 Schmader K et al. Abstract IDSA. Vancouver, BC, October 2010
Zoster Vaccine (Oka/Merck) 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 STORE FROZEN - Average temperature of –15 ° C or colder until it is reconstituted for injection DISCARD RECONSTITUTED VACCINE IF NOT USED WITHIN 30 MINS
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).
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
Zoster Vaccine in Canada 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 National Advisory Committee on Immunization (NACI). CCDR January 2010; vol. 36
WHO Information Centre on HPV and Cervical Cancer. Available at: Estimated HPV Contribution in Cancer Oropharynx35.6% Oral cavity23.5% Penis47.0% Vulva40.4% Anus84.2% Vagina69.9% Cervix> 99% Percentage
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).
Recommended Use GroupRecommendationComments Females Age 9–13 years Recommended Efficacy is greatest prior to first sexual intercourse Although efficacy not demonstrated, immunogenicity data imply high efficacy Females Age 14–26 years Recommended, even after onset of sexual activity May not have been infected Very unlikely to have been infected with all 4 vaccine HPV types Need to be aware that they may already have been infected Females Age 14–26 years with HPV-related cervical or genital disease or current infection Recommended May not have been infected with vaccine HPV types Very unlikely to have been infected with all 4 vaccine HPV types Need to be aware that vaccine probably has no therapeutic effect 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.
Yuk BC NWT AB SK MB ON QC Nun One Age Group Multiple Age Groups No Public Announcement NF PEI NS NB 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 Canadian HPV Vaccine Public Programs One Age Group Manitoba: Grade 6 Ontario: Grade 8 (55%) Prince Edward Island: Grade 6 (80%) February 2009
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 1 st dose) m
HPV2 and HPV4 – Efficacy L. Markowitz. CDC. Presented at ACIP Oct 2009
HPV Vaccine: Expanding Indications Older women >26 years of age Males
Quadrivalent HPV Vaccine: Efficacy in Women Aged Years: Future III PopulationVaccine (n=1911) Placebo (n=1908) Vaccine Efficacy 95% CI All subjects44191%74, yr22492%67, yr21789%52, 99 HPV 16 & %51, 96 HPV 6 & %79, 100 Muñoz N, et al. Lancet 2009; 373:
HPV Vaccine in Men 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 heterosexual 4 and homosexual men Partridge JM, et al. J Infect Dis 2007;196: Saraiya M, et al. Cancer 2008;113 (10 Suppl): Guris D. 25th International Papillomavirus Conference, Malmo. May Abstract P Giuliano A, Palefsky J. 25th International Papillomavirus Conference, Malmo. May Abstract O Palefsky J, Giuliano A. 25th International Papillomavirus Conference, Malmo. May Abstract O-27.01
Severity Quadrivalent HPV Vaccine (n = 1,397) Placebo (n = 1,408) % Efficacy95% CI Cases Inc. per 100 PYCases Inc. per 100 PY Condyloma3* , 97.9 PIN PIN 2/ Penile/perineal/ perianal cancer Efficacy Against HPV 6/11/16/18 Related External Genital Lesions (EGL) in Men yr 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. Per-protocol population *Two cases related to HPV 6 alone, and one case related to HPV 6/11/35 A. Giulano & J Palefsky. IPVC 2009; O-01.07
Use of Quadrivalent HPV Vaccine in Males Health Canada: Feb. 23 rd, 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
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%) nesandRelatedBiologicalProductsAdvisoryCommittee/ucm htmhttp://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/Vacci nesandRelatedBiologicalProductsAdvisoryCommittee/ucm htm; Einstein et al. Human Vaccines 2009
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 – cant 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)
99% 71% 61% 100% 68% 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 *In participants naïve to the relevant HPV type from day 1 through month 60. Adapted from Olsson S-E et al. Vaccine (2007), doi: /j.vaccine Demonstration of Immune Memory* with an Antigen Challenge at Month 60 Among Women Years of Age (HPV 18) Similar results seen with HPV 16, 6, and 11 Anti-HPV GMT levels [log 10 scale]) 60+1 week Immune memory demonstrated after immune challenge 10, GARDASIL (n=82) Placebo (Sero and PCR neg) (n=70) Months 6
WHO 2004 Global Immunization Data. Accessed June 7, Pneumococcal Disease Is the Leading Cause of Vaccine-preventable Deaths (WHO) a Polio, diphtheria, yellow fever. Estimated number of deaths (WHO 2002)
Age-Specific Incidence of Invasive Pneumococcal Disease, Toronto, 1995
Pneumococcal Vaccines Canadian Immunisation Guide 2. Canadian Adult National Immunization Coverage Survey Ann Intern Med. March 2009 Conjugate vaccine (PCV-7): – –Jan 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 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 asthma 3 – –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
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, 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, months) Previous PCV-7: 1 dose in 2 nd year of life – –Conjugated to Diphtheria CRM 197 protein – –Will be licensed for use in adults >55 yrs
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
Pandemic H1N1 2009: Multiple Waves of Morbidity and Mortality in Canada
National Advisory Committee on Immunization (NACI) Members: Dr. J. Langley (Chairperson), Dr. B. Warshawsky (Vice-Chair), Dr. S. Ismail (Executive Secretary), Dr.N. Crowcroft, Ms. A. Hanrahan, Dr. B. Henry, Dr. D. Kumar, Dr. S. McNeil, Dr. C. Quach-Thanh, Dr. B. Seifert, Dr. D. Skowronski, Dr. C. Cooper.
Trivalent Influenza Vaccine 2010/2011 Five vaccines (4 i.m. & 1 intradermal) licensed in Canada containing 3 influenza strains: – –2009 pandemic influenza A California (H1N1) - like – –2009 Influenza A Perth (H3N2) - like – –2008 Influenza B Brisbane – like None contains an adjuvant Publicly funded programs will use Fluviral (contains thimerosal but no antibiotics) and Vaxigrip (contains thimerosal and neomycin) vaccines – –Can be used in adults and children >6 months of age National Advisory Committee on Immunization (NACI). CCDR August 2010; vol. 36
Trivalent Influenza Vaccine 2010/2011 Recommended Recipients: 1. 1.Adults (including pregnant women) and children with chronic health conditions 2. 2.Residents of nursing homes 3. 3.People >65 yrs of age 4. 4.Healthy children 6 to 23 mos 5. 5.Healthy pregnant women (risk of influenza-related hospitalization increases with length of gestation) 6. 6.People capable of transmitting influenza to those at high risk (e.g. Healthcare workers, Household contacts, child care workers, etc.) National Advisory Committee on Immunization (NACI). CCDR August 2010; vol. 36
Trivalent Influenza Vaccine 2010/2011 Recommended Recipients (New for 2010/2011): 1. 1.Persons who are morbidly obese (BMI >40) 2. 2.Aboriginal peoples 3. 3.Healthy children 2 to 4 years of age The first time children <9 yrs receive TIV, a two-dose schedule is required REGARDLESS of whether or not the child received monovalent pH1N1 vaccine in National Advisory Committee on Immunization (NACI). CCDR August 2010; vol. 36
What Can Be Done to Improve Adult Immunization Rates?
Adult Immunization: Strategies to Improve Vaccine Uptake Communication Explaining the need for immunization Clearly conveying the risks 1 Strong physician/provider recommendation 1 1 Burns IT, Zimmerman RK. 2005:54:S PHAC 2006 Canadian Adult Immunization Coverage Survey Recommendation is critical 2
Adult Immunization: Strategies to Improve Vaccine Uptake Patient Visit Strategy Assess vaccination at all visits: stamped chart reminders Improve tracking system CCIAP Adult Immunization Wallet Card Empower patient to become more involved Adult Immunization Questionnaire Szilagyi, PG, et al. 2005:40:
Summary Immunization does not stop at childhood Prevention of infection by immunization is a lifelong process Health Care Practitioners need to Empower, Educate, Advocate and Recommend
Thank you for your attention!
Important Web-sites Public Health Agency of Canada – – Canadian Coalition for Immunization Awareness and Promotion (CCIAP) – – Centers for Disease Control and Prevention – –www.cdc.govwww.cdc.gov World Health Organization – –