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
Acknowledge burden of diseases worth preventing and recognize that immunization against adult infectious diseases is one of the most successful interventions to help protect the health of Canadians
Review (Understand) the recent clinical updates and what’s new in adult vaccines
Adapt current medical practices and empower patients in order to improve vaccine coverage rates

3. Ten Great Public Health Achievements 1900 - 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
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
Even if Vaccination is THE greatest achievement we can be proud of in the last milenium, are we where we should be yet?
MMWR, December 24, 1999
2. Canadian Coalition for Immunization Awareness & Promotion. 2005

4. Comparison of Maximum and Current Reported Morbidity: Vaccine-Preventable Diseases in the US
Prevaccine
Era*
Year
1999
% Decrease
Diphtheria
206,939
1921 1
99.99
Measles
894,134
1941
100
Mumps
152,209
1968
391
99.75
Pertussis
265,269
1934
7,288
97.25
Polio (wild)
21,269
1952
100.00
Rubella
57,686
1969
267
99.53
Cong. Rubella synd.
20,000+ 6
99.96
Tetanus
1,560+
1948 42
97.31
Invasive Hib disease
1984
1,309
99.65
Total
1,639,066
9,404
99.43
These are US data, Canadian data was not available for the actual numbers of decrease in prevalence of the infections.

5. 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
“Cost per life-year saved” is a number used in risk analysis to compare the cost-benefit ratios of different interventions in health and safety.
Adapted from 2006 Canadian Immunization Guide

6. 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/year1
1. Inf Disease Clinics of NA. 15(1):9-19, 2000 Mar
2. Poland 2005 Vaccine 23 p
3. Poland 2003 Am J Prev Med, 25(2):

7. Comparison of Pediatric & Adult Immunization Coverage
Pediatric Uptake
Rates1
2 years of age
n=4,988
Adult Uptake Rates 2
18-64 y.o.
Total
n = 2,237
with CMC
n=395
65 +
(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 A
25.1%
22.7%
10.3%
Meningococcoal Conjugate n(%)
94.2% n=4,701
Hepatitis B
30.2%
29.2%
10.5%
Pneumococcal Conjugate n(%)
83.8%
n=4,181
Pertussis
3.9%
2.4%
2.5%
MMR n(%)
93.0% n=4,641
Tetanus
46.5%
49.1%
28.5%
Varicella n(%)
86.8% n=4,328
Pneumococcal*
29.4%
n=599
16.7%
n=271
38.6%
n=287
1. 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

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
Adult Immunization Considerations:
Immunizing adults is a more complicated undertaking than is immunizing children.
Vaccination recommendations for adults depend on a person's age, occupation, health status, and behavior (e.g., sexual activity and drug use). For example, for adults younger than 50 years of age, influenza and pneumococcal vaccines are targeted to persons at high risk for illness-related complications or death.
This requires physicians and nurses to establish procedures to identify persons who are eligible, often from long lists of qualifying conditions, in contrast to childhood immunization, in which all are offered vaccine unless there are contraindications.
Reference: Plotkins, S. et al, Immunization in the United States. Vaccines 2008:
1. Plotkins, S. et al, Immunization in the United States. Vaccines 2008:
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
Physicians often question whether it is worthwhile to vaccinate older adults if the desirable immune response cannot be achieved.1
It should be strongly emphasized that unlike childhood vaccines that frequently prevent clinical illness altogether, most adult vaccines do not prevent illness but lessen the severity of a given infection.2
And are therefore bringing significant value and translate in meaningful gains.
Increasing morbidity & mortality from natural infection translate into an increased burden form individual disease as we age!
Kumar, R, et al, Expert Rev. Vaccines (4)

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

11. Posterior column spinal cord
VZV: Reactivation
Posterior column spinal cord
Dorsal root ganglion
Site of VZV replication
Herpes Zoster: Reactivation
In response to waning cell-mediated immunity (CMI) that often accompanies increasing age or to other conditions characterized by immunosuppression (eg, HIV, malignancies, and immunosuppressive therapy), VZV may reactivate and replicate within the ganglion. Spread of the virus within the ganglion causes inflammation and necrosis of the neurons, often accompanied by neuralgia.2
Virus is then transported down the sensory nerves, causing intense neuritis, and is released around the nerve endings in the skin.2
Because VZV reactivation usually involves a single sensory nerve, the consequent vesicular rash occurs in the characteristic unilateral dermatomal distribution of herpes zoster lesions.1
VZV can also spread proximally along the posterior nerve root to involve the motor neurons of the anterior spinal cord, which may produce local palsies.2
[Arvin p2741; Straus p2431]
[Arvin p2741]
[Straus p2431]
Arvin AM. Varicella-zoster virus. In: Knipe DM, Howley PM, eds. Fields Virology. 4th 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. Fitzpatrick’s Dermatology in General Medicine. 5th ed. Vol 2. New York, NY: McGraw-Hill; 1999:
[Arvin p2742]
[Straus p2431]
References:
1. Arvin AM. Varicella-zoster virus. In: Knipe DM, Howley PM, eds. Fields Virology. 4th ed. Vol 2. New York, NY: Lippincott Williams & Wilkins; 2001:2731–2767.
2. 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; 1999:2427–2450.

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 (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
Lifetime risk – comes from Manitoba database
Brisson M. et al. Human Vaccine 2008

14. Percent of patients reporting pain
Prevalence of PHN and Duration of Pain Associated with PHN Increase with Age
100
>1 yr mo 80
1 - 6 mo
<1 mo 60
Percent of patients reporting pain 40 20
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. Aging & Zoster Risk Varicella Exposure Silent reactivation?
Zoster vaccination
VZV
T-cells
Zoster Threshold
Varicella
Herpes Zoster
Varicella is the primary infection caused by VZV, and its resolution is associated
with the induction of VZV-specific memory T cells (black line).
Memory immunity to VZV may be boosted periodically by exposure to varicella or silent
reactivation from latency (red peaks).
VZV-specific memory T cells decline with age.
The decline below a threshold (dashed orange line) correlates with an
increased risk of zoster.
The occurrence of zoster, in turn, is associated with an increase in VZV-specific T cells.
The administration of zoster vaccine to older persons may prevent VZV-specific T cells from dropping below the threshold for zoster occurrence (dashed green line).
Age
Arvin A. Aging, Immunity, and the varicella-zoster virus. N Engl J Med 2005;352(22):
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
Randomized
1:1 Zoster Vaccine or placebo
Most doses administrated near proposed expiry potency
Double-blind, placebo-controlled multicenter trial
Study Timeline: Nov-1998 to April 2004
Dept. Of Veteran Affairs Cooperative Studies Program (VA CSP) collaboration with the National Institutes of Health (NIH) and Merck & Co. inc
Enrolled 38,546 subjects 60 years of age
Age-stratified (60 to 69 years, 70 years)
90% had one or more underlying medical conditions
Reference: Oxman M et al. N Engl J Med. 2005;352:
Oxman M et al. N Engl J Med. 2005;352:

17. Shingles Prevention Study Vaccine Efficacy: HZ Incidence by age
Efficacy (95% CI)
51.3% ( )
63.9%
37.6% 14
Vaccine 12
Placebo 10
Incidence of HZ 8 * 6
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
VEHZ 51.3% (95% CI [44.2%, 57.6%])
Criterion for success:
VEHZ 95% CI lower bound >25%
Evaluable cases: n=957
Vaccine 315
Placebo 642 4 2
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:

18. Shingles Prevention Study Vaccine Efficacy: PHN Incidence by age
Efficacy (95% CI)
66.5% ( )
65.7% ( )
66.8% ( )
0.0
0.5
1.0
1.5
2.0
2.5
All Subjects
60-69 yr
70 yr
Incidence of PHN
Vaccine
Placebo
Protocol definition of PHN
PHN is defined as the presence of pain (score 3 on a 0 to 10 scale) beyond 90 days after HZ rash onset
The threshold of 3 has been shown to correlate with interference of daily activities and other quality of life measures
Vaccine efficacy is measured as the relative reduction in PHN incidence in vaccine recipients compared with placebo recipients
VEPHN 66.5% (95% CI [47.5%, 79.2%])
PHN cases: n=107
Vaccine = 27
Placebo = 80 *
*P <0.001
N=38,546 subjects  60 years of age
Adapted from Oxman M et al. N Engl J Med. 2005;352:

19. Safety of Herpes Zoster Vaccine: Serious Adverse Events Among All Subjects
Vaccine Group
Placebo Group
No. Subjects
19,270
19,276
Day of Vaccination. To End of Study
Death
218 (2.1%)
246 (2.4%)
Vaccine-related SAE
2 (<0.1%)
3 (<0.1%)
Day of Vaccination. To Day 42
14 (0.1%)
16 (0.1%)
≥1 SAEs
255 (1.4%)
254 (1.4%)
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
Placebo
N=3249
>1 Inoculation-site adverse event
48.2%
16.6%
Erythema
35.8%
6.9%
Pain or Tenderness
34.4%
8.5%
Swelling
26.2%
4.5%
Pruritus
7.1%
1.0%
Temperature 38.3o C or higher
0.8%
Rash
0.3%
0.1%
*p<0.001
In the adverse-events sub-study, a significantly greater number of subjects in the vaccine group had one or more adverse events than in the placebo group,
reflecting a greater frequency of adverse events at the injection site among subjects in the vaccine group.
In the vaccine group, the most frequent adverse events at the injection site were:
erythema (in 35.8 percent of the vaccine group),
pain or tenderness (in 34.5 percent),
swelling (in 26.2 percent),
pruritus (in 7.1 percent).
No other adverse event at the injection site was observed in
more than 2 percent of the vaccine recipients.
Overall, the proportion of subjects with one or more systemic
adverse events was similar in the two groups.
Simberkoff MS, et al. Ann Intern Med 2010May;152(9); Oxman, M, et al, Shingles Prevention Study. NEJM 2005 20

21. 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

22. 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
Health Canada Approval
Zoster Vaccine for the prevention of shingles (herpes zoster) in individuals 60 years of age or older
Vaccine is now available through Canadian physicians and pharmacists.
STORE FROZEN - Average temperature of –15°C or colder until it is reconstituted for injection
DISCARD RECONSTITUTED VACCINE IF NOT USED WITHIN 30 MINS 22

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
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 25

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%
The slide shows the cancer sites for which HPV has been identified as a risk factor, with estimates of the proportion of cancer attributable to HPV at each site. Note that, for some of the estimates (i.e., oro-pharyngeal cancer) the attributable fractions continue to be updated (from 30% to 72%) as technology and sampling methods are being developed.
Reference:
WHO Information Centre on HPV and Cervical Cancer. Available at:
Oral cavity
23.5% 20 40 60 80
100
Percentage
WHO Information Centre on HPV and Cervical Cancer. Available at:

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 Group Recommendation Comments Females Age 9–13 years
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
with HPV-related cervical or genital disease or current infection
May not have been infected with vaccine HPV types
Need to be aware that vaccine probably has no therapeutic effect
scrapped
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. 29

30. Canadian HPV Vaccine Public Programs No Public Announcement
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
NWT
Multiple Age Groups
Nun
No Public Announcement
To give you a snapshot of where we are at with our public performance.
NACI recommendation
In January 2007 the National Advisory Committee on Immunization (NACI), a group of Canada’s leading experts in the fields infectious diseases, vaccines and public health that reports to the Chief Public Health Officer of Canada, made a strong and inclusive recommendation. GARDASIL® is recommended for ALL females 9-26 even if they are sexually active with or without history of disease and / or infection (warts, Pap abnormality cervical cancer) and a discretional recommendation in females >26 years of age.
NIS funding
In March 2007 the federal government, as part of the National Immunization Strategy, renewed funding for vaccines and put aside $300M for HPV vaccination programs over a three year period. This funding will allow the provinces to vaccinate up to 5 cohorts (or approx. 1.1M adolescent girls) over the next three years.
Public Programs
To date we have had several programs announced, some of which will be started this fall and others in Ontario will implement a program in the coming weeks for 1 cohort in Gr. 8, NS – Gr. 7, NF – Gr. 7, PEI – Gr. 6.
BC and Quebec have made public announcements that they will initiate multi-cohort programs in Q3, Specifics of these programs will be announced in the next few months. 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

34. Quadrivalent HPV Vaccine: Efficacy in Women Aged 24-45 Years: Future III
Population
Vaccine (n=1911)
Placebo (n=1908)
Vaccine Efficacy
95% CI
All subjects 4 41
91%
74, 98
24-34 yr 2 24
92%
67, 99
35-45 yr 17
89%
52, 99
HPV 16 & 18 23
83%
51, 96
HPV 6 & 11 19
100%
79, 100
Attention: Please note that comments were made by the CCCEP reviewers that this graph is complex and could be confusing. It will therefore require a detailed explanation and a clear take home message
Muñoz N, et al. Lancet 2009; 373: 34

35. 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 heterosexual4 and homosexual men.5
1. Partridge JM, et al. J Infect Dis 2007;196:
2. Saraiya M, et al. Cancer 2008;113 (10 Suppl):
3. Guris D. 25th International Papillomavirus Conference, Malmo. May Abstract P-27.16
4. Giuliano A, Palefsky J. 25th International Papillomavirus Conference, Malmo. May Abstract O-01.07
5. Palefsky J, Giuliano A. 25th International Papillomavirus Conference, Malmo. May Abstract O-27.01

36. Quadrivalent HPV Vaccine (n = 1,397)
Efficacy Against HPV 6/11/16/18 Related External Genital Lesions (EGL) in Men yr
Per-protocol population
Severity
Quadrivalent HPV Vaccine (n = 1,397)
Placebo (n = 1,408)
% Efficacy
95% CI
Cases
Inc. per 100 PY
Condyloma 3*
0.1 28
1.0
89.4
65.5, 97.9
PIN 1
0.0 2 --
PIN 2/3 1
Penile/perineal/ perianal cancer
Randomized (1:1), double-blind, placebo-controlled in male
3 doses of Quadrivalent HPV Vaccine or placebo at 0, 2, and 6 months
Planned 36 month follow-up (mean 30.1 months in current analysis)
Enrolled subjects:
Heterosexual men (HM)
16-23 year old
3463
Men having sex with men (MSM)
16-26 year old
602
Objectives:
Safety
Efficacy: Combined incidence of HPV 6/11/16/18‑related lesions
Main study: HM + MSM
External genital warts
Penile/perianal/perineal intraepithelial neoplasia (PIN)
Penile, perianal, or perineal cancer
Sub-study: MSM
Anal intraepithelial neoplasia (AIN)
Anal Cancer
Immunogenicity
Geometric mean titers, seroconversion
Secondary Objective:
Incidence of persistent HPV 6/11/16/18 infection*
Incidence of HPV 6/11/16/18 DNA detection at one or more visits
*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

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%)
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)

40. Seropositivity and Efficacy of quadrivalent vaccine against HPV 18 related CIN2/3 or AIS in Women 16–26 years
99%
71%
61%
100%
68%
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) 40

41. Immune memory demonstrated after immune challenge
Demonstration of Immune Memory* with an Antigen Challenge at Month 60 Among Women Years of Age (HPV 18)
Anti-HPV GMT levels
[log10 scale])
60+1 week
Immune memory demonstrated after immune challenge
10,000
1000
100 10
2 3 7 12 18 24 30 36 54 60 61
GARDASIL™ (n=82)
Placebo (Sero and PCR neg) (n=70)
Months 6
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: /j.vaccine 41

42. Pneumococcal Vaccine

43. Estimated number of deaths (WHO 2002)
Pneumococcal Disease Is the Leading Cause of Vaccine-preventable Deaths (WHO)
Estimated number of deaths (WHO 2002)
Key Points
As shown on the slide, pneumococcal disease is the leading vaccine-preventable cause of death for all ages as well as children aged younger than 5 years. (p1 para2-4)
This extraordinary disease burden supports the need for universal vaccination.
Reference
World Health Organization (WHO 2004 Global Immunization Data. Accessed June 7, 2009.
aPolio, diphtheria, yellow fever.
WHO 2004 Global Immunization Data. Accessed June 7, 2009. 43

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

45. Pneumococcal Vaccines
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 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
High Risk Groups include:
Immunosuppress.
Malignancy
Renal disease
Asplenia
Smokers
Diabetes mellitus
CHF
COPD
Sickle cell disease
Nephrotic syndrome
Steroids
Cirrhosis
Alcoholism
Canadian Immunisation Guide
2. Canadian Adult National Immunization Coverage Survey 2006
3. Ann Intern Med. March 2009

47. 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
Previous PCV-7: 1 dose in 2nd year of life
Conjugated to Diphtheria CRM197 protein
Will be licensed for use in adults >55 yrs

48. Pneumococcal Vaccines
PCV7
PCV10
PCV13
PPV23 4 2 6B 8 9V 9N 14
10A
18C
11A
19F
12F
23F
15B 1
17F 5
22F 7F
33F 3
19A 6A

49. 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

50. Influenza Vaccine

51. Pandemic H1N1 2009: Multiple Waves of Morbidity and Mortality in Canada

52. 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.

53. 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

54. Trivalent Influenza Vaccine 2010/2011
Recommended Recipients:
Adults (including pregnant women) and children with chronic health conditions
Residents of nursing homes
People >65 yrs of age
Healthy children 6 to 23 mos
Healthy pregnant women (risk of influenza-related hospitalization increases with length of gestation)
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

55. Trivalent Influenza Vaccine 2010/2011
Recommended Recipients (New for 2010/2011):
Persons who are morbidly obese (BMI >40)
Aboriginal peoples
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

56. What Can Be Done to Improve Adult Immunization Rates?56

57. Adult Immunization: Strategies to Improve Vaccine Uptake
Communication
Explaining the need for immunization
Clearly conveying the risks1
Strong physician/provider recommendation1
Recommendation is critical2
1Burns IT, Zimmerman RK. 2005:54:S58-62
2PHAC 2006 Canadian Adult Immunization Coverage Survey

58. 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
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
(completed by patient at scheduled appointment)
Szilagyi, PG, et al. 2005:40:

59. 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

60. Thank you for your attention!

61. Important Web-sites Public Health Agency of Canada
Canadian Coalition for Immunization Awareness and Promotion (CCIAP)
Centers for Disease Control and Prevention
World Health Organization