1. Vaccine Hesitancy: An Emerging Epidemic
Dean A. Blumberg, MD, FAAP
Disclosure
clinical research grants: Novartis
speakers bureau: sanofi pasteur
Discussion
vaccines not approved by FDA
“off label” use of FDA approved vaccines

2. Vaccine Hesitancy: An Emerging Epidemic
Vaccines and public health
Recent vaccine safety concerns in the news
HPV4 publicity
Other allegations
overwhelm the immune system
thimerosal
aluminum
autism
Addressing vaccine hesitancy

3. Vaccine-Preventable Diseases: Baseline 20th Century & Current Morbidity
*provisional
MMWR 1999;48:245, 2011;59:1700

4. HPV4: Adverse Experiences
package insert

5. Post-Licensure Vaccine Safety Monitoring
CDC/FDA
Vaccine Adverse Events Reporting System (VAERS)
Vaccine Safety Datalink (VSD)
Manufacturer
Post marketing studies
There are a variety of different post-licensure hpv vaccine
Safety monitoring activities—these include:
CDC/FDA
Vaccine Adverse Events Reporting System (VAERS)
Vaccine Safety Datalink (VSD)
Clinical Immunization Safety Assessment (CISA)
Manufacturer
Post marketing study in managed care
Pregnancy registry
Nordic Cancer Registry 5 5

6. Vaccine Adverse Events Reporting System (VAERS)
National post-licensure safety surveillance system jointly operated by CDC and FDA
Spontaneous reporting system in existence since 1990
reports submitted by clinicians, manufacturers, patients/parents and others
Subject to well-described limitations of passive surveillance
VAERS is one of the adverse events reporting systems.
This is a National post-licensure safety surveillance system
jointly operated by CDC and FDA
Spontaneous reporting system in existence since 1990;
reports submitted by clinicians, manufacturers,
patients/parents and others
Subject to well-described limitations of passive surveillance 6 6

7. VAERS Advantages Limitations covers US population
permits monitoring for known adverse events
detects signals for previously unrecognized /rare adverse events
generates hypothesis
Limitations
risk of underreporting or overreporting
incomplete data
lack of availability of denominator data
Advantages
Covers US population
Permits monitoring for known AEs
Detects signals for previously unrecognized /rare AEs
Generates hypothesis
Limitations
Risk of underreporting or overreporting of unfavorable events due to media/other
Incomplete data (no routine collection methods)
Lack of availability of denominator data (not population based) 7

8. VAERS HPV Data: Venous Thromboembolism
Total reports: 65; US reports: 41
Pending evaluation: 6; Unable to follow-up or “no case”: 17
Confirmed cases: 18
Hormonal contraception current use (n=14)
12 cases – Oral Contraceptive Pills
2 cases on Nuvaring (increase risk of clots)
Some have additional risk factors
No hormonal contraception use (n=4)
1 case of pregnancy
1 case obesity, smoking, truck driver
1 case long bus ride preceded to the VTE onset
1 case had no reported risk factors
This is an example of an evaluation of a specific outcome in vaers.
The reports on venous thromboembolism.
Total reports: 65
US reports: 41
Pending evaluation: 6
Unable to follow-up or “no case”: 17
Confirmed cases: 18
Hormonal contraception current use (n=14)
12 cases – Oral Contraceptive Pills
2 cases on Nuvaring (increase risk of clots)
Some have additional risk factors
No hormonal contraception use (n=4)
1 case of pregnancy
1 case obesity, smoking, truck driver
1 case long bus ride preceded to the VTE onset
1 case had no reported risk factors 8

9. Exposure window (days)
Rapid Cycle Analysis, VSD
Outcome
Exposure window (days)
Medical Setting
Signal?
Guillain Barré Syndrome (GBS)
1 to 42
All NO
Seizures
0 to 42
Inpatient, ED
Syncope
Appendicitis
Stroke
Venous Thromboembolism (VTE)
Anaphylaxis
0 to 2
Other Allergic rxns
0 to 2*
This is an example of an analysis in the VSD—a rapid cycle analysis.
Various outcomes, with specific exposure windows, are evaluated.
For each of these outcomes, a signol is generated if the number
Of cases meets a threshold compared to a control group.
As you can see, to date, none of these have produced
A signal. 9

10. Vaccine Hesitancy: Oregon Survey
Robison et al NIC 2008

11. Parental Vaccine Safety Concerns
Freed et al, Pediatr 2010;125:654

12. Vaccine Adverse Event Myths
No credible scientific evidence that vaccines cause:
autism
multiple sclerosis
diabetes
asthma
inflammatory bowel disease
SIDS
overwhelm immune system

13. Dr. Bob’s Alternative Vaccine Schedule
Vaccines not recommended
polio, HBV, diphtheria, tetanus uncommon in children
measles, mumps, rubella, HAV, rare and not serious for infants and toddlers
varicella not serious
Vaccines included
2 mo DTaP, PCV7
4 mo DTaP, Hib
6 mo Hib, PCV7
9 mo DTaP, PCV7
12 mo Hib
15 mo Hib, PCV7
5 years Tetanus booster

14. Overwhelm Immune System?
Infant immune system
naïve
can respond to thousands of antigens simultaneously
Challenges other than vaccines
natural environmental exposures
strep throat: >50 antigens
otitis media: >2,000 antigens

15. Number of Immunogens in Vaccines
1900
1960
1980
2011
Vaccine
Immunogens
Smallpox
~200
Diphtheria 1
Tetanus
Pert-WC
~3000
Pert-AC
2-5
Polio 15
Measles 10
Mumps 9
Rubella 5
Hib 2
Varicella 69
PCV 14
Hepatitis B
Hepatitis A
MCV RV
HPV
Influenza* 4
2-7
6-114
Total
~3217
~3041
Offit et al, Pediatrics 2002;109:124
*Influenza yearly, new strains every year

16. Thimerosal Concerns: Neurotoxin?
preservative
ethylmercury
Toxicity data
methylmercury
7 well done studies
methods
both retrospective & prospective
ecological & cohort
several 100,000 children
results: no association

17. Thimerosal Content: US Vaccines
Trade name
Manufacturer
Thimerosal Concentration
DTaP
Tripedia®
Sanofi Pasteur
≤ %
Infanrix®
GlaxoSmithKline
Daptacel®
DTaP-HepB-IPV
Pediarix®
Tdap
Adacel®
Boostrix®
Haemophilus influenzae type b conjugate (Hib)
ActHIB®
PedvaxHIB®
Merck & Co, Inc
Hib/Hepatitis B combo
Comvax®
Hepatitis B
Engerix B®
Recombivax HB®
Hepatitis A/Hepatitis B
Twinrix®
<0.0002%
Influenza*
Various
Varies

18. Aluminum Concerns Aluminum in vaccines Aluminum exposure adjuvant
maximum amount 0.85 mg/dose
Aluminum exposure
deodorant
food
adults average 7-9 mg/day
200 mg in antacids
breast milk
0.04 mg/L
formula
0.225 mg/L

19. Aluminum Exposure: 1st 6 Months of Life
Robison et al NIC 2008

20. MMR & Autism 1998: Wakefield Lancet publication
case series
12 children
Biological plausibility: no
10 well done studies
methods
both retrospective & prospective
ecological & case control
millions of children
results: no association

21. Permanent Medical Exemptions & Personal Beliefs Exemptions, Kindergarten Students, California
1977: Requirements for DTP, polio, measles passed, effective Jan 1, 1978;
Started annual assessments
1979: Requirements for mumps and rubella added, effective Jan 1, 1980
1995: Requirement for hepatitis B added, effective Aug 1, 1997
1999: Requirement for varicella added, effective Jul 1, 2001
Lee et al NVIC 2010 21

22. Refused pertussis vaccination
22.8 times increased risk of pertussis

23. Refused varicella vaccination
8.6 times increased risk of varicella

24. Why Parents Who Planned To Delay/Refuse Vaccine Changed Their Minds
Gust et al Pediatr 2009;122:718

25. Parental Immunization Refusal
Listen carefully to concerns
encourage questions
Discuss known risks and benefits
risks to unimmunized child
Concerns about specific vaccines
discuss
administer other vaccines
Multiple injection concerns
modify schedule
Revisit discussion in future visits
Document

26. Vaccine Safety Discussion Strategies
Empathize: acknowledge that there are many conflicting messages in the media
Assess level of scientific evidence desired
Maximize benefits to their child
not a public health discussion
vaccines provide protection
risk of disease for omitted vaccines
Provide appropriate resources
e.g., CDC, AAP, NNII, CHOP

27. Continued Vaccine Refusal
Challenges
time commitment for discussions
frustration
“Fire” patient from practice/clinic?
acknowledge differences
“it sounds like you and I have different philosophies”
offer referral to a different practice/clinic
“you might be more comfortable with this group”

30. Vaccine Hesitancy: An Emerging Epidemic
Immunization challenges
education of health care providers
education of patients and parents
discussion