Vaccine Safety and Vaccine Safety Communication Otherwise Known as The Vaccine Wars

Objectives
List some of the events that led to the current climate of vaccine safety concern Describe factors that contribute to parental concerns about vaccines Develop talking points to address common myths about vaccine safety Develop answers to the question-What is wrong with an alternative vaccine schedule?

Vaccination is the top Public Health achievement of the 20th Century

MMWR 1999; 48:241

CDC, Epidemiology and Prevention of Vaccine-Preventable Diseases, 9th ed., 2006

Vaccine-Preventable Diseases: Baseline 20th Century & Current Morbidity

Number of Cases Disease Baseline 2010* Smallpox 48,164 0 Diphtheria 175,885 0 Measles 503,282 57 Mumps 152,209 2,528 Pertussis 147,271 21,291 Polio (par.) 16,316 0 Rubella 47,745 6 CRS 823 0 Tetanus 1,314 8 Hib 20,000 16
*provisional

% Decrease 100.00 100.00 99.99 98.34 85.54 100.00 99.99 100.00 98.39 99.92
MMWR 1999;48:245, 2011;59:1700

 Are vaccines safe? Vaccines and autism MMR Thimerosal Other vaccine ingredients Vaccines in general Too many vaccines overwhelm the immune system Diseases no longer existor arent that dangerous It is all a giant money-fueled conspiracy Individual rights vs. public health needs

Parental Vaccine Safety Concerns

Freed et al, Pediatr 2010;125:654

Parents: Doubts About Vaccines

Gust et al Pediatr 2009;122:718

Why Parents Who Planned To Delay/Refuse Vaccine Changed Their Minds

Gust et al Pediatr 2009;122:718

How did we get here?

Real Vaccine Risks

1950-1980s: Whole cell DTP vaccine 1976: Guillain-Barr from influenza vaccine 1980s: OPV causing paralysis despite no cases of polio 1990s: intussusception from rotavirus vaccine

How have we dealt with real vaccine risks?

Responses to real vaccination risks and problems

Elimination of killed measles vaccine Transition from plasma derived Hep B vaccine to recombinant Hep B vaccine Transition from DTP to DTaP (Some countries suspended pertussis immunization) Transition from OPV to IPV Withdrawal of first rotavirus vaccine

Will H1N1 Influenza Vaccine Cause Guillain-Barre Syndrome?

H1N1 Influenza Vaccine Safety

Closely monitored by CDC and National Vaccine Program Office Multiple large population databases scoured for adverse events related to H1N1 vaccine Vaccine Safety Datalink VA Health System and Dept. of Defense PRISM Health Plan/Immunization Registry link Indian Health Service Emerging Infections Program More than 10 million post-H1N1 vaccination lives under observation

1998-99: The Vaccine Safety Concern 1-2 Punch

Wakefield History

Wakefield, A.J., et al. Lancet 351: 637-641, 1998

Thimerosal-the beginning

MMWR 1999; 48 (26):564-566

Wakefield and the rest of the story

Findings never reproduced Wakefield had serious financial conflicts Co-authors withdraw from paper Paper retracted from Lancet Hearings held by British Health Authorities Wakefield sanctioned and license revoked The details of an elaborate fraud published in the British Medical Journal

 Mercury content of recommended vaccines reviewed Recommendation to reduce mercury exposure Delay in Hepatitis B vaccination of newborns to minimize mercury exposure Once MMR couldnt be targeted as a cause of autism, thimerosal became an attractive target

Factors that have increased concern

Distrust Industry Government Doctors Uncertainty Rapid increase in the number of vaccines Rapid increase in the number of autism cases Internet/Media/Celebrities

Know Your Source

What has been the effect? Falsehood flies, and the truth comes limping after; so that when men come to be undeceived, it is too late: the jest is over and the tale has had its effect
Jonathan Swift, The Examiner Nov. 9, 1710

Permanent Medical Exemptions & Personal Beliefs Exemptions, Kindergarten Students, California

Lee et al NVIC 2010

30

Kindergarten PBEs by County

2000 2008

Lee et al NVIC 2010

San Diego Measles Outbreak 2008

<12 months old

Other Measles Outbreaks in the U.S.-2008

131 cases from Jan-June 2008 (Average cases =63 annually 2000-2007) Washington outbreak (n=19) included 16 schoolaged children-all unimmunized Illinois outbreak (n=30) included 25 school-aged children-all unimmunized Altogether 91% of cases were unimmunized 89% related to imported cases
MMWR 2008; 57:893

and in 2011
Measles outbreak in Minnesota centered in Somali population Measles in Utah Measles in Arizona Large mumps outbreak in New Jersey 2010 California pertussis outbreak-10 deaths
MMWR, 2011; 60(20):666-668 MMWR 2010;59:125-129

Individual Risk of Exemption Pertussis

Age Group Rate per 100,000 exemptors 191 142 35 0 80 Rate per 100,000 vaccinated 11 9.4 19 13 13 Relative Risk (95% CI) 17 (9 - 31) 15 (9 - 25) 1.9 (0.8 - 5) 0 (0 - 2) 5.9 (4 - 8)

3- 5 6-10 11-14 15 -18 3 -18

Feikin, JAMA, 2001;284:3145

Refused pertussis vaccination

22.8 times increased risk of pertussis

Refused varicella vaccination

8.6 times increased risk of varicella

Other Vaccine Components and Autism

It aint over til the fat lady sings

Aluminum Bovine serum albumen Adjuvants Yeast proteins Human cell line derivatives ..

How Can You Respond

 Are vaccines safe? Do vaccines cause autism? Arent we overwhelming the immune system? Isnt natural immunity better? Diseases no longer existor arent that dangerous It is all a giant money-fueled conspiracy Its my right to decide whats best for my child

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

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

Use personal stories Provide appropriate resources

e.g., CDC, AAP, NNII, CHOP

The Vaccine Safety Infrastructure

Vaccines are Safe Talking Points

Hundreds of millions of vaccines are given every year in U.S. with no problem Billions of vaccines are given in the world every year with no problem Vaccine safety infrastructure is large
VAERS VSD CISA FDA CDC

Sample Sizes Needed During Clinical Trials to Detect Increases in Rates of Rare Vaccine Adverse Events
Rates of Event (%) 0.1 vs. 0.2 0.1 vs. 0.3 0.05 vs. 0.1 0.01 vs. 0.02 0.01 vs. 0.03 Sample Size* 50,000 17,500 100,000 500,000 175,000 No. Potentially Affected Annually1 4,000 8,000 2,000 400 800

* Two-arm, power=80%, alpha (2 sided)=5% 1 If the entire birth cohort (approx. 4 million children) received the vaccine each year
Adapted from Ellenberg SS: Safety considerations for new vaccine development. Pharmacoepidemiol Drug Safety 10(5):411-5, 2001

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
Advantages covers US population permits monitoring for known adverse events detects signals for previously unrecognized/rare adverse events generates hypothesis Limitations risk of underreporting or over reporting incomplete data lack of availability of denominator data

VAERS

Advantages
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

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

Vaccine Safety Datalink (VSD)

Collaboration between CDC and 8 managed care organizations
Data from 8.8 million members captured annually (3% of US population) Group Health Cooperative Northwest Kaiser Permanente No. CA Kaiser Permanente Kaiser Permanente Colorado CDC HealthPartners Harvard Pilgrim

Marshfield Clinic

So. CA Kaiser Permanente

Rapid Cycle Analysis, VSD

Outcome Exposure Medical Setting window (days)
1 to 42 0 to 42 0 0 to 42 0 to 42 1 to 42 All Inpatient, ED All Inpatient, ED Inpatient, ED All

Signal?

Guillain Barr Syndrome (GBS) Seizures Syncope Appendicitis Stroke Venous Thromboembolism (VTE) Anaphylaxis Other Allergic rxns

NO NO NO NO NO NO

0 to 2 0 to 2*

All All

NO NO

Examples of VSD studies

Risk of seizures following pertussis and MMR vaccines Risk of inflammatory bowel disease after measles-containing vaccines Febrile seizures after MMRV and influenza vaccines Guillain-Barre syndrome after H1N1 influenza vaccine

Institute of Medicine Safety Reviews

MMR Vaccine and Autism Multiple Immunizations and Immune Dysfunction Vaccines and SIDS Thimerosal and Neurodevelopmental Disorders HBV Vaccine and Demyelination Vaccines and autism Influenza vaccine and neurological complications

Clinical Immunization Safety Assessment Network (CISA)

6 centers established to review vaccine safety

Northern CA Kaiser, Columbia, Johns Hopkins, Vanderbilt, Stanford, Boston University

Investigate immunologic, pathologic and genetic mechanisms of possible vaccine related adverse events Provide consultation to providers regarding vaccine adverse events

Talking Points on Vaccine Safety Issues

Know Your Source Talking Points

Majority of sites found on an Internet search of Vaccines are anti-vaccine sites NNII site provides tips on how to evaluate the credibility of Web sites http://www.immunizationinfo.org How to identify a credible web site
Scientific studies cited and are current Lack of financial conflict of interest (selling a book) Experience in field Lack of anecdotes

Vaccine Safety Information

Freed et al Pediatr 2011;127:S107

Vaccines and Autism

What we know about vaccines and autism

Wakefield retraction Danish study California study Recent studies Causes of autism Heritability Early recognition Changes that had to occur in utero

 1047 children 7-10 years of age Formal neuropsychological testing Correlated outcome with thimerosal exposure No evidence for a link between thimerosal exposure and neuropsychological functioning
Thompson WW, NEJM 2007;357:1281

Thimerosal and Neuropsychological Function

2008 California Study

Schechter R, Arch Gen Psych 2008:65:19-24

What we know about autism

Highly heritable (more than breast cancer) Behavioral changes of autism often present before 1 year of age Autism associated with an increase in the number of neurons (i.e. insult occurs in utero) Ongoing studies specifically looking at risk of vaccines: none identified Autism hasnt gone away despite thimerosal being taken out of vaccines Rates of autism may not be any different now than they were 40 years ago
Arch Gen Psychiatry 2011;68:459-465 J Peds 2011, April 19 epub

Aluminum Concerns

Aluminum in vaccines
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

Aluminum Exposure: 1st 6 Months of Life

Robison et al NIC 2008

Do vaccines overwhelm the Immune System?

Your immune system responds to hundreds of things every day There is no evidence that children get more infections right after they are immunized Clinical trials test multiple vaccines Increased vaccine purity

1900 Vaccine Smallpox AntigensVaccine ~200Smallpox Diphtheria Tetanus Pert-WC Polio

1960 AntigensVaccine ~200Diphtheria 1Tetanus 1Pert-WC ~3000Polio 15Measles Mumps Rubella

1980 AntigensVaccine 1Diphtheria 1Tetanus ~3000Pert-AC 15Polio 10Measles 9Mumps 5Rubella Hib Varicella PCV

2011 Antigens 1 1 2-5 15 10 9 5 2 69 14

Offit et al, Pediatrics 2002;109:124

Hepatitis B 1 Hepatitis A 1 MCV 4 RV 2-7 HPV 4 *Influenza yearly, new strains every year Influenza* 6-114

Is natural immunity better?

For some infections natural immunity is better because it lasts longer Natural immunity is not complete whooping cough, rotavirus Multiple types of some disease agents (Pneumococcus, influenza) Natural immunity is only better if you survive the illness without serious consequences Natural immunity comes at a price deafness, brain damage, hospitalization, pneumonia, paralysis, permanent scars

Diseases Are Not That Bad

Prior to the availability of pneumococcal vaccine there were 200 deaths/year from this disease Out of the 5 cases of Hib reported last year in Minnesota, one died San Diego measles outbreak-out of 12 cases, one hospitalized Quote your own experience.

Parents Choice vs. the Greater Good

Not vaccinating puts your child at risk Not vaccinating your child also puts others at risk 3 innocent bystanders infected during San Diego measles outbreak

Personal beliefs about immunization are affecting people who do not share those beliefs

You cant hide in the herd

Herd immunity is very important
Elimination of H. flu disease Decrease in influenza and pneumococcal disease in elderly because of pediatric immunization Drop in Hepatitis A disease in California But, you cant hide in the herd, especially if your herd thinks like you do

California Immunization Coalition materials

http://www.immunizeca.org

What about alternative vaccine schedules?

What about the Sears schedule?

The Sears Schedule

Based on the premise that it is better to spread out vaccines Based on Dr. Sears opinion about what diseases are dangerous and what diseases a child is likely to encounter Based on the assumption that aluminum in vaccines causes a problem Based on the premise that as long as enough people dont follow the schedule, herd immunity will be maintained

Whats Wrong with Alternative Vaccine Schedules?

Whats Wrong With Alternative Immunization Schedules?

There is no scientific basis for them They leave children at risk for disease They leave our community at risk for outbreaks, including among those who are immunized They increase healthcare costs

Being Unimmunized Leaves You at Risk Talking Points

The unimmunized are at increased risk to develop disease and expose others All of the measles cases in San Diego in 2008 were unimmunized 3 of them were too young to be immunized and were exposed in a doctors office Unimmunized children are at increased risk for pertussis, mumps, chickenpox in schools

The Details of Whats Wrong With Alternative Vaccine Schedules

Sears Message #1 Doctors dont understand vaccines

Possible Responses Find a doctor you trust Doctors do not blindly follow anyones recommendations CDC, ACIP, and the AAP Committee on Infectious Disease have experts in public health, infectious disease, and pediatrics whose job it is to gather and interpret ALL of the data

Sears Message #2 You Cant Trust CDC, AAP, your doctor

Possible Responses What motive does your individual physician have to recommend vaccines if they dont believe in them? Why do you trust your doctor when they recommend drugs or surgery? Show me a report that people at CDC make money from pharmaceutical companies

Sears Message #3

Diseases Are Not That Bad

Possible Responses Over 400 children died in the U.S. from H1N1 influenza At least 10% of people with meningococcal disease die San Diego measles outbreak-out of 12 cases, one hospitalized I just took care of a patient with..

Sears Message #4

Hide in the Herd

Possible Responses Everyone else is NOT immunized It depends on what herd you are in- a partially immunized herd is a dangerous herd 5 cases of Hib reported this week in Minnesota suggesting that herd immunity is waning You will be thrown out of the herd (quarantined) if an outbreak occurs

Sears Message #5

Natural Infection is Better

Possible Responses Natural immunity comes at a cost-death, deafness, mental retardation, paralysis, chronic hepatitis Natural immunity doesnt work for many diseases because there are so many types You are taking a chance with letting your child develop natural immunity

Why Should I Put My Child At Risk For The Greater Good? Talking Points
Because you are actually putting your child at risk by not having them immunized. Measles exemptors: 35x increased risk Pertussis exemptors: 5.9x increased risk When you or your child are not immunized, you put others at risk: measles in San Diego None of us want to see a resurgence of the diseases we have largely eliminated

California Immunization Coalition materials

http://immunizeca.org

Information for Health-Care Professionals

NNII (www.immunizationinfo.org) VEC (www.vaccine.chop.edu) IAC (www.immunize.org) CDC/NIP (www.cdc.gov/nip) AAP (www.aap.org) AAFP (www.aafp.org/) IVS (www.vaccinesafety.edu) Vaccine Page (www.vaccines.org) Every Child by Two (www.ecbt.org)