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* % Decrease Smallpox 48,164 0 100.00 Diphtheria 175,885 0 100.00 Measles 503,282 57 99.99 Mumps 152,209 2,528 98.34 Pertussis 147,271 21,291 85.54 Polio (par.) 16,316 0 100.00 Rubella 47,745 6 99.99 CRS 823 0 100.00 Tetanus 1,314 8 98.39 Hib 20,000 16 99.92

MMWR 1999;48:245, 2011;59:1700*provisional

Are vaccines safe? Vaccines and autism

MMR Thimerosal Other vaccine ingredients Vaccines in general

Too many vaccines overwhelm the immune system Diseases no longer exist—or aren’t 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

1950-1980’s: Whole cell DTP vaccine 1976: Guillain-Barré from influenza vaccine 1980’s: OPV causing paralysis despite no

cases of polio 1990’s: 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 vaccineVaccine Safety DatalinkVA Health System and Dept. of DefensePRISM Health Plan/Immunization Registry link Indian Health ServiceEmerging Infections Program

More than 10 million post-H1N1 vaccination lives under observation

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

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

Wakefield History

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 couldn’t be targeted as a cause of autism, thimerosal became an attractive target

Factors that have increased concern

DistrustIndustryGovernmentDoctors

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

Lee et al NVIC 2010

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

30

2008

Lee et al NVIC 2010

Kindergarten PBEs by County2000

<1

2 m

on

ths

old

San Diego Measles Outbreak 2008

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 school-aged 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):666-668MMWR 2010;59:125-129

Individual Risk of Exemption - Pertussis

Age Group Rate per 100,000

exemptors

Rate per 100,000

vaccinated

Relative Risk (95% CI)

3- 5 191 11 17 (9 - 31)

6-10 142 9.4 15 (9 - 25)

11-14 35 19 1.9 (0.8 - 5)

15 -18 0 13 0 (0 - 2)

3 -18 80 13 5.9 (4 - 8)

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 AutismIt ain’t over ‘til the fat lady sings…

AluminumBovine serum albumenAdjuvantsYeast proteinsHuman cell line derivatives…………………..

How Can You Respond

Are vaccines safe? Do vaccines cause autism? Aren’t we overwhelming the immune system? Isn’t natural immunity better? Diseases no longer exist—or aren’t that

dangerous It is all a giant money-fueled conspiracy It’s my right to decide what’s 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 largeVAERSVSDCISAFDACDC

Sample Sizes Needed During Clinical Trials to Detect Increases in Rates of Rare Vaccine Adverse Events

Rates of Event (%) Sample Size* No. Potentially Affected Annually1

0.1 vs. 0.2 50,000 4,000

0.1 vs. 0.3 17,500 8,000

0.05 vs. 0.1 100,000 2,000

0.01 vs. 0.02 500,000 400

0.01 vs. 0.03 175,000 800

* 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 populationpermits monitoring for known adverse

eventsdetects signals for previously

unrecognized/rare adverse eventsgenerates hypothesis

Limitationsrisk of underreporting or over reportingincomplete 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

So. CA Kaiser Permanente

Kaiser Permanente Colorado

HealthPartners

Marshfield ClinicHarvard Pilgrim

CDC

OutcomeExposure

window (days) Medical Setting Signal?Guillain Barré Syndrome

(GBS) 1 to 42 All NO

Seizures 0 to 42 Inpatient, ED NO

Syncope 0 All NO

Appendicitis 0 to 42 Inpatient, ED NO

Stroke 0 to 42 Inpatient, ED NO

Venous Thromboembolism (VTE) 1 to 42 All NO

Anaphylaxis 0 to 2 All NO

Other Allergic rxns 0 to 2* All NO

Rapid Cycle Analysis, VSD

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 siteScientific studies cited and are currentLack of financial conflict of interest (selling a

book)Experience in fieldLack 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

HeritabilityEarly recognitionChanges that had to occur in utero

Thimerosal and Neuropsychological

Function 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

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 hasn’t 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;68:459-465J 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 overwhelmthe 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 1960 1980 2011

Vaccine Antigens Vaccine Antigens Vaccine Antigens Vaccine Antigens

Smallpox ~200 Smallpox ~200 Diphtheria 1 Diphtheria 1

Diphtheria 1 Tetanus 1 Tetanus 1

Tetanus 1 Pert-WC ~3000 Pert-AC 2-5

Pert-WC ~3000 Polio 15 Polio 15

Polio 15 Measles 10 Measles 10

Mumps 9 Mumps 9

Rubella 5 Rubella 5

Hib 2

Varicella 69

PCV 14

Hepatitis B

Hepatitis A

MCV

RV

HPV

Influenza*

1

1

4

2-7

4

6-114

Total ~200 Total ~3217 Total ~3041 Total 142-258

Offit et al, Pediatrics 2002;109:124 *Influenza yearly, new strains every year

Is natural immunity Is natural immunity better?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 pricedeafness, 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’ ChoiceParents’ Choicevs. the “Greater Good”vs. the “Greater Good”

Not vaccinating puts your child at Not vaccinating puts your child at riskrisk

Not vaccinating your child also puts Not vaccinating your child also puts others at riskothers at risk

3 innocent bystanders infected 3 innocent bystanders infected during San Diego measles outbreakduring San Diego measles outbreak

Personal beliefs about immunization are

affecting people who do not share those

beliefs

You can’t 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 can’t hide in the herd, especially if your herd thinks like you do

http://www.immunizeca.org

California Immunization Coalition materials

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 don’t follow the schedule, herd immunity will be maintained

What’s Wrong with Alternative Vaccine Schedules?

What’s 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 othersAll of the measles cases in San Diego in

2008 were unimmunized3 of them were too young to be immunized

and were exposed in a doctor’s office Unimmunized children are at increased risk

for pertussis, mumps, chickenpox in schools

The Details of What’s Wrong With Alternative Vaccine Schedules

Sears Message #1Doctors don’t understand vaccines

Possible Responses

Find a doctor you trust Doctor’s do not blindly follow anyone’s

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 #2You Can’t Trust CDC, AAP, your

doctorPossible Responses

What motive does your individual physician have to recommend vaccines if they don’t 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 doesn’t 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 riskPertussis 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

http://immunizeca.org

California Immunization Coalition materials

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)