Vaccine Safety and Vaccine Safety Communication Otherwise Known

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 20 th Century MMWR 1999; 48: 241

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

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

The Things You Hear… § Are vaccines safe? § Vaccines and autism ü MMR ü Thimerosal ü Other vaccine ingredients ü 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 DTa. P (Some countries suspended pertussis immunization) § Transition from OPV to IPV § Withdrawal of first rotavirus vaccine

Will H 1 N 1 Influenza Vaccine Cause Guillain-Barre Syndrome?

H 1 N 1 Influenza Vaccine Safety § Closely monitored by CDC and National Vaccine Program Office § Multiple large population databases scoured for adverse events related to H 1 N 1 vaccine ü Vaccine Safety Datalink ü VA Health System and Dept. of Defense ü PRISM Health Plan/Immunization Registry link ü Indian Health Service ü Emerging Infections Program § More than 10 million post-H 1 N 1 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

Thimerosal history § 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 § Distrust üIndustry üGovernment üDoctors § 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

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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 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

u Refused pertussis vaccination • 22. 8 times increased risk of pertussis

u Refused varicella vaccination – 8. 6 times increased risk of varicella

Other Vaccine Components and Autism It ain’t over ‘til the fat lady sings… üAluminum üBovine serum albumen üAdjuvants üYeast proteins üHuman cell line derivatives ü…………………. .

How Can You Respond

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

Vaccine Safety Discussion Strategies u u u 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 u u 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 ü VAERS ü VSD ü CISA ü FDA ü CDC

Sample Sizes Needed During Clinical Trials to Detect Increases in Rates of Rare Vaccine Adverse Events Rates of Event (%) Sample Size* No. Potentially Affected Annually 1 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) u u 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 u Subject to well-described limitations of passive surveillance

VAERS § Advantages ücovers US population üpermits monitoring for known adverse events üdetects signals for previously unrecognized/rare adverse events ügenerates hypothesis § Limitations ürisk of underreporting or over reporting üincomplete data ülack of availability of denominator data

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

VAERS HPV Data: Venous Thromboembolism u 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 Health. Partners Marshfield Clinic No. CA Kaiser Permanente So. CA Kaiser Permanente Colorado CDC Harvard Pilgrim

Rapid Cycle Analysis, VSD Exposure window (days) Medical Setting Outcome 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

Examples of VSD studies u u 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 H 1 N 1 influenza vaccine

Institute of Medicine Safety Reviews u u u u 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) u 6 centers established to review vaccine safety – Northern CA Kaiser, Columbia, Johns Hopkins, Vanderbilt, Stanford, Boston University u u 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 ü Scientific studies cited and are current ü Lack of financial conflict of interest (selling a book) ü Experience in field ü Lack of anecdotes

Vaccine Safety Information Freed et al Pediatr 2011; 127: S 107

Vaccines and Autism

What we know about vaccines and autism § § § Wakefield retraction Danish study California study Recent studies Causes of autism üHeritability üEarly recognition üChanges 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 -465 J Peds 2011, April 19 epub

Aluminum Concerns u Aluminum in vaccines – adjuvant – maximum amount 0. 85 mg/dose u 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: 1 st 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 1960 Antigens Vaccine ~200 Smallpox 1980 Antigens Vaccine ~200 Diphtheria 2011 Antigens Vaccine 1 Diphtheria 1 Tetanus 1 Pert-WC ~3000 Pert-AC 2 -5 15 Polio 15 10 Measles 10 Mumps 9 Rubella 5 Hib 2 Pert-WC Polio ~3000 Polio 15 Measles Varicella 69 PCV 14 Hepatitis B Hepatitis A MCV RV HPV Influenza* Total Antigens ~200 Total Offit et al, Pediatrics 2002; 109: 124 ~3217 Total ~3041 Total 1 1 4 2 -7 4 6 -114 142 -258 *Influenza yearly, new strains every year

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 ü 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 can’t hide in the herd § Herd immunity is very important ü Elimination of H. flu disease ü Decrease in influenza and pneumococcal disease in elderly because of pediatric immunization ü Drop in Hepatitis A disease in California § But, you can’t 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 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 others üAll of the measles cases in San Diego in 2008 were unimmunized ü 3 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 #1 Doctors 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 #2 You Can’t Trust CDC, AAP, your doctor Possible 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 H 1 N 1 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. üMeasles exemptors: 35 x increased risk üPertussis exemptors: 5. 9 x 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)