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

2. 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?

3. Vaccination is the top Public Health achievement of the 20th Century MMWR 1999; 48:241

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

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

7.  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

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

9. Parents: Doubts About Vaccines Gust et al Pediatr 2009;122:718

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

11. How did we get here?

12. 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

13. How have we dealt with real vaccine risks?

14. 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

16. Will H1N1 Influenza Vaccine Cause Guillain-Barre Syndrome?

17. 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

19. 1998-99: The Vaccine Safety Concern 1-2 Punch

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

21. Thimerosal-the beginning MMWR 1999; 48 (26):564-566

22. 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

24.  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

25. 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

26. Know Your Source

28. 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

29. Lee et al NVIC 2010 Permanent Medical Exemptions & Personal Beliefs Exemptions, Kindergarten Students, California

30. 30

31. 2008 Lee et al NVIC 2010 Kindergarten PBEs by County 2000

33. Physician Office <12 months old Charter School 2º Transmission San Diego Measles Outbreak 2008

34. 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

36. …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

37. 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

38.  Refused pertussis vaccination 22.8 times increased risk of pertussis

39.  Refused varicella vaccination –8.6 times increased risk of varicella

40. Other Vaccine Components and Autism It ain’t over ‘til the fat lady sings… Aluminum Bovine serum albumen Adjuvants Yeast proteins Human cell line derivatives …………………..

41. How Can You Respond

42.  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

43. 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

44. 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

45. The Vaccine Safety Infrastructure

46. 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

47. 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. 0.250,0004,000 0.1 vs. 0.317,5008,000 0.05 vs. 0.1100,0002,000 0.01 vs. 0.02500,000400 0.01 vs. 0.03175,000800 * 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

48. 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

49. 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

51. 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

52. 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

53. 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 Clinic Harvard Pilgrim CDC

54. Outcome Exposure window (days)Medical SettingSignal? Guillain Barré Syndrome (GBS)1 to 42AllNO Seizures0 to 42Inpatient, EDNO Syncope0AllNO Appendicitis0 to 42Inpatient, EDNO Stroke0 to 42Inpatient, EDNO Venous Thromboembolism (VTE)1 to 42AllNO Anaphylaxis0 to 2AllNO Other Allergic rxns0 to 2*AllNO Rapid Cycle Analysis, VSD

55. 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

56. 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

57. 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

58. Talking Points on Vaccine Safety Issues

59. 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 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

60. Vaccine Safety Information Freed et al Pediatr 2011;127:S107

61. Vaccines and Autism

62. 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

66. 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

67. 2008 California Study Schechter R, Arch Gen Psych 2008:65:19-24

68. 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

69. 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

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

71. 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

72. 1900196019802011 VaccineAntigensVaccineAntigensVaccineAntigensVaccineAntigens Smallpox~200Smallpox~200Diphtheria1 1 1Tetanus1 1 1Pert-WC~3000Pert-AC2-5 Pert-WC~3000Polio15Polio15 Polio15Measles10Measles10 Mumps9 9 Rubella5 5 Hib2 Varicella69 PCV14 Hepatitis B Hepatitis A MCV RV HPV Influenza* 1 4 2-7 4 6-114 Total~200Total~3217Total~3041Total142-258 Offit et al, Pediatrics 2002;109:124 *Influenza yearly, new strains every year

73. 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

74. 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….

75. 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

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

77. 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

78. http://www.immunizeca.org California Immunization Coalition materials

79. What about alternative vaccine schedules?

80. What about the Sears schedule?

81. 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

82. What’s Wrong with Alternative Vaccine Schedules?

83. 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

84. 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 doctor’s office  Unimmunized children are at increased risk for pertussis, mumps, chickenpox in schools

85. The Details of What’s Wrong With Alternative Vaccine Schedules

86. 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

87. 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

88. 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…..”

89. 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

90. 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

91. 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

92. http://immunizeca.org California Immunization Coalition materials

93. 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)