1. Missing Information About Vaccine Safety Martin G. Myers, MD October 11, 2007 Vaccine Safety, Dealing with Uncertainty

2. Outline Background  Impact of vaccines  Community Immunity The Origins of Risk Benefit Misperceptions  Out of sight, Out of mind  Concerns about vaccine safety Missing Information  Scientific Uncertainty (but PH decisions MUST still be made).  The evolution to Misinformation Misinformation Has Adverse Consequences

3. The Immunization Programs have had Incredible Success

4. Disease# Cases prior to Vaccine 1 Year universal rec. # Cases 2005 2 # Cases 2006 3 Smallpox48,164Early 1900s00 Diphtheria175,885Mid 1940s00 Pertussis147,271Mid 1940s26,616 4 15,632 4 Tetanus1,314Mid 1940s2741 Paralytic Poliomyelitis 16,31619551515 0 Measles503,28219636658 Mumps152,20919673146,584 Rubella47,745196911 Congenital82311 Vaccine Disease Prevention-1 1 CDC. 1999. MMWR 48:243. 2 CDC. 2007. 54:2. 3 CDC. 2007. MMWR 56(33). 4 Cases of pertussis were at a historic low of 1010 in 1976. 5 Imported, vaccine-associated.

5. Disease# Cases/yr prior to Vaccine 1 Year universal rec. # Cases 2005 2 # Cases 2006 3 Invasive 6 H. influenzae, type b ~20,0001985929 Invasive 6 S. pneumoniae ~89,400200014951861 Hepatitis B (acute) 21,10219915,1194,713 Varicella~4,000,000199532,24248,445 deaths1153NA 8 Hepatitis A (acute) 26,7961999 7 /200644883579 Vaccine Disease Prevention-2 6 Children <6 years of age. 7 Recommended for highest risk communities in 1996, for communities and states with increased risk (1999) and then for universal use (2006). 8 Data not available.

6. If vaccines have been such a great success, Why have there been recent outbreaks of measles in UK, Ireland, Germany, China, Japan, Korea, Mongolia, Italy, Switzerland, Belgium, Marshall Islands? Why do >2000 children refuse immunization in New York? Why is immunization coverage higher in Mexico & Canada than in than the US?  Why do many communities permit low immunization coverage levels?  Why does it matter?

7. Community Protection Requires High Levels of Immunization

8. Community (Herd) Immunity Thresholds The proportion of immune individuals that is required to prevent sustained transmission of infection

9. Community (Herd) Immunity Thresholds Measles: >94% Poliomyelitis: 50-93% (following IPV, unknown) Diphtheria: 85% Mumps: 86% Pertussis: 94% Rubella: 83-85% Smallpox: 80-85% After Fine P. in Orenstein & Plotkin 4 th Edition, 2004.

10. Immunization Coverage (% immunized) is used as a Surrogate Marker for Community Immunity

11. US 1, Mexico 2, and Canada 2 Vaccine Coverage for 19-35 month olds, 2006 USACanadaMexico Polio92.99498 DTP85.29498 HBV93.673 Measles92.49496 Hib93.49473 PCV87.0 VZV89.3 1 www.cdc.gov/vaccines/stats-surv/nis/data/tables_2006.htm 2 www.who.int/vaccines/global.

12. Why are Under-Immunized Children so Important? The unimmunized children are at risk of disease. Those that can not be immunized are not protected. Those who are immunized may also be at risk, because no vaccine is 100% effective. For example, Measles:  the proportion of the population that needs to be immune to keep virus from transmitting person to person is 95% (but 5% remain susceptible after vaccination).  If 2 are unimmunized, 5 more are also susceptible (5% of the 98): the immune level is about 93%.  In the US, MMR coverage is 92.4%, immune level, therefore, is ~87.8%.

13. Why are immunization coverage levels low in some communities? There are Multiple Reasons:  Poverty.  Disparities in access to healthcare.  Fear of being identified by the government.  Risk-benefit misperceptions.

14. Children How Can Communities Knowingly Put Their Children At Risk?! The key word is: “knowingly”. One form of missing information is when:  The information is available, but unknown or unrecognized,  For example, some communities—and most parents—do not recognize the risk to their community and their children from vaccine- preventable diseases.

15. Missing Information The Lack of Community Understanding that their children are at Risk of harm from vaccine preventable diseases.  Loss of diseases visibility.  Loss of a sense of urgency.  Lack of fear. “The data are insufficient to support or reject the hypothesis”. The uninformed/incompletely informed person may unintentionally disseminate misinformation.

16. Misinformation The uninformed constitute the Unintentional Misinformers. Intentional Misinformers (disinformers) actively seek to mislead others.  Some truly believe vaccines injured their child.  Others seek personal gain. Misinformers have many sophisticated tools to disseminate misinformation.  Media loves a “controversy” – it makes the story interesting.  The Internet is a powerful but also a dangerous source of information. Many persons are not worried about diseases they don’t see (uninformed) and are confused about vaccine safety risk (misinformed).  Most do not understand risk measurements.

17. Information about Vaccines and Vaccine Safety Missing Information can Evolve into Misinformation

18. The Evolution of Missing Information Into Misinformation About Vaccine Safety Issues-1 A vaccine safety concern is suggested  The media may declare that there ‘may be a problem’.  Some parents become confused. Scientists won’t state that the vaccine did not cause the adverse event—because the information is insufficient (missing).  This creates a sense of scientific uncertainty.  Parents become confused.

19. The Evolution of Missing Information Into Misinformation About Vaccine Safety Issues-2 Public health officials compare the possible risks from the adverse event of concern with the known risk of the disease, based on whatever available data there is.  They must make recommendations to protect the public health, whether or not all the information is available.  The media often report a controversy (meaning a ‘difference of opinion’) between public health officials and parents.  True scientific controversy is rarely reported.  Pseudoscience is discounted by scientists but often reported in the media.  New data may become available that suggests a possible mechanism (but plausibility does not establish causality).  Parents become confused.

20. The Evolution of Missing Information Into Misinformation About Vaccine Safety Issues-3 With more data, scientists reach a consensus that the data “favor rejection of the hypothesis”- that is, the association is likely to be coincidental. Parents who are convinced—plus intentional mis- informers—state that the science is in error; they often try to discredit the scientists, etc.  The media describes a ‘controversy’.  Parents become confused.  Outbreaks of disease may occur if vaccine coverage (community immunity) has declined.

21. Measles-containing Vaccines and Autism Andrew Wakefield and MMR; 27 February, 1998. Case reports. UK media reports  Measles vaccine a possible cause of autism  Reassurance by public health community. Data which takes many years to obtain does not find an association. The IOM Vaccine Safety Committee Report s “the data favors rejection of an association” (2004) Consequences  MCV immunization levels drop and remain low in the UK (& several other countries).  Measles outbreaks occur in the UK, Ireland, Germany  Mumps outbreak occur in the UK (which spreads to US & Canada)

22. Measles-containing Vaccine Coverage – UK* *www.who.int/countries/global. Accessed Oct 5, 2007

23. Cases of Measles – UK* *www.who.int/countries/global. Accessed Oct 5, 2007

25. Mumps Cases – UK* *www.who.int/countries/global. Accessed Oct 5, 2007

26. Thimerosal Misinformation Despite many studies—and a careful review by the Institute of Medicine that ‘favored rejection of the hypothesis’:  The media continues to report a ‘controversy’.  Children (~10,000) are being treated with chelation therapy for ‘mercury poisoning’ (one has died).  Regions are reporting increasing delay of infant immunizations and numbers of children using school exemptions.  We have reported increasing information seeking behavior temporally associated with major news stories about thimerosal misinformation.

27. Compounding the Problem of Misinformation is our use of Language Expression/WordTechnical MeaningMeaning to Public BiasSystematic errorNot an open mind ControversyDiffering interpretations of the same data Difference of opinion NaïvePreviously unexposed Unsophisticated PlausibleTheoretically possible Worthy of belief, factual SafeLow riskNo risk SignificantThis may not be a chance difference Important * From Pineda D and Myers M. 2007. Do vaccines cause that?! I4PH Press.