Thimerosal –Related Changes in Vaccination Recommendations and Hepatitis B Vaccine

1. Thimerosal –Related Changes in Vaccination Recommendations and Hepatitis B Vaccine Coverage Among United States Children Harold S. Margolis, MD Anthony Fiore, MD, MPH Division of Viral Hepatitis Centers for Disease Control and Prevention

2. Thimerosal and Vaccines • Vaccine preservative that contains mercury • Until 1999, used in hepatitis B vaccine, some DTaP, Hib and influenza vaccines • 1999 FDA review: For some infants, mercury exposure from vaccines exceeds FDA, but not EPA, ATDSDR, or WHO guidelines • Concerns discussed among CDC, FDA and AAP representatives late June 1999 • No health effects from mercury in vaccines identified • Quick fix: Hepatitis B vaccine could be “deferred” for infants born to HBsAg negative women until 2 months old

3. Changes in Infant Vaccination Recommendations Related to Thimerosal • July 1999: Joint Statement on Thimerosal in Vaccines (AAP/USPHS) • Defer vaccination of infants born to HBsAg negative women until 2-6 months old • September 1999 : Thimerosal-free hepatitis B vaccine distribution begins • Resume previous vaccination practices • Vaccinate newborns at birth or by age 2 months • December 2000: Sufficient supply of preservative-free hepatitis B vaccines for all U.S. newborns

4. National Immunization Survey • Standard for assessing national vaccine coverage since 1994 • 34,000 households per year complete telephone interview • Target group: 19-35 month old children • Provider verification of vaccination • Largest ongoing telephone survey in the United States

5. Hepatitis B Vaccine 3 Dose Coverage Among 19-35 Month Old Children, by Year of Survey, 1990-2001* *Source: National Immunization Survey

6. Percentage of Children Who Received Hepatitis B Vaccine at Birth, by State, 1998 VT Overall: 55% Range: 26% - 82% >70% SO. 50-69% <50% Source: National Immunization Survey, 19-35 month olds

7. Percentage of Children Who Received Hepatitis B Vaccine at Birth, by State, 2001 VT Overall: 45% Range: 16% - 73% >70% SO. 50-69% <50% Source: National Immunization Survey, 19-35 month olds Preliminary data

8. Defining the Effects of Thimerosal- Related Changes in Immunization RecommendationsNational Immunization Survey, 2001 • Determine hepatitis B vaccine coverage (3 dose and birth dose) coverage among children born before, during and after recommendations changes • Compare changes in coverage for hepatitis B vaccine with other infant vaccines

9. Methods • Children born February 1998-May 2000 • Divided into 3 groups: • Group 1: born Feb 1998 - Jun 1999 • Group 2: born Jul 1999 - Dec 1999 • Group 3: born Jan 2000 - May 2000 • Only vaccinations given before 19 months counted to adjust for differences in age

10. 100 90 Joint Statement 80 70 59.4 Thimerosal-free vaccine 60 Percentage received birth dose 50 40 25 30 15.3 † 20 † 10 0 Feb98-Jun99 Jul99-Dec99 Jan00-May00 Birth time period †Significantly lower (p<0.05) compared to children born before 7/1/99 Hepatitis B Vaccine Birth Dose Coverage (<7 days after birth), 19 month old children, United States Preliminary data, 2001 National Immunization Survey

11. 100 90 Joint Statement 80 Thimerosal-free vaccine 70 60 44.8 Percent received birth dose 50 40 † 30 19 † 20 12 10 0 Feb98-Jun99 Jul99-Dec99 Jan00-May00 Birth time period †Significantly lower (p<0.05) compared to children born before 7/1/99 Hepatitis B vaccine birth dose coverage ( < 1 day after birth) among 19 month old children, United States Preliminary data, 2001 National Immunization Survey

12. Thimerosal-free vaccine Joint Statement 100 † 87.6 † 83.6 90 79.7 80 70 Percentage received 3 60 or more doses 50 40 30 20 10 0 Feb98-Jun99 Jul99-Dec99 Jan00-May00 Birth time period †Significantly lower (p<0.05) compared to children born before 7/1/99 Hepatitis B Vaccine Coverage (>3 doses) Among 19 Month Old Children, United States Preliminary data, 2001 National Immunization Survey

13. Received 0 doses Received 1 or 2 doses Thimerosal-free vaccine 24 21.3%† Joint Statement 20 16.4%† 16 12.4% Percent 12 8 4 † † 0 Feb98-Jun99 Jul99-Dec99 Jan00-May00 Birth time period †Significantly different (p<0.05) compared to children born before 7/1/99 Inadequate Vaccination (2 doses) Among 19 Month Old Children, United States, 2001 National Immunization Survey

14. Vaccination Coverage for Other Infant Vaccines, 2001 NIS • Coverage for DTaP, IPV, Hib, MMR, varicella and 4:3:1:3 increased or stayed the same compared to 2000* • No difference in coverage among 2001 time periods for DTP, IPV, Hib, MMR, 4:3:1:3 • Significant increase for varicella coverage *Source: MMWR 2002

15. Conclusions For infants participating in the 2001 NIS (born February 1998 – May 2000): • Hepatitis B birth dose and 3 dose coverage decreased significantly after thimerosal-related recommendations • Hepatitis B vaccine birth dose and 3 dose vaccine coverage remained lower than baseline even after preservative-free vaccine was made available • Vaccine coverage for other infant vaccines was not reduced after thimerosal recommendations • Reductions in birth dose coverage may have led to reductions in 3 dose coverage at 19 months

16. Limitations • NIS 2001 dataset not yet complete (expected February 2003) • Need to determine if children who did not receive birth dose were same children who did not who did not complete series • HBsAg status of mothers not available from NIS data • Vaccine coverage for children born after both preservative-free vaccines licensed not yet available (2002 NIS)

17. HepB Doses Administered Before Age 2 Months Oregon Immunization Registry, 2/99 – 3/00 1200 Joint Statement 1000 Preservative-free HepB available through VFC 800 Hep B given 0-56 days after birth Preservative-free HepB available in hospitals 600 Doses Administered 400 Hep B given 0-5 days after birth 200 0 02 06 10 14 18 22 26 30 34 38 42 46 50 02 06 10 1999 2000 Source: Oregon Immunization ALERT registry Week

18. Effects on Prevention of Perinatal HBV Infection

19. Prevention of Perinatal and Early Childhood HBV Infection Ensure hospital standing orders that require: • Documented HBsAg status or testing for mothers of all newborns before discharge • Routine postexposure prophylaxis for infants of HBsAg-positive mothers • Newborn vaccination of infants born to mothers without prenatal HBsAg testing • Newborn vaccination of infants at high risk of early childhood HBV infection

20. Effect of Thimerosal Recommendations on Hospital Policies for Newborn Hepatitis B Vaccination Maternal HBsAg status Before Statement After Jan-June ‘99 Jul-Oct ‘99 Nov-Dec ‘99 National Survey of Hospitals (n=773)

21. Fulminant Hepatitis B, Michigan, 1999 • Mother: 15 year old primagravida, Hmong teenager • Prenatal care: 10 visits, HBsAg (+) -- not reported to health department • July 1999 - hospital discontinued routine newborn hepatitis B vaccination • September 2, 1999 = term birth. Infant received no hepatitis B vaccine. Prenatal record = “hepatitis negative”. • November 29,1999 = first dose hepatitis B vaccine

22. Fulminant Hepatitis B, Michigan, 1999 • December 14, 1999: infant admitted to hospital with jaundice, diarrhea. Dx = HBV acute liver failure • December 17, 1999: infant died awaiting liver transplantation • Further work-up showed infant was HBeAg-negative with precore stop codon • Fall 2000 – mother dies from ectopic pregnancy

23. Proportion of MICHIGAN infants born to women of unknown status vaccinated, 1999-2000 P<0.001

24. Effect of Thimerosal Recommendations on Birth Dose for Infants of Mothers with Unknown HBsAg Status, Oregon • Identified infants born to mothers with unknown HBsAg status – used electronic birth certificate data • 3 time periods: before, after, thimerosal free • Reviewed charts = 64% of hospitals & 40% of births • Identified 308 mothers (1.9% of births) • 298 with adequate data • 147 (49%) remained unknown HBsAg at discharge

25. Hospitals Policy to Hepatitis B Vaccine to All Newborns Before Discharge (n=53)

26. Proportion of OREGON infants born to women of unknown status vaccinated, 1999-2000 P<0.001

27. States Report Hundreds of Medical Errors in Perinatal Hepatitis B Prevention Avoid tragic mistakes—vaccinate newborns against HBV in the hospital By Teresa A. Anderson, DDS, MPH, and Deborah L. Wexler, MD*

28. Other Effects on Immunization

29. Your resource for Thimerosal claims Get a free case assesment! Parker and Waichman has filed a Class Action Lawsuit against manufacturers of vaccines containing Thimerosal. Visit www.vaccineclassaction.com for more information. It is estimated that 17 percent of US children under the age of 18 are suffering from learning and/or behavioral disabilities. California's Department of Developmental Services reported a 20 percent increase over the previous year for diagnoses of level-one autism. Level-one autism is the number one disability in the state of California, accounting for 35 percent of all new cases. Of the 16,802 persons with level-one autism in the California system, two-thirds of them are between the ages of birth and 13. To see if you have an Thimerosal related case, click here

30. AAP News Vol. 22 No. 1 January 2003, p. 4 WASHINGTON REPORT Thimerosal cases in Oregon dismissed Marjorie TharpWashington Correspondent An Oregon judge has dismissedmost of the class action lawsuits filed in that state alleginginjury from thimerosal in vaccines, including the case thatnamed not only manufacturers, but also a pediatrician. This is the second time a judge has tossed out a case. Earlierthis summer, a federal court in Texas dismissed another thimerosal-relatedclass action lawsuit but said the plaintiffs could still suefor loss of consortium or companionship. At press time, however,more than a dozen states had individual or class action lawsuitspending. The suits have been filed by or on behalf of families who believetheir children were injured by vaccines containing thimerosal,a mercury-containing preservative. Although no evidence of harmexisted, the Academy and the federal government called for manufacturersto remove thimerosal as a precautionary measure in 1999.

31. Institute of Medicine Immunization Safety ReviewThimerosal-Containing Vaccines and Neurodevelopmental Disorders • Biologic Plausibility “….although the hypothesis that exposure to thimerosol-containing vaccines could be associated with neurodevelopmental disorders is not established and rests on indirect and incomplete information, primarily from analogies with methylmercury and levels of maximum mercury exposure given children in vaccines, the hypothesis is biologically plausible.” • Causality “….the evidence is inadequate to accept or reject a causal relationship between exposure to thimerosal from vaccines and the neurodevelopmental disorders of autism, ADHD, and speech or language delay.” • Significance Assessment National Academy Press, 2001

32. Institute of Medicine Immunization Safety ReviewThimerosal-Containing Vaccines and Neurodevelopmental Disorders • Significance Assessment • First. The diseases prevented by the vaccines under discussion are serious and important • Second. Understanding the risks of thimerosal is important because of the need for its continued use. • Third. Many countries still depend on the use of thimerosal in multi-dose vaccine supply • Fourth. Lessons can be learned from the decision making process surrounding policy changes for hepatitis B immunization • Finally. Concerns about adverse events from thimerosal have the potential to erode trust in immunization National Academy Press, 2001

33. Comments • Rapid changes in vaccination recommendations must be accompanied by effective communication messages • Changes in immunization policy should be evidence based – the risks of childhood HBV infection were ignored by decision makers • Communication about immunization policy changes must come from organizations that are seen by practitioners that immunize children as their soure of information • The AAP/PHS Joint statement differed from the AAP statement with respect to hepatitis B vaccination

34. Ann Thomas Beth Bell Eric Mast Beth Luman Tara Strine Hussain Yusuf Lawrence Barker Nancy Fasano Thomas Saari Acknowedgements