Thimerosal –Related Changes in Vaccination Recommendations

and Hepatitis B Vaccine Coverage Among United States

Children

Harold S. Margolis, MDAnthony Fiore, MD, MPHDivision of Viral Hepatitis

Centers for Disease Control and Prevention

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

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

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

Hepatitis B Vaccine 3 Dose Coverage Among 19-35 Month Old Children, by Year of Survey,

1990-2001*

816

37

68

82 87 88 90 8984

0

20

40

60

80

100

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

Year

Perc

enta

ge R

ecei

ved

3 D

oses

*Source: National Immunization Survey

VT

SO.>70%

50-69%

<50%

Overall: 55%Range: 26% - 82%

Percentage of Children Who Received Hepatitis B Vaccine at Birth, by State,

1998

Source: National Immunization Survey, 19-35 month olds

VT

SO.>70%

50-69%

<50%

Overall: 45%Range: 16% - 73%

Percentage of Children Who Received Hepatitis B Vaccine at Birth, by State,

2001

Source: National Immunization Survey, 19-35 month oldsPreliminary data

Defining the Effects of Thimerosal- Related Changes in Immunization Recommendations

National 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

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

Hepatitis B Vaccine Birth Dose Coverage (<7 days after birth), 19 month old children, United States

Preliminary data, 2001 National Immunization Survey

59.4

Feb98-Jun99

25

Jan00-May00

†

15.3

Jul99-Dec99

† Significantly lower (p<0.05) compared to children born before 7/1/99

†

0102030405060708090

100

Per

cen

tag

e re

ceiv

ed b

irth

do

se

Birth time period

Joint StatementThimerosal-free vaccine

Hepatitis B vaccine birth dose coverage ( < 1 day after birth) among 19 month old children, United

States Preliminary data, 2001 National Immunization Survey

19†

Jan00-May00

0102030405060708090

100

Pe

rce

nt

rece

ive

d b

irth

do

se

Birth time period

44.8

Feb98-Jun99

Joint Statement

12

† Significantly lower (p<0.05) compared to children born before 7/1/99

†

Jul99-Dec99

Thimerosal-free vaccine

Hepatitis B Vaccine Coverage (>3 doses) Among 19 Month Old Children, United

States Preliminary data, 2001 National Immunization Survey

83.6

Jan00-May00

†

0102030405060708090

100

Per

cen

tag

e re

ceiv

ed 3

or

mo

re d

ose

s

Birth time period

87.6

Feb98-Jun99

Joint Statement

Jul99-Dec99

† Significantly lower (p<0.05) compared to children born before 7/1/99

79.7†

Thimerosal-free vaccine

Inadequate Vaccination (2 doses) Among 19 Month Old Children, United States, 2001

National Immunization Survey

Joint Statement

Thimerosal-free vaccine

0

4

8

12

16

20

24

Per

cen

t

Received 0 doses Received 1 or 2 doses

Birth time period

Feb98-Jun99

12.4%

† Significantly different (p<0.05) compared to children born before 7/1/99

†

Jul99-Dec99

21.3%†

†

Jan00-May00

16.4%†

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

Conclusions

• 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

For infants participating in the 2001 NIS (born February 1998 – May 2000):

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)

HepB Doses Administered Before Age 2 MonthsOregon Immunization Registry, 2/99 – 3/00

0

200

400

600

800

1000

1200

02 06 10 14 18 22 26 30 34 38 42 46 50 02 06 10

Source: Oregon Immunization ALERT registry

Doses A

dm

inis

tere

d

Hep B given 0-56 days after birth

Hep B given0-5 days after birth

Joint Statement

Preservative-freeHepB available

in hospitals

Preservative-free HepB available through VFC

1999 2000Week

Effects on Prevention of Perinatal HBV Infection

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

Effect of Thimerosal Recommendations on Hospital Policies for Newborn Hepatitis B Vaccination

Positive 98% 86% 91%

Unknown 87% 60% 67%

Negative 85% 17% 34%

Maternal HBsAg

status Before Statement After

National Survey of Hospitals (n=773)

Jan-June ‘99 Jul-Oct ‘99 Nov-Dec ‘99

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

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

Proportion of MICHIGAN infants born to women of unknown status vaccinated,

1999-2000

0

10

20

30

40

50

60

Mar-Apr 99 Jul15-Sep1599

Mar-Apr 00

Vaccinated beforeD/C

Vaccinated w/in 12hours

P<0.001

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

Hospitals Policy to Hepatitis B Vaccine to All Newborns Before Discharge

(n=53)89

4

7074

0

20

40

60

80

100

Prior to July1999

Immediatelyafter AAPstatement

Apr-00 May-01

Proportion of OREGON infants born to women of unknown status vaccinated,

1999-2000

0

10

20

30

40

50

60

70

80

90

Apr-Jun 99 Aug-Oct 99 Apr-Jun 00

Vaccinated beforeD/C

Vaccinated w/in 12hoursP<0.001

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*

Other Effects on Immunization

Your resource for Thimerosal claims Get a free case assesment!

To see if you have an Thimerosal related case, click here

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.

Parker and Waichman has filed a Class Action Lawsuit against manufacturers of vaccines containing Thimerosal. Visit www.vaccineclassaction.com for more information.

WASHINGTON REPORT

Thimerosal cases in Oregon dismissed Marjorie Tharp

Washington Correspondent

AAP News Vol. 22 No. 1 January 2003, p. 4

An Oregon judge has dismissed most of the class action lawsuits filed in that state alleging injury from thimerosal in vaccines, including the case that named not only manufacturers, but also a pediatrician.

This is the second time a judge has tossed out a case. Earlier this summer, a federal court in Texas dismissed another thimerosal-related

class action lawsuit but said the plaintiffs could still sue for loss of consortium or companionship. At press time, however, more than a dozen states had individual or class action lawsuits pending.

The suits have been filed by or on behalf of families who believe their children were injured by vaccines containing thimerosal, a mercury-containing preservative. Although no evidence of harm existed, the Academy and the federal government called for manufacturers to remove thimerosal as a precautionary measure in 1999.

Institute of Medicine Immunization Safety

Review Thimerosal-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

Institute of Medicine Immunization Safety

Review Thimerosal-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

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

Acknowedgements

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