Thimerosal in Vaccines / AAFP Clinical Recommendations
AAFP Clinical Recommendations
Thimerosal in Vaccines
JOINT STATEMENT OF THE AMERICAN ACADEMY OF FAMILY
PHYSICIANS (AAFP), THE AMERICAN ACADEMY OF PEDIATRICS (AAP), THE ADVISORY
COMMITTEE ON IMMUNIZATION PRACTICES (ACIP), AND THE UNITED STATES PUBLIC HEALTH
SERVICE (PHS)
INTRODUCTION
This statement has been prepared by the American Academy
of Family Physicians, the American Academy of Pediatrics, the
Advisory Committee on Immunization Practices, and the U.S. Public Health Service
in response to 1) the progress being made in achieving the national goal
declared in July 1999 to remove thimerosal from vaccines, and 2) the results of
studies to better assess any potential relationship between exposure to
mercury in thimerosal containing vaccines and health effects.
BACKGROUND
A Joint Statement issued by AAP and the PHS in July 1999
and agreed to by the AAFP later in 1999 established the goal of removing
the vaccine preservative thimerosal as soon as possible from vaccines
routinely recommended for infants. Thimerosal is a derivative of
ethylmercury and has been used as an additive to biologics and vaccines since
the 1930s because it is effective in killing bacteria and in preventing
bacterial contamination, particularly in opened multi-dose
containers. While there was no evidence of any harm caused by low levels of thimerosal
in vaccines and the risk was only theoretical, this goal was established
as a precautionary measure. There is public concern about the health effects
of mercury exposure of any sort, and the elimination of mercury from vaccines was
judged a feasible means of reducing an infant’s total
exposure to mercury in a world where other environmental sources of exposure are
more difficult or impossible to eliminate (e.g. certain foods).
PROGRESS REPORT ON VACCINE SUPPLY
During the year since the original statement, substantial
progress has been made in removing thimerosal from vaccines. A hepatitis B
vaccine without thimerosal produced by Merck Vaccine Division was released
in August 1999, and in March 2000 a hepatitis B vaccine that does not
contain thimerosal as a preservative was approved for SmithKline Beecham
Biologicals. This SKBB product contains only a trace amount of mercury (less than
0.5mcg/dose), a greater than 96% reduction from the 12.5mcg in the
previous SKBB vaccine and an amount considered clinically insignificant. A
combination vaccine containing both hepatitis B and Haemophilus influenzae
type b (Hib) vaccine produced by Merck Vaccine Division, Inc. has always been
free of thimerosal.
Thus, as of March 2000, all US children had access to
hepatitis B vaccines that are free of thimerosal as a preservative.
In addition, three of the four Hib vaccines currently
licensed for use in the US do not contain thimerosal as a
preservative. The fourth vaccine is produced by Wyeth Lederle which has marketed
this Hib vaccine in both thimerosal free, single dose formulations and multidose,
thimerosal-containing preparations. As of July 2000, Wyeth
Lederle is expected to produce only the single dose, thimerosal-free
formulation for the US. Thus, the Hib vaccine supply being produced will
become entirely free of thimerosal as a preservative beginning in July 2000.
For DTaP vaccine, a thimerosal free vaccine produced by SKBB
has been
licensed and available in the United States since 1997.
There are three other vaccine manufacturers whose DTaP vaccines still
contain thimerosal as a preservative. Discussions are underway with these
manufacturers and it is hoped that at least one additional DTaP vaccine without
thimerosal as a preservative will become available in early 2001. Based on this progress, the most likely maximum amount of
ethylmercury that an infant may be exposed to from the routine immunization
schedule has been reduced by 60% from 187.5mcg to 75mcg. Measles mumps
rubella, varicella, inactivated polio, and pneumococcal conjugate vaccines
have never contained thimerosal.
PROGRESS REPORT ON RESEARCH
Since July 1999, efforts to remove thimerosal from the US
vaccine supply have been accompanied by research investigations to better
assess the potential health effects of exposure to thimerosal-containing
vaccines. First, NIH scientists are collaborating with investigators
from the University of Rochester and the Bethesda Naval Hospital to
determine retrospectively the blood levels of mercury achieved
following routine pediatric vaccination. Preliminary data from a very small
number of term infants in these studies indicate that the blood levels of
mercury produced by exposure to thimerosal preservative containing vaccines
are less than 2mcg/L, the level many experts consider as background.
These findings differ from those recently reported by
Stajich and coworkers (J Pediatr 2000;136:679-681) who found blood mercury
levels of greater than 2.9 mcg/L in 9 of 15 premature infants who had received a
hepatitis B immunization within the first week of life. However, all
of these infants were very premature (birth weights < 1000 grams, mean
birth weight of 748 grams). Hepatitis B immunization is not recommended for
infants < 2000 grams unless their mother is HBsAg positive.
Second, CDC is using large automated databases that link
vaccination and International Classification of Disease codes (ICD-9) stored
in medical records in managed care organizations (the Vaccine Safety
Datalink project, VSD) to rapidly screen for any possible association
between exposure to thimerosal containing vaccines and a variety of
neurologic, developmental, and renal outcomes.
In the preliminary screening phase of this investigation,
CDC and VSD investigators observed no association between exposure to thimerosal
containing vaccines and 12 of the 17 renal and neurologic
ICD-9 codes
examined from two of the managed care organizations
studied. These 12 ICD-9 codes examined were extrapyradimal disease, autism,
childhood psychosis, stammering, sleep, eating, misery disorders, mixed
emotional conditions, infantile cerebral palsy, epilepsy, migraines, and
unspecified renal conditions. From these preliminary data, an inconclusive
correlation (i.e., one that is inadequate to support or refute a causal link)
was observed between exposure to thimerosal containing vaccines and
five of the 17 ICD-9 codes, including language delays, speech delays, attention
deficit disorder, unspecified developmental delays and tics. There was no
evidence of any increased risk for these codes among premature infants. Reviews of these preliminary observations by expert
consultants first at CDC and then from outside PHS identified many important
shortcomings in the dataset and in this type of analytic approach. These
consultants concluded that the correlation is very weak and insufficient to
support a causal relationship. This inconclusive information does not
provide a sound scientific basis for making new policy decisions or
changes in current policies. Nevertheless, because of the potential
implications of this screening-phase observation, consultants urged further
investigation. In pursuit of these further studies, CDC investigators
have obtained preliminary data from a third managed care organization.
Analyses of these data using the same methods and having similar limitations
as in the two earlier managed care organizations showed no association
for two specific conditions, namely, speech delay, which in this dataset
included language delay, and attention deficit disorder. The number of
events was too small to examine the association with tics and the category of
unspecified developmental delays was not defined clearly enough to
permit reanalysis. Additional review of this dataset is planned and new
studies which can test the hypotheses of interest more directly and definitively
also are being considered by CDC.
POLICY
The AAFP, AAP, and the PHS in consultation with the ACIP
reaffirm the goal set in July 1999 to remove or greatly reduce thimerosal
from vaccines as soon as possible for the following reasons: 1) the removal
or substantial reduction of thimerosal from vaccines is feasible, 2) the
progress in removal which has been made to date is substantial, 3) the
discussions between the Food and Drug Administration and the vaccine
manufacturers in removing thimerosal are ongoing, and 4) the public concern
about the use of mercury of any sort remains high. Based on information
from the FDA and manufacturers, the PHS projects that the US
will complete its transition to a secure routine pediatric vaccine supply
free of thimerosal as a preservative (i.e. at least two vaccine products each
for Hep B, Hib, and DTaP) by the first quarter of 2001.
The use of any Hib or DTaP vaccine should continue
according to the currently recommended schedule. The risk of not
vaccinating children on time with DTaP to protect them against pertussis or with any
remaining Hib vaccine is believed to far outweigh the risk, if any, of
exposure to thimerosal containing DTaP and Hib vaccines which are
still available or still being produced. Any new information from ongoing
investigations will be monitored carefully by the PHS to determine if any
change in this assessment and in existing recommendations is warranted.
Other vaccines such as diphtheria-tetanus, meningococcal,
and influenza vaccines will still contain thimerosal after the first
quarter of 2001. Diphtheria-tetanus (DT) and meningococcal vaccines are not
recommended for children as part of the recommended childhood immunization
schedule. Influenza vaccine is not recommended routinely for infants
under 6 months of age, but should be given to infants and children 6 months
of age and older who are at high risk of morbidity and mortality from the
influenza virus. Continued use of these products as indicated is
recommended until thimerosal is removed or until new products without thimerosal are
licensed. The vaccination of children in much of the world will
continue to require the use of multi-dose vials for reasons of cost,
production, and storage capacity. Multi-dose vials require a preservative to
prevent microbial contamination after the vial is opened. While thimerosal
is currently the preferred preservative, manufacturers are encouraged to seek
alternatives.
SUMMARY
In 1999, family physicians, pediatricians, federal health
officials, and vaccine manufacturers stated that because any potential
risk from mercury is of concern, and the elimination of exposure to mercury in
the form of thimerosal from vaccines is feasible, thimerosal should be
removed from vaccines as soon as possible. However, there remains no
convincing evidence of harm caused by low levels of thimerosal in vaccines. Since mid-1999, two new hepatitis B vaccine products have
been introduced and one new Hib product will be produced next month to
make the new supply of both hepatitis b and Hib vaccines for infants entirely
free of thimerosal as a preservative. One of the four licensed DTaP vaccines
is already thimerosal free, and at least one other thimerosal free
DTaP vaccine is anticipated to be licensed by early 2001. Thus, the likely
maximum number of micrograms of ethylmercury that an infant may be exposed
to from the routine immunization schedule will have been reduced by 60%. This
amount will be reduced even further in early 2001 when at least two
vaccine products for hepatitis B, Hib, and DTaP are expected to be available.
Meanwhile, research on the potential health effects of exposure to thimerosal
is continuing, and information will be monitored closely by the PHS to
determine if any changes in policy are needed.
The AAFP, AAP, ACIP, and the PHS recommend continuation of
the current
policy of moving rapidly to vaccines which are free of
thimerosal as a preservative. Until an adequate supply of each vaccine is
available, use of
vaccines which contain thimerosal as a preservative is
acceptable.