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OCR for page 85
Appendix A
Committee
Recommendations and
Conclusions from Previous
Reports
MEASLES-MUMPS-RUBELLA VACCINE AND
AUTISM:
Conclusions
The committee concludes that the evidence favors rejection of a causal rela-
tionship at the population level between measles-mumps-rubella ~IMR) vac-
cine and autistic spectrum disorders (AS D). However, this conclusion does not
exclude the possibility that MMR vaccine could contribute to ASD in a small
number of children.
The committee concludes that further research on the possible occurrence of
ASD in a small number of children subsequent to MMR vaccination is war-
ranted, and it has identified targeted research opportunities that could lead to
firmer understanding of the relationship.
Recommendations
Public Health Response
The committee recommends that the relationship between the MMR vac-
cine and autistic spectrum disorders receive continued attention.
Policy Review
The committee does not recommend a policy review at this time of the li-
censure of MMR vaccine or of the current schedule and recommendations for
administration of MMR vaccine.
85
OCR for page 86
86
IMMUNIZATION SAFETY REVIEW
Research Regarding MMR and ASD
The committee recommends the use of accepted and consistent case defini-
tions and assessment protocols for ASD in order to enhance the precision and
comparability of results from surveillance, epidemiological, and biological in-
vestigations.
The committee recommends the exploration of whether exposure to MMR
vaccine is a risk factor for autistic spectrum disorder in a small number of chil-
dren.
The committee recommends the development of targeted investigations of
whether or not measles vaccine-strain virus is present in the intestines of some
children with ASD.
The committee encourages all who submit reports to VAERS of any diag-
nosis of ASD thought to be related to MMR vaccine to provide as much detail
and as much documentation as possible.
The committee recommends studying the possible effects of different MMR
. . .
Immunization exposures.
The committee recommends conducting further clinical and epidemiologi-
cal studies of sufficient rigor to identify risk factors and biological markers of
ASD in order to better understand genetic or environmental causes.
Communica~dons
The committee recommends that government agencies and professional or-
ganizations, CDC and the Food and Drug Administration (FDA) in particular,
review some of the most prominent forms of communication regarding the hy-
pothesized relationship between MMR vaccine and ASD, including information
they provide via the Internet and the ease with which Internet information can be
accessed.
OCR for page 87
APPENDIXA
87
THIMEROSAL-CONTAINING VACCINES AND
NEURODEVELOPMENTAL DISORDERS
Conclusions
The committee concludes that although the hypothesis that exposure to
thimerosal-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 from vaccines given in children, the hypothesis is biologically plausi-
ble.
The committee also concludes that the evidence is inadequate to accept or
reject a causal relationship between thimerosal exposures from childhood vac-
cines and the neurodevelopmental disorders of autism, ADHD, and speech or
language delay.
Public Health Response Recommendations
Policy Renew and Analysis
The committee recommends the use of the thimerosal-free DTaP, Hib, and
(?) hepatitis B vaccines in the United States, despite the fact that there might be
remaining supplies of thimerosal-containing vaccine available.
The committee recommends that full consideration be given by appropriate
professional societies and government agencies to removing thimerosal from
vaccines administered to infants, children, or pregnant women in the United
States.
The committee recommends that appropriate professional societies and
government agencies review their policies about the non-vaccine biological and
pharmaceutical products that contain thimerosal and are used by infants, chil-
dren, and pregnant women in the United States.
The committee recommends that policy analyses be conducted that will in-
form these discussions in the future.
OCR for page 88
88
IMMUNIZA TION SAFETY REVIEW
The committee recommends a review and assessment of how public health
policy decisions are made under uncertainty.
The committee recommends a review of the strategies used to communicate
rapid changes in vaccine policy, and it recommends research on how to improve
those strategies.
Public Health and Biomedical Research
The committee recommends a diverse public health and biomedical re-
search portfolio.
Epidemiological Research
The committee recommends case-control studies examining the potential
link between neurodevelopmental disorders and thimerosal-containing vaccines.
The committee recommends further analysis of neurodevelopmental disor-
ders in cohorts of children who did not receive thimerosal-containing doses as
part of a clinical trial of DTaP vaccine.
The committee recommends conducting epidemiological studies that com-
pare the incidence and prevalence of neurodevelopmental disorders before and
after the removal of thimerosal from vaccines.
The committee recommends an increased effort to identify the primary
sources and levels of prenatal and postnatal background exposure to thimerosal
(e.g., Rho (D) Immune Globulin) and other forms of mercury (e.g., maternal
consumption of fish) in infants, children, and pregnant women.
Clinical Research
The committee recommends research on how children, including those di-
agnosed with neurodevelopmental disorders, metabolize and excrete metals—
particularly mercury.
The committee recommends continued research on theoretical modeling of
ethylmercury exposures, including the incremental burden of thimerosal with
background mercury exposure from other sources.
OCR for page 89
APPENDIX A
89
The committee recommends careful, rigorous, and scientific investigations
of chelation when used in children with neurodevelopmental disorders, espe-
cially autism.
Basic Science Research
The committee recommends research to identify a safe, effective, and inex-
pensive alternative to thimerosal for countries that decide they need to switch
from using thimerosal as a preservative.
The committee recommends research in appropriate animal models on the
neurodevelopmental effects of ethylmercury.
OCR for page 90
9o
Scientific Assessment
Causality Conclusions
IMMUNIZATION SAFETY REVIEW
MULTIPLE IMMUNIZATIONS AND IMMUNE
DYSFUNCTION
Conclusions
The committee concludes that the epidemiological evidence favors rejection
of a causal relationship between multiple immunizations and an increase in het-
erologous infection.
The committee concludes that the epidemiological evidence favors rejection
of a causal relationship between multiple immunizations and an increased risk of
type 1 diabetes.
The committee concludes that the epidemiological evidence is inadequate to
accept or reject a causal relationship between multiple immunizations and in-
creased risk of allergic disease, particularly asthma.
Biological Mechanisms Conclusions
Autoimmune Disease
In the absence of experimental or human evidence regarding molecular
mimicry or mercury-induced modification of any vaccine component to create
an antigenic epitope capable of cross-reaction with self epitopes as a mechanism
by which multiple immunizations under the U.S. infant immunization schedule
could possibly influence an individual's risk of autoimmunity, the committee
concludes that these mechanisms are only theoretical.
The committee concludes that there is weak evidence for bystander activa-
tion, alone or in concert with molecular mimicry, as a mechanism by which mul-
tiple immunizations under the U.S. infant immunization schedule could possibly
influence an individual's risk of autoimmunity.
In the absence of experimental or human evidence regarding loss of protec-
tion against a homologous infection as a mechanism by which multiple immuni-
zations under the U.S. infant immunization schedule could possibly influence an
OCR for page 91
APPENDIXA
91
individual's risk of autoimmunity, the committee concludes that this mechanism
is only theoretical.
In the absence of experimental or human evidence regarding mechanisms
related to the hygiene hypothesis as a means by which multiple immunizations
under the U.S. infant immunization schedule could possibly influence an indi-
vidual's risk of autoimmunity, the committee concludes that this mechanism is
only theoretical.
Considering molecular mimicry, bystander activation, and impaired immu-
noregulation collectively rather than individually, the committee concludes that
there is weak evidence for these mechanisms as means by which multiple im-
munizations under the U.S. infant immunization schedule could possibly influ-
ence an individual's risk of autoimmunity.
Allergic Disease
The committee concludes that there is weak evidence for bystander activa-
tion as a mechanism by which multiple immunizations under the U.S. infant
immunization schedule could possibly influence an individual's risk of allergy.
In the absence of experimental or human evidence regarding mechanisms
related to the hygiene hypothesis as a means by which multiple immunizations
under the U.S. infant immunization schedule could possibly influence an indi-
vidual's risk of allergy, the committee concludes that this mechanism is only
theoretical.
The committee concludes that there is weak evidence for the existence of
any biological mechanisms, collectively or individually, by which multiple im-
munizations under the U.S. infant immunization schedule could possibly influ-
ence an individual's risk of allergy.
Heterologous Infection
The committee concludes that there is strong evidence for the existence of
biological mechanisms by which multiple immunizations under the U.S. infant
immunization schedule could possibly influence an individual's risk for het-
erologous infections.
Significance Assessment
The committee concludes that concern about multiple immunizations has
been, and could continue to be, of societal significance in terms of parental wor-
ries, potential health burdens, and future challenges for immunization policy-
making.
OCR for page 92
92
Policy Review
IMMUNIZATION SAFETY REVIEW
Public Health Response Recommendations
The committee recommends that state and federal vaccine policymal~ers
consider a broader and more explicit strategy for developing recommendations
for the use of vaccines.
The committee does not recommend a policy review by the CDC's Advi-
sory Committee on Immunization Practices (ACIP), the American Academy of
Pediatrics' Committee on Infectious Diseases, and the American Academy of
Family Physicians—of the current recommended childhood immunization
schedule on the basis of concerns about immune system dysfunction.
The committee does not recommend a policy review by the Food and Drug
Administration's Vaccines and Related Biologic Products Advisory Committee
of any currently licensed vaccines on the basis of concerns about immune sys-
tem dysfunction.
Research
Epidemiological Research
The committee recommends exploring the feasibility of using existing vac-
cine surveillance systems, alone or in combination, to study safety questions
related to asthma and other important allergic disorders, as well as to type 1 dia-
betes and other important autoimmune diseases.
The committee recommends exploring the use of cohorts for research on
possible vaccine-related disease risks. Furthermore, the committee recommends
that disease registries and research programs for autoimmune and allergic disor-
ders routinely collect immunization histories as part of their study protocol.
Basic Science and Clinical Research
The committee recommends continued research on the development of the
human infant immune system.
The committee endorses current research efforts aimed at identifying ge-
netic variability in human immune system development and immune system
OCR for page 93
APPENDIXA
93
responsiveness as a way to gain a better understanding of genetic susceptibility
to vaccine-based adverse events.
The committee recommends exploring the feasibility of collecting data on
surrogate markers for autoimmune and allergic disorders in the vaccine testing
and licensing process.
The committee recommends exploring surrogates for allergy and auto-
immunity in existing cohort studies of variations in the vaccine schedule.
Communication
The committee recommends that an appropriate panel of multidisciplinary
experts be convened by the Department of Health and Human Services. It would
develop a comprehensive research strategy for knowledge leading to the optimal
design and evaluation of vaccine risk-benefit communication approaches.
OCR for page 94
94
Causality Conclusions
IMMUNIZATION SAFETY REVIEW
HEPATITIS B VACCINE AND DEMYELINATING
NEUROLOGICAL DISORDERS
SCIENTIFIC ASSESSMENT
The committee concludes that the evidence favors rejection of a causal rela-
tionship between hepatitis B vaccine administered to adults and incident multi-
ple sclerosis.
The committee also concludes that the evidence favors rejection of a causal
relationship between hepatitis B vaccine administered to adults and multiple
sclerosis relapse.
The committee concludes that the evidence is inadequate to accept or reject
a causal relationship between hepatitis B vaccine and the first episode of a cen-
tral nervous system demyelinating disorder.
The committee concludes that the evidence is inadequate to accept or reject
a causal relationship between hepatitis B vaccine and ADEM.
The committee concludes that the evidence is inadequate to accept or reject
a causal relationship between hepatitis B vaccine and optic neuritis.
The committee concludes that the evidence is inadequate to accept or reject
a causal relationship between hepatitis B vaccine and transverse myelitis.
The committee concludes that the evidence is inadequate to accept or reject
a causal relationship between hepatitis B vaccine and GBS.
The committee concludes that the evidence is inadequate to accept or reject
a causal relationship between hepatitis B vaccine and brachial neuritis.
Biological Mechanisms Conclusions
The committee concludes that there is weak evidence for biological mecha-
nisms by which hepatitis B vaccination could possibly influence an individual's
OCR for page 95
APPENDIX A
95
risk of the central or peripheral nervous system disorders of MS, first episode of
CDD, ADEM, optic neuritis, transverse myelitis, GBS, or brachial neuritis.
SIGNIFICANCE ASSESSMENT
The committee concludes that concerns about the hepatitis B vaccine re-
main significant in the minds of some parents and workers who are required to
take the vaccine because of occupational risk.
PUBLIC HEALTH RESPONSE RECOMMENDATIONS
Policy Review
The committee does not recommend a policy review of the hepatitis B
vaccine by any of the national and federal vaccine advisory bodies on the
basis of concerns about demyelinating neurological disorders.
The committee recommends continued surveillance of hepatitis B disease
and increased surveillance of secondary diseases such as cirrhosis and hepato-
cellular carcinoma.
Basic and Clinical Science
The committee recommends continued research in animal and in vitro mod-
els, as well as in humans, on the mechanisms of immune-mediated neurological
disease possibly associated with exposure to vaccines.
Communication
The committee again recommends that government agencies and profes-
sional organizations responsible for immunizations critically evaluate their
communication services with increased understanding of, and input from, the
intended user.
Representative terms from entire chapter:
possibly influence
