Click for next page ( 86


The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

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 85
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 85
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 85
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 85
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 85
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 85
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 85
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 Physiciansof 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 85
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 85
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 85
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.