National Academies Press: OpenBook
Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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Adverse
Effects of
Vaccines
Evidence and Causality

Committee to Review Adverse Effects of Vaccines
Board on Population Health and Public Health Practice
Kathleen Stratton, Andrew Ford, Erin Rusch, and Ellen Wright Clayton,
Editors

INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
×

THE NATIONAL ACADEMIES PRESS      500  Fifth Street, N.W.      Washington, DC 20001

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This study was supported by Contract No. HHSH230200446009I, Task Order 13 between the National Academy of Sciences and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The Centers for Disease Control and Prevention and the National Vaccine Program Office also provided support through that contract. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

Library of Congress Cataloging-in-Publication Data

Institute of Medicine (U.S.). Committee to Review Adverse Effects of Vaccines.

  Adverse effects of vaccines : evidence and causality / Committee to Review Adverse Effects of Vaccines, Board on Population Health and Public Health Practice ; Kathleen Stratton … [et al.], editors.

      p. ; cm.

  Includes bibliographical references and index.

  ISBN 978-0-309-21435-3 (hardcover) — ISBN 978-0-309-21436-0 (PDF)

  ISBN 0-309-21439-4

  I. Stratton, Kathleen R. II. Title.

  [DNLM: 1. Vaccines—adverse effects. 2. Bacterial Infections—prevention & control. 3. Causality. 4. Virus Diseases—prevention & control. QW 805]

615.3’72—dc23

2012007052

Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; Internet, http://www.nap.edu.

For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu.

Copyright 2012 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.

Suggested citation: IOM (Institute of Medicine). 2012. Adverse effects of vaccines: Evidence and causality. Washington, DC: The National Academies Press.

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
×

“Knowing is not enough; we must apply.
Willing is not enough; we must do.”

                                                    —Goethe

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INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES

Advising the Nation. Improving Health.

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
×

THE NATIONAL ACADEMIES

Advisers to the Nation on Science, Engineering, and Medicine

The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.

The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.

The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.

The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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COMMITTEE TO REVIEW ADVERSE EFFECTS OF VACCINES

Ellen Wright Clayton (Chair), Craig-Weaver Professor of Pediatrics; Director, Center for Biomedical Ethics and Society; Professor of Law; Vanderbilt University

Inmaculada B. Aban, Associate Professor, Department of Biostatistics, University of Alabama, Birmingham

Douglas J. Barrett, Professor, Departments of Pediatrics, Molecular Genetics & Microbiology, Pathology, Immunology, & Laboratory Medicine, University of Florida College of Medicine

Martina Bebin, Associate Professor of Neurology and Pediatrics, University of Alabama at Birmingham

Kirsten Bibbins-Domingo, Associate Professor and Attending Physician, University of California, San Francisco

Graham A. Colditz,1 Associate Director for Prevention and Control, Alvin J. Siteman Cancer Center, and Niess-Gain Professor in the School of Medicine, Department of Surgery, Washington University School of Medicine

Martha Constantine-Paton, Investigator, McGovern Institute for Brain Research; Professor of Biology, Department of Biology, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology

Deborah J. del Junco, Senior Epidemiologist and Associate Professor of Biostatistics, Epidemiology, and Research Design, University of Texas Health Science Center at Houston

Betty A. Diamond, Head, Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, North Shore-LIJ Health System

S. Claiborne Johnston, Associate Vice Chancellor of Research; Director, Clinical and Translational Science, Institute Professor of Neurology and Epidemiology; Director, Neurovascular Disease and Stroke Center; University of California, San Francisco

Anthony L. Komaroff, Steven P. Simcox, Patrick A. Clifford, and James H. Higby Professor of Medicine; Senior Physician, Brigham and Women’s Hospital; Harvard Medical School

B. Paige Lawrence, Associate Professor of Environmental Medicine; Associate Professor of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry

M. Louise Markert, Associate Professor of Pediatrics and Immunology, Division of Pediatric Allergy and Immunology, Department of Pediatrics, Duke University Medical Center

___________

1 Committee member resigned August 2010.

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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Ruby H. N. Nguyen,2 Assistant Professor, Division of Epidemiology and Community Health, University of Minnesota School of Public Health

Marc C. Patterson, Chair, Division of Child and Adolescent Neurology; Professor of Neurology, Pediatrics, and Medical Genetics; Director, Child Neurology Training Program, Mayo Clinic

Hugh A. Sampson, Professor of Pediatrics and Immunology; Dean for Translational Biomedical Sciences; Director of the Jaffe Food Allergy Institute, Mount Sinai School of Medicine

Pauline A. Thomas, Associate Professor, Department of Preventive Medicine and Community Health, New Jersey Medical School; and Associate Professor, School of Public Health, University of Medicine and Dentistry of New Jersey

Leslie P. Weiner, Richard Angus Grant, Sr. Chair in Neurology; Professor of Neurology and Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California

Study Staff

Kathleen Stratton, Study Director

Andrew Ford, Program Officer

Erin Rusch, Research Associate

Trevonne Walford, Research Assistant (from August 2009)

William McLeod, Senior Research Librarian

Hope Hare, Administrative Assistant

Amy Pryzbocki, Financial Associate

Rose Marie Martinez, Director, Board on Population Health and Public Health Practice

___________

2 Committee member resigned March 2010.

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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Reviewers

This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:

Steven Black, Cincinnati Children’s Hospital

Patricia K. Crumrine, University of Pittsburgh School of Medicine

Anne A. Gershon, Columbia University College of Physicians & Surgeons

Marie R. Griffin, Vanderbilt University Medical Center

Neal Halsey, Johns Hopkins Bloomberg School of Public Health

Diane Harper, University of Missouri-Kansas City School of Medicine

Sean Hennessy, University of Pennsylvania School of Medicine

Gerald T. Nepom, University of Washington

Richard Platt, Harvard Medical School

Stanley A. Plotkin, University of Pennsylvania

Sam Shekar, Northrop Grumman

Donald Silberberg, University of Pennsylvania Medical Center

Page viii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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John J. Treanor, University of Rochester School of Medicine and Dentistry

Chris Wilson, The Bill & Melinda Gates Foundation

Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by Charles C. J. Carpenter, The Miriam Hospital, and Floyd E. Bloom, The Scripps Research Institute. Appointed by the National Research Council and Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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Preface

Vaccines are widely recognized as one of the greatest public health successes of the last century, significantly reducing morbidity and mortality from a variety of bacteria and viruses. Diseases that were once the cause of many outbreaks, common causes of loss of health and life, are now rarely seen, because they have been prevented by vaccines. However, vaccines can in rare cases themselves cause illness. A rare potential for harm can loom large when people no longer experience or fear the targeted disease. In this regard, the public opinion of vaccines can be a victim of their success. The Institute of Medicine (IOM) was charged by Congress when it enacted the National Childhood Vaccine Injury Act in 1986 with reviewing the literature regarding the adverse events associated with vaccines covered by the program, a charge which the IOM has addressed 11 times in the past 25 years. Following in this tradition, the task of this committee was to assess dispassionately the scientific evidence about whether eight different vaccines cause adverse events (AE), a total of 158 vaccine-AE pairs, the largest study undertaken to date, and the first comprehensive review since 1994.

The committee had a herculean task, requiring long and thoughtful discussions of our approach to analyzing the studies culled from more than 12,000 peer-reviewed articles in order to reach our conclusions, which are spelled out in the chapters that follow. In the process, we learned some lessons that may be of value for future efforts to evaluate vaccine safety. One is that some issues simply cannot be resolved with currently available epidemiologic data, excellent as some of the collections and studies are. Particularly for rare events, we look to the day when electronic medical records truly are universal and when society reaches a broad-based con-

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
×

sensus about how these records may be used to detect very rare adverse events from vaccines as well as other drugs and medical interventions. Even then, challenges will remain. Some adverse events caused by vaccines are also caused by the natural infection. These effects often cannot be detected by epidemiologic methods, which typically cannot distinguish between the adverse events that are caused by the vaccine itself and the decrease in adverse events due to the decreased rate of natural infection. In addition, even very large epidemiologic studies may not detect or rule out rare events. Subgroup analysis or more focused epidemiologic studies, informed by as yet incomplete knowledge of the biologic mechanisms of vaccine-induced injury, may be required.

Examining mechanistic evidence to assess causation is also challenging. Many of the case reports the committee reviewed simply cited a temporal relation between vaccine administration and an adverse event. Association, however, does not equal causation. More is required. The proof can be relatively straightforward, as when vaccine-specific virus is recovered from the cerebrospinal fluid of a patient who develops viral meningitis a few weeks after receiving the vaccine. Alleged adverse effects that appear to be immune mediated, as many of them are, are more challenging, in part because the biology is not completely understood. One potentially useful line of inquiry as science advances is to assess whether the vaccine recipient who suffers harm had a preexisting susceptibility to that particular adverse event as such studies may provide insight into the mechanisms by which such events occur. The committee is aware of the work funded by the Centers for Disease Control and Prevention (CDC) to study such individuals and looks forward to their findings. Most individuals, for example, who develop invasive infection from live vaccine viruses have demonstrated immunodeficiencies. Our work was also complicated by the wide variation in the case reports regarding what other tests had been done to rule out other potential causes. To improve the utility of these reports, periodically convening a group of experts to suggest guidelines, based on the best available science, for providing mechanistic evidence that a particular adverse event was caused by a vaccine may be useful. These guidelines could be made available on the Web, and perhaps more important, shared with clinicians who report cases to the Vaccine Adverse Event Reporting System so their reports can be as complete and useful as possible.

The value of dialogue between both epidemiologic and mechanisms approaches cannot be overstated. Epidemiologic studies can identify particular at-risk groups, who can then be examined with more in depth testing to explore predisposing factors. The findings of such studies can then inform more focused epidemiologic research as well as efforts to reduce risks. These conversations between different types of research can be difficult, but the results are worth it.

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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Although the committee is optimistic that more can and will be known about vaccine safety in the future, the limitations of the currently available peer-reviewed data meant that, more often not, we did not have sufficient scientific information to conclude whether a particular vaccine caused a specific rare adverse event. Where the data were inadequate to reach a scientifically defensible conclusion about causation, the committee specifically chose not to say which way the evidence “leaned,” reasoning that such indications would violate our analytic framework. Some readers doubtless will be disappointed by this level of rigor. The committee particularly counsels readers not to interpret a conclusion of inadequate data to accept or reject causation as evidence either that causation is either present or absent. Inadequate data to accept or reject causation means just that—inadequate. It is also important to recognize what our task was not. We were not charged with assessing the benefits of vaccines, with weighing benefits and costs, or with deciding how, when, and to whom vaccines should be administered. The committee was not charged with making vaccine policy. We did receive calls to stride into this contentious debate, but others, such as the Food and Drug Administration and the CDC, are tasked with formulating recommendations for use that balance the risk of vaccines with the benefits, with studying the safety of the vaccines during pre-release trials, and monitoring them closely once the vaccine is in use in the population.

Our work could not have been accomplished without the concerted efforts of the committee members who did their work carefully with good cheer and open minds. The committee’s talented and intrepid staff, Trevonne Walford, Erin Rusch, and Andrew Ford, led by the wisdom and experience of Kathleen Stratton, could not have been more wonderful to work with or more essential to the committee’s task.

Ellen Wright Clayton, Chair
Committee to Review Adverse Effects of Vaccines

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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4-3 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and Afebrile Seizures

4-4 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and Meningitis

4-5 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and Autism

4-6 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and MS Onset in Adults

4-7 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and Transient Arthralgia in Women

4-8 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and Transient Arthralgia in Children

4-9 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and Chronic Arthralgia in Women

4-10 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and Chronic Arthritis in Women

4-11 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and Arthropathy in Men

4-12 Studies Included in the Weight of Epidemiologic Evidence for MMR Vaccine and Type 1 Diabetes

4-13 Summary of Epidemiologic Assessments, Mechanistic Assessments, and Causality Conclusions for Measles, Mumps, and Rubella Vaccine

5-1 Summary of Epidemiologic Assessments, Mechanistic Assessments, and Causality Conclusions for Varicella Vaccine

6-1 Influenza Vaccines Licensed and Available in the United States

6-2 Studies Included in the Weight of Epidemiologic Evidence for Influenza Vaccine and Seizures

6-3 Studies Included in the Weight of Epidemiologic Evidence for Influenza Vaccine and Optic Neuritis

6-4 Studies Included in the Weight of Epidemiologic Evidence for Influenza Vaccine and MS Onset in Adults

6-5 Studies Included in the Weight of Epidemiologic Evidence for Influenza Vaccine and MS Relapse in Adults

6-6 Studies Included in the Weight of Epidemiologic Evidence for Influenza Vaccine and GBS

6-7 Studies Included in the Weight of Epidemiologic Evidence for Influenza Vaccine and Bell’s Palsy

6-8 Studies Included in the Weight of Epidemiologic Evidence for Inactivated Influenza Vaccine and Asthma Exacerbation or Reactive Airway Disease Episodes in Children and Adults

Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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6-9 Studies Included in the Weight of Epidemiologic Evidence for Live Attenuated Influenza Vaccine and Asthma Exacerbation or Reactive Airway Disease Episodes in Children Younger Than 5 Years of Age

6-10 Studies Included in the Weight of Epidemiologic Evidence for Live Attenuated Influenza Vaccine and Asthma Exacerbation or Reactive Airway Disease Episodes in Persons 5 Years of Age or Older

6-11 Studies Included in the Weight of Epidemiologic Evidence for Influenza Vaccine and Exacerbation of SLE

6-12 Studies Included in the Weight of Epidemiologic Evidence for Influenza Vaccine and Exacerbation of Vasculitis

6-13 Studies Included in the Weight of Epidemiologic Evidence for Influenza Vaccine and Oculorespiratory Syndrome

6-14 Summary of Epidemiologic Assessments, Mechanistic Assessments, and Causality Conclusions for Influenza Vaccine

7-1 Summary of Epidemiologic Assessments, Mechanistic Assessments, and Causality Conclusions for Hepatitis A Vaccine

8-1 Studies Included in the Weight of Epidemiologic Evidence for Hepatitis B Vaccine and Optic Neuritis

8-2 Studies Included in the Weight of Epidemiologic Evidence for Hepatitis B Vaccine and MS Onset in Adults

8-3 Studies Included in the Weight of Epidemiologic Evidence for Hepatitis B Vaccine and First Demyelinating Event in Adults

8-4 Summary of Epidemiologic Assessments, Mechanistic Assessments, and Causality Conclusions for Hepatitis B Vaccine

9-1 Summary of Epidemiologic Assessments, Mechanistic Assessments, and Causality Conclusions for HPV Vaccine

10-1 Diphtheria Toxoid–, Tetanus Toxoid–, and Acellular Pertussis– Containing Vaccines Licensed and Available in the United States

10-2 Studies Included in the Weight of Epidemiologic Evidence for Diphtheria Toxoid–, Tetanus Toxoid–, and Acellular Pertussis– Containing Vaccines and Seizures

10-3 Studies Included in the Weight of Epidemiologic Evidence for Diphtheria Toxoid–, Tetanus Toxoid–, and Acellular Pertussis– Containing Vaccines and MS Onset in Adults

Page xxiii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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Acronyms

AAP American Academy of Pediatrics
AAV ANCA-associated vasculitis
ACIP Advisory Committee on Immunization Practices
ADEM acute disseminated encephalomyelitis
ADI-R autism diagnostic index—revised
ADOS autism diagnostic observational schedule
ADRAC Adverse Drug Reactions Advisory Committee (Australia)
AE adverse event
AIDS acquired immune deficiency syndrome
ALL acute lymphoblastic leukemia
ALS amyotrophic lateral sclerosis
ALT alanine aminotransferase
AMAN acute motor axonal neuropathy
ANA anti-nuclear antibodies
ANCA antineutrophil cytoplasmic antibody
aP acellular pertussis
BPV bovine papillomavirus
BU Boston University
BVAS Birmingham Vasculitis Activity Score
CAIV cold-adapted influenza virus or cold-adapted, trivalent intranasal influenza virus vaccine
CDC Centers for Disease Control and Prevention
Page xxiv Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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CI confidence interval
CIDP chronic inflammatory disseminated polyneuropathy
CNS central nervous system
CRPS complex regional pain syndrome
CSF cerebrospinal fluid
DMSS Defense Medical Surveillance System
DNA deoxyriboneucleic acid
DSM Diagnostic and Statistical Manual of Psychological Disorders
DT diphtheria and tetanus toxoids
DTaP diphtheria toxoid, tetanus toxoid, acellular pertussis
DTP diphtheria toxoid, tetanus toxoid, pertussis
DTwP diphtheria toxoid, tetanus toxoid, whole cell pertussis
EAE experimental allergic encephalomyelitis
EIA enzyme immunoassay
ELISA enzyme linked immunosorbent assay
ER emergency room
EURODIAB ACE European diabetes: aetiology of childhood diabetes on an epidemiological basis
Fc Constant region
FDA U.S. Food and Drug Administration
FEV forced expiratory volume
FHA filamentous hemagglutin
FOIA Freedom of Information Act
FUS/TLS fused in sarcoma/translocated in liposarcoma
GBS Guillain-Barré syndrome
GHC Group Health Cooperative
GM-CSF granulocyte/macrophage colony-stimulating factor
GPRD General Practice Research Database
HAI hemagglutination inhibition assay
HAV hepatitis A virus
HBIG hepatitis B immune globulin
HBsAg hepatitis B surface antigen
HBV hepatitis B virus
HBVP hepatitis B virus polymerase
HHS U.S. Department of Health and Human Services
HiB Haemophilus influenzae type B
HIV human immunodeficiency virus
Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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HLA human leukocyte antigen
HMO health maintenance organization
HPMG HealthPartners Medical Group
HPV human papillomavirus
HRSA Health Resources and Services Administration
HTLV human T-lymphotropic virus
HZ herpes zoster
ICD International Classification of Diseases
IDDM insulin dependent diabetes mellitus
Ig immunoglobulin
IL interleukin
IOM Institute of Medicine
IPV inactivated poliovirus vaccine
ITP immune thrombocytopenic purpura
JIA juvenile idiopathic arthritis
KIDSEP French Kids Sclérose en Plaques
KP Kaiser Permanente
KPMCP Kaiser Permanente Medical Care Program
LAIV live attenuated influenza virus
LOS lipo-oligosaccharide
MAC membrane attack complex
MBP myelin basic protein
MCC Measles Control Campaign
MCO medical care organization
MHC major histocompatibility complex
MHC Ministry of Health Mother-Child Health (Israel)
MIT Massachusetts Institute of Technology
MMR measles, mumps, rubella
MMRV measles, mumps, rubella, and varicella
MPO myeloperoxidase
MPSV meningococcal polysaccharide vaccine
MR measles-rubella
MRI magnetic resonance imaging
MS multiple sclerosis
NCES National Childhood Encephalopathy Study
NCK Northern California Kaiser
NCKP Northern California Kaiser Permanente
Page xxvi Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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NCVIA National Childhood Vaccine Injury Act
NK natural killer
NMO neuromyelitis optica
OMS opsoclonus myoclonus syndrome
OPV oral polio vaccine
ON optic neuritis
OR odds ratio
ORS oculorespiratory syndrome
PAMP pathogen-associated molecular pattern
PAN polyarteritis nodosa
PCR polymerase chain reaction
PDD pervasive developmental disorder
PEF peak expiratory flow
PFU plaque-forming unit
PR3 proteinase 3
PRP polyribosylribitol phosphate
PRR pattern recognition receptor
RA rheumatoid arthritis
RCT randomized controlled trial
RNA ribonucleic acid
RR relative risk
RT-PCR reverse transcription polymerase chain reaction
SAFEVIC Surveillance of Adverse Events following Vaccination in the Community
SAFEVSS Serious Adverse Events Following Vaccination Surveillance Scheme
SIDS sudden infant death syndrome
SIP sympathetically independent pain
SLE systemic lupus erythematosus
SLEDAI SLE Disease Activity Index
SMP sympathetically maintained pain
SSPE subacute sclerosing panencephalitis
SWHP Scott & White Health Plan
TCR T cell receptor
TF tissue factor
TIV trivalent inactivated influenza vaccine
TT tetanus toxoid
Page xxvii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.
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VAERS Vaccine Adverse Event Reporting System
VAS visual analogue score
VICP National Vaccine Injury Compensation Program
VIS Vaccine Information Statement
VLP virus like particle
VSD Vaccine Safety Datalink
VZV varicella zoster virus
VZVIP Varicella Zoster Virus Identification Program
WAES Worldwide Adverse Experience System
WHO World Health Organization
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Adverse Effects of Vaccines: Evidence and Causality Get This Book
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In 1900, for every 1,000 babies born in the United States, 100 would die before their first birthday, often due to infectious diseases. Today, vaccines exist for many viral and bacterial diseases. The National Childhood Vaccine Injury Act, passed in 1986, was intended to bolster vaccine research and development through the federal coordination of vaccine initiatives and to provide relief to vaccine manufacturers facing financial burdens. The legislation also intended to address concerns about the safety of vaccines by instituting a compensation program, setting up a passive surveillance system for vaccine adverse events, and by providing information to consumers. A key component of the legislation required the U.S. Department of Health and Human Services to collaborate with the Institute of Medicine to assess concerns about the safety of vaccines and potential adverse events, especially in children.

Adverse Effects of Vaccines reviews the epidemiological, clinical, and biological evidence regarding adverse health events associated with specific vaccines covered by the National Vaccine Injury Compensation Program (VICP), including the varicella zoster vaccine, influenza vaccines, the hepatitis B vaccine, and the human papillomavirus vaccine, among others. For each possible adverse event, the report reviews peer-reviewed primary studies, summarizes their findings, and evaluates the epidemiological, clinical, and biological evidence. It finds that while no vaccine is 100 percent safe, very few adverse events are shown to be caused by vaccines. In addition, the evidence shows that vaccines do not cause several conditions. For example, the MMR vaccine is not associated with autism or childhood diabetes. Also, the DTaP vaccine is not associated with diabetes and the influenza vaccine given as a shot does not exacerbate asthma.

Adverse Effects of Vaccines will be of special interest to the National Vaccine Program Office, the VICP, the Centers for Disease Control and Prevention, vaccine safety researchers and manufacturers, parents, caregivers, and health professionals in the private and public sectors.

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