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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
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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 Preven-
tion 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)
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,
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For more information about the Institute of Medicine, visit the IOM home page at: www.
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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.
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“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
— Goethe
Advising the Nation. Improving Health.
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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 Acad-
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and technical matters. Dr. Ralph J. Cicerone is president of the National Academy
of Sciences.
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and recognizes the superior achievements of engineers. Dr. Charles M. Vest is presi-
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The National Research Council was organized by the National Academy of Sci-
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Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively,
of the National Research Council.
www.national-academies.org
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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.
v
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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.
vi
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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
vii
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viii REVIEWERS
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.
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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 litera-
ture 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-
ix
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x PREFACE
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. Associa-
tion, 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 Cen-
ters 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 im-
munodeficiencies. 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 con-
vening 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 par-
ticular at-risk groups, who can then be examined with more in depth test-
ing 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 dif-
ficult, but the results are worth it.
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xi
PREFACE
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 sci-
entifically defensible conclusion about causation, the committee specifically
chose not to say which way the evidence “leaned,” reasoning that such indi-
cations 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. In-
adequate 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 recom-
mendations 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
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xviii CONTENTS
Infantile Spasms, 537
Seizures, 539
Ataxia, 544
Autism, 545
Acute Disseminated Encephalomyelitis, 546
Transverse Myelitis, 547
Optic Neuritis, 549
Multiple Sclerosis Onset in Adults, 550
Multiple Sclerosis Relapse in Adults, 554
Multiple Sclerosis Relapse in Children, 555
Guillain-Barré Syndrome, 557
Chronic Inflammatory Disseminated Polyneuropathy, 558
Opsoclonus Myoclonus Syndrome, 560
Bell’s Palsy, 561
Anaphylaxis, 563
Chronic Urticaria, 565
Serum Sickness, 566
Arthropathy, 567
Type 1 Diabetes, 571
Myocarditis, 579
Fibromyalgia, 581
Sudden Infant Death Syndrome, 581
Immune Thrombocytopenic Purpura, 582
Concluding Section, 584
References, 589
11 MENINGOCOCCAL VACCINE 599
Introduction, 599
Encephalitis and Encephalopathy, 602
Acute Disseminated Encephalomyelitis, 603
Transverse Myelitis, 604
Multiple Sclerosis, 605
Guillain-Barré Syndrome, 606
Chronic Inflammatory Disseminated Polyneuropathy, 607
Anaphylaxis, 608
Chronic Headache, 610
Concluding Section, 610
References, 612
12 INJECTION-RELATED ADVERSE EVENTS 615
Complex Regional Pain Syndrome, 615
Deltoid Bursitis, 618
Syncope, 620
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xix
CONTENTS
Concluding Section, 624
References, 626
13 CONCLUDING COMMENTS 629
References, 633
APPENDIXES
A GLOSSARY 635
B LIST OF ADVERSE EVENTS 649
C LITERATURE SEARCH STRATEGY 655
D CAUSALITY CONCLUSION TABLES 673
E REFERENCES 749
F COMMITTEE BIOSKETCHES 827
G MEETING AGENDAS 835
INDEX 839
FIGURES
S-1 Epidemiologic and mechanistic evidence reviewed by the
committee, 11
S-2 Strength of evidence that determined the causality conclusions, 16
2-1 Epidemiologic and mechanistic evidence reviewed by the
committee, 41
2-2 Strength of evidence that determined the causality conclusions, 51
3-1 Present and past environmental exposures, 83
TABLES
S-1 Adverse Events and Causality Conclusions Included in the
Vaccine Chapters, 3
S-2 Summary of Causality Conclusions, 19
1-1 Adverse Events Included in the Vaccine Chapters, 31
4-1 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Encephalopathy or Encephalitis, 114
4-2 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Febrile Seizures, 125
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xx CONTENTS
4-3 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Afebrile Seizures, 135
4-4 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Meningitis, 140
4-5 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Autism, 149
4-6 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and MS Onset in Adults, 162
4-7 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Transient Arthralgia in Women, 177
4-8 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Transient Arthralgia in Children, 186
4-9 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Chronic Arthralgia in Women, 192
4-10 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Chronic Arthritis in Women, 197
4-11 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Arthropathy in Men, 203
4-12 Studies Included in the Weight of Epidemiologic Evidence for
MMR Vaccine and Type 1 Diabetes, 208
4-13 Summary of Epidemiologic Assessments, Mechanistic Assessments,
and Causality Conclusions for Measles, Mumps, and Rubella
Vaccine, 218
5-1 Summary of Epidemiologic Assessments, Mechanistic Assessments,
and Causality Conclusions for Varicella Vaccine, 283
6-1 Influenza Vaccines Licensed and Available in the United States, 297
6-2 Studies Included in the Weight of Epidemiologic Evidence for
Influenza Vaccine and Seizures, 305
6-3 Studies Included in the Weight of Epidemiologic Evidence for
Influenza Vaccine and Optic Neuritis, 312
6-4 Studies Included in the Weight of Epidemiologic Evidence for
Influenza Vaccine and MS Onset in Adults, 317
6-5 Studies Included in the Weight of Epidemiologic Evidence for
Influenza Vaccine and MS Relapse in Adults, 320
6-6 Studies Included in the Weight of Epidemiologic Evidence for
Influenza Vaccine and GBS, 328
6-7 Studies Included in the Weight of Epidemiologic Evidence for
Influenza Vaccine and Bell’s Palsy, 338
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, 351
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xxi
CONTENTS
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, 362
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, 370
6-11 Studies Included in the Weight of Epidemiologic Evidence for
Influenza Vaccine and Exacerbation of SLE, 376
6-12 Studies Included in the Weight of Epidemiologic Evidence for
Influenza Vaccine and Exacerbation of Vasculitis, 381
6-13 Studies Included in the Weight of Epidemiologic Evidence for
Influenza Vaccine and Oculorespiratory Syndrome, 395
6-14 Summary of Epidemiologic Assessments, Mechanistic Assessments,
and Causality Conclusions for Influenza Vaccine, 402
7-1 Summary of Epidemiologic Assessments, Mechanistic Assessments,
and Causality Conclusions for Hepatitis A Vaccine, 431
8-1 Studies Included in the Weight of Epidemiologic Evidence for
Hepatitis B Vaccine and Optic Neuritis, 445
8-2 Studies Included in the Weight of Epidemiologic Evidence for
Hepatitis B Vaccine and MS Onset in Adults, 451
8-3 Studies Included in the Weight of Epidemiologic Evidence for
Hepatitis B Vaccine and First Demyelinating Event in Adults, 461
8-4 Summary of Epidemiologic Assessments, Mechanistic Assessments,
and Causality Conclusions for Hepatitis B Vaccine, 491
9-1 Summary of Epidemiologic Assessments, Mechanistic Assessments,
and Causality Conclusions for HPV Vaccine, 521
10-1 Diphtheria Toxoid–, Tetanus Toxoid–, and Acellular Pertussis–
Containing Vaccines Licensed and Available in the United
States, 531
10-2 Studies Included in the Weight of Epidemiologic Evidence for
Diphtheria Toxoid–, Tetanus Toxoid–, and Acellular Pertussis–
Containing Vaccines and Seizures, 542
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, 552
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xxii CONTENTS
10-4 Studies Included in the Weight of Epidemiologic Evidence for
Diphtheria Toxoid–, Tetanus Toxoid–, and Acellular Pertussis–
Containing Vaccines and Arthropathy, 569
10-5 Studies Included in the Weight of Epidemiologic Evidence for
Diphtheria Toxoid–, Tetanus Toxoid–, and Acellular Pertussis–
Containing Vaccines and Type 1 Diabetes, 575
10-6 Summary of Epidemiologic Assessments, Mechanistic Assessments,
and Causality Conclusions for Diphtheria Toxoid (DT)–,
Tetanus Toxoid (TT)–, and Acellular Pertussis (aP)–Containing
Vaccines, 585
11-1 Summary of Epidemiologic Assessments, Mechanistic Assessments,
and Causality Conclusions for Meningococcal Vaccine, 611
12-1 Summary of Epidemiologic Assessments, Mechanistic Assessments,
and Causality Conclusions for Injection-Related Adverse
Events, 625
B-1 Adverse Events Included in the Vaccine Chapters, 650
D-1 Causality Conclusions Organized by Chapter and Adverse
Event, 674
D-2 Causality Conclusions Organized by Adverse Event and
Chapter, 689
D-3 Causality Conclusions Organized by Causality Conclusion,
Adverse Event, and Chapter, 704
D-4 Causality Conclusions Organized by Epidemiologic Assessment,
Adverse Event, and Chapter, 719
D-5 Causality Conclusions Organized by Mechanistic Assessment,
Adverse Event, and Chapter, 734
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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
xxiii
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xxiv ACRONYMS
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
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xxv
ACRONYMS
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
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xxvi ACRONYMS
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
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ACRONYMS
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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