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.

Contents

• THE NATIONAL ACADEMIES
• COMMITTEE TO REVIEW ADVERSE EFFECTS OF VACCINES
• Reviewers
• Preface
• Acronyms
• Summary
  • CHARGE TO THE COMMITTEE
  • ASSESSING THE WEIGHT OF EVIDENCE
  • CAUSALITY ASSESSMENT
  • CAUSALITY CONCLUSIONS
  • SUSCEPTIBILITY
  • CONCLUDING COMMENT
  • REFERENCES
• 1. Introduction
  • CHARGE TO THE COMMITTEE
  • COMMITTEE PROCESS
  • OUTLINE OF THE REPORT
  • REFERENCES
• 2. Approach
  • LITERATURE SEARCHING
  • WEIGHT OF EVIDENCE
  • CAUSALITY ASSESSMENT
  • SPECIAL CONSIDERATIONS
  • REFERENCES
• 3. Evaluating Biological Mechanisms of Adverse Events
  • LATENCY BETWEEN ANTIGEN EXPOSURE AND PEAK ADAPTIVE IMMUNE RESPONSE
  • IMMUNE-MEDIATED MECHANISMS
  • VIRAL ACTIVITY
  • INJECTION-RELATED ADVERSE EVENTS
  • COAGULATION AND HYPERCOAGULABLE STATES
  • INCREASED SUSCEPTIBILITY
  • ALTERATIONS IN BRAIN DEVELOPMENT
  • CONTRIBUTION OF ANIMAL MODELS
  • REFERENCES
• 4. Measles, Mumps, and Rubella Vaccine
  • INTRODUCTION
  • MEASLES INCLUSION BODY ENCEPHALITIS
  • ENCEPHALITIS AND ENCEPHALOPATHY
  • FEBRILE SEIZURES
  • AFEBRILE SEIZURES
  • MENINGITIS
  • ATAXIA
  • AUTISM
  • ACUTE DISSEMINATED ENCEPHALOMYELITIS
  • TRANSVERSE MYELITIS
  • OPTIC NEURITIS
  • NEUROMYELITIS OPTICA
  • MULTIPLE SCLEROSIS ONSET IN ADULTS
  • MULTIPLE SCLEROSIS ONSET IN CHILDREN
  • GUILLAIN-BARRÉ SYNDROME
  • CHRONIC INFLAMMATORY DISSEMINATED POLYNEUROPATHY
  • OPSOCLONUS MYOCLONUS SYNDROME
  • BRACHIAL NEURITIS
  • ANAPHYLAXIS
  • TRANSIENT ARTHRALGIA IN WOMEN
  • TRANSIENT ARTHRALGIA IN CHILDREN
  • CHRONIC ARTHRALGIA IN WOMEN
  • CHRONIC ARTHRITIS IN WOMEN
  • CHRONIC ARTHROPATHY IN CHILDREN
  • ARTHROPATHY IN MEN
  • TYPE 1 DIABETES
  • HEPATITIS
  • CHRONIC FATIGUE SYNDROME
  • FIBROMYALGIA
  • HEARING LOSS
  • CONCLUDING SECTION
  • REFERENCES
• 5. Varicella Virus Vaccine
  • INTRODUCTION
  • DISSEMINATED OKA VZV WITHOUT OTHER ORGAN INVOLVEMENT
  • DISSEMINATED OKA VZV WITH OTHER ORGAN INVOLVEMENT
  • VACCINE-STRAIN VIRAL REACTIVATION WITHOUT OTHER ORGAN INVOLVEMENT
  • VACCINE-STRAIN VIRAL REACTIVATION WITH OTHER ORGAN INVOLVEMENT
  • ENCEPHALOPATHY
  • SEIZURES
  • CEREBELLAR ATAXIA
  • ACUTE DISSEMINATED ENCEPHALOMYELITIS
  • TRANSVERSE MYELITIS
  • GUILLAIN-BARRÉ SYNDROME
  • SMALL FIBER NEUROPATHY
  • ANAPHYLAXIS
  • ONSET OR EXACERBATION OF ARTHROPATHY
  • STROKE
  • THROMBOCYTOPENIA
  • CONCLUDING SECTION
  • REFERENCES
• 6. Influenza Vaccine
  • INTRODUCTION
  • ENCEPHALITIS AND ENCEPHALOPATHY
  • SEIZURES
  • ACUTE DISSEMINATED ENCEPHALOMYELITIS
  • TRANSVERSE MYELITIS
  • OPTIC NEURITIS
  • NEUROMYELITIS OPTICA
  • MULTIPLE SCLEROSIS ONSET IN ADULTS
  • MULTIPLE SCLEROSIS RELAPSE IN ADULTS
  • GUILLAIN-BARRÉ SYNDROME
  • CHRONIC INFLAMMATORY DISSEMINATED POLYNEUROPATHY
  • BELL'S PALSY
  • BRACHIAL NEURITIS
  • SMALL FIBER NEUROPATHY
  • ANAPHYLAXIS
  • INACTIVATED INFLUENZA VACCINE AND ASTHMA EXACERBATION OR REACTIVE AIRWAY DISEASE EPISODES IN CHILDREN AND ADULTS
  • LIVE ATTENUATED INFLUENZA VACCINE AND ASTHMA EXACERBATION OR REACTIVE AIRWAY DISEASE EPISODES IN CHILDREN YOUNGER THAN 5 YEARS OF AGE
  • LIVE ATTENUATED INFLUENZA VACCINE AND ASTHMA EXACERBATION OR REACTIVE AIRWAY DISEASE EPISODES IN PERSONS 5 YEARS OF AGE OR OLDER
  • ONSET OR EXACERBATION OF SYSTEMIC LUPUS ERYTHEMATOSUS
  • ONSET OR EXACERBATION OF VASCULITIS
  • POLYARTERITIS NODOSA
  • ONSET OR EXACERBATION OF ARTHROPATHY
  • STROKE
  • MYOCARDIAL INFARCTION
  • FIBROMYALGIA
  • ALL-CAUSE MORTALITY
  • OCULORESPIRATORY SYNDROME
  • CONCLUDING SECTION
  • REFERENCES
• 7. Hepatitis A Vaccine
  • INTRODUCTION
  • ACUTE DISSEMINATED ENCEPHALOMYELITIS
  • TRANSVERSE MYELITIS
  • MULTIPLE SCLEROSIS
  • GUILLAIN-BARRÉ SYNDROME
  • CHRONIC INFLAMMATORY DISSEMINATED POLYNEUROPATHY
  • BELL'S PALSY
  • ANAPHYLAXIS
  • AUTOIMMUNE HEPATITIS
  • CONCLUDING SECTION
  • REFERENCES
• 8. Hepatitis B Vaccine
  • INTRODUCTION
  • ENCEPHALITIS AND ENCEPHALOPATHY
  • SEIZURES
  • ACUTE DISSEMINATED ENCEPHALOMYELITIS
  • TRANSVERSE MYELITIS
  • OPTIC NEURITIS
  • NEUROMYELITIS OPTICA
  • MULTIPLE SCLEROSIS ONSET IN ADULTS
  • MULTIPLE SCLEROSIS ONSET IN CHILDREN
  • MULTIPLE SCLEROSIS RELAPSE IN ADULTS
  • MULTIPLE SCLEROSIS RELAPSE IN CHILDREN
  • FIRST DEMYELINATING EVENT IN ADULTS
  • FIRST DEMYELINATING EVENT IN CHILDREN
  • GUILLAIN-BARRÉ SYNDROME
  • CHRONIC INFLAMMATORY DISSEMINATED POLYNEUROPATHY
  • BRACHIAL NEURITIS
  • ANAPHYLAXIS
  • ERYTHEMA NODOSUM
  • ONSET OR EXACERBATION OF SYSTEMIC LUPUS ERYTHEMATOSUS
  • ONSET OR EXACERBATION OF VASCULITIS
  • ONSET OR EXACERBATION OF POLYARTERITIS NODOSA
  • ONSET OR EXACERBATION OF PSORIATIC ARTHRITIS
  • ONSET OR EXACERBATION OF REACTIVE ARTHRITIS
  • ONSET OR EXACERBATION OF RHEUMATOID ARTHRITIS
  • ONSET OR EXACERBATION OF JUVENILE IDIOPATHIC ARTHRITIS
  • TYPE 1 DIABETES
  • FIBROMYALGIA
  • CONCLUDING SECTION
  • REFERENCES
• 9. Human Papillomavirus Vaccine
  • INTRODUCTION
  • ACUTE DISSEMINATED ENCEPHALOMYELITIS
  • TRANSVERSE MYELITIS
  • NEUROMYELITIS OPTICA
  • MULTIPLE SCLEROSIS
  • GUILLAIN-BARRÉ SYNDROME
  • CHRONIC INFLAMMATORY DISSEMINATED POLYNEUROPATHY
  • BRACHIAL NEURITIS
  • AMYOTROPHIC LATERAL SCLEROSIS
  • ANAPHYLAXIS
  • TRANSIENT ARTHRALGIA
  • PANCREATITIS
  • THROMBOEMBOLIC EVENTS
  • HYPERCOAGULABLE STATES
  • CONCLUDING SECTION
  • REFERENCES
• 10. Diphtheria Toxoid–, Tetanus Toxoid–, and Acellular Pertussis–Containing Vaccines
  • INTRODUCTION
  • ENCEPHALITIS AND ENCEPHALOPATHY
  • INFANTILE SPASMS
  • SEIZURES
  • ATAXIA
  • AUTISM
  • ACUTE DISSEMINATED ENCEPHALOMYELITIS
  • TRANSVERSE MYELITIS
  • OPTIC NEURITIS
  • MULTIPLE SCLEROSIS ONSET IN ADULTS
  • MULTIPLE SCLEROSIS RELAPSE IN ADULTS
  • MULTIPLE SCLEROSIS RELAPSE IN CHILDREN
  • GUILLAIN-BARRÉ SYNDROME
  • CHRONIC INFLAMMATORY DISSEMINATED POLYNEUROPATHY
  • OPSOCLONUS MYOCLONUS SYNDROME
  • BELL'S PALSY
  • ANAPHYLAXIS
  • CHRONIC URTICARIA
  • SERUM SICKNESS
  • ARTHROPATHY
  • TYPE 1 DIABETES
  • MYOCARDITIS
  • FIBROMYALGIA
  • SUDDEN INFANT DEATH SYNDROME
  • IMMUNE THROMBOCYTOPENIC PURPURA
  • CONCLUDING SECTION
  • REFERENCES
• 11. Meningococcal Vaccine
  • INTRODUCTION
  • ENCEPHALITIS AND ENCEPHALOPATHY
  • ACUTE DISSEMINATED ENCEPHALOMYELITIS
  • TRANSVERSE MYELITIS
  • MULTIPLE SCLEROSIS
  • GUILLAIN-BARRÉ SYNDROME
  • CHRONIC INFLAMMATORY DISSEMINATED POLYNEUROPATHY
  • ANAPHYLAXIS
  • CHRONIC HEADACHE
  • CONCLUDING SECTION
  • REFERENCES
• 12. Injection-Related Adverse Events
  • COMPLEX REGIONAL PAIN SYNDROME
  • DELTOID BURSITIS
  • SYNCOPE
  • CONCLUDING SECTION
  • REFERENCES
• 13. Concluding Comments
  • MMR vaccine
  • Varicella vaccine
  • Anaphylaxis
  • REFERENCES
• APPENDIXES
  • Appendix A Glossary
  • Appendix B List of Adverse Events
  • Appendix C Literature Search Strategy
  • Appendix D Causality Conclusion Tables
  • Appendix E References
  • Appendix F Committee Biosketches
  • Appendix G Meeting Agendas

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.

Suggested citation:

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

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.