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Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

Appendix D

Causality Conclusion Tables

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Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

TABLE D-1 Causality Conclusions Organized by Chapter and Adverse Event


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

4	MMR	Measles Inclusion Body Encephalitis	Insufficient	Strong (measles; in individuals with demonstrated immunodeficiencies) Lacking (mumps or rubella)	Convincingly Supports^a (in individuals with demonstrated immunodeficiencies)
4	MMR	Encephalitis	Limited	Weak	Inadequate
4	MMR	Encephalopathy	Limited	Weak	Inadequate
4	MMR	Febrile Seizures	High (increase)	Intermediate	Convincingly Supports
4	MMR	Afebrile Seizures	Limited	Lacking	Inadequate
4	MMR	Meningitis^b	Moderate (null)	Weak (mumps) Lacking (measles or rubella)	Inadequate
4	MMR	Ataxia	Insufficient	Weak (measles or mumps) Lacking (rubella)	Inadequate
4	MMR	Autism	High (null)	Lacking	Favors Rejection
4	MMR	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
4	MMR	Transverse Myelitis	Insufficient	Weak	Inadequate

Page 675 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

4	MMR	Optic Neuritis,^b	Limited	Weak	Inadequate
4	MMR	Neuromyelitis Optica^b	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
4	MMR	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
4	MMR	Guillain-Barré syndrome	Insufficient	Weak	Inadequate
4	MMR	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
4	MMR	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate
4	MMR	Brachial Neuritis	Insufficient	Inadequate
4	MMR	Anaphylaxis	Insufficient	Strong	Convincingly Supports
4	MMR	Transient Arthralgia in Women	Moderate (increase) (rubella) Insufficient (measles or mumps)	Intermediate (rubella) Lacking (measles or mumps)	Favors Acceptance
4	MMR	Transient Arthralgia in Children	Moderate (increase)	Weak (rubella) Lacking (measles or mumps)	Favors Acceptance^c

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Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

4	MMR	Chronic Arthralgia in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Chronic Arthritis in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Chronic Arthropathy in Children	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Arthropathy in Men	Limited	Weak (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Type 1 Diabetes	High (null)	Lacking	Favors Rejection
4	MMR	Hepatitis	Insufficient	Weak	Inadequate
4	MMR	Chronic Fatigue Syndrome	Insufficient	Lacking	Inadequate
4	MMR	Fibromyalgia	Insufficient	Lacking	Inadequate

Page 677 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

4	MMR	Hearing Loss	Insufficient	Low-Intermediate (measles or mumps) Lacking (rubella)	Inadequate
5	Disseminated Oka VZV without Other Organ Involvement	Insufficient	Varicella	Strong	Convincingly Supports
5	Disseminated Oka VZV with Subsequent Infection Resulting in Pneumonia, Meningitis, or Hepatitis	Limited (subsequent infection resulting in pneumonia) Insufficient (subsequent infection resulting in meningitis or hepatitis)	Varicella	Strong (in individuals with demonstrated immunodeficiencies)	Convincingly Supports (in individuals with demonstrated immunodeficiencies)
5	Vaccine Strain Viral Reactivation without Other Organ Involvement	Insufficient	Varicella	Strong	Convincingly Supports
5	Vaccine Strain Viral Reactivation with Subsequent Infection resulting in Meningitis or Encephalitis	Limited (subsequent infection resulting in encephalitis) Insufficient (subsequent infection resulting in meningitis)	Varicella	Strong	Convincingly Supports
5	Encephalopathy	Insufficient	Varicella	Lacking	Inadequate
5	Seizures	Limited	Varicella	Weak	Inadequate
5	Cerebellar Ataxia	Insufficient	Varicella	Weak	Inadequate
5	Acute Disseminated Encephalomyelitis	Insufficient	Varicella	Weak	Inadequate

Page 678 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

5	Varicella	Transverse Myelitis	Insufficient	Weak	Inadequate
5	Varicella	Guillain-Barre syndrome	Insufficient	Weak	Inadequate
5	Varicella	Small Fiber Neuropathy^b	Insufficient	Lacking	Inadequate
5	Varicella	Anaphylaxis	Limited	Strong	Convincingly Supports
5	Varicella	Onset or Exacerbation Arthropathy	Insufficient	Lacking	Inadequate
5	Varicella	Stroke^b	Limited	Weak	Inadequate
5	Varicella	Thrombocytopenia	Insufficient	Weak	Inadequate
6	Influenza	Encephalitis	Insufficient	Weak	Inadequate
6	Influenza	Encephalopathy	Insufficient	Weak	Inadequate
6	Influenza	Seizures^b	Moderate (null)	Lacking	Inadequate
6	Influenza	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
6	Influenza	Transverse Myelitis	Insufficient	Weak	Inadequate
6	Influenza	Optic Neuritis^b	Limited	Weak	Inadequate
6	Influenza	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
6	Influenza	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
6	Influenza	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
6	Influenza	Guillain-Barre syndrome	Moderate (null)	Weak	Inadequate
6	Influenza	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Weak	Inadequate

Page 679 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

6	Influenza	Inactivated Influenza Vaccine and Bell’s Palsy	High (null)	Lacking	Favors Rejection
6	Influenza	Brachial Neuritis	Insufficient	Lacking	Inadequate
6	Influenza	Small Fiber Neuropathy	Insufficient	Lacking	Inadequate
6	Influenza	Anaphylaxis	Limited	Strong	Convincingly Supports
6	Influenza	Inactivated Influenza Vaccine and Asthma Exacerbation or Reactive Airway Disease Episodes in Children and Adults	High (null)	Weak	Favors Rejection
6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Children Younger Than 5 Years of Age	Moderate (null)	Weak	Inadequate
6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Persons 5 Years of Age or Older	Moderate (null)	Weak	Inadequate
6	Influenza	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (exacerbation) Insufficient (onset)	Lacking	Inadequate
6	Influenza	Onset or Exacerbation of Vasculitis	Limited (exacerbation) Insufficient (onset)	Weak (exacerbation) Lacking (onset)	Inadequate

Page 680 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

6	Influenza	Polyarteritis Nodosa	Insufficient	Lacking	Inadequate
6	Influenza	Onset or Exacerbation of Arthropathy	Insufficient	Weak	Inadequate
6	Influenza	Stroke	Moderate (decrease)	Lacking	Inadequate
6	Influenza	Myocardial Infarction	Moderate (decrease)	Weak (Live Attenuated Influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate
6	Influenza	Fibromyalgia	Insufficient	Lacking	Inadequate
6	Influenza	All-Cause Mortality^b	Moderate (decrease)	Weak (Live Attenuated Influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate
6	Influenza	Oculorespiratory Syndrome	Moderate (increase)^d	Intermediate^d	Favors Acceptance^d
	Hepatitis A	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
	Hepatitis A	Transverse Myelitis	Insufficient	Weak	Inadequate
7	Hepatitis A	Multiple Sclerosis	Insufficient	Lacking	Inadequate

Page 681 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

7	Hepatitis A	Guillain-Barré syndrome	Insufficient	Weak	Inadequate
	Hepatitis A	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
7	Hepatitis A	Bell’s Palsy	Insufficient	Lacking	Inadequate
7	Hepatitis A	Anaphylaxis	Insufficient	Weak	Inadequate
7	Hepatitis A	Autoimmune Hepatitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Encephalitis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Encephalopathy	Insufficient	Lacking	Inadequate
8	Hepatitis B	Seizures	Limited	Lacking	Inadequate
8	Hepatitis B	Acute Disseminated Encephalomyelitis	Insufficient	Low-Intermediate	Inadequate
8	Hepatitis B	Transverse Myelitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Optic Neuritis^b	Limited	Lacking	Inadequate
8	Hepatitis B	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Children	Limited	Lacking	Inadequate
8	Hepatitis B	First Demyelinating Event in Adults	Moderate (null)	Low-Intermediate	Inadequate
8	Hepatitis B	First Demyelinating Event in Children	Limited	Lacking	Inadequate
8	Hepatitis B	Guillain-Barre syndrome	Insufficient	Lacking	Inadequate

Page 682 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

8	Hepatitis B	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
8	Hepatitis B	Brachial Neuritis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Anaphylaxis	Insufficient	Strong (in yeast-sensitive individuals)	Convincingly Supports (in yea st-sensitive individuals)
8	Hepatitis B	Erythema Nodosum^b	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (onset) Insufficient (exacerbation)	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Vasculitis	Insufficient	Low-Intermediate	Inadequate
8	Hepatitis B	Onset or Exacerbation of Polyarteritis Nodosa	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Psoriatic Arthritis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Reactive Arthritis	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset and Exacerbation of Rheumatoid Arthritis	Limited (exacerbation) Insufficient (onset)	Weak	Inadequate

Page 683 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

8	Hepatitis B	Onset or Exacerbation of Juvenile Idiopathic Arthritis	Insufficient	Weak	Inadequate
8	Hepatitis B	Type 1 Diabetes	Moderate (null)	Lacking	Inadequate
8	Hepatitis B	Fibromyalgia	Insufficient	Lacking	Inadequate
9	HPV	Acute Disseminated Encephalomyelitis	Insufficient	Lacking	Inadequate
9	HPV	Transverse Myelitis	Insufficient	Lacking	Inadequate
9	HPV	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
9	HPV	Multiple Sclerosis	Insufficient	Lacking	Inadequate
9	HPV	Guillain-Barre syndrome	Insufficient	Lacking	Inadequate
9	HPV	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
9	HPV	Brachial Neuritis	Insufficient	Lacking	Inadequate
9	HPV	Amyotrophic Lateral Sclerosis	Insufficient	Lacking	Inadequate
9	HPV	Anaphylaxis	Insufficient	Intermediate	Favors Acceptance
9	HPV	Transient Arthralgia	Limited	Lacking	Inadequate
9	HPV	Pancreatitis	Insufficient	Lacking	Inadequate
9	HPV	Thromboembolic Events	Insufficient	Lacking	Inadequate
9	HPV	Hypercoagulable States	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Encephalitis	Limited	Weak	Inadequate
10	DT, TT, or aP containing	Encephalopathy	Limited	Weak	Inadequate

Page 684 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

10	DT, TT, or aP containing	Infantile Spasms	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
10	DT, TT, or aP containing	Seizures	Limited	III	Inadequate
10	DT, TT, or aP containing	Ataxia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Autism	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Acute Disseminated Encephalomyelitis	Insufficient	Weak (tetanus toxoid) Lacking (diphtheria toxoid or acellular pertussis)	Inadequate
10	DT, TT, or aP containing	Transverse Myelitis	Insufficient	Lacking	Inadequate

Page 685 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

10	DT, TT, or aP containing	Optic Neuritis^b	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Onset in Adults	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Adults	Limited (tetanus toxoid) Insufficient (diphtheria toxoid or acellular pertussis)	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Children	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
10	DT, TT, or aP containing	Guillain-Barre syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate

Page 686 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

10	DT, TT, or aP containing	Bell’s Palsy	Limited (acel hilar pertussis) Insufficient (diphtheria toxoid or tetanus toxoid)	Weak (diphtheria toxoid or tetanus toxoid) Lacking (acellular pertussis)	Inadequate
10	TT containing	Anaphylaxis	Insufficient	Strong	Convincingly Supports
10	DT and aP containing	Anaphylaxis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Chronic Urticaria	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Serum Sickness	Insufficient	Weak (diphtheria toxoid or tetanus toxoid) Lacking (acellular pertussis)	Inadequate
10	DT, TT, or aP containing	Arthropathy	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
10	DT, TT, or aP containing	Type 1 Diabetes	High (null)	Lacking	Favors Rejection

Page 687 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

10	DT, TT, or aP containing	Myocarditis	Insufficient	Weak (diphtheria toxoid) Lacking (tetanus toxoid or acellular pertussis)	Inadequate
10	DT, TT, or aP containing	Fibromyalgia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Sudden Infant Death Syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Immune Thrombocytopenic Purpura	Insufficient	Lacking	Inadequate
	Meningococcal	Encephalitis	Limited	Lacking	Inadequate
	Meningococcal	Encephalopathy	Limited	Lacking	Inadequate
	Meningococcal	Acute Disseminated Encephalomyelitis	Insufficient	Lacking	Inadequate
	Meningococcal	Transverse Myelitis	Insufficient	Lacking	Inadequate
	Meningococcal	Multiple Sclerosis	Insufficient	Lacking	Inadequate
	Meningococcal	Guillain-Barre syndrome	Limited	Lacking	Inadequate
	Meningococcal	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
	Meningococcal	Anaphylaxis	Insufficient	Strong	Convincingly Supports
	Meningococcal	Chronic Headache	Insufficient	Lacking	Inadequate
12	Injection-Related Event	Complex Regional Pain Syndrome	Insufficient	Low-Intermediate	Inadequate

Page 688 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

12	Injection-Related Event	Deltoid Bursitis	Limited	Strong	Convincingly Supports
12	Injection-Related Event	Syncope	Insufficient	Strong	Convincingly Supports

NOTE: The measles-mumps-rubella; human papillomavirus; and diphtheria toxoid–, tetanus toxoid-, and acellular pertussis-containing vaccines have been abbreviated in the following ways: MMR; HPV; and DT, TT, and aP containing.

^aThe committee attributes causation to the measles component of the vaccine.

^bAlthough not originally charged to the committee by the sponsor, the committee considered this adverse event in its review of the literature.

^cThe committee attributes causation to the rubella component of the vaccine.

^dThe committee attributes causation to two particular vaccines used in three particular years in Canada.

Page 689 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

TABLE D-2 Causality Conclusions Organized by Adverse Event and Chapter


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

5	Varicella	Disseminated Oka VZV without Other Organ Involvement	Insufficient	Strong	Convincingly Supports
5	Varicella	Disseminated Oka VZV with Subsequent Infection Resulting in Pneumonia, Meningitis, or Hepatitis	Limited (subsequent infection resulting in pneumonia) Insufficient (subsequent infection resulting in meningitis or hepatitis)	Strong (in individuals with demonstrated immunodeficiencies)	Convincingly Supports (in individuals with demonstrated immunodeficiencies)
5	Varicella	Vaccine Strain Viral Reactivation without Other Organ Involvement	Insufficient	Strong	Convincingly Supports
5	Varicella	Vaccine Strain Viral Reactivation with Subsequent Infection resulting in Meningitis or Encephalitis	Limited (subsequent infection resulting in encephalitis) Insufficient (subsequent infection resulting in meningitis)	Strong	Convincingly Supports
4	MMR	Measles Inclusion Body Encephalitis	Insufficient	Strong (measles; in individuals with demonstrated immunodeficiencies) Lacking (mumps or rubella)	Convincingly Supports^a (in individuals with demonstrated immunodeficiencies)

Page 690 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

4	MMR	Encephalitis	Limited	Weak	Inadequate
6	Influenza	Encephalitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Encephalitis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Encephalitis	Limited	Weak	Inadequate
11	Meningococcal	Encephalitis	Limited	Lacking	Inadequate
4	MMR	Encephalopathy	Limited	Weak	Inadequate
5	Varicella	Encephalopathy	Insufficient	Lacking	Inadequate
6	Influenza	Encephalopathy	Insufficient	Weak	Inadequate
8	Hepatitis B	Encephalopathy	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Encephalopathy	Limited	Weak	Inadequate
11	Meningococcal	Encephalopathy	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Infantile Spasms	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
4	MMR	Febrile Seizures	High (increase)	Intermediate	Convincingly Supports
4	MMR	Afebrile Seizures	Limited	Lacking	Inadequate
5	Varicella	Seizures	Limited	Weak	Inadequate

Page 691 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

6	Influenza	Seizures^b	Moderate (null)	Lacking	Inadequate
8	Hepatitis B	Seizures	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Seizures	Limited	Weak (acellular pertussis) Lacking (diphtheria toxoid or tetanus toxoid)	Inadequate
4	MMR	Meningitis^b	Moderate (null)	Weak (mumps) Lacking (measles or rubella)	Inadequate
5	Varicella	Cerebellar Ataxia	Insufficient	Weak	Inadequate
4	MMR	Ataxia	Insufficient	Weak (measles or mumps) Lacking (rubella)	Inadequate
10	DT, TT, or aP containing	Ataxia	Insufficient	Lacking	Inadequate
4	MMR	Autism	High (null)	Lacking	Favors Rejection
10	DT, TT, or aP containing	Autism	Insufficient	Lacking	Inadequate
4	MMR	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
5	Varicella	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate

Page 692 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

6	Influenza	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
7	Hepatitis A	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Acute Disseminated Encephalomyelitis	Insufficient	Low-Intermediate	Inadequate
9	HPV	Acute Disseminated Encephalomyelitis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Acute Disseminated Encephalomyelitis	Insufficient	Weak (tetanus toxoid) Lacking (diphtheria toxoid or acellular pertussis)	Inadequate
11	Meningococcal	Acute Disseminated Encephalomyelitis	Insufficient	Lacking	Inadequate
4	MMR	Transverse Myelitis	Insufficient	Weak	Inadequate
5	Varicella	Transverse Myelitis	Insufficient	Weak	Inadequate
6	Influenza	Transverse Myelitis	Insufficient	Weak	Inadequate
7	Hepatitis A	Transverse Myelitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Transverse Myelitis	Insufficient	Weak	Inadequate
9	HPV	Transverse Myelitis	Insufficient	Lacking	Inadequate

Page 693 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

10	DT, TT, or aP containing	Transverse Myelitis	Insufficient	Lacking	Inadequate
11	Meningococcal	Transverse Myelitis	Insufficient	Lacking	Inadequate
4	MMR	Optic Neuritis^b	Limited	Weak	Inadequate
6	Influenza	Optic Neuritis^b	Limited	Weak	Inadequate
8	Hepatitis B	Optic Neuritis^b	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Optic Neuritis^b	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
4	MMR	Neuromyelitis Optica^b	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
6	Influenza	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
8	Hepatitis B	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
9	HPV	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
4	MMR	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
6	Influenza	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate

Page 694 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

10	DT, TT, or aP containing	Multiple Sclerosis Onset in Adults	Limited (diphtheria toxoid or tetanus toxoid) Insufficient acellular pertussis)	Lacking	Inadequate
4	MMR	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
6	Influenza	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Adults	Limited (tetanus toxoid) Insufficient (diphtheria toxoid or acellular pertussis)	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Children	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Children	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
7	Hepatitis A	Multiple Sclerosis	Insufficient	Lacking	Inadequate
9	HPV	Multiple Sclerosis	Insufficient	Lacking	Inadequate

Page 695 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

11	Meningococcal	Multiple Sclerosis	Insufficient	Lacking	Inadequate
8	Hepatitis B	First Demy el ina ting Event in Adults	Moderate (null)	Low-Intermediate	Inadequate
8	Hepatitis B	First Demyel ina ting Event in Children	Limited	Lacking	Inadequate
4	MMR	Guillain-Barre syndrome	Insufficient	Weak	Inadequate
5	Varicella	Guillain-Barre syndrome	Insufficient	Weak	Inadequate
6	Influenza	Guillain-Barre syndrome	Moderate (null)	Weak	Inadequate
7	Hepatitis A	Guillain-Barre syndrome	Insufficient	Weak	Inadequate
8	Hepatitis B	Guillain-Barre syndrome	Insufficient	Lacking	Inadequate
9	HPV	Guillain-Barre syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Guillain-Barre syndrome	Insufficient	Lacking	Inadequate
11	Meningococcal	Guillain-Barre syndrome	Limited	Lacking	Inadequate
4	MMR	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
6	Influenza	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Weak	Inadequate
7	Hepatitis A	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
8	Hepatitis B	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
9	HPV	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate

Page 696 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

10	DT, TT, or aP containing	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
11	Meningococcal	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
4	MMR	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate
7	Hepatitis A	Bell’s Palsy	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Bell’s Palsy	Limited (acellular pertussis) Insufficient (diphtheria toxoid or tetanus toxoid)	Weak (diphtheria toxoid or tetanus toxoid) Lacking (acellular pertussis)	Inadequate
6	Influenza	Inactivated Influenza Vaccine and Bell’s Palsy	High (null)	Lacking	Favors Rejection
4	MMR	Brachial Neuritis	Insufficient	Lacking	Inadequate
6	Influenza	Brachial Neuritis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Brachial Neuritis	Insufficient	Lacking	Inadequate
9	HPV	Brachial Neuritis	Insufficient	Lacking	Inadequate
9	HPV	Amyotrophic Lateral Sclerosis	Insufficient	Lacking	Inadequate
5	Varicella	Small Fiber Neuropathy6	Insufficient	Lacking	Inadequate

Page 697 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

6	Influenza	Small Fiber Neuropathy	Insufficient	Lacking	Inadequate
4	MMR	Anaphylaxis	Insufficient	Strong	Convincingly Supports
5	Varicella	Anaphylaxis	Limited	Strong	Convincingly Supports
6	Influenza	Anaphylaxis	Limited	Strong	Convincingly Supports
7	Hepatitis A	Anaphylaxis	Insufficient	Weak	Inadequate
8	Hepatitis B	Anaphylaxis	Insufficient	Strong (in yeast-sensitive individuals)	Convincingly Supports (in yea st-sensitive individuals)
9	HPV	Anaphylaxis	Insufficient	Intermediate	Favors Acceptance
10	DT and aP containing	Anaphylaxis	Insufficient	Lacking	Inadequate
10	TT containing	Anaphylaxis	Insufficient	Strong	Convincingly Supports
11	Meningococcal	Anaphylaxis	Insufficient	Strong	Convincingly Supports
10	DT, TT, or aP containing	Chronic Urticaria	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Serum Sickness	Insufficient	Weak (diphtheria toxoid or tetanus toxoid) Lacking (acellular pertussis)	Inadequate
6	Influenza	Inactivated Influenza Vaccine and Asthma Exacerbation or Reactive Airway Disease Episodes in Children and Adults	High (null)	Weak	Favors Rejection

Page 698 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Children Younger Than 5 Years of Age	Moderate (null)	Weak	Inadequate
6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Persons 5 Years of Age or Older	Moderate (null)	Weak	Inadequate
8	Hepatitis B	Erythema Nodosum^b	Insufficient	Weak	Inadequate
6	Influenza	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (exacerbation) Insufficient (onset)	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (onset) Insufficient (exacerbation)	Weak	Inadequate
6	Influenza	Onset or Exacerbation of Vasculitis	Limited (exacerbation) Insufficient (onset)	Weak (exacerbation) Lacking (onset)	Inadequate
8	Hepatitis B	Onset or Exacerbation of Vasculitis	Insufficient	Low-Intermediate	Inadequate
6	Influenza	Polyarteritis Nodosa	Insufficient	Lacking	Inadequate

Page 699 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

8	Hepatitis B	Onset or Exacerbation of Polyarteritis Nodosa	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Psoriatic Arthritis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Reactive Arthritis	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset and Exacerbation of Rheumatoid Arthritis	Limited (exacerbation) Insufficient (onset)	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Juvenile Idiopathic Arthritis	Insufficient	Weak	Inadequate
4	MMR	Transient Arthralgia in Women	Moderate (increase) (rubella) Insufficient (measles or mumps)	Intermediate (rubella) Lacking (measles or mumps)	Favors Acceptance^c
4	MMR	Transient Arthralgia in Children	Moderate (increase)	Weak (rubella) Lacking (measles or mumps)	Favors Acceptance
9	HPV	Transient Arthralgia	Limited	Lacking	Inadequate
4	MMR	Chronic Arthralgia in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate

Page 700 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

4	MMR	Chronic Arthritis in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Chronic Arthropathy in Children	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Arthropathy in Men	Limited	Weak (rubella) Lacking (measles or mumps)	Inadequate
5	Varicella	Onset or Exacerbation Arthropathy	Insufficient	Lacking	Inadequate
6	Influenza	Onset or Exacerbation of Arthropathy	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Arthropathy	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
4	MMR	Type 1 Diabetes	High (null)	Lacking	Favors Rejection
8	Hepatitis B	Type 1 Diabetes	Moderate (null)	Lacking	Inadequate

Page 701 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

10	DT, TT, or aP containing	Type 1 Diabetes	High (null)	Lacking	Favors Rejection
7	Hepatitis A	Autoimmune Hepatitis	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Myocarditis	Insufficient	Weak (diphtheria toxoid) Lacking (tetanus toxoid or acellular pertussis)	Inadequate
9	HPV	Pancreatitis	Insufficient	Lacking	Inadequate
4	MMR	Hepatitis	Insufficient	Weak	Inadequate
9	HPV	Thromboembolic Events	Insufficient	Lacking	Inadequate
5	Varicella	Stroke^b	Limited	Weak	Inadequate
6	Influenza	Stroke	Moderate (decrease)	Lacking	Inadequate
9	HPV	Hypercoagulable States	Insufficient	Lacking	Inadequate
6	Influenza	Myocardial Infarction	Moderate (decrease)	Weak (Live Attenuated Influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate
4	MMR	Chronic Fatigue Syndrome	Insufficient	Lacking	Inadequate
11	Meningococcal	Chronic Headache	Insufficient	Lacking	Inadequate
4	MMR	Fibromyalgia	Insufficient	Lacking	Inadequate

Page 702 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

6	Influenza	Fibromyalgia	Insufficient	Lacking	Inadequate
8	Hepatitis B	Fibromyalgia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Fibromyalgia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Sudden Infant Death Syndrome	Insufficient	Lacking	Inadequate
4	MMR	Hearing Loss	Insufficient	Low-Intermediate (measles or mumps) Lacking (rubella)	Inadequate
6	Influenza	All-Cause Mortality^b	Moderate {decrease)	Weak (Live Attenuated Influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate
6	Influenza	Oculorespiratory Syndrome	Moderate (increase)^d	Intermediate^d	Favors Acceptance^d
5	Varicella	Thrombocytopenia	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Immune Thrombocytopenic Purpura	Insufficient	Lacking	Inadequate
12	Injection-Related Event	Complex Regional Pain Syndrome	Insufficient	Low-Intermediate	Inadequate

Page 703 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

12	Injection-Related Event	Deltoid Bursitis	Limited	Strong	Convincingly Supports
12	Injection-Related Event	Syncope	Insufficient	Strong	Convincingly Supports

NOTE: The measles-mumps-rubella; human papillomavirus; and diphtheria toxoid–, tetanus toxoid-, and acellular pertussis-containing vaccines have been abbreviated in the following ways: MMR; HPV; and DT, TT, and aP containing.

^a The committee attributes causation to the measles component of the vaccine.

^b Although not originally charged to the committee by the sponsor, the committee considered this adverse event in its review of the literature.

^c The committee attributes causation to the rubella component of the vaccine.

^d The committee attributes causation to two particular vaccines used in three particular years in Canada.

Page 704 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

TABLE D-3 Causality Conclusions Organized by Causality Conclusion, Adverse Event, and Chapter


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

5	Varicella	Disseminated Oka VZV without Other Organ Involvement	Insufficient	Strong	Convincingly Supports
5	Varicella	Disseminated Oka VZV with Subsequent Infection Resulting in Pneumonia, Meningitis, or Hepatitis	Limited (subsequent infection resulting in pneumonia) Insufficient (subsequent infection resulting in meningitis or hepatitis)	Strong (in individuals with demonstrated immunodeficiencies)	Convincingly Supports (in individuals with demonstrated immunodeficiencies)
5	Varicella	Vaccine Strain Viral Reactivation without Other Organ Involvement	Insufficient	Strong	Convincingly Supports
5	Varicella	Vaccine Strain Viral Reactivation with Subsequent Infection resulting in Meningitis or Encephalitis	Limited (subsequent infection resulting in encephalitis) Insufficient (subsequent infection resulting in meningitis)	Strong	Convincingly Supports
4	MMR	Measles Inclusion Body Encephalitis	Insufficient	Strong (measles; in individuals with demonstrated immunodehc iencies) Lacking (mumps or rubella)	Convincingly Supports^a (in individuals with demonstrated immunodeficiencies)
4	MMR	Febrile Seizures	High (increase)	Intermediate	Convincingly Supports

Page 705 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

4	MMR	Anaphylaxis	Insufficient	Strong	Convincingly Supports
5	Varicella	Anaphylaxis	Limited	Strong	Convincingly Supports
6	Influenza	Anaphylaxis	Limited	Strong	Convincingly Supports
8	Hepatitis B	Anaphylaxis	Insufficient	Strong (in yeast-sensitive individuals)	Convincingly Supports (in yeast-sensitive individuals)
10	TT containing	Anaphylaxis	Insufficient	Strong	Convincingly Supports
11	Meningococcal	Anaphylaxis	Insufficient	Strong	Convincingly Supports
12	Injection-Related Event	Deltoid Bursitis	Limited	Strong	Convincingly Supports
12	Injection-Related Event	Syncope	Insufficient	Strong	Convincingly Supports
9	HPV	Anaphylaxis	Insufficient	Intermediate	Favors Acceptance
4	MMR	Transient Arthralgia in Women	Moderate (increase) (rubella) Insufficient (measles or mumps)	Intermediate (rubella) Lacking (measles or mumps)	Favors Acceptance^b
4	MMR	Transient Arthralgia in Children	Moderate (increase)	Weak (rubella) Lacking (measles or mumps)	Favors Acceptance
6	Influenza	Oculorespiratory Syndrome	Moderate (increase)^c	Intermediate^c	Favors Acceptance^c
4	MMR	Autism	High (null)	Lacking	Favors Rejection

Page 706 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

6	Influenza	Inactivated Influenza Vaccine and Bell’s Palsy	High (null)	Lacking	Favors Rejection
6	Influenza	Inactivated Influenza Vaccine and Asthma Exacerbation or Reactive Airway Disease Episodes in Children and Adults	High (null)	Weak	Favors Rejection
4	MMR	Type 1 Diabetes	High (null)	Lacking	Favors Rejection
10	DT, TT, or aP containing	Type 1 Diabetes	High (null)	Lacking	Favors Rejection
4	MMR	Encephalitis	Limited	Weak	Inadequate
6	Influenza	Encephalitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Encephalitis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Encephalitis	Limited	Weak	Inadequate
11	Meningococcal	Encephalitis	Limited	Lacking	Inadequate
4	MMR	Encephalopathy	Limited	Weak	Inadequate
5	Varicella	Encephalopathy	Insufficient	Lacking	Inadequate
6	Influenza	Encephalopathy	Insufficient	Weak	Inadequate
8	Hepatitis B	Encephalopathy	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Encephalopathy	Limited	Weak	Inadequate

Page 707 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

11	Meningococcal	Encephalopathy	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Infantile Spasms	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
4	MMR	Afebrile Seizures	Limited	Lacking	Inadequate
5	Varicella	Seizures	Limited	Weak	Inadequate
6	Influenza	Seizures^d	Mjxlerate (null)	Lacking	Inadequate
8	Hepatitis B	Seizures	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Seizures	Limited	Weak (acellular pertussis) Lacking (diphtheria toxoid or tetanus toxoid)	Inadequate
4	MMR	Meningitis	Moderate (null)	Weak (mumps) Lacking (measles or rubella)	Inadequate
5	Varicella	Cerebellar Ataxia	Insufficient	Weak	Inadequate
4	MMR	Ataxia	Insufficient	Weak (measles or mumps) Lacking (rubella)	Inadequate

Page 708 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

10	DT, TT, or aP containing	Ataxia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Autism	Insufficient	Lacking	Inadequate
4	MMR	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
5	Varicella	Acute Disseminated Encephalomyeliris	Insufficient	Weak	Inadequate
6	Influenza	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
	Hepatitis A	Acute Disseminated Encephalomyeliris	Insufficient	Weak	Inadequate
8	Hepatitis B	Acute Disseminated Encephalomyeliris	Insufficient	Low-Intermediate	Inadequate
9	HPV	Acute Disseminated Encephalomyeliris	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Acute Disseminated Encephalomyeliris	Insufficient	Weak (tetanus toxoid) Lacking (diphtheria toxoid or acellular pertussis)	Inadequate
11	Meningococcal	Acute Disseminated Encephalomyeliris	Insufficient	Lacking	Inadequate

Page 709 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

4	MMR	Transverse Myelitis	Insufficient	Weak	Inadequate
5	Varicella	Transverse Myelitis	Insufficient	Weak	Inadequate
6	Influenza	Transverse Myelitis	Insufficient	Weak	Inadequate
	Hepatitis A	Transverse Myelitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Transverse Myelitis	Insufficient	Weak	Inadequate
9	HPV	Transverse Myelitis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Transverse Myelitis	Insufficient	Lacking	Inadequate
11	Meningococcal	Transverse Myelitis	Insufficient	Lacking	Inadequate
4	MMR	Optic Neuritis^d	Limited	Weak	Inadequate
6	Influenza	Optic Neuritis^d	Limited	Weak	Inadequate
8	Hepatitis B	Optic Neuritis^d	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Optic Neuritis^d	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
4	MMR	Neuromyelitis Optira^d	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
6	Influenza	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
8	Hepatitis B	Neuromyelitis Optica	Insufficient	Lacking	Inadequate

Page 710 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

9	HPV	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
4	MMR	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
6	Influenza	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Onset in Adults	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
4	MMR	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
6	Influenza	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Adults	Limited (tetanus toxoid) Insufficient (diphtheria toxoid or acellular pertussis)	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Children	Limited	Lacking	Inadequate

Page 711 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Children	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
7	Hepatitis A	Multiple Sclerosis	Insufficient	Lacking	Inadequate
9	HPV	Multiple Sclerosis	Insufficient	Lacking	Inadequate
11	Meningococcal	Multiple Sclerosis	Insufficient	Lacking	Inadequate
8	Hepatitis B	First Demy el ina ting Event in Adults	Moderate (null)	Low-Intermediate	Inadequate
8	Hepatitis B	First Demyelinating Event in Children	Limited	Lacking	Inadequate
4	MMR	Guillain-Barre syndrome	Insufficient	Weak	Inadequate
5	Varicella	Guillain-Barre syndrome	Insufficient	Weak	Inadequate
6	Influenza	Guillain-Barre syndrome	Moderate (null)	Weak	Inadequate
7	Hepatitis A	Insufficient	Weak	Inadequate
8	Hepatitis B	Guillain-Barre syndrome	Insufficient	Lacking	Inadequate
9	HPV	Guillain-Barre syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Guillain-Barre syndrome	Insufficient	Lacking	Inadequate
11	Meningococcal	Guillain-Barre syndrome	Limited	Lacking	Inadequate
4	MMR	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
6	Influenza	Chronic Inflammatory Disseminated	Insufficient	Weak	Inadequate

Page 712 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

7	Hepatitis A	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
8	Hepatitis B	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
9	HPV	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
11	Meningococcal	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
4	MMR	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate
7	Hepatitis A	Bell’s Palsy	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Bell’s Palsy	Limited (acellular pertussis) Insufficient (diphtheria toxoid or tetanus toxoid)	Weak (diphtheria toxoid or tetanus toxoid) Lacking (acellular pertussis)	Inadequate
4	MMR	Brachial Neuritis	Insufficient	Lacking	Inadequate
6	Influenza	Brachial Neuritis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Brachial Neuritis	Insufficient	Lacking	Inadequate

Page 713 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

9	HPV	Brachial Neuritis	Insufficient	Lacking	Inadequate
9	HPV	Amyotrophic Lateral Sclerosis	Insufficient	Lacking	Inadequate
5	Varicella	Small Fiber Neuropathy^d	Insufficient	Lacking	Inadequate
6	Influenza	Small Fiber Neuropathy	Insufficient	Lacking	Inadequate
7	Hepatitis A	Anaphylaxis	Insufficient	Weak	Inadequate
10	DT and aP containing	Anaphylaxis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Chronic Urticaria	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Serum Sickness	Insufficient	Weak (diphtheria toxoid or tetanus toxoid) Lacking (acellular pertussis)	Inadequate
6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Children Younger Than 5 Years of Age	Moderate (null)	Weak	Inadequate
6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Persons 5 Years of Age or Older	Moderate (null)	Weak	Inadequate
8	Hepatitis B	Erythema Nodosum^d	Insufficient	Weak	Inadequate

Page 714 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

6	Influenza	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (exacerbation) Insufficient (onset)	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (onset) Insufficient (exacerbation)	Weak	Inadequate
6	Influenza	Onset or Exacerbation of Vasculitis	Limited (exacerbation) Insufficient (onset)	Weak (exacerbation) Lacking (onset)	Inadequate
8	Hepatitis B	Onset or Exacerbation of Vasculitis	Insufficient	Low-Intermediate	Inadequate
6	Influenza	Polyarteritis Nodosa	Insufficient	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Polyarteritis Nodosa	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Psoriatic Arthritis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Reactive Arthritis	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset and Exacerbation of Rheumatoid Arthritis	Limited (exacerbation) Insufficient (onset)	Weak	Inadequate

Page 715 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

8	Hepatitis B	Onset or Exacerbation of Juvenile Idiopathic Arthritis	Insufficient	Weak	Inadequate
9	HPV	Transient Arthralgia	Limited	Lacking	Inadequate
4	MMR	Chronic Arthralgia in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Chronic Arthritis in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Chronic Arthropathy in Children	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Arthropathy in Men	Limited	Weak (rubella) Lacking (measles or mumps)	Inadequate
5	Varicella	Onset or Exacerbation Arthropathy	Insufficient	Lacking	Inadequate
6	Influenza	Onset or Exacerbation of Arthropathy	Insufficient	Weak	Inadequate

Page 716 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

10	DT, TT, or aP containing	Arthropathy	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (acellular pertussis)	Lacking	Inadequate
8	Hepatitis B	Type 1 Diabetes	Moderate (null)	Lacking	Inadequate
7	Hepatitis A	Autoimmune Hepatitis	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Myocarditis	Insufficient	Weak (diphtheria toxoid) Lacking (tetanus toxoid or acellular pertussis)	Inadequate
9	HPV	Pancreatitis	Insufficient	Lacking	Inadequate
4	MMR	Hepatitis	Insufficient	Weak	Inadequate
9	HPV	Thromboembolic Events	Insufficient	Lacking	Inadequate
5	Varicella	Stroke^d	Limited	Weak	Inadequate
6	Influenza	Stroke	Moderate (decrease)	Lacking	Inadequate
9	HPV	Hypercoagulable States	Insufficient	Lacking	Inadequate

Page 717 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

6	Influenza	Myocardial Infarction	Moderate (decrease)	Weak (Live Attenuated influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate
4	MMR	Chronic Fatigue Syndrome	Insufficient	Lacking	Inadequate
11	Meningococcal	Chronic Headache	Insufficient	Lacking	Inadequate
4	MMR	Fibromyalgia	Insufficient	Lacking	Inadequate
6	Influenza	Fibromyalgia	Insufficient	Lacking	Inadequate
8	Hepatitis B	Fibromyalgia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Fibromyalgia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Sudden Infant Death Syndrome	Insufficient	Lacking	Inadequate
4	MMR	Hearing Loss	Insufficient	Low-Intermediate (measles or mumps) Lacking (rubella)	Inadequate
6	Influenza	All-Cause Mortality^d	Moderate (decrease)	Weak (Live Attenuated Influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate

Page 718 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

5	Varicella	Thrombocytopenia	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Immune Thrombocytopenic Purpura	Insufficient	Lacking	Inadequate
12	Injection-Related Event	Complex Regional Pain Syndrome	Insufficient	Low-Intermediate	Inadequate

NOTE: The measles-mumps-rubella; human papillomavirus; and diphtheria toxoid–, tetanus toxoid-, and acellular pertussis-containing vaccines have been abbreviated in the following ways: MMR; HPV; and DT, TT, and aP containing.

^a The committee attributes causation to the measles component of the vaccine.

^b The committee attributes causation to the rubella component of the vaccine.

^a The committee attributes causation to two particular vaccines used in three particular years in Canada.

^a Although not originally charged to the committee by the sponsor, the committee considered this adverse event in its review of the literature.

Page 719 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

TABLE D-4 Causality Conclusions Organized by Epidemiologic Assessment, Adverse Event, and Chapter


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

4	MMR	Febrile Seizures	High (increase)	Intermediate	Convincingly Supports
4	MMR	Autism	High (null)	Lacking	Favors Rejection
6	Influenza	Inactivated Influenza Vaccine and Bell’s Palsy	High (null)	Lacking	Favors Rejection
6	Influenza	Inactivated Influenza Vaccine and Asthma Exacerbation or Reactive Airway Disease Episodes in Children and Adults	High (null)	Weak	Favors Rejection
4	MMR	Type 1 Diabetes	High (null)	Lacking	Favors Rejection
10	DT, TT, or aP containing	Type 1 Diabetes	High (null)	Lacking	Favors Rejection
4	MMR	Transient Arthralgia in Women	Moderate (increase) (rubella) Insufficient (measles or mumps)	Intermediate (rubella) Lacking (measles or mumps)	Favors Acceptance^a
4	MMR	Transient Arthralgia in Children	Moderate (increase)	Weak (rubella) Lacking (measles or mumps)	Favors Acceptance
6	Influenza	Oculorespiratory Syndrome	Moderate (increase)^b	Intermediate^b	Favors Acceptance^b
6	Influenza	Seizures^c	Moderate (null)	Lacking	Inadequate

Page 720 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

4	MMR	Meningitis^c	Moderate (null)	Weak (mumps) Lacking (measles or rubella)	Inadequate
8	Hepatitis B	First Dcmyclinating Event in Adults	Moderate (null)	Low-Intermediate	Inadequate
6	Influenza	Guillain-Barrc syndrome	Moderate (null)	Weak	Inadequate
6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Children Younger Than 5 Years of Age	Moderate (null)	Weak	Inadequate
6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Persons 5 Years of Age or Older	Moderate (null)	Weak	Inadequate
8	Hepatitis B	Type 1 Diabetes	Moderate (null)	Lacking	Inadequate
6	Influenza	Stroke	Moderate (decrease)	Lacking	Inadequate
6	Influenza	Myocardial Infarction	Moderate (decrease)	Weak (Live Attenuated Influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate

Page 721 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

6	Influenza	All-Cause Mortality^c	Moderate (decrease)	Weak (Live Attenuated Influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate
5	Varicella	Disseminated Oka VZV with Subsequent Infection Resulting in Pneumonia, Meningitis, or Hepatitis	Limited (subsequent infection resulting in pneumonia) Insufficient (subsequent infection resulting in meningitis or hepatitis)	Strong (in individuals with demonstrated immunodeficiencies)	Convincingly Supports (in individuals with demonstrated immunodeficiencies)
5	Varicella	Vaccine Strain Viral Reactivation with Subsequent Infection Resulting in Meningitis or Encephalitis	Limited (subsequent infection resulting in encephalitis) Insufficient (subsequent infection resulting in meningitis)	Strong	Convincingly Supports
4	MMR	Encephalitis	Limited	Weak	Inadequate
10	DT, TT, or aP containing	Encephalitis	Limited	Weak	Inadequate
11	Meningococcal	Encephalitis	Limited	Lacking	Inadequate
4	MMR	Encephalopathy	Limited	Weak	Inadequate
10	DT, TT, or aP containing	Encephalopathy	Limited	Weak	Inadequate

Page 722 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

11	Meningococcal	Encephalopathy	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Infantile Spasms	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate
4	MMR	Afebrile Seizures	Limited	Lacking	Inadequate
5	Varicella	Seizures	Limited	Weak	Inadequate
8	Hepatitis B	Seizures	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Seizures	Limited	Weak (accllular pertussis) Lacking (diphtheria toxoid or tetanus toxoid)	Inadequate
4	MMR	Optic Neuritis^c	Limited	Weak	Inadequate
6	Influenza	Optic Neuritis^c	Limited	Weak	Inadequate
8	Hepatitis B	Optic Neuritis^c	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Optic Neuritis^c	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate

Page 723 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

4	MMR	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
6	Influenza	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Onset in Adults	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate
4	MMR	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
6	Influenza	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Adults	Limited (tetanus toxoid) Insufficient (diphtheria toxoid or accllular pertussis)	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Children	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Children	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate
8	Hepatitis B	First Dcmyclinating Event in Children	Limited	Lacking	Inadequate

Page 724 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

11	Meningococcal	Guillain-Barrc syndrome	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Bell’s Palsy	Limited (accllular pertussis) Insufficient (diphtheria toxoid or tetanus toxoid)	Weak (diphtheria toxoid or tetanus toxoid) Lacking (accllular pertussis)	Inadequate
5	Varicella	Anaphylaxis	Limited	Strong	Convincingly Supports
6	Influenza	Anaphylaxis	Limited	Strong	Convincingly Supports
6	Influenza	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (exacerbation) Insufficient (onset)	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (onset) Insufficient (exacerbation)	Weak	Inadequate
6	Influenza	Onset or Exacerbation of Vasculitis	Limited (exacerbation) Insufficient (onset)	Weak (exacerbation) Lacking (onset)	Inadequate

Page 725 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

8	Hepatitis B	Onset and Exacerbation of Rheumatoid Arthritis	llll	Weak	Inadequate
9	HPV	Transient Arthralgia	Limited	Lacking	Inadequate
4	MMR	Chronic Arthralgia in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Chronic Arthritis in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Arthropathy in Men	Limited	Weak (rubella) Lacking (measles or mumps)	Inadequate
10	DT, TT, or aP containing	Arthropathy	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate
5	Varicella	Stroke^c	Limited	Weak	Inadequate
12	1 njection- Related Event	Deltoid Bursitis	Limited	Strong	Convincingly Supports

Page 726 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

5	Varicella	Disseminated Oka VZV without Other Organ Involvement	Insufficient	Strong	Convincingly Supports
5	Varicella	Vaccine Strain Viral Reactivation without Other Organ Involvement	Insufficient	Strong	Convincingly Supports
4	MMR	Measles Inclusion Body Encephalitis	Insufficient	Strong(measles; in with demon immunodef Lacking)	Convincingly Supports^d
6	Influenza	Encephalitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Encephalitis	Insufficient	Lacking	Inadequate
5	Varicella	Encephalopathy	Insufficient	Lacking	Inadequate
6	Influenza	Encephalopathy	Insufficient	Weak	Inadequate
8	Hepatitis B	Encephalopathy	Insufficient	Lacking	Inadequate
5	Varicella	Cerebellar Ataxia	Insufficient	Weak	Inadequate
4	MMR	Ataxia	Insufficient	Weak (measles or i Lacking (rubella)	Inadequate
10	DT, TT, or aP containing	Ataxia	Insufficient	Lacking	Inadequate

Page 727 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

10	DT, TT, or aP containing	Autism	Insufficient	Lacking	Inadequate
4	MMR	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
5	Varicella	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
6	Influenza	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
7	Hepatitis A	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Acute Disseminated Encephalomyelitis	Insufficient	Low-Intermediate	Inadequate
9	HPV	Acute Disseminated Encephalomyelitis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Acute Disseminated Encephalomyelitis	Insufficient	Weak (tetanus toxoid) Lacking (diphtheria toxoid or acellular pertussis)	Inadequate
11	Meningococcal	Acute Disseminated Encephalomyelitis	Insufficient	Lacking	Inadequate
4	MMR	Transverse Myelitis	Insufficient	Weak	Inadequate
5	Varicella	Transverse Myelitis	Insufficient	Weak	Inadequate
6	Influenza	Transverse Myelitis	Insufficient	Weak	Inadequate

Page 728 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

7	Hepatitis A	Transverse Myelitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Transverse Myelitis	Insufficient	Weak	Inadequate
9	HPV	Transverse Myelitis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Transverse Myelitis	Insufficient	Lacking	Inadequate
11	Meningococcal	Transverse Myelitis	Insufficient	Lacking	Inadequate
4	MMR	Neuromyelitis Optica^c	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
6	Influenza	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
8	Hepatitis B	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
9	HPV	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
	Hepatitis A	Multiple Sclerosis	Insufficient	Lacking	Inadequate
9	HPV	Multiple Sclerosis	Insufficient	Lacking	Inadequate
11	Meningococcal	Multiple Sclerosis	Insufficient	Lacking	Inadequate
4	MMR	Guillain-Barrc syndrome	Insufficient	Weak	Inadequate
5	Varicella	Guillain-Barrc syndrome	Insufficient	Weak	Inadequate
7	Hepatitis A	Guillain-Barrc syndrome	Insufficient	Weak	Inadequate
8	Hepatitis B	Guillain-Barrc syndrome	Insufficient	Lacking	Inadequate

Page 729 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

9	HPV	Guillain-Barrc syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Guillain-Barrc syndrome	Insufficient	Lacking	Inadequate
4	MMR	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
6	Influenza	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Weak	Inadequate
	Hepatitis A	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
8	Hepatitis B	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
9	HPV	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
11	Meningococcal	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
4	MMR	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate
/	Hepatitis A	Bell's Palsy	Insufficient	Lacking	Inadequate
4	MMR	Brachial Neuritis	Insufficient	Lacking	Inadequate
6	Influenza	Brachial Neuritis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Brachial Neuritis	Insufficient	Lacking	Inadequate

Page 730 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

9	HPV	Brachial Neuritis	Insufficient	Lacking	Inadequate
9	HPV	Amyotrophic Lateral Sclerosis	Insufficient	Lacking	Inadequate
5	Varicella	Small Fiber Ncuropathy^c	Insufficient	Lacking	Inadequate
6	Influenza	Small Fiber Neuropathy	Insufficient	Lacking	Inadequate
4	MMR	Anaphylaxis	Insufficient	Strong	Convincingly Supports
7	Hepatitis A	Anaphylaxis	Insufficient	Weak	Inadequate
8	Hepatitis B	Anaphylaxis	Insufficient	Strong (in yeast-sensitive individuals)	Convincingly Supports (in yeast-sensitive individuals)
9	HPV	Anaphylaxis	Insufficient	Intermediate	Favors Acceptance
10	TT containing	Anaphylaxis	Insufficient	Strong	Convincingly Supports
10	DT and aP containing	Anaphylaxis	Insufficient	Lacking	Inadequate
11	Meningococcal	Anaphylaxis	Insufficient	Strong	Convincingly Supports
10	DT, TT, or aP containing	Chronic Urticaria	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Scrum Sickness	Insufficient	Weak (diphtheria toxoid or tetanus toxoid) Lacking (accllular pertussis)	Inadequate

Page 731 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

8	Hepatitis B	Erythema Nodosum^c	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Vasculitis	Insufficient	Low-Intermediate	Inadequate
6	Influenza	Polyarteritis Nodosa	Insufficient	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Polyarteritis Nodosa	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Psoriatic Arthritis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Reactive Arthritis	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Juvenile Idiopathic Arthritis	Insufficient	Weak	Inadequate
4	MMR	Chronic Arthropathy in Children	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
5	Varicella	Onset or Exacerbation Arthropathy	Insufficient	Lacking	Inadequate
6	Influenza	Onset or Exacerbation of Arthropathy	Insufficient	Weak	Inadequate
7	Hepatitis A	Autoimmune Hepatitis	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Myocarditis	Insufficient	Weak (diphtheria toxoid) Lacking (tetanus toxoid or accllular pertussis)	Inadequate

Page 732 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

9	HPV	Pancreatitis	Insufficient	Lacking	Inadequate
4	MMR	Hepatitis	Insufficient	Weak	Inadequate
9	HPV	Thromboembolic Events	Insufficient	Lacking	Inadequate
9	HPV	Hypcrcoagulablc States	Insufficient	Lacking	Inadequate
4	MMR	Chronic Fatigue Syndrome	Insufficient	Lacking	Inadequate
11	Meningococcal	Chronic Headache	Insufficient	Lacking	Inadequate
4	MMR	Fibromyalgia	Insufficient	Lacking	Inadequate
6	Influenza	Fibromyalgia	Insufficient	Lacking	Inadequate
8	Hepatitis B	Fibromyalgia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Fibromyalgia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Sudden Infant Death Syndrome	Insufficient	Lacking	Inadequate
4	MMR	Hearing Loss	Insufficient	Low-Intermediate (measles or mumps) Lacking (rubella)	Inadequate
5	Varicella	Thrombocytopenia	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Immune Thrombocytopenic Purpura	Insufficient	Lacking	Inadequate

Page 733 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

12	Injcction- Related Event	Complex Regional Pain Syndrome	Insufficient	Low-Intermediate	Inadequate
12	Injcction- Related Event	Syncope	Insufficient	Strong	Convincingly Supports

NOTE: The measles-mumps-rubella; human papillomavirus; and diphtheria toxoid–, tetanus toxoid-, and acellular pertussis-containing vaccines have been abbreviated in the following ways: MMR; HPV; and DT, TT, and aP containing.

^aThe committee attributes causation to the rubella component of the vaccine.

^bThe committee attributes causation to two particular vaccines used in three particular years in Canada.

^cAlthough not originally charged to the committee by the sponsor, the committee considered this adverse event in its review of the literature.

^dThe committee attributes causation to the measles component of the vaccine.

Page 734 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

TABLE D-5 Causality Conclusions Organized by Mechanistic Assessment, Adverse Event, and Chapter


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

5	Varicella	Disseminated Oka VZV without Other Organ Involvement	Insufficient	Strong	Convincingly Supports
5	Varicella	Disseminated Oka VZV with Subsequent Infection Resulting in Pneumonia, Meningitis, or Hepatitis	Limited (subsequent infection resulting in pneumonia)	Strong (in individuals with demonstrated immunodeficiencies)	Convincingly Supports (in individuals with demonstrated immunodeficiencies)
5	Varicella	Vaccine Strain Viral Reactivation without Other Organ Involvement	Insufficient	Strong	Convincingly Supports
5	Varicella	Vaccine Strain Viral Reactivation with Subsequent Infection resulting in Meningitis or Encephalitis	Limited (subsequent infection resulting in encephalitis) Insufficient (subsequent infection resulting in meningitis)	Strong	Convincingly Supports
4	MMR	Measles Inclusion Body Encephalitis	Insufficient	Strong (measles; in individuals with demonstrated immunodeficiencies) Lacking (mumps or rubella)	Convincingly Supports^a (in individuals with demonstrated immunodeficiencies)
4	MMR	Anaphylaxis	Insufficient	Strong	Convincingly Supports

Page 735 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

5	Varicella	Anaphylaxis	Limited	Strong	Convincingly Supports
6	Influenza	Anaphylaxis	Limited	Strong	Convincingly Supports
8	Hepatitis B	Anaphylaxis	Insufficient	Strong (in yeast-sensitive individuals)	Convincingly Supports (in yeast-sensitive individuals)
10	TT containing	Anaphylaxis	Insufficient	Strong	Convincingly Supports
11	Meningococcal	Anaphylaxis	Insufficient	Strong	Convincingly Supports
12	Injection- Related Event	Deltoid Bursitis	Limited	Strong	Convincingly Supports
12	Injection- Related Event	Syncope	Insufficient	Strong	Convincingly Supports
4	MMR	Febrile Seizures	High (increase)	Intermediate	Convincingly Supports
9	HPV	Anaphylaxis	Insufficient	Intermediate	Favors Acceptance^b
4	MMR	Transient Arthralgia	Moderate (increase) (rubella) Insufficient (measles or mumps)	Intermediate (rubella) Lacking (measles or mumps)	Favors Acceptance^c
6	Influenza	Oculorespiratory Syndrome	Moderate (increase)	Intermediate	Favors Acceptance'
8	Hepatitis B	Acute Disseminated	Encephalomyelitis	Low-Intermediate	Inadequate
8	Hepatitis B	First Dcmyclinating	Event in Adults	Low-Intermediate	Inadequate
8	Hepatitis B	Onset or Exacerbation of Vasculitis	Insufficient	Low-Intermediate	Inadequate

Page 736 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

4	MMR	Chronic Arthralgia in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	phronic Arthritis in Women	Limited (rubella) Insufficient (measles or mumps)	Low-Intermediate (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Hearing Loss	Insufficient	Low-Intermediate (measles or mumps) Lacking (rubella)	Inadequate
12	Injection- Related Event	Complex Regional Pain Syndrome	Insufficient	Low-Intermediate	Inadequate
4	MMR	Encephalitis	Limited	Weak	Inadequate
6	Influenza	Encephalitis	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Encephalitis	Limited	Weak	Inadequate
4	MMR	Encephalopathy	Limited	Weak	Inadequate
6	Influenza	Encephalopathy	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Encephalopathy	Limited	Weak	Inadequate

Page 737 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

5	Varicella	Seizures	Limited	Weak	Inadequate
10	DT, TT, or aP containing	Seizures	Limited	Weak (accllular pertussis) Lacking (diphtheria toxoid or tetanus toxoid)	Inadequate
4	MMR	Meningitis^d	Moderate (null)	Weak (mumps) Lacking (measles or rubella)	Inadequate
5	Varicella	Cerebellar Ataxia	Insufficient	Weak	Inadequate
4	MMR	Ataxia	Insufficient	Weak (measles or mumps) Lacking (rubella)	Inadequate
4	MMR	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
5	Varicella	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
6	Influenza	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
7	Hepatitis A	Acute Disseminated Encephalomyelitis	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Acute Disseminated Encephalomyelitis	Insufficient	Weak (tetanus toxoid) Lacking (diphtheria toxoid or accllular pertussis)	Inadequate

Page 738 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

4	MMR	Transverse Myelitis	Insufficient	Weak	Inadequate
5	Varicella	Transverse Myelitis	Insufficient	Weak	Inadequate
6	Influenza	Transverse Myelitis	Insufficient	Weak	Inadequate
7	Hepatitis A	Transverse Myelitis	Insufficient	Weak	Inadequate
8	Hepatitis B	Transverse Myelitis	Insufficient	Weak	Inadequate
4	MMR	Optic Neuritis1^d	Limited	Weak	Inadequate
6	Influenza	Optic Neuritis^d	Limited	Weak	Inadequate
4	MMR	Neuromyelitis Optica^d	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Guillain-Barrc syndrome	Insufficient	Weak	Inadequate
5	Varicella	Guillain-Barrc syndrome	Insufficient	Weak	Inadequate
6	Influenza	Guillain-Barrc syndrome	Moderate (null)	Weak	Inadequate
7	Hepatitis A	Guillain-Barrc syndrome	Insufficient	Weak	Inadequate
6	Influenza	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Weak	Inadequate

Page 739 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

10	DT, TT, or aP containing	Bell’s Palsy	Limited (accllular pertussis) Insufficient (diphtheria toxoid or tetanus toxoid)	Weak (diphtheria toxoid or tetanus toxoid) Lacking (accllular pertussis)	Inadequate
7	Hepatitis A	Anaphylaxis	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Scrum Sickness	Insufficient	Weak (diphtheria toxoid or tetanus toxoid) Lacking (accllular pertussis)	Inadequate
6	Influenza	Inactivated Influenza Vaccine and Asthma Exacerbation or Reactive Airway Disease Episodes in Children and Adults	High (null)	Weak	Favors Rejection
6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Children Younger Than 5 Years of Age	Moderate (null)	Weak		Inadequate
6	Influenza	Live Attenuated Influenza Vaccine or Asthma Exacerbation or Reactive Airway Disease Episodes in Persons 5 Years of Age or Older	Moderate (null)	Weak	Inadequate
8	Hepatitis B	Erythema Nodosum^d	Insufficient	Weak	Inadequate

Page 740 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

8	Hepatitis B	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (onset) Insufficient (exacerbation)	Weak	Inadequate
6	Influenza	Onset or Exacerbation of Vasculitis	Limited (exacerbation) Insufficient (onset)	Weak (exacerbation) Lacking (onset)	Inadequate
8	Hepatitis B	Onset or Exacerbation of Polyarteritis Nodosa	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Reactive Arthritis	Insufficient	Weak	Inadequate
8	Hepatitis B	Onset and Exacerbation of Rheumatoid Arthritis	Limited (exacerbation) Insufficient (onset)	Weak	Inadequate
8	Hepatitis B	Onset or Exacerbation of Juvenile Idiopathic Arthritis	Insufficient	Weak	Inadequate
4	MMR	Transient Arthralgia in Children	Moderate (increase)	Weak (rubella) Lacking (measles or mumps)	Favors Acceptance

Page 741 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

4	MMR	Chronic Arthropathy in Children	Insufficient	Weak (rubella) Lacking (measles or mumps)	Inadequate
4	MMR	Arthropathy in Men	Limited	Weak (rubella) Lacking (measles or mumps)	Inadequate
6	Influenza	Onset or Exacerbation of Arthropathy	Insufficient	Weak	Inadequate
7	Hepatitis A	Autoimmune Hepatitis	Insufficient	Weak	Inadequate
10	DT, TT, or aP containing	Myocarditis	Insufficient	Weak (diphtheria toxoid) Lacking (tetanus toxoid or acellular pertussis)	Inadequate
4	MMR	Hepatitis	Insufficient	Weak	Inadequate
5	Varicella	Stroke^d	Limited	Weak	Inadequate
6	Influenza	Myocardial Infarction	Moderate (decrease)	Weak (Live Attenuated Influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate

Page 742 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

6	Influenza	All-Cause Mortality^d	Moderate (decrease)	Weak (Live Attenuated Influenza Vaccine) Lacking (Inactivated Influenza Vaccine)	Inadequate
5	Varicella	Thrombocytopenia	Insufficient	Weak	Inadequate
8	Hepatitis B	Encephalitis	Insufficient	Lacking	Inadequate
11	Meningococcal	Encephalitis	Limited	Lacking	Inadequate
5	Varicella	Encephalopathy	Insufficient	Lacking	Inadequate
8	Hepatitis B	Encephalopathy	Insufficient	Lacking	Inadequate
11	Meningococcal	Encephalopathy	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Infantile Spasms	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate
4	MMR	Afebrile Seizures	Limited	Lacking	Inadequate
6	Influenza	Seizures^d	Moderate (null)	Lacking	Inadequate
8	Hepatitis B	Seizures	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Ataxia	Insufficient	Lacking	Inadequate

Page 743 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

4	MMR	Autism	High (null)	Lacking	Favors Rejection
10	DT, TT, or aP containing	Autism	Insufficient	Lacking	Inadequate
9	HPV	Acute Disseminated Encephalomyelitis	Insufficient	Lacking	Inadequate
11	Meningococcal	Acute Disseminated Encephalomyelitis	Insufficient	Lacking	Inadequate
9	HPV	Transverse Myelitis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Transverse Myelitis	Insufficient	Lacking	Inadequate
11	Meningococcal	Transverse Myelitis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Optic Neuritis^d	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Optic Neuritis^d	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate
6	Influenza	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
8	Hepatitis B	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
9	HPV	Neuromyelitis Optica	Insufficient	Lacking	Inadequate
4	MMR	Multiple Sclerosis Onset in Adults	Lacking	Limited	Inadequate
6	Influenza	Multiple Sclerosis Onset in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Adults	Lacking	Limited	Lacking

Page 744 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

10	DT, TT, or aP containing	Multiple Sclerosis Onset in Adults	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate
4	MMR	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Onset in Children	Limited	Lacking	Inadequate
6	Influenza	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Adults	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Adults	Limited (tetanus toxoid) Insufficient (diphtheria toxoid or accllular pertussis)	Lacking	Inadequate
8	Hepatitis B	Multiple Sclerosis Relapse in Children	Limited	Lacking	Inadequate
10	DT, TT, or aP containing	Multiple Sclerosis Relapse in Children	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate
7	Hepatitis A	Multiple Sclerosis	Insufficient	Lacking	Inadequate
9	HPV	Multiple Sclerosis	Insufficient	Lacking	Inadequate

Page 745 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

11	Meningococcal	Multiple Sclerosis	Insufficient	Lacking	Inadequate
8	Hepatitis B	First Dcmyclinating Event in Children	Limited	Lacking	Inadequate
8	Hepatitis B	Guillain-Barrc syndrome	Insufficient	Lacking	Inadequate
9	HPV	Guillain-Barrc syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Guillain-Barrc syndrome	Insufficient	Lacking	Inadequate
11	Meningococcal	Guillain-Barrc syndrome	Limited	Lacking	Inadequate
4	MMR	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
7	Hepatitis A	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
8	Hepatitis B	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
9	HPV	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
11	Meningococcal	Chronic Inflammatory Disseminated Polyneuropathy	Insufficient	Lacking	Inadequate
4	MMR	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Opsoclonus Myoclonus Syndrome	Insufficient	Lacking	Inadequate
6	Influenza	Inactivated Influenza Vaccine and Bell’s Palsy	High (null)	Lacking	Favors Rejection

Page 746 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

7	Hepatitis A	Bell’s Palsy	Insufficient	Lacking	Inadequate
4	MMR	Brachial Neuritis	Insufficient	Lacking	Inadequate
6	Influenza	Brachial Neuritis	Insufficient	Lacking	Inadequate
8	Hepatitis B	Brachial Neuritis	Insufficient	Lacking	Inadequate
9	HPV	Brachial Neuritis	Insufficient	Lacking	Inadequate
9	HPV	Amyotrophic Lateral Sclerosis	Insufficient	Lacking	Inadequate
5	Varicella	Small Fiber Neuropathy^d	Insufficient	Lacking	Inadequate
6	Influenza	Small Fiber Neuropathy	Insufficient	Lacking	Inadequate
10	DT and aP containing	Anaphylaxis	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Chronic Urticaria	Insufficient	Lacking	Inadequate
6	Influenza	Onset or Exacerbation of Systemic Lupus Erythematosus	Limited (exacerbation) Insufficient (onset)	Lacking	Inadequate
6	Influenza	Polyarteritis Nodosa	Insufficient	Lacking	Inadequate
8	Hepatitis B	Onset or Exacerbation of Psoriatic Arthritis	Insufficient	Lacking	Inadequate
9	HPV	Transient Arthralgia	Limited	Lacking	Inadequate
5	Varicella	Onset or Exacerbation Arthropathy	Insufficient	Lacking	Inadequate

Page 747 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.

l0	DT, TT, or aP containing	Arthropathy	Limited (diphtheria toxoid or tetanus toxoid) Insufficient (accllular pertussis)	Lacking	Inadequate
4	MMR	Type 1 Diabetes	High (null)	Lacking	Favors Rejection
8	Hepatitis B	Type 1 Diabetes	Moderate (null)	Lacking	Inadequate
10	DT, TT, or aP containing	Type 1 Diabetes	High (null)	Lacking	Favors Rejection
9	HPV	Pancreatitis	Insufficient	Lacking	Inadequate
9	HPV	Thromboembolic Events	Insufficient	Lacking	Inadequate
6	Influenza	Stroke	Moderate (decrease)	Lacking	Inadequate
9	HPV	Hypcrcoagulablc States	Insufficient	Lacking	Inadequate
4	MMR	Chronic Fatigue Syndrome	Insufficient	Lacking	Inadequate
11	Meningococcal	Chronic Headache	Insufficient	Lacking	Inadequate
4	MMR	Fibromyalgia	Insufficient	Lacking	Inadequate
6	Influenza	Fibromyalgia	Insufficient	Lacking	Inadequate
8	Hepatitis B	Fibromyalgia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Fibromyalgia	Insufficient	Lacking	Inadequate
10	DT, TT, or aP containing	Sudden Infant Death Syndrome	Insufficient	Lacking	Inadequate

Page 748 Cite Bookmark

Suggested Citation: "Appendix D: Causality Conclusion Tables." Institute of Medicine. 2012. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press. doi: 10.17226/13164.


Chapter	Vaccine	Adverse Event	Epidemiologic Assessment	Mechanistic Assessment	Causality Conclusion

10	DT, TT, or aP containing	Immune Thrombocytopenic Purpura	Insufficient	Lacking	Inadequate

NOTE: The measles-mumps-rubella; human papillomavirus; and diphtheria toxoid–, tetanus toxoid-, and acellular pertussis-containing vaccines have been abbreviated in the following ways: MMR; HPV; and DT, TT, and aP containing.

^aThe committee attributes causation to the measles component of the vaccine.

^bThe committee attributes causation to the rubella component of the vaccine.

^cThe committee attributes causation to two particular vaccines used in three particular years in Canada.

^dAlthough not originally charged to the committee by the sponsor, the committee considered this adverse event in its review of the literature.