Potential Adverse Events Following Immunization

The Vaccine Safety pages address the numerous potential adverse events that have been studied in order to determine if an association exists with routine immunization in the United States, and supplements the vaccine information summaries for those seeking more information about a specific adverse event.

The independent 2012 report by the Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), entitled Adverse Effects of Vaccines: Evidence and Causality [1] was relied upon heavily to compile both the list of adverse events and the sources providing the best evidence for each adverse event. The 2014 report by the Agency for Healthcare Research and Quality (AHRQ) entitled Safety of Vaccines Used for Routine Immunization in the United States: Evidence Report/Technology Assessment No. 215 [2] was used to update and supplement the IOM report, as well as our own systematic literature searches and general knowledge. The aforementioned AHRQ report was summarized in a review article in the journal Pediatrics [3].

In order to consistently and succinctly characterize the frequency of adverse events in this section, definitions used by the World Health Organization are used here, as outlined in the table below.

Standard categories of frequency for adverse drug reactions

provided by "Guidelines for Preparing Core Clinical-Safety Information on Drugs" - Report of CIOMS Working Group III (1995)

Category

Definition

Very common
Common
Uncommon
Rare
Very rare

≥ 1/10 (≥ 10%)
≥ 1/100 and < 1/10 (~1%-10%)
≥ 1/1,000 and < 1/100 (~0.1-1%)
≥ 1/10,000 and < 1/1,000 (~0.01-0.1%)
< 1/10,000 (< 0.01%)

In order to summarize the evidence regarding potential adverse events in an accurate, concise, practical and standardized manner, the authors established the categories of causality conclusions outlined the table below.

Categories of causality conclusions*

Category

Definition

Vaccines can cause the event.

The evidence shows a clear association between the event and at least one vaccine routinely recommended in the U.S.

Vaccines did cause the event.

The evidence showed a clear association between the event and at least one previously recommended vaccine. However, these vaccine(s) are no longer used in the U.S., if they ever were.

Vaccines have not been shown to cause the event.

The evidence of an association between the event and vaccines currently routinely recommended to the general population in the United States is insufficient or non-existent.

Vaccines do not cause the event.

The evidence shows clear lack of association between the event and vaccines currently routinely recommended to the general population in the United States.

*These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel).

The summaries of potential adverse events have been organized by the conclusions drawn in the tables below for convenience purposes. For the vast majority of these potential adverse events, there are no studies of quality that show an association with routine immunization in the United States.

SPECIAL TOPICS OF INTEREST RELATED TO
VACCINES CURRENTLY ROUTINELY RECOMMENDED TO THE GENERAL POPULATION IN THE UNITED STATES*

Topic

Conclusion

Combination Vaccines or Simultaneous Vaccination MMRV can rarely cause febrile seizures in infants and young children, at slightly higher rates than individual administration of MMR and varicella vaccines. Simultaneous administration of influenza and pneumococcal conjugate vaccines can rarely cause febrile seizures in infants and young children, at slightly higher rates than separate administration of these vaccines. No other adverse events have been shown to be caused by combination vaccines or simultaneous vaccination as compared to separate administration of available individual vaccine components.
Vaccine Ingredients Certain ingredients found in some vaccines, such as gelatin or neomycin, can very rarely cause severe hypersensitivity reactions (e.g. anaphylaxis) in those who are allergic to these specific ingredients.
   

CAUSAL RELATIONSHIP ESTABLISHED WITH
VACCINES CURRENTLY ROUTINELY RECOMMENDED TO THE GENERAL POPULATION IN THE UNITED STATES*

Adverse Event

Conclusion

Anaphylaxis Vaccine components can very rarely cause.
Deltoid Bursitis Incorrect administration of vaccine can cause.
Disseminated Varicella Infection Varicella vaccine can rarely cause in immune deficient individuals for whom the vaccine is contraindicated.
Encephalitis Measles vaccine can very rarely cause. Mumps vaccine used in other countries did cause (but not the vaccine licensed in the U.S.).
Febrile Seizures Vaccines that induce fever in infants and young children, such as MMRV, influenza, and PCV vaccines, can rarely cause.
Guillain-Barré Syndrome (GBS) Influenza vaccine can cause very rarely in adults. An old formulation of rabies vaccine did cause (but is no longer available). Other vaccines, including current rabies vaccine, have not been shown to cause.
Hepatitis Varicella vaccine can rarely cause if administered to persons with certain immune deficiencies. Vaccines given to immunocompetent persons do not cause.
Immune Thrombocytopenic Purpura (ITP) MMR vaccine can very rarely cause in children.
Meningitis Reactivation of varicella vaccine can very rarely cause. Mumps vaccine used in other countries did cause (but not the vaccine licensed in the U.S.).
Syncope Vaccines (and other injections) can rarely cause.
Vaccine-Strain Viral Reactivation Varicella vaccine can rarely cause.
   

NO CAUSAL RELATIONSHIP ESTABLISHED WITH
VACCINES CURRENTLY ROUTINELY RECOMMENDED TO THE GENERAL POPULATION IN THE UNITED STATES*

Adverse Event

Conclusion

Acute Disseminated Encephalomyelitis An old formulation of rabies vaccine did cause (but is no longer available). Other vaccines, including current rabies vaccine, have not been shown to cause.
Arthralgia/Arthritis (chronic) Vaccines have not been shown to cause.
Asthma Vaccines do not cause.
Ataxia Vaccines have not been shown to cause.
Autism Vaccines do not cause.
Bell’s Palsy One influenza vaccine used in other countries did cause (but is no longer available). U.S. vaccines have not been shown to cause.
Brachial Neuritis Vaccines have not been shown to cause.
Chronic Fatigue Syndrome Vaccines have not been shown to cause.
Chronic Inflammatory Disseminated Polyneuropathy Vaccines have not been shown to cause.
Chronic Urticaria Vaccines have not been shown to cause.
Complex Regional Pain Syndrome  Vaccines have not been shown to cause.
Epilepsy Vaccines have not been shown to cause.
Erythema Nodosum Vaccines have not been shown to cause.
Fibromyalgia Vaccines have not been shown to cause.
Hearing Loss Vaccines have not been shown to cause.
Infantile Spasms Vaccines have not been shown to cause.
Multiple Sclerosis Influenza vaccine does not cause in adults. Influenza vaccine has not been shown to cause in children. Other vaccines have not been shown to cause.
Myocardial Infarction Vaccines have not been shown to cause.
Myocarditis Smallpox vaccine can very rarely cause, but is not routinely recommended to the general population in the U.S. Other vaccines have not been shown to cause.
Narcolepsy Current vaccines have not been shown to cause. AS03-adjuvanted 2009 pandemic H1N1 influenza vaccine used in Europe did very rarely cause (but was not used in the U.S. and is no longer recommended in children).
Neuromyelitis Optica Vaccines have not been shown to cause.
Oculorespiratory syndrome (ORS) Two influenza vaccines used in Canada did cause. U.S. vaccines have not been shown to cause.
Opsoclonus Myoclonus Syndrome Vaccines have not been shown to cause.
Optic Neuritis Vaccines have not been shown to cause.
Polyarteritis Nodosa Vaccines have not been shown to cause.
Primary Ovarian Failure Vaccines have not been shown to cause.
Transverse Myelitis Vaccines have not been shown to cause.
Type 1 diabetes Vaccines do not cause.
Serum Sickness Vaccines have not been shown to cause.
Small Fiber Neuropathy Vaccines have not been shown to cause.
Stroke Vaccines have not been shown to cause.
Sudden Infant Death Syndrome Vaccines have not been shown to cause.
Systemic Lupus Erythematosus Vaccines have not been shown to cause.
Vasculitis Vaccines have not been shown to cause.

References

1. Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.
2. Maglione MA GC, Das L, Raaen L, Smith A, Chari R, Newberry S, Hempel S, Shanman R, Perry T, Goetz MB. Safety of Vaccines Used for Routine Immunization in the United States. Evidence Report/Technology Assessment No. 215. Rockville, MD: Agency for Healthcare Research and Quality; 2014 July 2014.
3. Maglione MA, Das L, Raaen L, et al. Safety of vaccines used for routine immunization of U.S. children: a systematic review. Pediatrics 2014;134:325-37.