Can Smallpox and Monkeypox Vaccine Cause Injury and Death?

Updated November 12, 2022


The Institute of Medicine (IOM) has acknowledged that there is individual susceptibility to vaccine reactions for genetic, biological and environmental reasons, but that vaccine providers cannot accurately predict prior to the administration of a vaccine who will suffer from vaccine complications, injury or death. However, a person who has previously had a serious reaction to a vaccination or is acutely or chronically ill should become informed about all potential risks associated with vaccination and discuss any concerns with a trusted health care professional before receiving a smallpox vaccine or any other vaccine. Individuals with a personal or familial history of a vaccine reaction or who have a history of neurological or immune system dysfunction may be at an increased risk of a vaccine reaction, injury or even death.1

Dryvax, a live smallpox (vaccinia) virus vaccine manufactured by Wyeth Laboratories, was used for decades in the U.S., when smallpox vaccination was routine. Health officials recognized that Dryvax was not a safe vaccine, and reactions occurred frequently following vaccination.2

Mild reactions following vaccination included fever, muscle aches, inflammation of the lymph nodes, nausea, fatigue, headache, rashes, soreness at the vaccination site and formation of satellite lesions. Approximately one-third of vaccine recipients missed work or school following vaccination.3  

One of the most common adverse reactions following Dryvax was inadvertent vaccination. This occurred when a vaccine recipient transferred the virus from the injection site to another part of the body, usually the nose, mouth, eyes, or genitalia.4  Treatment with for this reaction with vaccinia immune globulin (VIG) was not usually necessary unless lesions persisted.5

Serious adverse reactions that occurred following vaccination included progressive vaccinia, eczema vaccinatum, postvaccinial encephalitis, generalized vaccinia, and death.6   

Progressive vaccinia, also known as vaccinia gangrenosum or vaccinia necrosum, was a serious condition that involved the uncontrolled replication of the vaccine’s virus at the injection site which led to tissue death at and around the vaccination site. Necrotic lesions often formed in other organs or tissues. If left untreated, this condition would result in death. Treatment for progressive vaccinia generally included the use of VIG or the antiviral medication cidofovir. Some individuals who developed progressive vaccinia required surgical debridement of the site or amputation of the affected limb. In the 1960s, it was estimated that 1.5 out of 1 million vaccinations resulted in progressive vaccinia.7

Eczema vaccinatum occurred when the vaccine’s vaccinia virus spread on the skin, usually among persons with a history of eczema. While some cases were mild, some reactions were severe and even fatal, especially in younger individuals. When death occurred, it was usually as a result of extensive spread of the virus, bacterial sepsis, or fluid and electrolyte imbalance.  This complication was estimated to occur in 39 out of a million vaccinations.8

Post-vaccinial encephalitis was a swelling of the brain that occurred after smallpox vaccination and was more commonly seen among infants and small children. Death occurred in 9 to 40 percent of cases, and between 10 and 25 percent of survivors were left with permanent neurological damage. No risk factors for this reaction were identified and treatment with VIG was not considered effective. Approximately 12 out of a million vaccinations resulted in encephalitis.9

Generalized vaccinia occurred when the vaccine’s vaccinia virus spread in the blood. Affected persons usually had a generalized rash that was frequently self-limited. While no therapy was usually required, VIG may have been given to speed recovery. Immunosuppressed individuals were more susceptible to this complication but it could still occur in healthy individuals. In the 1960s, generalized vaccinia occurred in about 241 out of a million vaccinations.10

Death following Dryvax vaccination was estimated to occur in about 1 out of a million vaccinations.11 On February 29, 2008, the CDC reported that Wyeth, the manufacturer of Dryvax smallpox vaccine, was withdrawing its license and requested the immediate destruction of all vaccine doses. The CDC denied that the withdrawal was related to any quality, safety, or purity concerns, but rather due to a contractual agreement between the CDC and Wyeth. Dryvax was replaced by ACAM 2000, a live vaccinia virus vaccine, manufactured by Acambis, Inc. (now Emergent Product Development Gaithersburg, Inc).12

Smallpox (Vaccinia) Vaccine, Live (ACAM 2000)

Common adverse events following ACAM 2000 smallpox vaccine administration include injection site redness, swelling, bruising, and pain. Systemic adverse events include feeling hot, fatigue, malaise, and decreased exercise tolerance. In persons receiving the smallpox vaccine for the first time, 10 percent experienced at least one severe adverse event. In those who had previously been vaccinated with smallpox vaccine, severe adverse events occurred in 3 percent of individuals.13

Serious complications following ACAM 2000 smallpox vaccination or revaccination include encephalitis, encephalomyelitis, encephalopathy, generalized vaccinia, progressive vaccinia (vaccinia necrosum), severe vaccinial skin infections, eczema vaccinatum, erythema multiforme major (including Stevens-Johnson syndrome), blindness, and fetal death in pregnant women. These complications have the potential to cause severe disability, permanent neurological deficits, and death.14

Nervous system disorders affect about 50 percent of people receiving the vaccine for the first time, and 34 percent of previously vaccinated individuals. Neurological complications include encephalitis, meningitis, myelitis, Bell Palsy, seizures, Guillain-Barre Syndrome, limb paresthesias, pain, vertigo or dizziness, and headache. Additional adverse events include back pain, myalgia, arthralgia, extremity pain, lymphadenopathy, lymph node pain, diarrhea, nausea, vomiting, constipation, toothache, and severe abdominal pain. A rash after vaccination is common and is considered a hypersensitivity reaction in individuals who do not have underlying health issues.15

According to the FDA, 1 in 175 people who receive ACAM 2000 for the first time will suffer from pericarditis and/or myocarditis (inflammation of the heart or surrounding tissues). Symptoms of myocarditis and pericarditis include difficulty breathing, rapid or irregular heartbeat and chest pain.16

Ischemic and non-ischemic cardiac adverse events have occurred following vaccination, and fatalities have been reported. Complications include ocular vaccinia and this can cause scarring of the cornea, keratitis, and blindness. The risk may be higher in persons using corticosteroid eye drops.17

ACAM 2000 is a live virus vaccine which has the potential to spread to other areas of the body or to other people. This can occur if the vaccine recipient touches the injection site and then touches another body part or touches someone else.18

Persons with immunodeficiencies are at high risk of developing serious complications from the smallpox vaccine. This includes individuals with eczema, pregnant women and newborn infants, and persons living with HIV infection. Individuals with eye disease and heart disease are also at high risk of complications if they come into contact with the smallpox virus from the vaccine. Care should be taken to ensure that these individuals are not vaccinated or not exposed to a person who was recently vaccinated.19

The vaccinia virus from the vaccine is shed from the site of the injection from the time of papule development at day 2 to 5 until the scab falls off between 2 and 3 weeks post-vaccination. Persons vaccinated with ACAM 2000 should ensure that the injection site is covered loosely with a gauze until the scab comes off. All contaminated bandages should be placed in a sealed bag and disposed of in the trash. Additionally, any items such as clothing, towels, and bedding, that come into contact with the injection site or drainage from the wound should be washed separately in hot water with detergent or bleach to prevent the risk of transmission to others.20

Smallpox and Monkeypox Vaccine, Live, Non-Replicating (JYNNEOS)

Common adverse events following JYNNEOS smallpox and monkeypox vaccine administration include injection site pain, redness, swelling, itching, and induration. Systemic adverse events include fatigue, nausea, muscle pain, headache, chills, and fever.21

In pre-licensing clinical trials, serious side effects that could not be ruled out as being related to vaccination included Crohn’s disease, sarcoidosis, extraocular muscle paresis and throat tightness. Cardiac events that were considered to be related to JYNNEOS vaccination included tachycardia, electrocardiogram T wave inversion, electrocardiogram abnormal, electrocardiogram ST segment elevation, electrocardiogram T wave abnormal, and palpitations. Additionally, asymptomatic post-vaccination elevations of troponin-I in the blood were reported in over 100 vaccine recipients, however, the significance of the elevation is not yet known. 22 Troponin is a protein found in heart muscle and is only detected in the blood when damage to the heart has occurred. Elevated troponin levels can indicate a current or recent heart attack.23 There  were no fatal outcomes associated with the vaccine in pre-licensing clinical trials.24

Reported Adverse Events following Smallpox vaccination

Using the MedAlerts search engine, as of August 31, 2022, there have been 6,230 adverse events reported to the Vaccine Adverse Events Reporting System (VAERS) in connection with smallpox-containing vaccines since 1990. Nearly 82 percent of smallpox vaccine-related adverse events have occurred in adults 17-44 years of age. Of these smallpox-vaccine related adverse event reports to VAERS, 948 were classified as serious, and 18 deaths were reported. Over half of the deaths occurred in adults 17-44 years of age.

Even though the National Childhood Vaccine Injury Act of 1986 legally required pediatricians and other vaccine providers to report serious health problems following vaccination to federal health agencies (VAERS), many doctors and other medical workers giving vaccines to children and adults fail to report vaccine-related health problem to VAERS. There is evidence that only between 1 and 10 percent of serious health problems which occur after use of prescription drugs or vaccines in the U.S. are ever reported to federal health officials, who are responsible for regulating the safety of drugs and vaccines and issue national vaccine policy recommendations.25 26 27 28

In the U.S., vaccine manufacturers are shielded from liability under the 2005 Public Readiness and Emergency Preparedness (PREP) Act if a vaccine or drug developed in response to a health emergency causes the death or permanent injury of an individual who receives it during pre-licensure clinical trials or after it is released for public use.29 30 The PREP Act was part of a series of “Bioshield” laws created in response to national security fears after 9/11 and subsequent reports of weaponized microbe threats, which prompted Congress to encourage pharmaceutical companies to develop anti-bioterrorism vaccines by, in part, eliminating liability for injuries and deaths caused by those vaccines.31

Individuals who die or suffer serious harm due to the administration of covered countermeasures, such as smallpox vaccines, may be eligible to receive compensation through the Countermeasures Injury Compensation Program (CICP), whether the harm was a result of willful misconduct on the part of the vaccine manufacturer or person administering the vaccine.32

Between 2010 and May 2022, only three claims for injuries sustained from smallpox vaccine have been deemed eligible for compensation from the CICP; however only one claim, myocarditis following smallpox vaccine, received compensation. Two claims, one for myocarditis and one for serum sickness, were reported to have had no losses or expenses related to the injury. Four smallpox vaccine injury claims were denied due to failure to submit medical records, four smallpox vaccine injury claims were denied because government officials ruled that the injury was not related to vaccination, and four were denied due to missing the one year filing deadline.33

IMPORTANT NOTE: NVIC encourages you to become fully informed about smallpox and the smallpox vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself. This information is for educational purposes only and is not intended as medical advice.


References:

[1] Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality. Evaluating Biological Mechanisms of Adverse Events (p. 57-102), Increased Susceptibility (p. 82). Washington, DC: The National Academies Press. 2012.

[2] Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. Apr. 2003;1(2):87-92.

[3] Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. Apr. 2003;1(2):87-92.

[4] Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. Apr. 2003;1(2):87-92.

[5] U.S. Centers for Disease Control and Prevention. Smallpox vaccination and adverse reactions. Guidance for clinicians. MMWR Feb. 2003;52(RR-4):1-28. 

[6] Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. Apr. 2003;1(2):87-92.

[7] Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. Apr. 2003;1(2):87-92.

[8] Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. Apr. 2003;1(2):87-92.

[9] Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. Apr. 2003;1(2):87-92.

[10] Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. Apr. 2003;1(2):87-92.

[11] Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. Apr. 2003;1(2):87-92.

[12] U.S. Centers for Disease Control and Prevention. Notice to Readers: Newly Licensed Smallpox Vaccine to Replace Old Smallpox Vaccine. MMWR Feb. 29, 2008; 57(08): 207-208.

[13] Emergent Product Development Gaithersburg, Inc. ACAM2000 – Package Insert. U.S. Food and Drug Administration Dec. 13, 2019.

[14] Emergent Product Development Gaithersburg, Inc. ACAM2000 – Package Insert. U.S. Food and Drug Administration Dec. 13, 2019.

[15] Emergent Product Development Gaithersburg, Inc. ACAM2000 – Package Insert. U.S. Food and Drug Administration Dec. 13, 2019.

[16] Emergent Product Development Gaithersburg, Inc. ACAM2000 - Medication Guide U.S. Food and Drug Administration Dec. 13, 2019.

[17] Emergent Product Development Gaithersburg, Inc. ACAM2000 – Package Insert. U.S. Food and Drug Administration Dec. 13, 2019.

[18] Emergent Product Development Gaithersburg, Inc. ACAM2000 – Package Insert. U.S. Food and Drug Administration Dec. 13, 2019.

[19] Emergent Product Development Gaithersburg, Inc. ACAM2000 – Package Insert. U.S. Food and Drug Administration Dec. 13, 2019.

[20] Emergent Product Development Gaithersburg, Inc. ACAM2000 – Package Insert. U.S. Food and Drug Administration Dec. 13, 2019.

[21] Bavarian Nordic A/S Package Insert – JYNNEOS. U.S. Food and Drug Administration June 21, 2021.

[22]  Bavarian Nordic A/S Package Insert – JYNNEOS. U.S. Food and Drug Administration June 21, 2021.

[23] National Library of Medicine MedlinePlus. Troponin Test. Sept. 9, 2021.

[24]  Bavarian Nordic A/S Package Insert – JYNNEOS. U.S. Food and Drug Administration June 21, 2021.

[25] Kessler DA, the Working Group, Natanblut S, et al. A New Approach to Reporting Medication and Device Adverse Effects and Product Problems. JAMA 1993;269(21):2765-2768.

[26] FDA.gov. Kessler DA. Introducing MEDWatch: A New Approach to Reporting Medication and Device Adverse Effects and Product Problems. Reprint from JAMA. June 9, 1993.

[27] Rosenthal S, Chen R. The reporting sensitivities of two passive surveillance systems for vaccine adverse events. Am J Public Health 1995; 85: pp. 1706-9.

[28] AHRQ. Electronic Support for Public Health–Vaccine Adverse Event Reporting System (ESP:VAERS). Dec 1, 2007-Sep. 30, 2010.

[29] U.S. Department of Health & Human Services. Public Readiness and Emergency Preparedness Act of 2005 (PREP Act). PREP Act Q&A. Jan. 7, 2022.

[30] Garde D, Branswell H. 6 burning questions Congress could push Covid-19 vaccine makers to answer todayStat News. July 20, 2020.

[31] Fisher BL. US Marines and Navy Prepare to Execute Pandemic Plan As Questions Resurface About Coronavirus Origin: After 9/11 Congress Gave More Power to Executive Branch. The Vaccine Reaction Feb. 20, 2020.

[32] Health Resources & Services Administration. Countermeasures Injury Compensation Program (CICP). Nov. 2020.

[33] Health Resources & Services Administration. Countermeasures Injury Compensation Program (CICP) Data. May 2022.

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