Smallpox & Monkeypox Overview



Smallpox (right) Monkeypox (left) CDC PHIL

Smallpox/Monkeypox: The Disease


Smallpox is an illness caused by the variola virus, a virus belonging to the orthopoxvirus family of viruses.1 Symptoms of the disease include head and backache, anorexia, severe abdominal pain, vomiting, extreme exhaustion, malaise, chills, rash, and high fever. When the fever resolved, rash lesions would begin to develop and appear in the back of the mouth, behind the oral cavity (oropharynx), followed by the face, arms, legs, and then would have spread to the torso, palms and soles.2 When smallpox was circulating in the environment, there were several forms of the disease, with some more severe and life-threatening than others.3

Monkeypox is an infection caused by the monkeypox virus and like smallpox is also a member of the Orthopoxvirus family.4 Symptoms of monkeypox are similar to smallpox but are generally milder. Individuals infected with monkeypox usually present with headache, backache, fever, chills, muscle aches, extreme fatigue and exhaustion. Swelling of the lymph nodes also occurs, which is a symptom not present with smallpox infection.5 A rash, which usually appears on the face, begins within one to three days of fever, and spreads throughout the body.6 Monkeypox is rare and is generally found in Africa, although cases and outbreaks have occurred globally.7 Learn more about smallpox/monkeypox…

Smallpox/Monkeypox: The Vaccine

There are two smallpox vaccines approved by the U.S. Food and Drug Administration (FDA): ACAM 2000, a live smallpox (vaccinia) vaccine, and JYNNEOS, a live, non-replicating, smallpox and monkeypox vaccine. A third vaccine, Aventis Pasteur Smallpox Vaccine (APSV), is an unapproved vaccine that has been added to the Strategic National Stockpile (SNS).8 Learn more about smallpox/monkeypox vaccine…

Smallpox/Monkeypox Quick Facts

Smallpox/Monkeypox

  • Smallpox is an illness caused by the variola virus, belonging to the orthopoxvirus family. There are several forms of smallpox illness, including Variola Major, modified-type smallpox, hemorrhagic smallpox, malignant (flat-type) smallpox, and Variola Minor. Variola Major was the most common form of the illness when smallpox was circulating in the environment.9 Initial symptoms of smallpox illness included anorexia, vomiting, malaise, high fever, chills, headache, backache, severe abdominal pain, pharyngitis, and extreme exhaustion. A rash might have also been visible in light-skinned individuals. Rash lesions would begin after the fever resolved and appear in the back of the mouth, behind the oral cavity (oropharynx), followed by the face, arms, and legs, and would eventually spread to the torso, palms, and soles.10
  • Monkeypox, another orthopoxvirus, is similar in symptoms to smallpox but generally milder. With monkeypox, infected individuals develop swelling of the lymph nodes.11

Smallpox/Monkeypox Vaccine

  • There are two smallpox vaccines approved by the U.S. Food and Drug Administration (FDA). The ACAM 2000 vaccine is a live smallpox (vaccinia) vaccineapproved for use in persons considered at high risk for smallpox infection. The JYNNEOS vaccine is a live, non-replicating, smallpox and monkeypox vaccine and approved for use in adults 18 years of age and older who are considered to be at high-risk of smallpox or monkeypox.12
  • Serious adverse events reported following ACAM 2000 vaccination include encephalitis (brain inflammation), encephalomyelitis (inflammation of brain and spinal cord), encephalopathy (disease of brain causing alteration of brain function or structure), generalized vaccinia (systemic spread of the virus from the inoculation site), progressive vaccinia (vaccinia necrosum – death of bodily tissues), severe vaccinial skin infections, eczema vaccinatum, erythema multiforme major including Stevens-Johnson syndrome (severe and potentially life threatening skin and/or mucus membrane lesions), blindness, and fetal death in pregnant women. These complications have the potential to cause severe disability, permanent neurological deficits, and death.13 Serious adverse events reported during clinical trials for the JYNNEOS vaccine noted in the product insert include Crohn’s disease, sarcoidosis (inflammatory disease affecting organs), extraocular muscle paresis (weakening of eye muscles) and throat tightness.14 Continue reading quick facts…

Learn More About Smallpox/Monkeypox and Smallpox/Monkeypox Vaccine

NVIC encourages you to become fully informed about Smallpox/Monkeypox and the Smallpox/Monkeypox vaccine by reading all sections in the Table of Contents provided on this webpage. NVIC provides highly referenced information that allow the public to click through to the reference material used to compile this information, such as the manufacturer product information inserts maintained on the U.S. Food & Drug Administration's website and vaccine information statements issued by the U.S. Centers for Disease Control and Prevention. As you consider vaccination, we encourage the public to educate themselves on the disease and vaccine and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

smallpox

 

 

CDC Plan to Release Smallpox Vaccine

Statement on
CDC PLAN TO RELEASE SMALLPOX VACCINE
National Vaccine Information Center
Barbara Loe Fisher, President
June 24, 2002

The National Vaccine Information Center (NVIC), the oldest and largest vaccine safety advocacy organization in the U.S., endorses the June 21 decision by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control (CDC) advising against releasing vaccinia (smallpox) virus vaccine for mass use by the general population. However, we maintain that the federal advisory committee's recommendation to use the live virus vaccine in up to 20,000 health care workers is premature in the absence of actual disease.

NVIC representatives attended and gave statements at public meetings the CDC held in Atlanta, New York, San Francisco, San Antonio and St. Louis. In all of the meetings to discuss smallpox vaccination options, there was no credible evidence presented to suggest that the smallpox virus was going to be intentionally released or could be successfully used by terrorists as a bioterrorism weapon. In fact, CDC experts continued to insist the theoretical probability of the eradicated virus being intentionally released was "very low." And yet, plans are now going forward to intentionally release the very reactive live vaccinia virus into our population by exposing at least 20,000 health care workers and their close contacts to the very real risks of injury and death from the most reactive vaccine humans have ever used.

NVIC agrees that stockpiling smallpox and other vaccines to respond to potential bioterrorism is an important part of the nation's emergency preparedness plan. However, we are not in an emergency situation. There has been no bioterrorism attack using smallpox virus and the CDC should stand by the policy of restricting vaccinia virus vaccination to researchers exposed to vaccinia virus in lab work. Beyond that, vaccinia virus transmission into the general population could be minimized by confining the vaccination of potential emergency first responders to several hundred special personnel selected to investigate any suspected intentional release of the smallpox virus.

Outstanding questions remain about the wisdom of re-introducing the live vaccinia virus into the world, where it has not been circulating for more than three decades, in the absence of real disease or proof that weaponized smallpox virus has been acquired by terrorists and can be successfully deployed. It appears that the only reason bringing smallpox vaccine back into general use is being discussed is because of the anthrax-laced letters sent to politicians and the media immediately after September 11, 2001. And yet, the information the American public has been given about the anthrax "bioterrorism" attack is that it was an inside job and most likely involved a disgruntled scientist familiar with anthrax research at a U.S. government lab. Correcting lapses in internal security would be a much safer alternative to placing more American's lives at risk with a vaccine designed to prevent a disease that has been eradicated.

NVIC opposes the release of live vaccinia virus vaccine into the general population for the following reasons:

  • smallpox was eradicated and the U.S. halted routine use of the vaccinia virus vaccine in 1971 after recognition of the vaccine's serious side effects;
  • the live virus vaccine causes reactions in almost everyone who gets it (fever, spread of vaccine virus to other parts of the body) and causes life threatening reactions in 1 in 4,000 persons;
  • the vaccine spreads vaccinia virus from one person to another and immune compromised individuals are at highest risk;
  • up to 25 percent of the US population is estimated to be immune compromised and at risk for injury or death if exposed to vaccinia virus;
  • at high risk of vaccinia virus infection complications are people who have a history of eczema or atopic dermatitis and it has been estimated that these individuals and their close contacts comprise as much as 50 percent of the US population;
  • there is a window of opportunity to vaccinate individuals within four days of being exposed to the smallpox virus;
  • smallpox infection used to kill up to 30 percent of those infected; however, today's medical care and treatment options in the U.S. would lower that death rate to 2-3 percent according to CDC experts (unless the virus has been genetically engineered to be more lethal);
  • any use of smallpox virus in a bioterrorism attack is likely to be genetically engineered and diminish the effectiveness of the current vaccine;
  • the smallpox vaccine was never tested in clinical trials before it was used on a mass basis and mandated;
  • drug companies making old and new smallpox vaccines want normal federal vaccine standards to be suspended so the vaccines can be used quickly;
  • drug companies do not want to be held liable for any injuries or deaths caused by old and new smallpox vaccines;

There is genuine concern among many parents that the plan to use vaccinia virus vaccine in 20,000 health care workers is simply a first step toward mass, mandatory use of the smallpox vaccine by all Americans, including children. History shows that once a vaccine is mass produced in this country, it is soon mandated in response to heavy lobbying by industry, federal health officials and special interest groups. We hope this is not where this policy change is heading. If it is, there will be a backlash among a growing number of parents questioning the need for and safety of the 36 doses of 11 vaccines already being given to all American children.

Among those who will be at highest risk for vaccinia virus injury will be the tens of thousands of children who are already suffering from vaccine-induced neuroimmune dysfunction, including learning disabilities, ADHD, autism, intestinal bowel disease, seizure disorders, multiple allergies, asthma, diabetes and other immune and brain disorders. NVIC urges immediate research into the safety and effectiveness of old and new smallpox vaccines and opposes lowering of federal standards to prove safety. NVIC remains committed to defending the human right to informed consent to any medical procedure which can cause injury or death, including vaccination, and opposes all attempts to suspend informed consent rights in emergency or non-emergency situations.

The National Vaccine Information Center was founded in 1982 by parents of vaccine injured children and represents parents, grandparents and health care professionals. NVIC worked with Congress on the National Childhood Vaccine Injury Act of 1986 and was instrumental in obtaining a safer pertussis vaccine for American babies licensed in 1996. A watchdog on vaccine research, development and policy, the parent organization advocates the institution of safety and informed consent reforms in the mass vaccination system.

A special report on smallpox vaccine and new state laws giving health officials police power to arrest, quarantine and force vaccination is available on NVIC's website at Smallpox and Forced Vaccination

 

What is Smallpox and Monkeypox?

Smallpox (right) Monkeypox (left) CDC PHIL

Smallpox is an illness caused by the variola virus. This virus belongs to the orthopoxvirus family of viruses. When smallpox was circulating in the environment, there were several forms of the disease, with some more severe and life-threatening than others.1

Variola Major

According to the Centers for Disease Control (CDC), Variola Major was the most common form of the illness when smallpox was circulating. The incubation period of Variola Major ranged from seven to 19 days, but most frequently lasted between 10 and 14 days. Persons infected with the virus were not contagious and had no symptoms of illness during this period.

The first symptoms of illness occurred in the prodrome period, which began immediately following the incubation period, and lasted approximately four days. Symptoms included:

  • Anorexia
  • Vomiting
  • Malaise
  • High fever (between 101°F to 105°F)
  • Chills
  • Headache
  • Backache
  • Severe abdominal pain
  • Pharyngitis
  • Extreme exhaustion
  • A rash, mostly seen in light-skinned individuals.

When the fever resolved, rash lesions would begin to develop and appear in the back of the mouth, behind the oral cavity (oropharynx), followed by the face, arms, legs, and then would have spread to the torso, palms and soles. Rash lesions would develop evenly during the illness and progress from macules to papules to vesicles within four to five days. In another one or two days, the vesicles would evolve to pustules that were round, firm, and found deep in the dermis. Crusting and scabbing of the lesions usually began on the ninth day and the crusts generally began to fall off about 2 weeks after the onset of the rash.2

Complications of smallpox included severe bacterial infections of the skin and organs, sepsis, pneumonia, encephalitis, and keratitis.3

The most common long-term health consequence of smallpox was scarring which occurred all over the body but most often on the face. Additional sequelae included stillbirths and spontaneous abortions, infertility in males, osteomyelitis, encephalitis, and blindness. Persons who recovered from smallpox illness developed long-term immunity.4

Historically, Variola Major was fatal in approximately 30 percent of cases.5

Modified-type Smallpox

When the vaccine failed to prevent illness, previously vaccinated individuals would develop a condition known as modified-type smallpox. Symptoms of illness were usually the same as in persons who developed Variola Major; however, the rash generally resolved within 10 days, instead of 2 weeks, and fever was not always present. There were usually fewer lesions, and lesions were often superficial.6 Modified-type smallpox infections were rarely fatal.7

Hemorrhagic Smallpox

Hemorrhagic smallpox usually occurred in adults but could still develop in children. Additionally, pregnant women were also more at risk of developing this particular form of the disease. Symptoms of hemorrhagic smallpox were similar to Variola Major except that the incubation period was shorter and prodromal symptoms were usually more severe. Additionally, after the onset of illness, skin redness would occur and progress to a petechial rash (small pinpoint purple or red rash) and hemorrhaging of the skin and mucous membranes. Hemorrhagic smallpox was usually fatal by the fifth or sixth day after rash onset, and frequently as a result of multi-system organ failure due to toxemia. Vaccination was ineffective against hemorrhagic smallpox.8

Malignant (Flat-type) Smallpox

Most common among children, flat-type smallpox was rare and identified by skin lesions that developed slowly, merged together, and became soft and flat. Most cases of flat-type smallpox were fatal due to toxemia, however, if a patient survived, the rash would heal without scabbing.9 This type of smallpox was fatal in approximately 97 percent of cases.10

Variola Minor (Alastrim)

Variola Minor was a less severe form of illness and was rarely fatal. Death occurred in less than one percent of cases.11 This form was most common in the U.S. by the early part of the 20th Century.12 By the 1930s and until smallpox was eliminated from the U.S., variola minor, the mildest form of smallpox, had emerged as the predominant strain.13

Additional Orthopoxvirus Diseases

Monkeypox

Monkeypox is an infection caused by the monkeypox virus and like smallpox is also a member of the Orthopoxvirus family.14 The incubation period of monkeypox is usually between 7 and 14 days.15 Symptoms of monkeypox are similar to smallpox but are generally milder. Individuals infected with monkeypox usually present with headache, backache, fever, chills, muscle aches, extreme fatigue and exhaustion. Swelling of the lymph nodes also occurs, which is a symptom not present with smallpox infection.16

A rash, which usually appears on the face, begins within one to three days of fever, and spreads throughout the body. The lesions of the rash progress from macules to papules to vesicles before erupting as pustules and scab over. Most individuals recover from monkeypox within two to four weeks.17

Monkeypox is rare and is generally found in Africa, although cases and outbreaks have occurred globally. The virus was first identified among monkeys involved in research in 1958, While the main species that harbors the virus remains unknown, health officials believe that African rodents, monkeys, and other primates likely harbor and transmit the virus. The first known case of human infection was documented in the Democratic Republic of the Congo (DRC) in 1970.18Transmission of monkeypox virus is thought to occur through the respiratory tract, breaks in the skin, or mucous membranes.19

Complications of monkeypox illness include sepsis, encephalitis, eye infections that may result in blindness, bronchopneumonia, and other secondary infections. According the World Health Organization (WHO), death from monkeypox has historically occurred in 0 and 11 percent of cases. More recently, the WHO estimates death rates from monkey pox to be between 3 and 6 percent.20

There are two main clades (types) of monkeypox that have been identified: the West African (WA) and the Congo Basin (CB). The CB clade of monkeypox is considered more easily transmissible and associated with higher rates of mortality. Historically, those most at risk have been individuals hunt, kill, and eat bushmeat.21

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.

 

Is Smallpox and Monkeypox Contagious?

When smallpox was circulating in the environment, it was contagious; however, transmission generally required extended face-to-face contact with an infected person. It was also transmitted through respiratory droplets when an infected individual sneezed or coughed. Rarely, the virus was spread through airborne transmission. This meant that the virus could have remained in the air for an extended period of time and possibly even circulated throughout a building’s ventilation system. Coming into contact with scabs or the fluid (pus) contained in the smallpox rash pustules or bedding and clothing that has come into contact with scabs or fluid can also cause smallpox infection.1 2 Smallpox is only contagious to humans and there is no evidence that the virus can be spread to other species or to insects.3

Smallpox was declared extinct in May 1980 by the World Health Organization (WHO). There are, however, two known stores of smallpox virus remaining. One is located in the U.S. at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia and the other in a laboratory outside of Moscow, Russia. Some government health officials believe that secret smallpox stores exist and could someday be used for bioterrorism.4

Monkeypox virus is considered to be closely related to the smallpox virus5 and is contagious. The virus can be transmitted from animals to humans by scratches or bites, through direct contact with the rash lesions or other bodily fluids, or through meat from contaminated animals. Infected humans can spread the virus to others through respiratory secretions or other bodily fluids. Direct contact with the lesions or contact with items contaminated by the lesions such as clothing or linen can also transmit the infection.6 The virus can also be transmitted sexually.7

The last known case of smallpox reportedly occurred in Somalia in October 1977. In May 1980, smallpox was declared extinct by the World Health Organization (WHO). There are two known smallpox virus stores remaining. One is located in the U.S. at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia and the other in a laboratory outside of Moscow, Russia. Some government health officials believe that secret smallpox stores exist and could someday be used for bioterrorism.8

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.

 

What is the History of Smallpox and Monkeypox in America and Other Countries?

Smallpox

Smallpox is believed to have originated in Eastern Africa around 10,000 B.C.1 The emergence of the virus has been linked to farming practices which included animal domestication and the establishment of large community settlements.2 While descriptions of the disease are notably absent from the Bible, the Talmud, and early Greek and Roman literature, researchers believe that ancient Indian texts compiled prior to the birth of Christ documented the illness.3 4 Merchants from Egypt may have been responsible for the spread of smallpox to India.5

Documents from China dating back to the 4th Century A.D. are considered the first to accurately describe the disease. Additional evidence indicates that the smallpox (variola) virus was initially imported into China in the 3rd Century A.D. It is also believed that the virus was imported to Greece in 430 B.C. during the Peloponnesian War, and into Rome in 170 A.D.6 By this time, it was known that persons who survived the illness were immune from re-infection, and due to their immunity, they were frequently called upon to care for those afflicted.7

Additional documents indicate that the virus was present in Europe by the 6th Century A.D.8 During the 6th, 7th, and 8th Centuries smallpox spread throughout North Africa and Europe by Arab invaders.9

Smallpox first occurred in England during the 16th Century. Queen Elizabeth I contracted the disease in October 1562 and was left permanently disfigured. During this same period, smallpox spread to South and Central America from West Africa by ships transporting slaves to the Americas.10

Early epidemics of the West African subtype of the smallpox (variola) virus in the Americas were highly lethal; however, subsequent outbreaks were less so.11 It is estimated that approximately 3.5 million Aztecs in Mexico died during the 1520-1522 epidemic. Additional outbreaks in Peru and Brazil were also devastating to the Native populations.12

Throughout the 17th and 18th Centuries, smallpox outbreaks and epidemics occurred throughout Great Britain and in many European cities. An estimated 400,000 people died yearly from smallpox and more than one-third of all cases of blindness were caused by the disease.13 Most cases of smallpox in Great Britain occurred in children under 10 years of age while in the United States during the same time period, smallpox impacted persons of all ages. A smallpox epidemic in Boston, Massachusetts that occurred between April 1721 and February 1722 resulted in nearly 6,000 cases and 855 deaths among the 10,700 residents.14

Smallpox was used as a weapon against Native Americans who were hostile to Great Britain during the French and Indian War (1754-1767). The disease was introduced into this population by Sir Jeffrey Amherst, the British Army Commander in North America, with devastating results.15

During the American Revolutionary War, the Continental Army was plagued by disease. Because soldiers were recruited from all over North America and the arrival of soldiers from England and Germany bringing smallpox to America created the opportunity for greater exposure to smallpox, which was especially devastating due to its high mortality rate of between 10 and 60 percent.

Smallpox inoculation, which differs from and was prior to the interventions known as vaccination, was considered safer than natural disease but the procedure came with the risk of serious side effects including death. However, inoculation, also called variolation, was not hygienic and involved taking pus from a person with active smallpox and injecting it under the skin of a healthy individual. The belief was that this process would induce a mild illness and spare an individual from serious illness or death.16 The process was known to spread syphilis and would even start disease outbreaks within the community. Strict quarantine measures were also implemented to control the disease, and historians credit these strategies with reducing mortality rates.17

George Washington, a survivor of smallpox, implemented quarantine measures to prevent the spread of smallpox within the Revolutionary Army, While Washington supported the benefits of smallpox inoculation, in May of 1776 he ordered that active-duty troops were not to be inoculated and violation of the order was met with severe penalties. The order was issued due to the inoculation’s side effects that could incapacitate a large portion of the army from engaging in battle and thereby provide the British with an advantage. By 1777, Washington had instituted a system whereby new recruits were mandated to be inoculated upon enlistment. This system ensured that recruits had fully healed from the inoculation and any side effects while being outfitted and prior to being sent into battle, thereby limited the spread of disease in active duty troops.18

In 1798, Edward Jenner reported that exposure to cowpox, a virus believed to be related to smallpox and considered relatively harmless, would protect a person from smallpox. Smallpox vaccination was introduced in the U.S. in 1800 by Boston physician Benjamin Waterhouse and was quickly embraced by many in the medical community.19

Despite vaccination, smallpox cases and outbreaks continued to occur, even among those previously infected with or vaccinated against smallpox. Throughout the 19th Century, medical journals reported on the failure of the vaccine to prevent smallpox. It was during this time that supporters of vaccination reported that while the procedure did not always offer protection from illness, it lessened the severity of the disease. In 1844, when an outbreak of smallpox occurred in the U.K., one-third of the vaccinated individuals who contracted the illness had only mild symptoms, while two-thirds suffered severely from the illness. During this outbreak, approximately eight percent of persons previously vaccinated died. Newspapers frequently reported on smallpox deaths that occurred in persons previously vaccinated.20 21

Europe experienced an epidemic of smallpox in 1871 and 1872. It was noted during this epidemic that vaccinated individuals were often inflicted with severe illness faster than those who were not vaccinated. Severe smallpox illness and death among vaccinated persons occurred frequently. Globally, highly vaccinated countries were significantly impacted during this pandemic. Yet, despite the failure of smallpox vaccinations to fully prevent illness and death, many countries imposed compulsory vaccination laws.22

On January 6, 1899, the U.S. Marine-Hospital Service published a report entitled “Precis upon the diagnosis and treatment of smallpox” under the guidance of the Surgeon-General. In this document, public health officials reported that smallpox was contagious but the microbe had not yet been discovered. Respiratory secretions and scabs from the smallpox lesions were considered infectious and the dried materials could live for months on furniture and clothing. It was also believed that the illness was contagious during the four days prior to rash appearance, however, this was not yet confirmed. While it was reported that the illness could affect anyone, persons of color were considered at higher risk “probably on account of their conditions of living in small, crowded rooms, with slight regard for cleanliness.”23

Several forms of smallpox were identified and these included true smallpox, confluent smallpox, two forms of hemorrhagic smallpox, and varioloid, a modified form that occurred in previously vaccinated individuals. This document expressed the importance of not mistaking the illness for chickenpox, measles, scarlet fever, typhus fever, syphilis, cerebro-spinal fever, impetigo contagiosa, or glanders. Report also contained quarantine and disinfection guidelines and sulphur dioxide, bichloride of mercury, carbolic acid (phenol), and formaldehyde gas were approved products for disinfection. Vaccination was reported as the most effective way to stop the spread of smallpox provided that the vaccine was pure and obtained from a reputable source and public health officials recommended that glycerinized lymph derived from bovines be used.24

According to a published report from 1936, between 1921 and 1930, U.S. smallpox rates were highest among the 26 countries that provided data to the League of Nations. High infection rates, however, were attributed to the better reporting systems in the U.S. in comparison to other countries. By 1936, the most common form of smallpox was a mild form known as Variola Minor, with a fatality rate of 0.2 percent or less. It was also reported that in most countries where smallpox vaccination was required, rates were lower; however, in Australia and New Zealand, where smallpox was rarely seen, fewer than one percent of infants were vaccinated.25

The last reported case of indigenous smallpox in the U.S. was reported in 1934. Importations into the U.S., however, continued to occur until 1949.26 When smallpox was eliminated from the United States, variola minor, the mildest form of smallpox, had emerged as the predominant strain in circulation.27

In 1959, the World Health Assembly announced its endorsement of global smallpox eradication and called for vaccination of at least 80 percent of the world’s population. The global eradication program was launched by the World Health Organization (WHO) in 1967 with a plan for complete eradication within 10 years. Smallpox cases declined until 1971 but in 1972, cases increased by 23 percent. Epidemics occurred in Botswana and Bangladesh, two countries previously reported as being free of smallpox.28The last known case of smallpox in South America occurred in Brazil in April of 1971, and Indonesia reported its last case in January of 1972.29

When public health officials realized that mass vaccination campaigns targeting at least 80 percent of the population were not effective, a new plan was initiated. The plan involved the detection and containment of cases through the implementation of a surveillance and reporting system in smallpox endemic countries.30 This strategy was the result of observations that smallpox could still be eliminated in regions where vaccination was not widely practiced if health officials tracked down and isolated persons with smallpox and quarantined their contacts.31

The last known case of human to human smallpox transmission occurred in Somalia in October 1977. Two additional cases were reported in Birmingham, England in August and September of 1978, however, health officials believed that they were related to laboratory exposures.32

In May 1980, WHO declared that smallpox had been eradicated globally. There are, however, two known location where smallpox virus continues to be stored, the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia and a laboratory outside of Moscow, Russia. Despite eradication, some government health officials believe that secret smallpox stores exist and could someday be used for bioterrorism.33

Monkeypox

Monkeypox was first identified in 1958 after two outbreaks occurred among monkey colonies involved in research. The first human case was reported in 1970 in the Democratic Republic of Congo (DRC). Between 1981 and 1986, there were 37 cases reported in the DRC.34

A large outbreak of monkeypox occurred in the same region between February 1996 and February 1997. Seventy-one cases and six deaths were reported in Zaire between February and August 1996. An additional 170 cases were reported between March and May 1997, although WHO officials believed that some cases may have been mistaken for chickenpox.35

An outbreak of monkeypox associated with exotic animals imported from Ghana occurred in the U.S. in 2003. The initial case occurred in a 3-year-old child who was bitten by an infected prairie dog. Health officials initially believed the case was an isolated incident; however, two weeks later, additional cases were reported. Seventy-two cases were linked to the outbreak, with most cases occurring between May 29 and June 9, 2003.36

Since 2017, Nigeria has experienced outbreaks of monkeypox, with health officials reporting at least 200 confirmed cases with a death rate of 3 percent. As of May 2022, the WHO is reporting that monkeypox outbreak in this region is still ongoing.37

In May 2022, health officials in the United Kingdom reported two linked cases of monkeypox. The reported cases were not associated with travel to monkeypox-endemic areas. By May 19, 2022, 38 cases had been confirmed worldwide, with 26 cases reported in the European region, 9 cases reported in the UK, two cases in Canada, and one in the U.S.38

As of November 25, 2022, the CDC is reporting 29,248 confirmed cases of monkeypox and 14 associated deaths in the U.S. 39 

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.

 

Can Smallpox and Monkeypox Cause Injury and/or Death?

Smallpox

Smallpox was declared eradicated in May 1980 by the World Health Organization (WHO), however, when the virus was circulating in the environment, serious illness and even death often occurred.

Symptoms include of Variola Major, the most common form of smallpox illness, included:

  • Anorexia
  • Vomiting
  • Malaise
  • High fever (between 101°F to 105°F)
  • Chills
  • Headache
  • Backache
  • Severe abdominal pain
  • Pharyngitis
  • Extreme exhaustion
  • Rash, more frequently seen in light-skinned individuals

When the fever resolved, rash lesions would begin to develop and appear in the back of the mouth, behind the oral cavity (oropharynx), followed by the face, arms, legs, and then would spread to the torso, and palms and soles. Rash lesions developed evenly during the illness and progressed from macules to papules to vesicles within 4 to 5 days. In another one or two days, the vesicles evolved to pustules that were round, firm, and found deep in the dermis. Crusting and scabbing of the lesions usually began on the ninth day and the crusts generally began to fall off about 2 weeks after the onset of the rash.1

Complications of smallpox included severe bacterial infections of the skin and organs, sepsis, pneumonia, encephalitis, and keratitis.2

The most common long-term health consequence of smallpox was scarring which could occur all over the body but most often on the face. Additional sequelae included stillbirths and spontaneous abortions, infertility in males, osteomyelitis, encephalitis, and blindness. Persons who recovered from smallpox illness developed long-term immunity.3 Historically, Variola Major was fatal in approximately 30 percent of cases.4

Malignant (Flat-type) Smallpox, a rare form of smallpox that was more common among children, was identified by skin lesions that developed slowly, merged together, and would become soft and flat. Most cases of flat-type smallpox were fatal due to toxemia, however, if a patient survived, the rash would heal without scabbing.5 This type of smallpox was fatal in approximately 97 percent of cases.6

Hemorrhagic smallpox, a form of smallpox similar to Variola Major, had a shorter incubation period and prodromal symptoms that were usually more severe. Additionally, after the onset of illness, skin redness would occur and progress to a petechial rash (small pinpoint purple or red rash) and hemorrhaging of the skin and mucous membranes. Hemorrhagic smallpox was usually fatal by the fifth or sixth day after rash onset, and frequently as a result of multi-system organ failure due to toxemia.7 Nearly all cases of hemorrhagic smallpox were fatal.8

Persons who developed modified smallpox, a form of the disease that occurred in smallpox vaccinated individuals when the vaccine failed to protect, would frequently suffer from fever, severe headache, backache and would have a rash lasting as long as a typical illness. The rash, however, would generally evolve through its stages more quickly and lesions were more superficial.9 Modified-type smallpox infections we rarely fatal.10

Monkeypox

Symptoms of monkeypox are similar to smallpox but are generally milder. Individuals infected with monkeypox usually present with headache, backache, fever, chills, muscle aches, extreme fatigue and exhaustion. Swelling of the lymph nodes also occurs, which is a symptom not present with smallpox infection.11

Complications of monkeypox illness include sepsis, encephalitis, eye infections that may result in blindness, bronchopneumonia, and other secondary infections. According the World Health Organization (WHO), death from monkeypox has historically occurred in 0 and 11 percent of cases. More recently, the WHO estimates death rates from monkey pox to be between 3 and 6 percent.12

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.

 

Who is at Highest Risk for Getting Smallpox and Monkeypox?

Smallpox

The last known case of smallpox reportedly occurred in Somalia in 1977. In May 1980, smallpox was declared eradicated by the World Health Organization (WHO). There are two known smallpox virus stores remaining. One is located in the U.S. at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia and the other in a laboratory outside of Moscow, Russia. Some government health officials believe that secret smallpox stores exist and could someday be used for bioterrorism.1 Scientists who work in laboratories that contain the remaining smallpox stores are at highest risk for developing smallpox.2

An April 2018 published study examining the risk of smallpox reemergence concluded that persons between birth and 19 years were most at risk for developing smallpox if an outbreak were to occur. This conclusion was made due to the higher number of contacts that occur with others from those within this demographic.3

Monkeypox

Monkeypox is generally found in the tropical rainforest regions of west and central Africa. Health officials believe that individuals who are at highest risk of developing monkeypox are those who come into direct contact with bodily fluids and blood, or the skin lesions and mucous membranes of infected animals. Persons who hunt, kill, and eat bushmeat in these regions are considered at highest risk of infection. Human to human transmission is believed to occur through respiratory secretions or by coming into contact with the skin lesions of an infected person. Contact may also occur if an individual touches items that have been recently contaminated by an infected individual. Transmission may also occur from mother to baby through the placenta, or during and after birth.4

Since May 2022, most cases of monkeypox outside of west and central Africa have occurred in men who have sex with other men.5

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.

 

Who is at Highest Risk for Suffering Complications from Smallpox and Monkeypox?

Smallpox

The last known case of smallpox reportedly occurred in Somalia in 1977. In May 1980, smallpox was declared eradicated by the World Health Organization (WHO).1

When smallpox was common, persons who developed malignant (flat-type) smallpox, a rare form of smallpox that was more common among children, were at high-risk of complications. This form of smallpox was identified by skin lesions that developed  slowly, merged together, and became soft and flat. Most cases of flat-type smallpox were fatal due to toxemia,2  and 97 percent of individuals who developed this form of smallpox died.3 Persons who developed hemorrhagic smallpox, another form of the disease, were also at high-risk of complications and death. Hemorrhagic smallpox had prodromal symptoms that were usually more severe than the more common form of the disease, Variola Major, and was usually fatal by the fifth or sixth day after rash onset. Death usually occurred from toxemia that caused multi-system organ failure.4 Nearly all cases of hemorrhagic smallpox were fatal.5

An April 2018 published study examining the risk of smallpox reemergence concluded that individuals 40 years of age and older were more at risk of death from smallpox. While persons in this age range were more likely to have been previously vaccinated, higher rates of immunosuppression were prevalent in this population. Persons with immunosuppressive conditions are considered at higher risk of death from smallpox.6

Monkeypox

Individuals most at risk for complications from monkeypox are those who are immunocompromised or have other underlying medical conditions. Young children who are exposed to large amounts of the virus may also be at a greater risk of suffering complications from the illness.7

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.

 

Can Smallpox and Monkeypox be Prevented and Are There Treatment Options?

In May 1980, smallpox was declared eradicated by the World Health Organization (WHO), however, public health officials remain concerned that the virus could be used for biological warfare.1

The FDA has approved an antiviral medication, tecovirimat (TPOXX), for the treatment of smallpox2 and monkeypox.3 This drug was approved in July 2018; however, it is not known whether it is effective against smallpox. It was approved because the drug appeared to stop the virus in a laboratory setting and was effective in animals with diseases similar to smallpox. Tecovirimat was also approved for use under an investigational new drug (IND) protocol for the treatment of smallpox vaccine reactions.

Two additional antivirals, cidofovir and brincidofovir, are not FDA-approved for the treatment of smallpox; however, in the event of an outbreak, they could be given under an IND protocol or Emergency Use Authorization (EUA). They might also be permitted for use to treat smallpox vaccine reactions.4 Cidofovir is also authorized for the treatment of monkeypox during an outbreak.5

While tecovirimat, cidofovir, and brincidofovir are currently stockpiled in the National Strategic Stockpile, they have never been used to treat a person with smallpox and their effectiveness is not yet known.6

The oral form of tecovirimat has been approved for use in Europe for the treatment of smallpox, cowpox, and monkeypox.7

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.

 

What is Smallpox and Monkeypox Vaccine?

There are two smallpox vaccines approved by the U.S. Food and Drug Administration (FDA): ACAM 2000, a live smallpox (vaccinia) vaccine, developed and manufactured by Emergent Product Development Gaithersburg, Inc., and JYNNEOS, a live, non-replicating, smallpox and monkeypox vaccine, developed and manufactured by Bavarian Nordic.

A third vaccine, Aventis Pasteur Smallpox Vaccine (APSV), is an unapproved vaccine that has been added to the Strategic National Stockpile (SNS). This investigational vaccine is only available in the event that all stores of ACAM 2000 vaccine have been used, or on a case-by-case bases when ACAM 2000 is contraindicated.1

Smallpox (Vaccinia) Vaccine, Live (ACAM 2000)

ACAM 2000 is a live smallpox (vaccinia) vaccine approved for use in persons considered at a high-risk of smallpox infection. The vaccine is made from plaque purification cloning of the Dryvax® vaccine – a vaccine manufactured by Wyeth Laboratories, (Marietta, PA) and a calf lymph vaccine (New York City Board of Health Strain) and grown in African Green Monkey kidney (Vero) cells.

Ingredients found in ACAM 2000 include HEPES, 2 percent human serum albumin, 0.5 - 0.7 percent sodium chloride USP, 5 percent Mannitol USP, neomycin, polymyxin B, 0.25 percent phenol USP and 50 percent Glycerin USP.2

ACAM 2000 is administered by the percutaneous route (scarification) using 15 jabs of a bifurcated needle and must be given by someone trained on the safe administration of the vaccine.3

The CDC’s Advisory Committee on Immunization Practice (ACIP) recommends ACAM 2000 vaccination for laboratory personnel who directly handle cultures or animals infected or contaminated with vaccinia viruses or other orthopoxviruses that are capable of infecting humans. Health care personnel who treat or who anticipate treating individuals with vaccinia virus infections or who may have contact with the virus due to handling of contaminated materials as well as persons who administer ACAM 2000 may also be offered the vaccine.4

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

JYNNEOS is a live, non-replicating smallpox and monkeypox vaccine that received FDA approval for use in adults 18 years of age and older considered at high-risk of smallpox or monkeypox infection.5

JYNNEOS is a live vaccine made from the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) strain, an attenuated, non-replicating orthopoxvirus. MVA-BN is grown in Chicken Embryo Fibroblast (CEF) cells in a serum-free medium that does not contain any direct animal material. Additional ingredients include benzonase, tromethamine, sodium chloride, gentamicin, and residual host-cell DNA.

JYNNEOS is recommended to be given as a 2-dose series, 4 weeks apart.6 The CDC’s Advisory Committee on Immunization Practices (ACIP) has authorized use of the vaccine in persons who are at risk of occupational exposure to orthopoxviruses. This includes laboratory personnel working with orthopoxviruses, healthcare providers administering ACAM2000 or those treating individuals with orthopoxvirus infection. Booster doses of the vaccine have also been approved for persons at continued risk of exposure to orthopoxviruses, and this vaccine may be given as a booster dose for persons who received a primary series of ACAM2000.7

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.

 

What is the History of Smallpox and Monkeypox Vaccine Use in America?

The earliest form of vaccination against smallpox, a procedure known as inoculation or variolation, involved the lancing of a smallpox pustule from an infected individual and introducing this fluid under the skin of a smallpox susceptible individual. This procedure was believed to have been practiced in China, India, and Africa hundreds of years prior to its introduction in Europe in the early 18th Century. French philosopher Voltaire reported that in ancient China, smallpox scabs were inhaled as a powder through the nose. This practice spread to Persia and Turkey, however, instead of inhalation, the scabs were ingested.1

In 1679, variolation was reportedly introduced in Turkey by a man who inoculated many children against smallpox. This practice was also believed to be used in young women who inhabited the region north of the Caucasus Mountains, near the Black Sea. The people of this region were poor and often sold their beautiful daughters to the Shahs of Persia or the Sultans of the Ottoman Empire.2

Lady Mary Wortley Montagu, the wife of Lord Edward Wortley Montagu, the British Ambassador to Turkey, was credited for introducing smallpox inoculation in Britain. At the age of 26, Lady Mary had developed smallpox and was left permanently scarred. After witnessing the practice of variolation, Lady Mary allowed for her 6 year old son to undergo the procedure on March 18, 1718, in Turkey, without consent from her husband. Three years later, in 1721, a deadly smallpox epidemic broke out in London. Lady Mary chose to have her three year old daughter Mary inoculated. This was the first time the procedure was performed in Britain and as a result of its reported success, the practice began to gain favor within the medical community.3

Early experimentation with smallpox variolation had mixed results. While some practitioners reported success with the procedure, others noted that the practice could result in complications that included death. In Britain, early practitioners would take the smallpox pus from an infected individual and inject it into the bloodstream. Eventually, they realized that superficial scratches performed in Turkey were as effective. It was at this time that it also became known that recently inoculated individuals could spread the disease on to others.4

Information on the practice of smallpox variolation in Colonial America was introduced in 1706 by a slave from North Africa. The Reverend Cotton Mather of Boston was gifted a slave who told him of the procedure, which prompted Mather to learn more about it. When a smallpox outbreak occurred in 1721, Mather attempted to persuade Boston physicians to perform variolation. Only one, Zabdiel Boylston, chose to try the procedure and inoculated his young son, his slave, and his slave’s son.5

The procedure was opposed by most Boston doctors but six prominent clergyman supported Boylston and his experiments. Boylston reported that of the 242 people that he inoculated, only 6 had died. The procedure was reported as having a fatality rate of 2.5 percent which was much better than the estimated 15 percent death rate from natural disease. Authorities in Boston halted Boylston’s experiments in May of 1722. Many who expressed opposition considered it a violation of God’s Will.6 7

In 1738, a variation to smallpox variolation was introduced in Charleston, South Carolina. When a smallpox outbreak occurred, inoculation was performed by taking pus from a person who had recently undergone variolation. It was reported that this procedure could effectively be repeated up to 6 times and was said to significantly reduce the risk of death from the disease. Scottish physician, Dr. James Kirkpatrick, was involved in the variolation activities in South Carolina, and upon return to London, he published an essay on his experience. Kirkpatrick also assisted with the founding of the Smallpox and Inoculation Hospital of London which provided free care to those afflicted with smallpox and offered inoculations to the public.8

Variolation became more widespread in the mid-18th Century in Western Europe. Members of the Russian Royal Family were inoculated and the procedure, performed by various methods depending on the practitioner, was also introduced in the Netherlands, Germany, Switzerland, Denmark, France, and Sweden.9

Smallpox inoculations were performed during the Revolutionary War in America but frequently caused the disease to spread. Certain cities and several of the 13 colonies placed restrictions or banned its practice at one time or another.10

In 1798, British physician Dr. Edward Jenner reported that exposure to cowpox, a related virus that was considered harmless, would protect a person from smallpox.11

One of Jenner’s early experiments involved infecting an eight-year-old boy with cowpox by scraping pus from lesions of a child infected with cowpox onto the skin of the boy. Jenner then twice challenged the boy’s immunity to smallpox by scraping pus from the lesions of a person with smallpox onto the boy’s skin. The boy did not develop smallpox and Jenner widely promoted his discovery and advocated cowpox inoculation as a prevention of smallpox.12

Eventually, Jenner’s procedure was modified and standardized for mass production by the pharmaceutical industry. As Jenner refined the cowpox inoculation process, a new virus called vaccinia evolved. It is still not known exactly how the vaccinia virus came into being but theories are that it is a weakened form of the smallpox or cowpox virus or, more likely, a hybrid of the two viruses.13 14

This procedure, which Jenner referred to as vaccination, was initially rejected by prominent physicians of the time. Despite their public opposition to Jenner’s vaccination, several doctors began performing the procedure using materials obtained from the pustules of cows. These same physicians refused to credit Jenner for his work and made attempts to stop him from furthering his research. Jenner, however, was awarded a significant amount of money from the British government to continue his work.15

Physicians from outside of Britain also criticized Jenner’s vaccination and reported that it was ineffective. Even though the procedure was criticized by many prominent physicians of the time, vaccination campaigns began outside of Britain. The procedure was introduced to the Mediterranean region in 1800 and eventually was used in areas of Italy, France, and even Russia.16

This procedure was introduced in the U.S. in 1800 by Boston physician Benjamin Waterhouse who used it to vaccinate his son, several of his house servants, and an additional eight patients. Later that year, Dr. Elisha Story vaccinated several children and adults near Boston with vaccine materials obtained from his son who procured it from a sailor in London. The substance, which was thought to be cowpox, turned out to be smallpox, and it caused an outbreak of the disease. Many of the vaccinated individuals developed smallpox and 68 people died. This outbreak caused a backlash against vaccination.17

Waterhouse was able to secure new vaccine materials from London in March of 1801 and granted permission to use it in May of 1802. The Boston Board of Health permitted vaccination of multiple children from the poorhouse who were subsequently exposed to smallpox and did not develop the disease. As Waterhouse was the only person who possessed the vaccine, he set up a monopoly in the U.S. and would issue it only to practitioners who agreed to give him at least one-fourth of the profits from vaccination. It would take more than a year for the monopoly to be broken. It was Waterhouse who wrote to then President Thomas Jefferson and requested that he sponsor vaccine distribution in the Southern United States.18

The first vaccine shipment proved to be ineffective, however, the next shipment was reported to be effective and was used to vaccinate Jefferson’s family and many people in the surrounding area. Vaccine materials were also brought to Washington D.C. and used to vaccinate many Native Americans.19

In 1813, President James Madison appointed Dr. James Smith of Baltimore as a Federal Vaccine agent to ensure that the smallpox vaccine was effective and to distribute it to all U.S. citizens. It was Smith who discovered that smallpox vaccination did not offer lifelong protection after a previously vaccinated child developed the disease and died. Revaccination was suggested by a colleague but Smith felt that it may be better to return to variolation. Smith’s loss of confidence in vaccination called the practice into question, and in 1821, when smallpox scabs were inadvertently used in vaccination campaigns and caused disease and death, national vaccination efforts dwindled.20

For the first part of the 19th Century, vaccination was performed by an arm to arm technique. The vaccine was frequently administered to a child and then shared to others. In the mid-1840s, the vaccine was propagated in cows. Human lymph was initially used, followed by bovine lymph. In 1850, the bovine lymph was combined with glycerol to prevent the vaccine from breaking down. This vaccine was introduced in France in 1864 and distributed throughout Europe. Smallpox vaccines formulated from calf lymph were initially introduced in the U.S. in 1870 and Britain in the 1880s. Arm to arm vaccinations were finally outlawed in Britain in 1898 when the Vaccination Act was passed.21 22

In 1853, Britain mandated smallpox vaccination for the entire population of England, Scotland, and Wales.23 The mandates, however, were not strictly imposed as there were no mechanisms in place to enforce it. By the 1860s, further legislation enabled the appointment of vaccination officers to enforce the mandate, and these stricter laws prompted the founding of the Anti-compulsory Vaccination League in London, with chapters around the country. Many who opposed vaccine mandates did so due to personal or family harm from vaccination.24

One town in particular became known as the “Mecca” for persons who opposed vaccination. In the 1870s and 1880s, opposition to smallpox vaccination in the town of Leicester increased significantly. In turn, vaccination officers began strict enforcement of the law and parents who refused to get their children vaccinated were prosecuted. Prosecutions increased dramatically, however, in Leicester, those who were fined and imprisoned for refusing vaccination were considered heroes. In 1886, prosecutions were finally halted and vaccination rates in Leicester plummeted.25

Conscientious exemptions to vaccination were finally permitted by law in 1898, and smallpox vaccination rates dropped considerably. Public health officials prophesized that the decrease in vaccination rates would cause an increase of smallpox outbreaks and epidemics that would result in severe illness and death; however, this did not occur. In fact, as smallpox vaccination rates declined, cases of smallpox also decreased. Additionally, other diseases such as typhus, enteric fever and scarlet fever also decreased significantly during this same time period even though there were no vaccinations for these illnesses. Improved sanitation and higher standards of living were reported as playing a major role in the decrease of disease and death.26

In the U.S. in 1904, Henning Jacobson, a Lutheran Minister, objected to a Cambridge, Massachusetts Board of Health law that required all adults to get a second smallpox vaccination or pay a $5 dollar fine. Pastor Jacobson and his son had suffered severe reactions to previous smallpox vaccinations and he argued that a genetic predisposition placed him at higher risk for dying or being injured if he was revaccinated. Jacobson also concluded that smallpox vaccine ingredients were toxic and often caused injury and even death and that medical doctors were unable to predict who would be harmed. He made the ethical and legal argument that being required to get revaccinated was an assault on his person and a violation of his 14th Amendment right to liberty and equal protection under the law.27

The attorneys representing the medical doctors persuaded judges in the state court that Jacobson did not know what he was talking about and they ruled against him. Instead of simply paying a $5 fine, Jacobson appealed to the U.S. Supreme Court. In a split decision with one dissenting vote, the Court majority, including Oliver Wendell Holmes, said that citizens do not have the right under the U.S. Constitution to be free at all times because there are “manifold restraints to which every person is necessarily subjected for the common good.” They said that state legislatures have the constitutional authority to enact compulsory vaccination laws and exercise police power to restrict or eliminate liberty during smallpox epidemics to “secure the general comfort, health and prosperity of the state.”28

The judges dismissed Jacobson’s concern about being genetically susceptible to vaccine harm. Instead they chose to incorrectly affirm the infallibility of doctors and stated that: “The matured opinions of medical men everywhere, and the experience of mankind, as all must know, negative the suggestion that it is not possible in any case to determine whether vaccination is safe.”29

In 1935, Federal Public Health Officials published a listing of biological products that possessed licenses issued through the Treasury Department in accordance with the July 1, 1902 Act of Congress entitled “An act to regulate the sale of viruses, serums, toxins, and analogous products in the District of Columbia, to regulate interstate traffic in said articles, and for other purposes.”30

Licensing of a product was not an endorsement that the claims made by the manufacturer were accurate. However, to obtain a license, the product did undergo routine evaluation to ensure it was free of contaminants and the production facilities were inspected. In 1935, several pharmaceutical companies manufactured smallpox vaccines. These included Parke Davis & Company, Mulford Biological Laboratories, Sharp & Dohme, The Cutter Laboratory, New York City Department of Health Laboratories, Lederle Laboratories, E.R Squibb and Sons, Eli Lilly & Company, Gilli Laboratories, Commonwealth of Massachusetts Department of Health Antitoxin and Vaccine Laboratory, United States Standard Products Company, the Michigan State Department of Health Bureau of Laboratories, and the National Drug Company.31

Initiatives to eradicate smallpox in the 20th century involved the use of vaccines containing the live vaccinia virus cultured mainly on cow skins. There were many live vaccinia virus strains used in vaccination campaigns. One vaccine, a lyophilized formulation called Dryvax derived from the New York City Board of Health live vaccinia virus strain, was manufactured by Wyeth Laboratories. Dryvax, like other vaccines manufactured during this time, used preparation methods that would have produced a mixture of viruses and frequently contained bacteria and other adventitious agents.32

In the 1950s, a method was introduced that permitted the smallpox vaccine to be freeze-dried and heat-stable which enabled the vaccine to be stored long-term without the need for refrigeration. The vaccine, however, was well recognized as highly reactive and capable of causing harm and even death. Serious adverse events reported after vaccination included progressive vaccinia, generalized vaccinia, eczema vaccinatum, postvaccinial encephalitis, and death. In persons vaccinated for the first time, serious adverse reactions were ten times more likely to occur than among revaccinated individuals. Additionally, death from vaccination was four times higher in persons initially vaccinated when compared to revaccinated individuals.33

Even though Dryvax was in use for decades in the U.S., vaccine efficacy and the level of antibodies considered protective against smallpox was never determined. Public health officials believed that a single dose of smallpox would be protective for about five years or less but antibodies could persist for over ten years. Revaccination was thought to offer more protection and boost antibody levels. Routine smallpox vaccination in the U.S. came to an end in 1971 and vaccination of health care workers stopped in 1976.34

In 1982, Wyeth Laboratories discontinued production of Dryvax for use by the general population. The vaccine, however, was still in use for routine administration of all active duty military personnel. In the discontinuation notice issued by the CDC, public health officials reported that the product’s discontinuation would stop the misuse of the vaccine as a treatment or preventative for other diseases such as herpes.35 By January 1982, smallpox vaccination for international travel was no longer required.36

Public health officials began recommending smallpox vaccination for laboratory workers in 1980 as a precaution against orthopoxviruses such as monkeypox and vaccinia. Vaccination was only recommended for laboratory workers who had direct contact with cultures or animals infected or contaminated with vaccinia, recombinant vaccinia viruses, or other orthopoxviruses that infect humans such as cowpox and monkeypox. Doctors and nurses who may have contact with these viruses through contaminated materials such as dressings, but who followed appropriate infection control guidelines were considered less likely to come into contact with these viruses than laboratory workers; however, they could also consider vaccination.37

As Dryvax was a live vaccinia virus vaccine, transmission of the vaccine virus from recently vaccinated individuals to close contacts occurred and frequently involved serious complications. These transmissions prompted public health officials to caution that recently vaccinated individuals avoid contact with others, especially those with immunodeficiencies, eczema, and children under the age of one.38 39 Additionally, the vaccine virus could also be transmitted from the vaccination site to other parts of the body and cause complications especially through open skin lesions or acne.40

In response to growing international concern of bioterrorism, the CDC’s Advisory Committee on Immunization Practices (ACIP) published guidelines on the use of smallpox vaccination. In this recommendation, laboratory workers with direct exposure to orthopoxviruses were the only population that were recommended to receive smallpox vaccination. The potential for smallpox as a bioweapon was discussed but public health officials considered it unlikely. They did, however, recommend that in the event of a bioterrorism event, the following populations would be considered for vaccination:

  • Persons initially exposed to the virus on its release;
  • Individuals who had close contact with a confirmed or suspected smallpox patient at any time between the onset of the patient's fever until all scabs had fallen off;
  • Persons directly involved in providing medical care or assistance to confirmed or suspected smallpox patients;
  • Laboratory workers involved in collecting or processing clinical specimens from confirmed or suspected smallpox patients; and
  • Additional individuals who may be at an increased risk of infection through contact with infectious materials from a smallpox patient.

In a pre-event situation, contraindications to smallpox vaccination included persons:41

  • with a presence or history of eczema or atopic dermatitis;
  • who have acute, chronic, or exfoliative skin conditions;
  • who have immunosuppression;
  • who are less than 12 months of age;
  • who are pregnant or breastfeeding; or
  • who have previously had a serious allergy to the vaccine or who are allergic to any component of the vaccine.

The vaccine was also contraindicated for persons living with household members with a presence or history of eczema, atopic dermatitis, or acute, chronic, or exfoliative skin conditions, with immunosuppressive conditions, and those who were pregnant.

Public health officials, however, stated that in the event of a smallpox emergency, no contraindications to vaccination existed as persons considered at serious risk of injury from vaccination were also at higher risk of complications and death from the disease.42

In December 2002, President George W. Bush announced that the military and government officials in high-risk areas would begin receiving smallpox vaccination. Front-line health care workers who wanted to be vaccinated would also be given the opportunity to receive the vaccine; however, the vaccine, which was not licensed at the time of his recommendation, would not yet be available for members of the general public. In his announcement, President Bush reported that while there was no known imminent threat, preparing for the possibility of a smallpox bioterrorism attack was prudent.43

The White House stated that the U.S. Department of Health and Human Services was “in the process of establishing an orderly process to make unlicensed vaccine available to those adult members of the general public without medical contraindications who insist on being vaccinated either in 2003, with an unlicensed vaccine, or in 2004, with a licensed vaccine."44

Between January 24, 2003 and December 31, 2003, nearly 40,000 civilian healthcare providers received smallpox vaccination. Ninety-seven serious and 712 non-serious adverse events occurred following vaccination.45 Two vaccine associated ischemic cardiac deaths were reported among civilians who received the vaccine.46

Additionally, between December 2002 and January 2004, nearly 580,000 U.S. military personnel were administered smallpox vaccines. The vaccine’s vaccinia virus was transferred to at least 30 contacts, with most cases occurring in spouses or adult intimate contacts. One breastfed infant was also infected and developed lesions in the mouth and on the face but recovered without serious complications.47 At least one vaccine associated cardiac death was reported among military vaccinees.48

By June of 2003, the smallpox vaccination program was quietly halted by the CDC following reports of serious cardiac adverse events and deaths. Further, several hospitals refused to participate in the vaccination program due to concerns over the transmission vaccine virus between vaccinees and susceptible contacts, including those with immunosuppressive conditions.49

In August 2007, the U.S. Food and Drug Administration (FDA) approved ACAM 2000, a live smallpox (vaccinia) virus vaccine, for use in persons considered at high-risk for smallpox.50 Six months later, on February 29, 2008, the CDC issued a notice that distribution of ACAM 2000 had begun. In this notice, 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.51

ACIP updated their smallpox recommendations in 2015 and recommended vaccination for all laboratory personnel who directly handle cultures or animals infected or contaminated with recombinant vaccinia viruses, replication-competent vaccinia virus, or additional infectious orthopoxviruses (e.g. cowpox, monkeypox, variola). Health care personnel treating individuals with vaccinia virus infections and those administering ACAM2000 smallpox vaccine could also be offered vaccination, and revaccination was recommended at least every 10 years. In non-emergency situations, many contraindications to vaccination were reported by ACIP and included the use of the vaccine in persons:52

  • with a presence or history of eczema or atopic dermatitis;
  • who have acute, chronic, or exfoliative skin conditions;
  • who have immunosuppression;
  • who are less than 12 months of age;
  • who are pregnant or breastfeeding;
  • who have previously had a serious allergy to the vaccine or who are allergic to any component of the vaccine;
  • with known heart disease or who have three or more cardiac risk factors;
  • living with household members who have a presence or history of eczema, atopic dermatitis, or acute, chronic, or exfoliative skin conditions, those with immunosuppressive conditions, those who are pregnant and/or breastfeeding, infants under 12 months of age; or
  • under the age of 18 years.

On September 24, 2019, the FDA approved Jynneos, a live, non-replicating smallpox and monkeypox vaccine for use in persons 18 years of age and older who are considered at high-risk of smallpox and monkeypox vaccine.53

The CDC’s Advisory Committee on Immunization Practices (ACIP) has authorized use of the vaccine in persons who are at risk of occupational exposure to orthopoxviruses. This includes laboratory personnel working with orthopoxviruses, healthcare providers administering ACAM2000 or those treating individuals with orthopoxvirus infection. Booster doses of the vaccine have also been approved for persons at continued risk of exposure to orthopoxviruses, and this vaccine may be given as a booster dose for persons who received a primary series of ACAM2000.54

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.

 

How Effective is Smallpox and Monkeypox Vaccine?

There are two smallpox vaccines approved by the U.S. Food and Drug Administration (FDA): ACAM 2000, a live smallpox (vaccinia) vaccine, developed and manufactured by Emergent Product Development Gaithersburg, Inc., and JYNNEOS, a live, non-replicating, smallpox and monkeypox vaccine, developed and manufactured by Bavarian Nordic.1

Smallpox (Vaccinia) Vaccine, Live (ACAM 2000)

The ACAM 2000 smallpox vaccine does not contain smallpox virus (variola) and can’t cause or transmit smallpox. The vaccine contains the vaccinia virus, which is a member of the same family of viruses as smallpox (the orthopoxvirus genus). Vaccine-acquired immunity from the vaccinia virus found in ACAM 2000 may offer protection against the smallpox (variola) virus through cross-protection.

The vaccinia virus in ACAM 2000 causes an infection of the epidermis, dermal, subcutaneous tissues, and lymph nodes at the injection site. Health experts report that successful vaccination against smallpox with the ACAM 2000 vaccinia virus is determined by the development of a vesicular skin lesion at the injection site, referred to as a “take.”

The virus replicates within the body’s cells and neutralizing antibodies and T and B cells are believed to provide protection against smallpox, although the level of neutralizing antibody protection is not known. According to the vaccine manufacturer, it is estimated that more than 95 percent of individuals vaccinated with smallpox vaccine for the first time develop neutralizing antibodies to vaccinia.2

There are two types of smallpox vaccine responses that have been identified by the World Health Organization (WHO) and the CDC’s Advisory Committee on Immunization Practices (ACIP). The first is the skin reaction or “take” considered to be an indication of successful vaccination. The second is an equivocal reaction and this is usually associated with prior smallpox vaccination. An equivocal reaction mean that the vaccine was not properly administered or the administered vaccine was rendered inactive and incapable of producing an immune response.3 4 5

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

The effectiveness of JYNNEOS vaccine against smallpox was inferred by comparing the immunogenicity of this vaccine to ACAM 2000 smallpox vaccine. The outcomes were supported by efficacy data collected through animal challenge studies. Vaccine effectiveness against monkeypox was inferred from the immunogenicity of the vaccine from efficacy data from animal challenge studies and in a clinical study. In immunogenicity clinical studies, JYNNEOS was considered non-inferior to ACAM 2000.6

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.

 

Can Smallpox and Monkeypox Vaccine Cause Injury and Death?

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.

 

Who is at Highest Risk for Complications from Smallpox and Monkeypox Vaccine?

There is a gap in medical knowledge in terms of doctors being able to predict who will have an adverse reaction to smallpox vaccination, and who will not.

Smallpox (Vaccinia) Vaccine, Live (ACAM 2000)

Individuals considered at a higher risk for complications from ACAM 2000 include persons with:1

  • Cardiac disease;
  • Eye disease, including those receiving treatment with corticosteroids; and
  • History of skin disorders which include the presence of eczema or additional skin conditions.

Additionally, pregnant women and infants under 1 year of age are considered at a higher risk for complications.

Persons with a history of severe allergic reaction to a prior smallpox vaccine are also at a higher risk of complications. This includes people with a history of allergic reaction to polymyxin B and Neomycin, two ingredients contained within the vaccine.2

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

Persons who have previously experienced a severe allergic reaction to JYNNEOS vaccine may be at a higher risk of experiencing an additional serious reaction to a second dose.3

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.

 

Who Should Not Get Smallpox/Monkeypox Vaccine?

Smallpox (Vaccinia) Vaccine, Live (ACAM 2000)

In non-emergency situations, ACAM 2000 is contraindicated in persons with active exfoliative skin conditions that include eczema, severe acne, psoriasis, varicella zoster virus infection, herpes simplex virus infection, burns, impetigo, severe diaper dermatitis with extensive areas of raw skin, keratosis follicularis and in persons with a history or presence of atopic dermatitis. Persons with immunosuppressive conditions such as HIV infection or acquired immune deficiency syndrome (AIDS), autoimmune disease, lymphoma, leukemia, cancer, solid organ and stem cell transplant recipients, and those receiving cancer treatments or steroids.1

Infants under one year of age, women who are pregnant or breastfeeding, and persons who are allergic to any component of smallpox vaccine should not receive ACAM 2000.2

Persons with known underlying cardiac disease or who have three or more known significant cardiac risk factors such as diabetes, hypertension, high cholesterol, smoking, or family history of heart disease. Persons receiving smallpox vaccination for the first time are at a higher risk for myopericarditis (inflammation of the heart muscle and surrounding tissues). While specific risk factors for myopericarditis are not known, persons with cardiac risk factors and a history of heart disease are more likely to have severe outcomes when compared to those without cardiac conditions.3

Non-emergency use of ACAM 2000 is also contraindicated in individuals with household contacts who have a history of active exfoliative skin conditions that include eczema, severe acne, psoriasis, varicella zoster virus infection, herpes simplex virus infection, burns, impetigo, severe diaper dermatitis with extensive areas of raw skin, keratosis follicularis and in persons with a history or presence of atopic dermatitis. Persons with immunosuppressive conditions such as HIV infection or acquired immune deficiency syndrome (AIDS), autoimmune disease, lymphoma, leukemia, cancer, solid organ and stem cell transplant recipients, and those receiving cancer treatments or steroids. The vaccine is also contraindicated in persons with household contacts who are under one year of age, or pregnant women.

Persons with inflammatory eye disease may be at an increased risk for inadvertent inoculation from rubbing or touching the eye. Persons with inflammatory eye disease who require steroid treatment should not receive ACAM 2000 until therapy is completed and the condition is resolved.

Non-emergency vaccination with ACAM 2000 is not recommended in children and adolescents under the age of 18 years.

ACAM 2000 has not been studied for use in pregnant women and is a Pregnancy Category D product. This means that the live vaccinia vaccine can cause fetal harm when administered to pregnant women. If administered to a pregnant woman, congenital infection, generalized vaccinia, and fetal death can occur.4

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

Persons who have previously experienced a severe allergic reaction to JYNNEOS vaccine may be at a higher risk of experiencing an additional serious reaction after receiving a second vaccine dose.

JYNNEOS is approved for use in adults 18 years of age and older considered at a high risk for smallpox or monkeypox. JYNNEOS should not be administered to persons under 18 years of age.

While JYNNEOS has been studied in pregnant rabbits and rats, there is no data to support safety of its use in pregnant women. It is also not known whether the vaccine is excreted in human milk or what the effects may be on the breastfed infant.5

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.

 

What Questions Should I Ask My Doctor About the Smallpox and Monkeypox Vaccine?

NVIC’s If You Vaccinate, Ask 8! Webpage downloadable brochure suggests asking eight questions before you make a vaccination decision for yourself, or for your child. If you review these questions before your appointment, you will be better prepared to ask your doctor questions. Also, make sure that the nurse or doctor gives you the relevant Vaccine Information Statement (VIS) for the vaccine or vaccines you are considering well ahead of time to allow you to review it before you or your child gets vaccinated. Copies of VIS for each vaccine are also available on the CDC's website and there is a link to the VIS for vaccines on NVIC's “Quick Facts” at the top of this page.

Due to the brevity of information provided in the VIS, NVIC suggests that consumers also read the vaccine manufacturer product insert that can be obtained from your doctor or public health clinic. Because federal law requires drug companies marketing vaccines to include certain kinds of vaccine benefit, risk and use information in product information inserts, they represent additional information that may not be available on the CDC Smallpox/Monkeypox VIS or FDA Medical Guide for vaccination with ACAM2000. Smallpox vaccine package inserts are located on the Food and Drug Administration’s website.

Other questions that may be useful to discuss with your doctor before getting the smallpox vaccine are:

  • If other vaccines in addition to smallpox vaccine are scheduled for me or for my child at this office visit, does your policy provide me the flexibility of spreading these vaccines out over time, rather than receiving the recommended vaccines all at one time?
  • What should I do if my child or I become ill after vaccination?
  • What other kinds of reaction symptoms should I call to report after smallpox vaccination?
  • If the smallpox vaccine doesn’t protect me or my child, do we have any other options for preventing smallpox infection?

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 like a bioterrorism attack 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.1 2 The PREP Act was part of a series of “Bioshield” laws created in response to national security fears after 9/11 and subsequent reported 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.3

Individuals who die or suffer serious harm due to the administration of covered countermeasures, such as 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.4

The U.S Department of Health and Human Services (HHS) has interpreted state and federal law to include tort and contract law, as well as claims for loss relating to compliance with local, state, or federal laws, regulations or other legal requirements. The definition of “loss” under the Act is broad, encompassing both physical and emotional injuries. Although the PREP Act does provide immunity to the pharmaceutical industry from smallpox vaccine injury lawsuits, vaccine manufacturers are not immune from injunctive relief or enforcement actions by the U.S. Food and Drug Administration (FDA) or other federal agencies.5

The CICP is administered by employees in HHS’s Health Resources and Services Administration (HRSA). HRSA is the same agency responsible for administering the federal vaccine injury compensation program (VICP) created by Congress in 1986 under the National Childhood Vaccine Injury Act, which partially shielded vaccine manufacturers from liability for injuries and deaths caused by FDA licensed vaccines that are recommended by the CDC for children and mandated by states for school entry.6 The 1986 Act was later amended to eliminate civil liability from doctors and other vaccine administrators and, in 2011, the U.S. Supreme Court eliminated remaining liability from vaccine manufacturers for defectively designed vaccines.7

HHS regulations govern CICP’s procedures and eligibility determinations. In general, eligible individuals (or their survivors) who suffer death or serious physical injury directly caused by the administration of a covered countermeasure may receive reimbursement for reasonable medical expenses, loss of employment income and survivor benefits in the case of death. Serious physical injuries under CICP are generally limited to those that warrant hospitalization or result in a significant loss of function or disability. Congress funds CICP awards through emergency appropriations to the Covered Countermeasure Process Fund.8

The CICP and the National Vaccine Injury Compensation Program (VICP) are separate programs managed by HRSA. The CICP applies to countermeasures (vaccines and drugs) covered by a PREP Act declaration of a public health emergency, such as those issued for the H1N1 “swine flu” influenza pandemic in 2009, the Ebola virus outbreak in 2016,9 and the 2019 outbreak of SARS-CoV-2/COVID-19 (cite please). The VICP applies to vaccines routinely recommended by the CDC for children and, as of 2016 under the 21st Century Cures Act, vaccines recommended for pregnant women.10

Under the National Childhood Vaccine Injury Act of 1986, doctors and all vaccine providers are legally required to give you vaccine benefit and risk information before vaccination (CDC’s VIS); record serious health problems following vaccination in the permanent medical record; keep a permanent record of all vaccines given, including the manufacturer’s name and lot number; and report serious health problems, injuries and deaths that follow vaccination to the federal vaccine adverse event reporting system (VAERS).

Remember, if you choose to vaccinate, always keep a written record of exactly which shots/vaccines you or your child have received, including the manufacturer’s name and vaccine lot number. Write down and describe in detail any serious health problems that develop after vaccination and keep vaccination records in a file you can access easily.

It also is important to be able to recognize a vaccine reaction and seek immediate medical attention if the reaction appears serious, as well as know how to make a vaccine reaction to VAERS. NVIC’s Report Vaccine Reactions—It’s the Law webpage can help you file a vaccine reaction report yourself to VAERS if your doctor fails or refuses to make a report.

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.

 

NVIC Press Releases, Statements & Commentaries Related to Smallpox and Monkeypox

NVIC Special Reports

NVIC’s The Vaccine Reaction

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.

 

Smallpox and Monkeypox Disease & Vaccine Quick Facts

Smallpox/Monkeypox

  • Smallpox is an illness caused by the variola virus, belonging to the orthopoxvirus family. There are several forms of smallpox illness, including Variola Major, modified-type smallpox, hemorrhagic smallpox, malignant (flat-type) smallpox, and Variola Minor. Variola Major was the most common form of the illness when smallpox was circulating in the environment.1
  • Initial symptoms of smallpox illness included anorexia, vomiting, malaise, high fever, chills, headache, backache, severe abdominal pain, pharyngitis, and extreme exhaustion. A rash might have also been visible in light-skinned individuals. Rash lesions would begin after the fever resolved and appear in the back of the mouth, behind the oral cavity (oropharynx), followed by the face, arms, and legs, and would eventually spread to the torso, palms, and soles. Within four days, rash lesions developed and progressed from macules to papules, then to vesicles within 4 to 5 days. In another one or two days, the vesicles evolved into round, firm pustules found deep in the dermis. Crusting and scabbing of the lesions usually began on the ninth day and the crusts generally began to fall off about 2 weeks after the onset of the rash.2 Monkeypox, another orthopoxvirus, is similar in symptoms to smallpox but generally milder. With monkeypox, infected individuals develop swelling of the lymph nodes.3
  • Complications of smallpox included severe bacterial infections of the skin and organs, sepsis, pneumonia, encephalitis (brain inflammation), and keratitis (inflammation of the cornea).4 The most common long-term health consequence of smallpox was scarring, which occurred all over the body but most often on the face. Additional sequelae included stillbirths and miscarriages, infertility in males, osteomyelitis, encephalitis, and blindness. Persons who recover from smallpox illness developed long-term immunity.5 Historically, Variola Major was fatal in approximately 30 percent of cases.6 Complications of monkeypox include sepsis, encephalitis, eye infections that may result in blindness, bronchopneumonia, and other secondary infections. According the World Health Organization (WHO), death from monkeypox has historically occurred in 0 and 11 percent of cases. More recently, the WHO estimates death rates from monkey pox to be between 3 and 6 percent.7
  • Smallpox is contagious; however, transmission generally requires extended face-to-face contact with an infected person. It can also be transmitted through respiratory droplets when an infected individual sneezes or coughs. The virus is rarely spread through airborne transmission – meaning the virus remains in the air for an extended period of time and may even circulate in a building’s ventilation system. Coming into contact with scabs or the fluid (pus) contained in the smallpox rash pustules or bedding and clothing that has come into contact with scabs or fluid can also cause smallpox infection.8 9
  • The last known case of smallpox reportedly occurred in Somalia in October of 1977. In May 1980, smallpox was declared eradicated by the World Health Organization (WHO). There are two known locations where smallpox virus is stored; the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia and a laboratory outside of Moscow, Russia. Some government health officials believe that secret smallpox stores exist and could someday be used for bioterrorism.10

Smallpox/Monkeypox Vaccine

  • There are two smallpox vaccines approved by the U.S. Food and Drug Administration (FDA). The ACAM 2000 vaccine is a live smallpox (vaccinia) vaccine, developed and manufactured by Emergent Product Development Gaithersburg, Inc. approved for use in persons considered at high risk for smallpox infection. The JYNNEOS vaccine is a live, non-replicating, smallpox and monkeypox vaccine, developed and manufactured by Bavarian Nordic11 and approved for use in adults 18 years of age and older who are considered to be at high-risk of smallpox or monkeypox.
  • Serious adverse events reported following ACAM 2000 vaccination include encephalitis (brain inflammation), encephalomyelitis (inflammation of brain and spinal cord), encephalopathy (disease of brain causing alteration of brain function or structure), generalized vaccinia (systemic spread of the virus from the inoculation site), progressive vaccinia (vaccinia necrosum – death of bodily tissues), severe vaccinial skin infections, eczema vaccinatum, erythema multiforme major including Stevens-Johnson syndrome (severe and potentially life threatening skin and/or mucus membrane lesions), blindness, and fetal death in pregnant women. These complications have the potential to cause severe disability, permanent neurological deficits, and death.12
  • Serious adverse events reported during clinical trials for the JYNNEOS vaccine noted in the product insert include Crohn’s disease, sarcoidosis (inflammatory disease affecting organs), extraocular muscle paresis (weakening of eye muscles) and throat tightness.13 JYNNEOS is approved for use as an alternative to ACAM2000 in persons at risk for occupational exposure to orthopoxviruses. This includes laboratory personnel, healthcare providers administering ACAM2000 or those treating patients infected with orthopoxviruses. Booster doses of the vaccine have also been approved for persons who are at continued risk of exposure to orthopoxviruses.14
  • Using the MedAlerts search engine, as of the CDC's October 31, 2022 VAERS data release, there had been 7,064 adverse events reported to the Vaccine Adverse Events Reporting System (VAERS) in connection with smallpox-containing vaccines. Nearly 85 percent of smallpox vaccine-related adverse events occurring in adults 17-49 years of age. Of these smallpox-vaccine related adverse event reports to VAERS, 964 were classified as serious, and 20 deaths were reported. Over half of the reported deaths occurred in adults 17-49 years of age.
  • Smallpox and monkeypox vaccine manufacturers are shielded from liability under the 2005 Public Readiness and Emergency Preparedness (PREP) Act when 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.15 16 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).17 For more information on the liability shield and injury compensation, visit NVIC’s FAQ on Emergency Use Vaccines (EUA) & Vaccine Injury Compensation.

Food & Drug Administration (FDA)

Centers for Disease Control (CDC)

World Health Organization (WHO)

National Institute of Allergy & Infectious Diseases (NIAID)

NIAID on Smallpox


Vaccine Reaction Symptoms & Ingredients

NVIC’s Ask 8, If You Vaccinate webpage contains vaccine reaction symptoms and more.

Search for Vaccine Reactions

NVIC hosts MedAlerts, a powerful VAERS database search engine. MedAlerts examines symptoms, reactions, vaccines, dates, places, and more.


Reporting a Vaccine Reaction

Since 1982, the NVIC has operated a Vaccine Reaction Registry, which has served as a watchdog on VAERS. Reporting vaccine reactions to VAERS is required by federal law under the National Childhood Vaccine Injury Act of 1986. If your doctor will not report a reaction, you have the right to report a suspected vaccine reaction to VAERS.

IMPORTANT NOTE: NVIC encourages you to become fully informed about smallpox/monkeypox and the smallpox/monkeypox 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] Babkin IV, Babkina IN. The origin of the variola virus. Viruses Mar. 2015;7(3):1100-12.

[2] U.S. Centers for Disease Control and Prevention. Clinical Disease. In: Smallpox. Dec. 5, 2016.

[3] Babkin IV, Babkina IN. The origin of the variola virus. Viruses Mar. 2015;7(3):1100-12.

[4] U.S Centers for Disease Control and Prevention. About Monkeypox. In: Monkeypox. Nov. 23, 2021.

[5] U.S Centers for Disease Control and Prevention. Signs and Symptoms. In: Monkeypox. July 16, 2021.

[6] U.S Centers for Disease Control and Prevention. Signs and Symptoms. In: Monkeypox. July 16, 2021.

[7] U.S. Centers for Disease Control and Prevention. About Monkeypox. In: Monkeypox. Nov. 23, 2021.

[8] U.S. Centers for Disease Control and Prevention. Vaccines. In: Smallpox. Dec. 2, 2019.

[9] U.S. Food and Drug Administration. Smallpox. Mar. 23, 2018.

[10] U.S Centers for Disease Control and Prevention. Clinical Disease. In: Smallpox. Dec. 5, 2016.

[11] U.S Centers for Disease Control and Prevention. Signs and Symptoms. In: Monkeypox. July 16, 2021.

[12] U.S Food and Drug Administration. Vaccines Licensed for Use in the United States. Jan. 31, 2022.

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

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

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