Disease: Smallpox

    Smallpox facts

    • Smallpox is a contagious disease caused by the variola virus.
    • Smallpox was the first disease to be eliminated from the world through public-health efforts and vaccination.
    • Smallpox still poses a threat because existing laboratory strains may be used as biological weapons.
    • Smallpox causes high fever, prostration, and a characteristic rash. The rash usually includes blister-like lesions that occur everywhere on the body.
    • Approximately one-third of people with smallpox died from the disease. Survivors were scarred for life. If the eye was infected, blindness often resulted.
    • There are new experimental medications that might be effective in smallpox, but these have not been tested in human cases since the disease has been eradicated.
    • The vaccine contains a live virus called vaccinia. It is administered by dipping a pronged piece of metal into the vaccine and then pricking the skin.
    • The vaccine has uncommon side effects that may be fatal, including infection of the heart and brain with the vaccinia strain. Serious side effects are more common with the initial vaccine and are uncommon with second doses.
    • The vaccine is currently only given to selected military personnel and laboratory workers who handle the smallpox virus.

    What is smallpox?

    Smallpox is an infectious disease of the past that was eliminated by vaccination. The disease was caused by the variola virus, which spread from person to person. Affected people became very ill with a high fever and a characteristic rash. Up to one-third of people with smallpox died. Although the disease has been wiped out, samples of the virus still exist in high-security laboratories in the United States and Russia. This has led to concerns about use of the virus in biological warfare. For this reason, some military personnel are still vaccinated against smallpox.

    What is the history of smallpox?

    Smallpox is thought to have existed for more than 12,000 years. Evidence of infection can be found in mummies from ancient Egypt, including the mummy of Ramses V. Smallpox entered the New World in the 16th century, carried by European explorers and conquistadors. Because the aboriginal inhabitants had no immunity to the disease, smallpox often decimated native populations. There are even reports where infected blankets were used to intentionally infect Native American populations in the 18th century -- one of the early examples of biological warfare. During the 20th century, it is estimated that there were 300 million to 500 million deaths from smallpox worldwide, compared to 100 million from tuberculosis.

    It was not until the end of the 18th century that an effective method of vaccination was developed. It was an English scientist named Edward Jenner who discovered it. Jenner observed that milkmaids often got a mild disease called cowpox and that this seemed to make them immune to smallpox. His vaccination strategy involved transferring the blister fluid from a person with cowpox to a person who had not yet had smallpox. This gave the susceptible person a cowpox infection (which was usually mild) and conveyed protection from smallpox. After a time, a virus similar to cowpox, called vaccinia, was substituted in the vaccine.

    The last naturally occurring case of smallpox was in Somalia in 1977. In 1980, the World Health Organization (WHO) certified that the world was finally free of smallpox. Thus, smallpox was the first disease to be entirely eradicated. Campaigns are now under way to try to eliminate other diseases such as polio and measles.

    The WHO has encouraged all member nations to destroy any remaining laboratory cultures of the virus. However, the rise of biological warfare technology led to concerns that smallpox could be weaponized and used in bioterrorism. Both the U.S. and Russia decided to retain their stockpiles in case they were needed to produce novel vaccines against a biological agent. This has understandably stirred up controversy. Supporters of retaining the cultures note that existing stocks of the virus have been used to develop and test new treatments and vaccines. The entire viral genome has been sequenced, leading to concerns that the virus may be recreated even if current stocks are destroyed.

    Smallpox is a deadly disease and is on the list of potential biological weapons that are considered to pose the greatest threat to public health. Other agents on this list include anthrax, plague, smallpox, botulism, tularemia, and the viral hemorrhagic fevers, including Ebola and Marburg viruses.

    What causes smallpox?

    Smallpox is caused by a poxvirus called variola (Poxviridiae family of viruses). Variola is a relatively large virus that contains double-stranded DNA. The virus can be found in large numbers in many organs (skin, kidneys, spleen, liver, and other organs). Death occurs because of overwhelming toxemia, thought to be due to immune complexes trying to react to the large number of viral particles. Variola infection only occurs in humans, which was helpful in eradicating the disease. There are two strains called respectively variola major and variola minor (also known as alastrim). As implied by the names, variola major is more likely to cause serious disease and death than variola minor.

    How is smallpox transmitted?

    Most transmission of smallpox is directly from person to person. Large, infectious droplets of saliva are expelled during coughing or sneezing and then inadvertently inhaled by another person. This usually requires close face-to-face contact and is similar to the way that mumps, measles, and influenza are spread. On average, a single individual would infect approximately 60% of their household contacts. Infected objects, such as used silverware or heavily contaminated bedding, may carry sufficient numbers of organisms to infect another person if improperly handled, although this route of transmission is much less common.

    What are smallpox symptoms and signs?

    Symptoms develop seven to 17 days after exposure. Fever is the most common initial symptom and can be quite high. This is accompanied by body aches. Often, the patient is too unwell to get out of bed. Within 24 to 48 hours, a rash begins to appear everywhere on the body but especially on the legs, arms, mouth, and face. The eyes may also be affected, leading to potential blindness among survivors. Symptoms in children are similar to adults. The rash also appears on the palms and soles and goes through stages as the disease progresses. At the beginning, the rash consists of red dots that become raised. The lesions (see Figure 1) rapidly fill with fluid resembling a blister or cold sore and are known as "vesicles." The fluid in the vesicles may turn yellow, resembling pus. Rarely, the rash may start to fill with blood (hemorrhagic smallpox), which is a poor prognostic sign. After one to two weeks, the lesions scab over and eventually fall off, leaving deep scars. One of the defining features of smallpox is that all the lesions on the body are always at the same stage of development. This is in contrast to chickenpox where new lesions form while old ones are healing.

    Figure 1: Picture of smallpox in a young child. SOURCE: Dr. Michael Schwartz/CDC

    Approximately one-third of people with smallpox died from the infection. People who had an extensive rash were at higher risk to die. People who had only a few lesions or a milder rash had a lower risk of death. Infections caused by the variola minor strain were less severe and death occurred in only approximately 1% of cases.

    How is smallpox diagnosed?

    When smallpox was common, an experienced clinician could make the diagnosis simply by looking at the rash and examining the patient. Any case that occurs now will likely be a result of bioterrorism or biological warfare. In that event, misdiagnosis or delays in diagnosis could cause the infection to spread. Thus, it is still important for clinicians to be able to diagnose smallpox. The CDC has developed an online tool to help clinicians assess the likelihood that a rash is due to smallpox.

    If smallpox appears possible, public-health authorities should be notified immediately and their instructions on the protective measures for medical caregivers and others are followed carefully. They can help determine if additional testing is warranted. Material from blisters, throat swabs, and blood samples may be tested for the presence of variola DNA or cultured. These tests are done at the CDC and require prior authorization. The person(s) obtaining the specimens should have a recent smallpox vaccination (within three years) or no contraindication to immediate vaccination.

    Figure 2: Picture of smallpox in a child. SOURCE: Dr. Jean Roy/CDC

    What is the treatment for smallpox?

    Treatment for smallpox is supportive, meaning that the patient should be kept hydrated, fever should be treated with acetaminophen (Tylenol) or a similar medication, and the patient should be closely monitoring to determine if there is a need for blood pressure support. Although there are no medications that have been proven to work against human infection, some medications have shown promise in the laboratory, including a derivative of the antiviral drug cidofovir (Vistide).

    Learn more about: Tylenol | Vistide

    Can smallpox be prevented with a vaccine?

    There is an effective vaccine for the prevention of smallpox. The vaccine is made from a virus called vaccinia. The similarity between these two names (vaccine and vaccinia) is not coincidental because smallpox was the first disease to be prevented by vaccination. In 2007, a second-generation smallpox vaccine (ACAM2000) was licensed. The vaccine contains live vaccinia virus but does not contain any smallpox virus. It is not a shot and is administered in a unique manner: a sharp, pronged piece of metal is dipped in the vaccine and then used to prick the skin of the recipient. This is done several times. If successful, the site of vaccination will develop small blisters that scab and heal, leaving a scar. This process is called scarification. While the blisters are active, the site should be kept clean, dry and covered to prevent the vaccinia virus from spreading to others.

    Many older adults still have a vaccine scar on their arms from being vaccinated when they were younger. Smallpox vaccine, like other live vaccines including the yellow fever vaccine, teaches the body's immune system to remember how to make antibodies. There may still be a level of protection, even decades after vaccination. However, revaccination would be recommended in the event of a smallpox exposure. Interestingly, vaccination after exposure provides some protection against severe disease.

    Vaccination is no longer recommended for the general population because the disease has been eradicated. Currently, the vaccine is given only to selected military personnel and laboratory workers who handle the smallpox virus.

    Vaccination side effects are uncommon but are sometimes serious and potentially fatal. Because the vaccine contains live vaccinia virus, the virus may spread and infect the heart, causing myocarditis (infection of the heart muscle) or pericarditis (infection of the sac around the heart). This occurs in approximately one in 175 adults who are vaccinated for the first time. The vaccine can also infect the brain (encephalitis) or eye or cause a generalized rash. Vaccine complications lead to death in approximately six people for every million people who are newly vaccinated. Complications are much less common in revaccination. People with weak immune systems and those with skin conditions like eczema are at higher risk for complications. Pregnant women should not be vaccinated because of the risk of fetal death.

    What is the history of smallpox?

    Smallpox is thought to have existed for more than 12,000 years. Evidence of infection can be found in mummies from ancient Egypt, including the mummy of Ramses V. Smallpox entered the New World in the 16th century, carried by European explorers and conquistadors. Because the aboriginal inhabitants had no immunity to the disease, smallpox often decimated native populations. There are even reports where infected blankets were used to intentionally infect Native American populations in the 18th century -- one of the early examples of biological warfare. During the 20th century, it is estimated that there were 300 million to 500 million deaths from smallpox worldwide, compared to 100 million from tuberculosis.

    It was not until the end of the 18th century that an effective method of vaccination was developed. It was an English scientist named Edward Jenner who discovered it. Jenner observed that milkmaids often got a mild disease called cowpox and that this seemed to make them immune to smallpox. His vaccination strategy involved transferring the blister fluid from a person with cowpox to a person who had not yet had smallpox. This gave the susceptible person a cowpox infection (which was usually mild) and conveyed protection from smallpox. After a time, a virus similar to cowpox, called vaccinia, was substituted in the vaccine.

    The last naturally occurring case of smallpox was in Somalia in 1977. In 1980, the World Health Organization (WHO) certified that the world was finally free of smallpox. Thus, smallpox was the first disease to be entirely eradicated. Campaigns are now under way to try to eliminate other diseases such as polio and measles.

    The WHO has encouraged all member nations to destroy any remaining laboratory cultures of the virus. However, the rise of biological warfare technology led to concerns that smallpox could be weaponized and used in bioterrorism. Both the U.S. and Russia decided to retain their stockpiles in case they were needed to produce novel vaccines against a biological agent. This has understandably stirred up controversy. Supporters of retaining the cultures note that existing stocks of the virus have been used to develop and test new treatments and vaccines. The entire viral genome has been sequenced, leading to concerns that the virus may be recreated even if current stocks are destroyed.

    Smallpox is a deadly disease and is on the list of potential biological weapons that are considered to pose the greatest threat to public health. Other agents on this list include anthrax, plague, smallpox, botulism, tularemia, and the viral hemorrhagic fevers, including Ebola and Marburg viruses.

    What causes smallpox?

    Smallpox is caused by a poxvirus called variola (Poxviridiae family of viruses). Variola is a relatively large virus that contains double-stranded DNA. The virus can be found in large numbers in many organs (skin, kidneys, spleen, liver, and other organs). Death occurs because of overwhelming toxemia, thought to be due to immune complexes trying to react to the large number of viral particles. Variola infection only occurs in humans, which was helpful in eradicating the disease. There are two strains called respectively variola major and variola minor (also known as alastrim). As implied by the names, variola major is more likely to cause serious disease and death than variola minor.

    How is smallpox transmitted?

    Most transmission of smallpox is directly from person to person. Large, infectious droplets of saliva are expelled during coughing or sneezing and then inadvertently inhaled by another person. This usually requires close face-to-face contact and is similar to the way that mumps, measles, and influenza are spread. On average, a single individual would infect approximately 60% of their household contacts. Infected objects, such as used silverware or heavily contaminated bedding, may carry sufficient numbers of organisms to infect another person if improperly handled, although this route of transmission is much less common.

    What are smallpox symptoms and signs?

    Symptoms develop seven to 17 days after exposure. Fever is the most common initial symptom and can be quite high. This is accompanied by body aches. Often, the patient is too unwell to get out of bed. Within 24 to 48 hours, a rash begins to appear everywhere on the body but especially on the legs, arms, mouth, and face. The eyes may also be affected, leading to potential blindness among survivors. Symptoms in children are similar to adults. The rash also appears on the palms and soles and goes through stages as the disease progresses. At the beginning, the rash consists of red dots that become raised. The lesions (see Figure 1) rapidly fill with fluid resembling a blister or cold sore and are known as "vesicles." The fluid in the vesicles may turn yellow, resembling pus. Rarely, the rash may start to fill with blood (hemorrhagic smallpox), which is a poor prognostic sign. After one to two weeks, the lesions scab over and eventually fall off, leaving deep scars. One of the defining features of smallpox is that all the lesions on the body are always at the same stage of development. This is in contrast to chickenpox where new lesions form while old ones are healing.

    Figure 1: Picture of smallpox in a young child. SOURCE: Dr. Michael Schwartz/CDC

    Approximately one-third of people with smallpox died from the infection. People who had an extensive rash were at higher risk to die. People who had only a few lesions or a milder rash had a lower risk of death. Infections caused by the variola minor strain were less severe and death occurred in only approximately 1% of cases.

    How is smallpox diagnosed?

    When smallpox was common, an experienced clinician could make the diagnosis simply by looking at the rash and examining the patient. Any case that occurs now will likely be a result of bioterrorism or biological warfare. In that event, misdiagnosis or delays in diagnosis could cause the infection to spread. Thus, it is still important for clinicians to be able to diagnose smallpox. The CDC has developed an online tool to help clinicians assess the likelihood that a rash is due to smallpox.

    If smallpox appears possible, public-health authorities should be notified immediately and their instructions on the protective measures for medical caregivers and others are followed carefully. They can help determine if additional testing is warranted. Material from blisters, throat swabs, and blood samples may be tested for the presence of variola DNA or cultured. These tests are done at the CDC and require prior authorization. The person(s) obtaining the specimens should have a recent smallpox vaccination (within three years) or no contraindication to immediate vaccination.

    Figure 2: Picture of smallpox in a child. SOURCE: Dr. Jean Roy/CDC

    What is the treatment for smallpox?

    Treatment for smallpox is supportive, meaning that the patient should be kept hydrated, fever should be treated with acetaminophen (Tylenol) or a similar medication, and the patient should be closely monitoring to determine if there is a need for blood pressure support. Although there are no medications that have been proven to work against human infection, some medications have shown promise in the laboratory, including a derivative of the antiviral drug cidofovir (Vistide).

    Learn more about: Tylenol | Vistide

    Can smallpox be prevented with a vaccine?

    There is an effective vaccine for the prevention of smallpox. The vaccine is made from a virus called vaccinia. The similarity between these two names (vaccine and vaccinia) is not coincidental because smallpox was the first disease to be prevented by vaccination. In 2007, a second-generation smallpox vaccine (ACAM2000) was licensed. The vaccine contains live vaccinia virus but does not contain any smallpox virus. It is not a shot and is administered in a unique manner: a sharp, pronged piece of metal is dipped in the vaccine and then used to prick the skin of the recipient. This is done several times. If successful, the site of vaccination will develop small blisters that scab and heal, leaving a scar. This process is called scarification. While the blisters are active, the site should be kept clean, dry and covered to prevent the vaccinia virus from spreading to others.

    Many older adults still have a vaccine scar on their arms from being vaccinated when they were younger. Smallpox vaccine, like other live vaccines including the yellow fever vaccine, teaches the body's immune system to remember how to make antibodies. There may still be a level of protection, even decades after vaccination. However, revaccination would be recommended in the event of a smallpox exposure. Interestingly, vaccination after exposure provides some protection against severe disease.

    Vaccination is no longer recommended for the general population because the disease has been eradicated. Currently, the vaccine is given only to selected military personnel and laboratory workers who handle the smallpox virus.

    Vaccination side effects are uncommon but are sometimes serious and potentially fatal. Because the vaccine contains live vaccinia virus, the virus may spread and infect the heart, causing myocarditis (infection of the heart muscle) or pericarditis (infection of the sac around the heart). This occurs in approximately one in 175 adults who are vaccinated for the first time. The vaccine can also infect the brain (encephalitis) or eye or cause a generalized rash. Vaccine complications lead to death in approximately six people for every million people who are newly vaccinated. Complications are much less common in revaccination. People with weak immune systems and those with skin conditions like eczema are at higher risk for complications. Pregnant women should not be vaccinated because of the risk of fetal death.

    Source: http://www.rxlist.com

    Smallpox is caused by a poxvirus called variola (Poxviridiae family of viruses). Variola is a relatively large virus that contains double-stranded DNA. The virus can be found in large numbers in many organs (skin, kidneys, spleen, liver, and other organs). Death occurs because of overwhelming toxemia, thought to be due to immune complexes trying to react to the large number of viral particles. Variola infection only occurs in humans, which was helpful in eradicating the disease. There are two strains called respectively variola major and variola minor (also known as alastrim). As implied by the names, variola major is more likely to cause serious disease and death than variola minor.

    Source: http://www.rxlist.com

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