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Smallpox

Smallpox Introduction

Smallpox (also called variola) is the only disease that has been completely wiped out throughout the world. Smallpox is also potentially one of the most devastating biological weapons ever conceived.
Due to the success of an intense worldwide public health initiative, not one documented naturally occurring case of this highly infectious, deadly disease has occurred since October 26, 1977. (An unvaccinated hospital cook in Somalia was the last person to naturally contract smallpox.) The World Health Organization (WHO) officially declared smallpox eradicated in 1980.
At that time, all remaining collected supplies of the smallpox virus were supposed to be destroyed or sequestered in two laboratories, one in the United States and one in Russia. Geopolitical events in the last decade and revelations concerning offensive biological warfare programs by certain foreign governments have raised concern that this virus may have fallen into the hands of other foreign states who might seek to use the virus as a biological weapon.
  • History of smallpox: For centuries, smallpox affected political and social agendas. Smallpox epidemics plagued Europe and Asia until 1796, when Edward Jenner tested his theory of disease protection. He did this by inoculating a young boy with material obtained from a milkmaid who was infected with the milder cowpox virus. The success of that experiment led to the development of a vaccine (from vacca, the Latin word for cow). Afterward, the incidence of smallpox infection in Europe steadily declined.
  • In the Americas, smallpox severely weakened the native population. They had never been exposed to smallpox, which the European explorers brought with them to the Americas in the 1600s. The British forces at Fort Pitt (later to become Pittsburgh, Pennsylvania) purposefully gave smallpox-contaminated blankets and goods to Native Americans during the French and Indian Wars in an attempt to weaken the Native American resistance to colonial expansion. Due to this and through natural spread, the epidemic that followed killed half of the Native American population.
  • Once the disease and its method of spread were understood more thoroughly, smallpox vaccination became mandatory in developed countries in the early 1900s. The development of the vaccinia virus, coupled with aggressive immunization, led to the eventual control and eradication of smallpox in 1977.
  • Since the last documented "naturally occurring" case in 1977, only 2 deaths from smallpox have been reported (1978 in Birmingham, England). Both deaths were the result of laboratory accidents.
  • Current locations of smallpox virus: Only two laboratories in the world are known to house smallpox virus: the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the State Research Center of Virology and Biotechnology in Koltsovo, Russia.
  • Various sources from the Soviet Union allege that the Russian military had pursued and currently pursues an active biological warfare program. In 1992, Russian President Boris Yeltsin confirmed a suspected outbreak from an accidental release of aerosolized anthrax (anthrax stored in a container that allows it to be released into the air) near a military microbiology laboratory in 1979.
  • Dr. Ken Alibek, a former senior microbiologist in the Russian Offensive Biological Weapons Program has alleged that, in 1980, the Soviet Union started large-scale production of the smallpox virus and genetic recombination of more potent strains. Since the fall of the Soviet Union, concern exists that this knowledge may be used in other countries. The extent of smallpox stockpiles in other countries is unknown but may have become substantial since the collapse of the Soviet Union.
  • The consequences of a smallpox outbreak can only be estimated. About 30% of unprotected people who are exposed to a person with smallpox would themselves become infected. Of these, 30% would probably die from infection. Diagnosis is difficult during early stages of the disease. Presently, insufficient supplies of vaccine exist to ensure eradication of smallpox in case the disease is released intentionally in a large-scale attack.
  • Are previous vaccinations still protective? Routine vaccination of the general population in the United States stopped after 1980. Vaccination of military personnel was discontinued in 1989. Researchers estimate that vaccinated people retain immunity for about 10 years, although the duration has never been fully evaluated. Therefore, the current population in the United States is considered vulnerable to smallpox. About 42% of the US population is younger than 30 years and has never been vaccinated.
  • The ease of production and aerosolization of the virus is well documented. Researchers estimate that only 10-100 virus particles are necessary to infect someone. Thus, smallpox is a potential biological weapon of staggering danger.  


Smallpox Causes

Variola (the virus that causes smallpox) is a member of the orthopoxvirus genus, which also includes viruses such as cowpox, monkeypox, orf, and molluscum contagiosum. Poxviruses are the largest animal viruses, visible with a light microscope. They are larger than some bacteria.
Poxviruses are the only viruses that do not need a cell’s nucleus to replicate inside the cell. The variola virus is the only known cause of smallpox. The disease affects only humans. No animal reservoirs or insect vectors (insects that spread a disease) exist, and no carrier state (period when the virus is in the body, but the person is not actively sick) occurs. Before smallpox was wiped out, the disease survived through continual person-to-person transmission. Pregnant women and children had a heightened risk for the illness. Smallpox also affected them more severely than normal.
The virus is acquired from inhalation (breathing into the lungs). Virus particles can remain on such items as clothing, bedding, and surfaces for up to 1 week.
The virus starts in the lungs. From there, the virus invades the bloodstream and spreads to the skin, intestines, lungs, kidneys, and brain. The virus activity in the skin cells creates a rash that starts as macules (flat, red lesions). After this, vesicles (raised blisters) form. Then, pustules (pus-filled pimples) appear about 12-17 days after a person becomes infected. Survivors of smallpox often have severely deformed skin from the pustules.
  • Types: Variola major, or smallpox, has a death rate of 30%. Variola minor, or alastrim, is a milder form of the virus with a death rate of 1%. Four types of variola exist: classic, hemorrhagic, malignant, and modified.

    • Classic smallpox is believed to be the most communicable disease—about 30% of unvaccinated people who come in contact with it become infected.

    • The hemorrhagic variety of variola has a much higher death rate (95%) than classic smallpox and leads to death more quickly. Infected people often die before the pustules form. This variety is recognizable by certain types of bleeding sores in mucous tissues. Comprehensive studies documenting almost 7,000 cases of variola found 200 people had this form of the disease (192 died). Pregnant women are more likely to contract this version.

    • Prior to eradication, the malignant or flat form of smallpox affected 6% of the population and evolved more slowly than the classic type. Lesions were flat, often described as feeling velvety. The death rate for this form approaches 100%.

    • The modified variety of smallpox essentially affects people who have been vaccinated and still have some immune response to the vaccine. In a vaccinated population, this version could affect about 15%.


    Smallpox Signs and Symptoms

    After infection, symptoms may take from 7-17 days to appear for major types of smallpox. The virus begins growing in the bloodstream 72-96 hours after infection, but no obvious symptoms appear immediately.
  • People who have contracted smallpox initially develop such symptoms as fever, body aches, headache, chills, and, particularly, backache. Over half of people with smallpox experience chills and vomiting. About 15% become confused.

  • A rash appears 48-72 hours after the initial symptoms and turns into virus-filled sores, which later scab over. The process can take up to 2 weeks.

  • Just after the rash appears, the virus is highly contagious as it moves into the mucous membranes. The body sheds the cells, and virus particles are released, coughed, or sneezed into the environment. The infected person can be infectious for up to 3 weeks (until the scabs fall off the rash). Live virus can be present in the scabs. After the scabs or crusts fall off (in 2-4 weeks), a depression or light-skinned scar remains.

  • Early in the course of the disease, the rash and pus-filled sores can easily be mistaken for chickenpox. Lesions occur first in the mouth and spread to the face, then to the forearms and hands, and finally to the lower limbs and trunk. In contrast, rash from chickenpox progresses from the arms and legs to the trunk and rarely forms in the armpits, palms, soles, and elbow areas.

Diagnosis

Initial diagnosis of smallpox is most likely based on a history and physical examination findings.


  • The doctor may take a throat swab to make the diagnosis of smallpox. A sample from a freshly opened pustule may also be useful in diagnosis. For suspected cases of hemorrhagic smallpox, the doctor may sample fluid from a spinal tap (lumbar puncture). Under certain conditions, cytoplasmic inclusion bodies (also known as Guarnieri bodies) may be visible within the cells. This is also evidence of smallpox infection.

  • Technicians isolate the variola virus in labs with only the highest biosafety levels (Biosafety level IV). The CDC in Atlanta and the US Army Medical Research Institute of Infectious Diseases (USAMRIID) at Ft. Detrick, Maryland, are the only laboratories in the US with these capabilities right now.

  • The doctor sends the possible smallpox sample using special means. Viral cultures, polymerase chain reaction (PCR), and/or enzyme-linked immunoabsorbent assay (ELISA) may be undertaken to make a definitive diagnosis once the sample arrives as the lab.

  • Even one case of smallpox is considered an international public health emergency, and public health officials must be notified of a possible case of smallpox immediately.   



Smallpox Treatment

In the hospital's emergency department, a suspected smallpox victim is isolated. All emergency medical services and hospital personnel exposed to someone with smallpox require quarantine and vaccination if they have not been previously vaccinated.


  • Quarantine: The infected person and anyone who has come into contact with the infected person for up to 17 days prior to illness (including the treating doctor and nursing staff) may be required to remain in isolation until a definite diagnosis is made. If the suspected case is indeed smallpox, these individuals will have to remain in isolation for at least 17 days to ensure that they are not also infected with the virus.

    • The most likely scenario of a smallpox outbreak is from a terrorist attack. Given the highly infectious nature of the organism, researchers estimate that 1 infected person can infect up to 20 new contacts during the infectious stage of the illness. If 1 infected person appears at a hospital, it is assumed that a more people have been infected.

    • Because of the medical, legal, and social implications of quarantine and isolation, coordinated involvement at the federal, state, and local levels is mandatory. In reality, strict quarantine of a large segment of the population is probably not possible.

    • Infectious disease specialists are consulted, along with state, federal, and local health authorities.

  • Treatment: Medical treatment for smallpox eases its symptoms. This includes replacing fluid lost from fever and skin breakdown. Antibiotics may be needed for secondary skin infections. The infected person is kept in isolation for 17 days or until the scabs fall off.

    • Experiments testing new antiviral medications are in progress, but it will be some time before they produce results. Vaccinations and postexposure interventions are the mainstays of treatment.


Smallpox Vaccine

Reports vary concerning the number of existing smallpox vaccine doses in the US and abroad. Studies are under way to determine how much a vaccine dose can be diluted without compromising its effectiveness. The Department of Health and Human Services’ goal is to have one dose for every American in case of a bioterrorism attack. Until then, the executive branch of the federal government, via the CDC, decides who is vaccinated. The state health departments also have access to limited local stock. Reports also vary concerning the World Health Organization’s current storage of smallpox vaccine.


  • The vaccinia (smallpox) vaccine and vaccinia immune globulin (VIG) are available only through the CDC and state health agencies. The calf lymph vaccine is the only one still available although a replacement vaccinia vaccine produced from cell cultures is under development.

  • Currently, the only licensed smallpox vaccine is Dryvax. However, several other vaccines are being assessed in clinical trials. The National Institute of Allergy and Infectious Disease has awarded 2 contracts to Acambis Inc. to develop, test, and supply the US with enough doses of smallpox vaccine to manage a potential outbreak in case of smallpox bioterrorism. Some studies on the existing American vaccine stockpiles indicate that the vaccine would be effective in dilutions of 1:10. However, the occurrence of the "take," a small scab that forms when a vaccination is successful, would be insufficient at this dilution to ensure eradication among an infected population. Further studies at 1:5 dilution are in progress.

  • The US government is unlikely to restart a smallpox vaccination program any time soon, even after obtaining enough vaccine to immunize everyone in the country. This is because the vaccine itself is dangerous to people with immunological disorders, such as HIV, or other immunocompromising conditions, such as certain forms of cancer.

  • The smallpox vaccine actually contains live viral particles of vaccinia, a virus similar to smallpox. This virus usually does not cause disease in humans. However, vaccination with this vaccine could prove deadly in a person with an impaired immunity because the virus is allowed to spread uncontrolled throughout the body. No one with a weakened immune system should receive the vaccine. People with the skin conditions such as eczema or atopic dermatitis should not have the vaccination because of the risk of rare but life-threatening reactions.

  • Most vaccine experts would only recommend a large-scale vaccination program if smallpox were released into the general population as a biological weapon. Vaccination of first responders to a smallpox outbreak has begun. President Bush received the vaccinia protection against smallpox in support of the US troops receiving theirs.

  • Researchers estimate that of the previously vaccinated population, many probably retain some varying degree of residual immunity. This means that if an outbreak were to occur, some people vaccinated years ago, if exposed to smallpox, may respond by developing full-blown disease, mild disease, or no disease. How many years it has been since a person’s last vaccination and, possibly, the total number of vaccinations an individual has received may determine that person’s reaction to exposure to smallpox. Smallpox researchers usually are revaccinated every 3 years.

References

1. Abramowicz M, ed. Drugs and vaccines against biological weapons. Med Lett Drugs Ther. Feb 12 1999;41(1046):15-6. [Medline].
2. Benenson AS, Kaslow RA, eds. Smallpox: end of the story?. In: Viral Infections of Humans: Epidemiology and Control. NY: Plenum Publishing; 1997:861-64.
3. Blanchard T, Smith GL, Whittle H. Vaccines for smallpox. Lancet. Jul 31 1999;354(9176):422. [Medline].
4. Christopher GW, Cieslak TJ, Pavlin JA, et al. Biological warfare. A historical perspective. JAMA. Aug 6 1997;278(5):412-7. [Medline].
5. Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. Aug 6 1997;278(5):399-411. [Medline].
6. Gordon SM. The threat of bioterrorism: a reason to learn more about anthrax and smallpox. Cleve Clin J Med. Nov-Dec 1999;66(10):592-5, 599-600. [Medline].
7. Henderson DA, Inglesby TV, Bartlett JG, et al. Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. Jun 9 1999;281(22):2127-37. [Medline].
8. Katz J. Smallpox vaccine. Science. Sep 24 1999;285(5436):2067. [Medline].
9. Krause RM, ed. Introduction to Epidemiology. Emerging Infections. NY: Academic Press; 1998:14-15.
10. McGovern TW, Christopher GW, Eitzen EM. Cutaneous manifestations of biological warfare and related threat agents. Arch Dermatol. Mar 1999;135(3):311-22. [Medline].
11. The Lancet. Is smallpox history?. Lancet. May 8 1999;353(9164):1539. [Medline].

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