Smallpox
Smallpox
Disease History, Characteristics, and Transmission
Introduction
Smallpox is a infectious disease caused by a virus. It was eradicated by 1980 thanks to a global vaccination program, but stocks of variola virus are still held by at least two governments, those of the United States and the Russian Federation. The smallpox virus, also called the variola virus or simply variola, is most often spread by ingestion of virus particles in saliva, either by direct contact or through inhaling droplets dispersed in the air by coughing. When ingested, the smallpox virus first infects the tissues of the throat and nasal cavities, followed by the blood and lymph nodes. About 12 days after infection, a variety of flulike symptoms appear, including fever. Pustules (pus-filled lumps) develop on the skin and are painful at first, then itchy. The more deadly of variola's two varieties, Variola major, kills about 30% of the people that it infects. Sixty-five percent to 80% of those that do survive the disease are disfigured by pitted scars (pockmarks). Some survivors are also blinded by scarring of the retina. Before a vaccine was developed, smallpox was one of the most common causes of blindness worldwide.
Disease History, Characteristics, and Transmission
History
The evolutionary origin of the variola (smallpox) virus, a member of the genus Orthopoxvirus, family Poxviridae, is still obscure. It probably began as a virus in rodents and first infected humans in Africa about 12,000 years ago. The oldest historical reference is in a Chinese document dating to the fourth century. The name “variola,” from the Latin for “spotted,” dates to the sixth century. The term “smallpox” dates to the 1400s, when it was used to distinguish smallpox from syphilis (the “great pox”).
North and South America were free of smallpox until European explorers arrived in the late 1400s. The disease soon spread to the Native American population, which had a much higher mortality rate than the Old World population, probably because there had been no history of natural selection for resistance to the disease. Some historians estimate that 90% of the population of the New World was killed by smallpox. For example, the Aztec population in South America fell from 25 million in 1519 to only 3 million in 1569. Smallpox was not originally spread deliberately by the Europeans, although in the French and Indian wars of the mid-1700s British military forces gave smallpox-infected blankets to Indians who were cooperating with the French—one of the earliest recorded efforts at biological warfare.
In 1796, English physician Edward Jenner (1749– 1823) showed that inoculating a person with pus from a cowpox lesion could prevent smallpox. Inoculation had been discovered before—the earliest known use of smallpox inoculation dates to about 1000 BC, in India—but the idea of inoculation with the harmless cowpox virus had not yet been put forward in Europe by somebody with the professional and class standing to establish it as a known medical fact.
At the time of Jenner's work, smallpox was killing about 400,000 people a year in Europe and millions worldwide. The practice of variolation had already been used to fight smallpox for some decades in Europe and for centuries in Asia. Variolation (named after the disease, variola—the existence of viruses was not yet understood) involved infecting a healthy person with smallpox from a mild case of the disease, either by inserting smallpox-scab material into the nostrils or by rubbing it onto a scratch on the skin. People inoculated in this way were far less likely to die from the more severe form of smallpox than were un-inoculated people. However, there was still a significant death rate from smallpox contracted through variolation (1–2%). Jenner's method of inoculation with cowpox virus was much safer. Although his views were not accepted for a few years, they did catch on. Over 100,000 inhabitants of Britain had been vaccinated with cowpox by 1800 and the British Parliament passed the Vaccination Act in 1840 to make vaccination of infants mandatory and to outlaw variolation. Mandatory smallpox vaccination of children soon became the standard in industrialized countries.
So successful was vaccination that the disease was eradicated from prosperous countries. The last case of smallpox in the United States occurred in 1949. At that time, smallpox was still infecting about 50 million people every year worldwide, about 30% of whom died. Thanks to vaccination, the number of infections dropped to about 15 million per year by 1967. In that year, the World Health Organization (WHO) of the United Nations started a program—the WHO Intensified Smallpox Eradication Program—to eliminate smallpox completely. In 1972, the United States began phasing out mandatory vaccination of schoolchildren. In 1977, the last natural case of smallpox on Earth was seen in Somalia, and in 1980, WHO declared that the eradication campaign had been a success. Smallpox had become the first (and, as of 2007, still the only) major infectious disease to be completely eradicated by human effort.
Characteristics
Smallpox occurs in two forms, variola major and variola minor. Both forms cause similar symptoms, but variola minor is fatal only about 1–2% of the time, compared to 30% or higher for variola major. These two varieties of variola have been recognized for centuries, even before the viral nature of the disease was understood. The two varieties of virus are similar enough that immunity to one confers immunity to the other. Variolation with scabs or pus from mild smallpox cases—an ancient method of immunizing people against smallpox—usually involved infected people with variola minor, granting them immunity from variola major with a fairly low risk of death from the treatment.
The variola virus is most often caught by inhalation of saliva droplets coughed out by a person who already has the disease. Virus particles lodge in the nasal cavities or throat and infect those tissues first, then grow in the lymph nodes nearest the site of infection. (Lymph nodes are small, bean-shaped organs that filter lymph, a clear fluid that is drained from tissues through the system of lymphatic vessels and then returned to the blood.) The patient has no symptoms during this phase of the disease. After three or four days, virus particles spread through the bloodstream to the bone marrow, spleen, and other parts of the lymphatic system, where they multiply. The smallpox virus, like all viruses, multiplies by tricking body cells into manufacturing more virus particles, using genetic material supplied by the virus itself. More smallpox virus particles appear in the blood 8–10 days after infection. During these initial phases— termed the incubation period—the patient feels healthy and cannot infect other persons. About 12–14 days after infection (with a range of 7–17 days), the incubation period ends and the next phase of the illness—termed the prodrome, prodromal stage, or preeruptive stage— begins suddenly. In this stage, symptoms appear, but do not yet include the skin eruptions or lesions that make the patient capable of spreading the infection. Prodromal symptoms may include fever and last 2–4 days. After the prodromal stage, the disease can next show four distinct courses or clinical presentations. These are termed ordinary smallpox, modified smallpox, flat smallpox, and hemorrhagic smallpox.
Ordinary Smallpox Ordinary smallpox accounts for about 90% of cases. After the prodromal stage, the fever may drop and the patient feels less sick. The smallpox rash then appears as small red spots (lesions) on the tongue, on the inside of the mouth, and at the back of the throat (on the pharynx). The mouth-and-throat lesions grow, releasing billions of virus particles into the saliva that may then be transmitted to other people. The lesions in the throat trigger coughing, which tends to spread the disease. About 24 hours after the appearance of the mouth-and-throat rash, a rash appears on the skin, first on the face and limbs and then on the trunk. The rashes become lumpier and fill with fluid. In about a week the lumps, now filled with pus and called pustules, have become round, raised, and hard to the touch, like beads under the skin. Generally, the more severe the rash, the greater the chance that the patient will die. In another week the fluid in the pustules has been absorbed and a crust or scab begins to form over them. Finally, a week later, the crusts fall off, leaving bleached skin and indented scars. At this point the patient has ceased to be infectious.
Modified Smallpox Modified smallpox is a milder form of the disease that sometimes occurs in persons who have been vaccinated. The fever does not return after the prodromal phase and the rash appears more quickly but produces fewer and smaller lesions. This form of the disease is almost never fatal.
Flat Smallpox In flat smallpox, the raised lesions or pustules of ordinary smallpox do not develop on the skin. This form of the disease has been observed in a study in India to occur about 5–10% of the time, usually in children. The prodromic stage is more severe in flat smallpox, and so is the rash on the tongue and at the back of the throat. The skin lesions appear slowly and are flatter than in ordinary smallpox. This form of the disease is usually fatal.
Hemorrhagic Smallpox Hemorrhagic smallpox occurs about 2% of the time in India. It is called “hemorrhagic” because to hemorrhage means to bleed; patients with this form of smallpox begin to bleed—sometimes only a few days into the course of the disease—in the eyes, gums, mouth, and skin lesions. Death usually occurs about a week after the onset of symptoms, before the skin rash has had a chance to develop much.
Transmission
Variola virus is quite virulent, that is, easy to spread from one person to another. Only a small number of virus particles need be taken into the body to cause the disease. Virus concentrations in the saliva and mucus are highest during the first week of symptomatic illness (after the prodromic stage), and it is during this time that the patient is most infectious. However, the patient remains infectious until all crusts have separated from the healing pustules on the skin. Virus particles can be transmitted through the air or by direct contact with the patient or materials they have touched. They do not enter through the skin, but may be transferred to the mucous membranes of the mouth, eyes, or nose by hand contact.
Scope and Distribution
Smallpox infection no longer occurs naturally. As of 2007, the only stocks of the virus known to exist are held by the governments of Russia and the United States.
Treatment and Prevention
Since smallpox is caused by a virus, it cannot be treated using antibiotics (which kill only bacteria). Nor, as of 2006, had any antiviral drug had been approved by the U.S. Food and Drug Administration for the treatment of smallpox. The Centers for Disease Control and Prevention suggested that the antiviral drug cidofovir might be used for smallpox under the supervision of an infectious diseases specialist, but warns that the drug can injure the kidneys. The usual treatment is strictly supportive: the patient is kept clean, sheltered, and hydrated, while their own immune system fights the infection.
The main method of preventing transmission of smallpox is to avoid having other people ingest the virus. To this end, all persons having contact with a smallpox patient should wear fitted breathing masks and disposable gloves, gowns, and shoes. Breathing masks prevent the inhalation of virus particles.
Where high-technology medical settings are available, a smallpox patient should be isolated in a room with negative pressure, that is, one where the air-circulation system draws air into the room and filters it before pumping it out rather than allowing it to escape. This is because smallpox transmission can be caused by virus particles conveyed in tiny, airborne particles. Air that has contacted a smallpox patient must be assumed to be potentially carrying the disease.
WORDS TO KNOW
ERADICATION: The process of destroying or eliminating a microorganism or disease.
PRODROME: A prodrome of a disease is a symptom indicating the disease's onset; it may also be called a prodroma. For example, painful swallowing is often a prodrome of infection with a cold virus.
VARIOLATION: Variolation was the pre-modern practice of deliberately infecting a person with smallpox in order to make them immune to a more serious form of the disease. It was dangerous, but did confer immunity on survivors.
The primary method of preventing smallpox infection is the smallpox vaccine. It is not made using smallpox virus, but a live vaccinia virus strain. The standard vaccine available today was developed in the early 1980s and is supplied as a freeze-dried powder in 100-dose units. The dry vaccine mixture contains several antibiotics and is mixed with a special liquid consisting of water, glycerin, and phenol as a preservative. The vaccine is guaranteed to confer immunity for at least 10 years, but there is evidence that it may confer immunity for far longer. About 15 million doses of this vaccine are stockpiled in the United States as of 2007; this number could be increased in an emergency by diluting the vaccine to increase its volume by a factor as great as 5.
Smallpox vaccine causes a number of medical complications, but death is rare. It should not be taken by pregnant women, because the vaccinia virus can cause fetal vaccinia, an infection of the fetus with the vaccinia virus. This usually causes stillbirth or death of the child soon after birth.
Impacts and Issues
The eradication of smallpox was one of the major public health success stories of the twentieth century. This effort demonstrated that international cooperation on important health issues could be achieved. Moreover, it also demonstrated that it is possible to eradicate an infectious disease with an effective vaccination program, and that vaccination is a useful preventative method in the fight against infectious diseases. Smallpox stocks still exist, however, and if released into the environment, could cause an epidemic in an unvaccinated population. As of 2007, a large but unknown percentage of Americans were not immune to smallpox. This uncertainty arises because nobody is sure how much immunity is still conferred by immunizations received before 1972.
SMALLPOX: AN ANCIENT DISEASE
As a disease, smallpox has an ancient history. Studies of the mummy of Pharaoh Ramses V, who died in 1157 BC, revealed symptoms of smallpox infection.
Smallpox has long been considered as a biological weapon of war or terror. In the mid–1700s, British army commanders in what is now Canada gave smallpox-infested blankets to Indians who were collaborating with the French (the enemies of the British at that time). Systematic bioweapons research by the U.S., Japan, the Soviet Union, and other countries began during World War II but concentrated on bacteria (e.g., anthrax) rather than viruses for some years. In the 1950s, American bioweapon developers, concerned that the Soviet Union might be developing smallpox and other viruses as well, began studying techniques for producing freezedried smallpox powder that could be efficiently spread over a wide area. In the mid-1960s, Army planners approached the U.S. bioweapons labs at Fort Detrick, Maryland, to see whether biological weapons could be used to attack military traffic between North and South Vietnam. Smallpox was considered the best candidate, but the idea was abandoned because U.S. use of biological warfare might be exposed, North Vietnam might retaliate in kind, and the disease might spread to friendly forces. At about this time, Soviet agents secretly sampled highly virulent smallpox strains in India for use in the large Soviet bioweapons program. In 1969, President Richard Nixon abolished the U.S. biological warfare program and supported an international ban on biological weapons. This was formalized as the 1972 Biological and Toxic Weapons Convention Treaty, which was eventually signed by the Soviet Union and most of the rest of the countries of the world.
After biological attacks using anthrax occurred in the United States in 2001, the issue of smallpox as a potential agent of biological terror again surfaced. In the United States, researchers, members of the military, key health personnel, and first responders in the community were vaccinated against smallpox so that response to any future threat by the smallpox virus can be prompt. Large reserves of smallpox vaccine are maintained by many countries in the developed world and the World Health Organization.
Today, the smallpox virus is only known to exist in two secure repositories, both authorized by WHO: one is at the Centers for Disease Control and Prevention in the United States and the other is at the State Research Center of Virology and Biotechnology of the Russian Federation in Siberia. Debate continues on whether the last remaining stocks of smallpox virus should be used for research or destroyed.
Primary Source Connection
Disease outbreaks are reported by World Health Organization (WHO, Epidemic and Pandemic Alert and Response (EPR), Disease Outbreak News.
WHO maintains the EPR as a “major pillar of global health security aimed at the detection, verification and containment of epidemics. In the event of the intentional release of a biological agent these activities would be vital to effective international containment efforts.”
As the bulletin below indicates, the system is also used to clarify information and allay fear concerning infectious agents that could be used as biological weapons.
ACCIDENTAL EXPOSURE TO SMALLPOX VACCINE IN THE RUSSIAN FEDERATION
20 JUNE 2000
DISEASE OUTBREAK REPORTED
The recent report of illness amongst 8 young children in Vladivostock who had played with discarded ampoules of smallpox vaccine has now been confirmed by the Ministry of Health of the Russian Federation. Laboratory confirmation of the illness in the children is being sought. The report has evoked much public concern. In some of the reports, there were misconceptions about the components of the vaccine used to prevent smallpox, and about why any country might still be retaining stocks of smallpox vaccine. This note aims to clarify these issues.
- Smallpox vaccine is not made from smallpox virus. The vaccine which was used for centuries to vaccinate against smallpox was not made from smallpox, but from vaccinia virus. Vaccinia is a different virus from the virus which causes smallpox. However, it is a member of the same family of viruses to which the smallpox virus belongs. The smallpox virus is also known as variola virus. Mass vaccinations with smallpox vaccine made from vaccinia virus led to the eradication of smallpox announced by WHO in 1980. People vaccinated with smallpox vaccine (vaccinia) develop reactions to it which range from mild and transient to severe, and very rarely, fatal.
- Two countries still keep smallpox virus (variola) stocks. Although smallpox disease has been eradicated, two laboratories still hold stocks of smallpox virus (variola). These are the WHO Collaborating Centres in Atlanta, USA and Koltsovo, Russian Federation.
- Many countries still hold smallpox vaccine (vaccinia) stocks. WHO recommends that countries which still have stocks of smallpox vaccine (vaccinia) maintain these stocks. This recommendation has been made for two reasons. Firstly, small amounts of vaccine are still needed to vaccinate laboratory personnel handling vaccinia virus and other members of this virus family. Some of these viruses are found in nature and cause illness among animals, and some are used in research to make new, safer vaccines against a variety of infectious diseases. Secondly, smallpox vaccine (vaccinia) will also be needed in case of a deliberate or accidental release of smallpox virus (variola), which is a very unlikely event but currently of great concern to some countries. For further information on this topic, see the summary of the recent meeting of the WHO Advisory Committee on Variola Virus Research, published in the Weekly Epidemiological Record.
- Disposal of biological materials and pharmaceuticals. All biological materials and pharmaceuticals such as vaccines, drugs and diagnostic specimens should be disposed of safely. Some may require inactivation before disposal. This can be accomplished by autoclaving or incineration.
World Health Organization
WORLD HEALTH ORGANIZATION, EPIDEMIC AND PANDEMIC ALERT AND RESPONSE (EPR), DISEASE OUTBREAK NEWS “ACCIDENTAL EXPOSURE TO SMALLPOX VACCINE IN THE RUSSIAN FEDERATION: 20 JUNE, 2000.” <HTTP://WWW.WHO.INT/CSR/DON/2000_06_20E/EN/INDEX.HTML> (ACCESSED APRIL 12, 2007)
See AlsoSmallpox Eradication and Storage; Viral Disease; World Health Organization (WHO).
BIBLIOGRAPHY
Books
Ian, Glynn, and Jennifer Glynn. Life and Death of Smallpox. London: Profile Books, 2005.
Miller, Judith, et al. Germs: Biological Weapons and America's Secret War. New York: Simon & Schuster, 2002.
Rodriguez, Ana Maria. Edward Jenner: Conqueror of Smallpox. Springfield, NJ: Enslow, 2006.
Periodicals
Cohen, Jon. “Leaks Produce a Torrent of Denials.” Science 298 (2002): 1313–1314.
Esposito, Joseph J., et al. “Genome Sequence Diversity and Clues to the Evolution of Variola (Smallpox) Virus.” Science 313 (2006): 807–812.
Koopman, Jim. “Controlling Smallpox.” Science 298 (2002): 1342–1344.
Web Sites
Centers for Disease Control and Prevention. “Emergency Preparedness and Response: Smallpox.” <http://www.bt.cdc.gov/agent/smallpox/> (accessed February 21, 2007).
Journal of Young Investigators. “Smallpox: Historical Review of a Potential Bioterrorist Tool.” September 2002. <http://www.jyi.org/volumes/volume6/issue3/features/bourzac.html> (accessed February 21, 2007).
World Health. “Smallpox.” <http://www.who.int/mediacentre/factsheets/smallpox/en/> (accessed February 20, 2007).
Larry Gilman