Anthrax, a zoonotic disease caused by Bacillus anthracis, primarily occurs in domesticated animals, typically herbivores. Humans usually become infected through contact with infected animals or contaminated animal products.1, 2 Several historical references suggest that humans have been aware of anthrax and its effects for thousands of years. The biblical fifth and sixth Egyptian plagues are consistent with anthrax. Historians speculate the fifth plague (occurring around 1500 BC), which affected livestock, led to the sixth plague, known as the plague of boils, as humans became infected through contact with the livestock.1, 2, 3 Homer's Iliad (around 850 BC) describes how, as punishment imposed by Apollo, a “burning wind of plague” first affects domesticated animals, but soon affects soldiers as well. In 29 BC, Virgil describes in his Georgics how handling or wearing “rotten” hides and fleeces would lead to “feverish blisters and foul sweats.” Such symptoms suggest cutaneous anthrax, the most common manifestation of infection with B. anthracis. The cutaneous infection, which spreads by exposure through open wounds, typically develops from a small papule that progresses to a 1 to 2 cm black necrotic ulcer. The disease “anthrax” received its name from the Greek “anthracis,” for coal.4
Major outbreaks have been recorded throughout history. Epizootics are believed to have killed 40,000 horses and 100,000 cattle herded by the Huns during their movement across Eurasia.1 Major outbreaks occurred in Germany in the 14th century and in Russia in the 17th century. During the 1600s, large-scale epizootics, known collectively as the "Black Bane," killed 60,000 cattle in Europe. The economic loss created by the Black Bane was significant and the scientific community of the time recognized the need for the investigation of its cause.5
Anthrax is intertwined with the origins of modern microbiology and immunology. Anthrax was the first disease in history proven to be caused by a microbe. French bacteriologist Casimir-Joseph Davaine first observed the presence of anthrax bacilli in infected sheep's blood in 1863. In 1876, Robert Koch, through his research in Wollstein, Germany, went on to empirically prove that the anthrax bacillus was the etiological agent of anthrax. He did so by isolating the bacilli from cutaneous lesions of sheep, obtaining pure cultures by growing the bacilli on the aqueous humor of ox's eye, and proceeding to inject the bacteria into uninfected sheep.6 In 1881, Louis Pasteur successfully produced a vaccine to protect livestock against anthrax, the first effective live bacterial vaccine to be developed.
Around 1877, John Bell first described inhalational or pulmonary anthrax in England. “Woolsorter's disease,” as it became commonly known, was one of the first recognized occupational hazards caused by a microorganism. Woolsorter's disease is linked to the processing of infected hides and wool, and typically results from inhalation of anthrax spore-containing dust in enclosed factory spaces. John Bell, as it turned out, was passionate about his concern about the working conditions of the woolsorters, at one point chiding the workers themselves for not standing up for their needs: “Do you consider yourselves of less value than horses? Would you quietly go on being poisoned from day to day… rather than speak out like men, and refuse to touch the abominable [wool] till its properly cleaned…” He recommended the implementation of several preventive measures, such as: washing the bale several times before sorting, using a sorting room that is well ventilated and routinely sanitized, storing wool and hair in a room separate from the sorting room, and using general hygienic measures, such as not eating in the sorting room and making provisions for the workers to wash in water. Bell's recommendations were implemented slowly (wool disinfection plants were created by the 1920s) and were not legally enforced until the enactment of the 1897 Regulations by the Home Office.7 These procedures became the standard for the British woolen industry.1, 3 Despite such measures, industrial anthrax continued to be a problem worldwide until the 1950s.
In 1950, Arthur Wolff and Harry Heimann addressed the increasing problem of industrial anthrax in the United States in an epidemiological study. The actual number of industrial anthrax cases in the United States was difficult to estimate and, likely, underreported. One 30-year series (1919-1949) reported over 2,400 cases of anthrax in the United States, 61% of which were of industrial origin.8
Lack of or unreliable reporting methods makes it difficult to estimate with accuracy the true incidence of human anthrax. It was estimated in 1958 that between 20,000 and 100,000 cases occurred worldwide each year. In addition to endemic occupational foci, there were two major recorded anthrax outbreaks in humans during the 20th century. On April 2, 1979, an unusual anthrax outbreak affected over 94 people and killed at least 64 of them in the Soviet city of Sverdlovsk (now called Ekaterinburg). The first victim died after four days; the last one died six weeks later. Officials in the Carter administration suspected the outbreak was caused by an accidental released of aerosolized anthrax from an alleged biological weapons facility located in the city. 1, 9 The United States believed that the Soviet Union was violating the Biological Weapons Convention (BWC) signed in 1972. It was not until 1992 that President Boris Yeltsin admitted, without going into details, that the anthrax outbreak was the result of military activity at the facility.
The world's largest recorded anthrax epidemic in humans occurred during the civil war in Zimbabwe (1979 to 1980). Over 9,400 cases (most of them cutaneous), including 182 fatalities, were reported in a two-year period. Anthrax had been endemic in Zimbabwe (formerly called Rhodesia) before the war. However, fewer than 500 cases had been reported from the years 1926 to 1977.10 The dramatic increase in the number of anthrax cases in 1978 has been attributed to the effects of war in the country, including lack of food, which forced people to handle and eat diseased animals. During this epidemic anthrax among cattle preceded human anthrax in almost all affected areas.
Although health experts saw a need for a human anthrax vaccine early on, the use of live bacterial vaccines was considered too risky for use in humans. It was not until 1904 that investigators considered the possibility of developing acellular vaccines by using filtrates of artificially cultivated B. anthracis.
During the 1950s, clinical trials on the anthrax vaccine were conducted in the United States. This controlled field study involved workers in four mills in the northeast that processed imported animal hides. A human anthrax vaccine was first licensed in the United States in 1970 and produced by Bioport Corporation, Lansing, Michigan. The vaccine, termed Anthrax Vaccine Adsorbed, was developed from an attenuated strain of B. anthracis. The vaccine is derived from cell-free culture filtrate of this strain and, in its final formulation, is adsorbed onto an aluminum salt.3 Since its licensure, the anthrax vaccine has been safely administered to at-risk wool mill workers, veterinarians, laboratory workers, livestock handlers, and members of the United States military.
The introduction of an anthrax vaccine for humans in the United States contributed to the decline in the number of anthrax cases throughout the 20th century. By the close of the 20th century, reports had dwindled to around a case every other year in the United States. There were no cases reported between 1992 and 2000, according to the Centers for Disease Control and Prevention.11 The decline is also attributed to several other factors. The first was the introduction of federal regulations requiring better ventilation systems in wool and animal hair mills in the 1950s. Secondly, there are fewer woolen mills today than in the 1950s; the few remaining mills in the United States buy most of their wool from overseas, where it is fully cleaned before being shipped.3, 5 Finally, the decline is also linked to the widespread use of an improved animal vaccine beginning in the 1960s. This greatly reduced the incidence of cutaneous anthrax from handling livestock.
Anthrax is an endemic cause of human and animal illness in practically all countries. The disease is still endemic in many developing countries, especially where livestock is subject to limited veterinary control. From the 1960s to the 1990s, anthrax cases among animals have been recorded in 27 European countries, more than 20 Asian countries, more than 20 African countries, and Australia. In the New World, anthrax has been reported in the United States, Argentina, Brazil, Uruguay, Venezuela and many others countries. Cases of animal anthrax in the United States occur in Texas, Louisiana, Mississippi, Oklahoma, and South Dakota.
Human cases of anthrax are reported regularly in countries in the Middle East, Africa, and the former Soviet Union.12 In the United States, the annual incidence of human anthrax has declined from approximately 130 cases annually in the early 1900s to no cases during 1993--2000. The last confirmed case of human anthrax reported in the United States prior to the 2001 attacks was a cutaneous case reported in 1992.13 In Texas, there were 24 cases of human anthrax from 1946 to 1998. There was one suspected human cutaneous anthrax case in 2001, which was associated with an anthrax epizootic in Val Verde, Uvalde, Real, Kinney, Bandera, and Edwards counties. The case occurred in a ranch hand who skinned a buffalo that had died.
Anthrax as a biological weapon
Research on anthrax as a biological weapon began more than 80 years ago. Today, at least 17 nations are believed to have offensive biological weapons programs. The US military's concern with the potential use of anthrax as a biological weapon is due to the infectiousness and high mortality rate of inhalational anthrax.2
Germany developed an ambitious biological warfare program during World War I, including covert operations in neutral countries to infect livestock and contaminate animal feed to be exported to the Allied forces. B. anthracis was used to infect Romanian sheep for export to Russia. Argentinean livestock intended for export to the Allied forces were infected with B. anthracis, resulting in the death of more than 200 mules from 1917 to 1918. German sympathizers in the United States attempted to contaminate animal feed and to infect horses intended for United States troops. 2, 5, 8
Japan conducted biological weapons research in occupied Manchuria from 1932 until the end of World War II. Unit 731, a biological warfare research located near the town of Pingfan, was the center of the Japanese biological weapons development program. Prisoners of war were infected with B. anthracis and other pathogens. At least 10,000 prisoners died as a result of experimental infection or execution following experimentation during the Japanese program between 1932 and 1945. At least 11 Chinese cities were attacked with biological agents, including anthrax.2
During World War II, the British started their biological weapons program to counter suspected Japanese and German biological threats. The program's research focused on the viability and "range of spread" of anthrax spores when delivered with a conventional bomb. Testing was conducted on Gruinard Island, off the coast of Scotland. The program ceased when an anthrax outbreak occurred in a coastal town near the island. The island proved surprisingly difficult to decontaminate, the anthrax spores remained viable in the soil for over 36 years. Initially, the British attempted to burn the soil and vegetation, but soil samples still showed viable spores. In 1986, the government hired a contractor to decontaminate the island. The process consisted of saturating the soil with 280 tons of formaldehyde diluted in seawater and removing tons of topsoil; this was followed by a final formaldehyde wash.5 In July of 1989, the British government lifted travel restrictions and declared the island safe.
In 1942, the United States began an offensive biological program in a research and development facility at Camp Detrick, Maryland, where 5,000 bombs filled with B. anthracis spores were produced. After the war, basic research and development activities continued at Camp Detrick. The United States program was expanded during the Korean War (1950-1953). In 1953, the United States began developing countermeasures, such as vaccines and antisera, to protect troops from biological attacks.2, 11 In 1954, a new production facility was built at Pine Bluff, Arkansas. Technical advances by this time allowed large-scale fermentation, concentration, storage, and weaponization of microorganisms.
During the summer 1968, the United States conducted open-air biological tests over the Pacific Ocean, 1,000 miles southwest of Hawaii. These tests further increased international pressure for biological disarmament. On November 25, 1969, during a visit to Fort Detrick, President Nixon renounced the development, production, stockpiling, and use of biological warfare agents. The Department of Defense was required to dispose of existing biological weapons and scale down the program to include research only for defensive measures.1, 5, 11 In the wake of the announcement, the US Army Medical Unit changed its name to the US Army Medical Research Institute of Infectious Diseases (USAMRIID) and shifted its focus to the development of vaccines, protective measures, and detection systems.
During the decades following the ratification of the Biological Weapons Convention of 1972, Iraq and the Soviet Union continued covert biological research programs. The Soviet Union activities were slowly exposed in the years following the 1979 Sverdlovsk anthrax epidemic.
Before the Persian Gulf War, United States intelligence officials had suspected that Iraq had been sponsoring an offensive biological weapons program. In preparation for biological warfare, approximately 150,000 United States troops were given the anthrax vaccine and 30 million 500-mg oral doses of ciprofloxacin were stockpiled. Although no biological weapons were used during the war, Iraqi officials admitted to having biological weapons program that included the research and production of B. anthracis.1, 2 In the early 1990s, it was discovered that Iraq had produced 8,000 liters of anthrax spores. Iraq claims that its biological weapons arsenal was destroyed after the war. Nevertheless, findings during and after the Persian Gulf War lead the United States Army to implement the Anthrax Vaccine Immunization Program on March 10, 1998. Over 340,000 military personnel received 1,023,460 doses of Anthrax Vaccine Adsorbed by July 29, 1999.
The threat of anthrax used as a biological weapon continues. The Aum Shinrikyo religious sect, infamous for releasing sarin gas in a Tokyo subway in 1995, developed a number of biological weapons. It is believed that the sect unsuccessfully tested anthrax-containing weapons before the sarin attack. In the Fall of 2001, anthrax-contaminated letters were sent through the United States Postal Service in the fall of 2001 resulted in 5 fatalities from inhalational anthrax. The first anthrax case of this attack was reported on October 4 by the Palm Beach County Health Department. As of December 5, a total of 22 cases of anthrax had been identified; 11 were confirmed as inhalational anthrax and 11 (seven confirmed and four suspected) were cutaneous.14 Six fatalities occurred due to inhalational anthrax.
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12. 1996-97 Global anthrax report. Presented at the Third Annual Conference on Anthrax, 7–11 September 1998, Plymouth, England.
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14. Anon. Update: Investigation of bioterrorism-related anthrax: Connecticut, 2001. MMWR. December 7, 2001; 50: 1077-1100.
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