Anthrax: Background and Epidemiology

by CDC

Anthrax is one of the great infectious diseases of antiquity. The fifth and sixth plagues in the Bible's book of Exodus may have been outbreaks of anthrax in cattle and humans, respectively. The "Black Bane," a disease that swept through Europe in the 1600s causing large numbers of human and animal deaths, was likely anthrax. In 1876, anthrax became the first disease to fulfill Koch's postulates (i.e., the first disease for which a microbial etiology was firmly established), and 5 years later, in 1881, the first bacterial disease for which immunization was available. Large anthrax outbreaks in humans have occurred throughout the modern era- more than 6,000 (mostly cutaneous) cases occurred in Zimbabwe between October 1979 and March 1980, and 25 cutaneous cases occurred in Paraguay in 1987 after the slaughter of a single infected cow.

Anthrax, in the minds of most military and counterterrorism planners, represents the single greatest biological warfare threat. A World Health Organization report estimated that 3 days after the release of 50 kg of anthrax spores along a 2-km line upwind of a city of 500,000 population, 125,000 infections would occur, producing 95,000 deaths. This number represents far more deaths than predicted in any other scenario of agent release. Moreover, it has been estimated that an aerial spray of anthrax along a 100-km line under ideal meteorologic conditions could produce 50% lethality rates as far as 160 km downwind. Finally, the United States chose to include anthrax in the now-defunct offensive biological weapons program of the 1950s, and the Soviet Union and Iraq also admitted to possessing anthrax weapons. An accident at a Soviet military compound in Sverdlovsk in 1979 resulted in at least 66 deaths due to inhalational anthrax, an inadvertent demonstration of the viability of this weapon. The epidemiology of this inadvertent release was unusual and unexpected. None of the persons affected were children. Whether this is due to differences in susceptibility between children and adults or purely to epidemiologic factors (children may not have been outdoors at the time of release) is unclear.

Anthrax is caused by infection with Bacillus anthracis, a gram-positive spore-forming rod. The spore form of this organism can survive in the environment for many decades. Certain environmental conditions appear to produce "anthrax zones," areas wherein the soil is heavily contaminated with anthrax spores. Such conditions include soil rich in organic matter (pH < 6.0) and dramatic changes in climate, such as abundant rainfall following a prolonged drought. Partly because of its persistence in soil, anthrax is a rather important veterinary disease, especially of domestic herbivores. In addition to encountering anthrax while grazing in areas of high soil contamination, these herbivores may also acquire the disease from the bite of certain flies. Vultures may mechanically spread the organism in the environment. Anthrax zones in the United States closely parallel the cattle drive trails of the 1800s.

Anthrax spores lend themselves well to aerosolization and resist environmental degradation. Moreover, these spores, at 2-6 microns in diameter, are the ideal size for impinging on human lower respiratory mucosa, optimizing the chance for infection. It is the manufacture and delivery of anthrax spores in this particular size range (avoiding clumping in larger particles) that presents a substantial challenge to the terrorist attempting to use the agent as a weapon. The milling process imparts a static charge to small anthrax particles, making them more difficult to work with and, perhaps, enabling them to bind to soil particles. This, in part, may account for the relatively low secondary aerosolization potential of anthrax, as released spores bind to soil, now clumping in particles substantially in excess of 6 microns. This clumping tendency, together with a high estimated ID50 of 8,000-10,000 spores may help explain the rarity of human anthrax in most of the Western world, even in areas of high soil contamination. Other potential bioweapons, such as Q fever and tularemia, have ID50 values as low as 1 and 10 organisms, respectively.

The Disease

Most endemic anthrax cases are cutaneous and are contracted by close contact of abraded skin with products derived from infected herbivores, principally cattle, sheep, and goats. Such products might include hides, hair, wool, bone, and meal. Cutaneous anthrax is readily recognizable, presents a limited differential diagnosis, is amenable to therapy with any number of antibiotics, and is rarely fatal. While common in parts of Asia and sub-Saharan Africa, cutaneous anthrax is very rare in the United States; the last case was reported in 1992. Inhalational anthrax, also known as woolsorters' disease, has been an occupational hazard of slaughterhouse and textile workers; immunization of such workers has all but eliminated this hazard in Western nations. As a weapon, however, anthrax would likely be delivered by aerosol and, consequently, be acquired by inhalation. A third type of anthrax, acquired through the gastrointestinal route (e.g., consuming contaminated meat) is exceedingly rare but was initially offered by Soviet scientists as an explanation for the Sverdlovsk outbreak.

Inhalational anthrax begins after exposure to the necessary inoculum, with the uptake of spores by pulmonary macrophages. These macrophages carry the spores to tracheobronchial or mediastinal lymph nodes. Here, B. anthracis finds a favorable milieu for growth and is induced to vegetate. The organism begins to produce an antiphagocytic capsule and at least three proteins, which appear to play a major role in virulence. These proteins are known as edema factor (EF), lethal factor (LF), and protective antigen (PA). Following the A-B model of toxicity, PA serves as a necessary carrier molecule for EF and LF and permits penetration into cells. Edema toxin results from the combination of EF + PA, lethal toxin results from the combination of LF + PA. These toxins result in necrosis of the lymphatic tissue, which in turn causes the release of large numbers of B. anthracis. The organisms gain access to the circulation, and an overwhelming fatal septicemia rapidly ensues. At autopsy, widespread hemorrhage and necrosis involving multiple organs is seen.

About the Author

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