Anthrax: The Bioterrorists Weapon of Choice

Highly deadly and extremely insidious, anthrax is not contagious like a common cold. It invades the body via any one of the following routes: a) through a break in the skin, causing cutaneous disease; b) by breathing in the bacterial spores, causing inhalational disease; and c) by ingesting the bacterial spores, causing gastrointestinal disease. All three forms can be deadly but mortality from inhalational or gastrointestinal anthrax approaches 100% if the infection is not treated aggressively and rapidly with antibiotics and supportive care. Even with such intervention, mortality remains close to 50% as a result of delayed detection and diagnosis of infection. For example of the eleven people who contracted inhalational anthrax during the anthrax attacks in 2001, five or nearly 45% died. Such grim statistics underscore the urgent need for newer and better therapies to prevent and treat anthrax infection.

Anthrax is a highly desirable choice for use as a biological weapon by terrorists for several reasons. Large quantities are relatively easy and inexpensive to produce in fermentation tanks. The anthrax bacillus produces spores that resist desiccation, heat, and ultraviolet light and thus have the ability to survive for decades, allowing the bacteria to be easily stockpiled in large quantities. Finally, spores can be aerosolized and delivered in a myriad of ways, including: aircraft, missiles, bombs, contaminated mail, rooftop air-conditioning units, or subway air-handlingsystems.

Even in the hands of a technologically unsophisticated enemy, a large-scale air attack in a dense urban population could produce massive casualties. An aerosol release would be odorless, invisible, and could travel many miles before dissipating. The delayed onset of symptoms that is characteristic of anthrax infection makes detection unlikely before many have died. Anthrax spores are tiny, yet exceedingly deadly. A pinhead can hold enough spores to kill 500 people. In fact, a U.S. Congressional Office of Technology analysis estimated that the release of 100 kg of anthrax could result in a mortality rate comparable to that of a nuclear weapon.

Anthrax Disease
Anthrax disease is caused by Bacillus anthracis, a spore forming bacterium that is naturally found in soil samples throughout the world. Naturally-occurring anthrax disease is rare and somewhat of a medical curiosity, but anthrax as a biological warfare agent has been a long-feared possibility. The Pentagon estimates that up to 10 countries may possess anthrax weapons (stockpiles of which cannot all be accounted for) and 25 countries have other biowarfare agents.

In the fall of 2001, anthrax-contaminated mail was sent through the U.S. Postal Service to Government officials and members of the media — the long-feared possibility thus became a reality. There were seven confirmed and four probable cases of cutaneous anthrax and eleven cases of inhalational anthrax. In spite of aggressive supportive care and antibiotic therapy, five of the eleven patients with inhalational anthrax died. The source of these attacks remains unknown, however, their occurrence prompted the realization that anthrax is a civilian threat as well as a military threat. The mortality of nearly 50% of those exposed to anthrax, even in the face of appropriate medical care, underscores the need for more effective anthrax treatments.

Anthrax: Mechanism of Lethal Action
The major symptoms of anthrax are caused by toxins produced by actively multiplying B. anthracis. Once a critical concentration of the toxin has been reached within the body of an infected individual, death may ensue even if the replicating bacteria are eradicated through administration of antibiotics. This explains why nearly 50% of those infected with inhalational anthrax died in 2001 despite receiving aggressive therapy with antibiotics.

After their secretion from B. anthracis as monomeric proteins, the anthrax toxins PA (protective antigen), LF (lethal factor), and EF (edema factor) combine at the surface of mammalian cells to form toxic cell-bound complexes. Initially, PA binds to its receptor, becomes activated, and spontaneously self-associates to form heptamers, which then bind LF and EF. This assembly of proteins is taken into the cell, resulting in the modification of cytosolic proteins. The outcome is highly toxic: EF and PA produce edema (swelling), particularly in the lungs and chest; LF and PA cause shock and death. Without PA as the assembly and delivery vehicle, EF and LF cannot enter living cells and produce their deadly effects.