to survive for long periods of time in soil, its natural reservoir. The disease occurs worldwide, and there are occasional outbreaks of anthrax in livestock in the United States and Canada.

The course and outcome of human anthrax depend on dose and on whether the infection is acquired via the skin, gastrointestinal tract, or inhalation. Most cases of human anthrax involve skin lesions (cutaneous anthrax), whereby the infection is usually acquired as a result of handling infected animal hides or wool, leading to contamination of skin abrasions with B. anthracis. Cutaneous anthrax is the least lethal form of the disease, but still can cause significant mortality of up to 20 percent (Atlas, 2002) if not treated with antimicrobial therapy. Ingestion of food, such as meat contaminated with B. anthracis, can produce gastrointestinal anthrax, which is a serious disease with 25 to 60 percent fatality. This form of the disease is extremely rare in developed countries. The most fulminant and lethal manifestation of anthrax is due to inhalation of B. anthracis spores, causing a highly fatal disease. Inhalational anthrax is generally rare and is observed mainly in individuals who work with animal skins. In the 19th century, it was known as “woolsorter’s disease” and is believed to have been the first documented occupational illness (Leffel and Pitt, 2006). Inhalational anthrax in individuals not likely to have suffered occupational exposure, however, can be a sign of a biological attack with B. anthracis spores.

Inhalational anthrax is a rapidly progressive disease with high mortality and morbidity even when treated with antimicrobial therapy. Anthrax spores germinate when placed in blood or other human or animal tissues that provide a nutrient-rich environment (Inglesby et al., 2002). Upon inhalation, the host’s macrophages (a type of immune system cell) attack and ingest the spores, which are protected from these host cells by the spore coat. The macrophages unwittingly transport the spores to lymph nodes in the respiratory system (Liddington, 2002), where they are released. The lymph nodes provide sufficient nutrients to allow the spores to germinate and begin to proliferate. Proliferation in the lymphatic system in turn allows the bacteria in their “vegetative” state to spread into the blood stream and be disseminated to multiple organs.

The genetic determinants of virulence in B. anthracis reside primarily on two large plasmids, which are extrachromosomal DNA molecules. These plasmids are known as pXO1 and pXO2, and they contain genes that encode for anthrax toxin and a poly-D-glutamate capsule, respectively. Anthrax toxins are composed of a combination of three proteins that work together: protective antigen (PA), edema factor (EF), and lethal factor (LF). When PA combines with EF and LF, toxicity to host cells and a buildup of fluids (edema) in infected tissues (e.g., the lungs) are produced. EF is an adenylate cyclase enzyme that promotes the accumulation of cyclic adenosine monophosphate (AMP), producing a loss of cellular regulation of water and ion metabolism. LF is a metallopeptidase that cleaves proteins of signal transduction pathways, resulting in profound effects that range from cell death to interference with the

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