Anthrax

Anthrax (Greek anthrax, coal) is a highly infectious animal disease caused by the Gram-positive, endospore-forming Bacillus anthracis. B. anthracis is found worldwide and can be transmitted to humans by direct contact with infected animals (cattle, goats, sheep) or their products, especially hides. B. anthracis spores can remain viable in soil and animal products for decades. Although B. anthracis is one of the most molecularly monomorphic bacteria, it is now possible to separate all known strains into five categories (providing some clues to their geographic sites of origin) based on the number of tandem repeats in various genes.


There are three forms of anthrax disease. When the bacterium enters through a cut or abrasion of the skin, cutaneous anthrax results. Inhaling spores may result in pulmonary anthrax, also known as woolsorter's disease. If spores reach the gastrointestinal tract, gastrointestinal anthrax may result. B. anthracis bacteremia can develop from any form of anthrax. Discounting the 2001 bioterrorism events in the United States, more than 95% of anthrax is the cutaneous form. Spores and vegetative bacteria are detected by skin macrophages and dendritic cells. In pulmonary anthrax, the spores ( 1 to 2 J.Lm in diameter) are inhaled and lodge in the alveolar spaces, where they are engulfed by alveolar macrophages. Symptoms of gastrointestinal anthrax typically occur after the ingestion of undercooked meat containing spores and include nausea, vomiting, fever, and abdominal pain.

For a successful infection, B. anthracis uses two principal virulence factors to evade host defenses. These are encoded on two plasmids-one involved in the synthesis of a polyglutamyl capsule that inhibits phagocytosis and the other bearing the genes for the synthesis of its exotoxin. B. anthracis produces a complex exotoxin composed of three proteins: protective antigen (PA), edema factor (EF), and lethal factor (LF). Macrophages have many receptors on their plasma membranes to which the PA portion of the anthrax exotoxin attaches. Attachment continues until seven FA-receptor complexes gather in a doughnut-shaped ring. The ring acts like a syringe, boring through the plasma membrane of the macrophage. It then binds EF and LF, and the entire complex is engulfed by the macrophages' plasma membrane and shuttled to an endosome inside the cell.


Once there, the PA molecules form a pore that pierces the endosomal membrane, and EF and LF enter the cytoplasm. Toxin activity results in fluid release, with the formation of edema. Additionally LF prevents the transcription factor nuclear factor kappa B (NFKB) from regulating numerous cytokine and other immunity genes needed to promote macrophage survival. As thousands of macrophages die, they release their lysosomal contents, leading to fever, internal bleeding, septic shock, and rapid death. Without antibiotic treatment and supportive therapy, mortality rates approach 100% for inhalational and gastrointestinal anthrax, and between 20 and 50% for cutaneous anthrax.



Between 20,000 and 100,000 cases of anthrax are estimated to occur worldwide annually; in the United States, the annual incidence was less than one case per year-a rate maintained for 20 years until 2001. The 2001 occurrence of 22 cases of anthrax has spotlighted the real concern about anthrax as a weapon of bioterrorism.

Treatment of anthrax is with ciprofloxacin, penicillin, ordoxycycline (the same antibiotics may be used for all three forms of anthrax) and is successful only if begun before a critical concentration of toxin has accumulated. Although antibiotics may kill the bacterium or suppress its growth, the exotoxin can still eventually kill the patient. Vaccination of animals, primarily cattle, is an important control measure. However, people with a high occupational risk, such as those who handle infected animals or their products, including hides and wool, should be immunized. U.S. military personnel also receive the vaccine.
Treatment of anthrax
THANKS

No comments