Etiological agent = Bacillus anthracis
The malicious distribution of anthrax spores in the United
States during the fall of 2001 (leading to 6 cutaneous and 6 inhalational
anthrax cases) acutely heightened awareness of anthrax as a bioterrorist
agent. However, anthrax is clearly not a new disease. It has been
suggested that the 5th and 6th biblical plagues were systemic
and cutaneous anthrax, respectively, Virgil described outbreaks
of anthrax-like disease among people and animals in Rome in 70
BC and references were made repeatedly to anthrax in the "Hippokratika,"
a series of writing about animal health that was produced in the
900s AD. In addition, this disease is famous in the history of
science because Koch's postulates in 1876 were defined using anthrax
as the model infection.
Bacillus anthracis is a very large, gram (+) rod with characteristic
square ends.
- The name "anthracis" comes from the Greek word
"anthrakis" meaning "coal," referring to
the blackened eschar skin lesions that can develop in people
with anthrax.
- The bacteria commonly grow in long chains in culture.
- The bacteria are encapsulated in vivo.
- The capsule (D-glutamyl polypeptide) inhibits engulfment
by phagocytes.
- Extremely resistant spores develop following vegetative
growth in the environment.
- High CO2 levels in decaying bodies
inhibit sporulation, but sporulation occurs as soon as the organism
is exposed to O2 outside the body.
- Evidence of resistance:
- recovered from 200+ year-old remains in archeological digs!
- resistant to microwave irradiation at 100C for 30 min!
- resistant to conventional pasteurization (will be killed
by ultrapasteurization)
- Bacillus anthracis is found characteristically in
specific regions in the world called "incubator zones"
or "anthrax districts" or "cursed fields."
- These are areas where infected animals die, contaminate the
soils with spores, and these reinfect new animals in a cyclical
pattern. Typically these areas also have alkaline, high N2 content
soils and often alternating periods of rain and drought.
- Anthrax is endemic in tropical and subtropical areas of India,
Pakistan, the Middle East, Asia, Africa, South America and Haiti,
with an estimated 20,000-100,000 human cases/year globally.
- In the U.S., incubator zones remain, and anthrax in animals
continues to occur periodically, in the Dakotas, Nebraska, Missouri,
Oklahoma, Texas, Arkansas, Louisiana, Mississippi and parts of
New Mexico and Minnesota.
- Often the incubator zones follow the routes of old cattle
drive trails, such as the Sedalia cattle trail in Oklahoma. However,
the occurrence of anthrax in cattle in Santa Clara, CA in 2001
points out that anthrax can appear anywhere that local conditions
are conducive to perpetuation of the soils.
Pathogenesis of anthrax:
Spores are ingested by macrophages at the site of entry (skin
wounds or mucosa) and then germinate to the replicative form of
the organism. The organism can spread rapidly via lymphatics
and the bloodstream to colonize phagocytic cells (esp. macrophages)
throughout the body. Ultimately, a high level bacteremia develops,
eventually overcoming the ability of the spleen to filter out
the organism.
- The lesions of anthrax are caused by the coordinate action
of 3 components (edema factor [EF], lethal factor [LF] and protective
factor, which serves as a receptor for EF and LF]) that make
up a holotoxin.
- Edema factor is an adenylate cyclase that increases cAMP
levels and ultimately leads to fluid loss from cells.
- Lethal factor is a protease that induces macrophage death,
with release of massive quantities of inflammatory mediators.
- Lethal factor has also been reported to inactivate MAP-kinase-kinase,
thereby inhibiting the MAP kinase signal transduction pathway
that helps to control cell growth.
- Together the effects of these toxins lead to the edema, hemorrhage
and necrosis that typify anthrax.
- The genes for these toxins and the capsule are carried on
plasmids in the bacteria, and relative virulence may depend not
only on the presence or absence of the plasmids, but also how
many copies of each plasmid a strain carries.
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