Webcast Transcript
Anthrax: What Every Clinician Should Know, Part 1
(October 18, 2001)
(View the webcast on the University of North Carolina School of Public Health site.)
Segment 3 of 6
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Dr. Baker (moderator):
Welcome back. You have just heard about issues that relate
to this broadcast in general terms. But now we are going to turn
to Dr. David Stephens, who is in the Meningitis and Special Pathogens
branch here at CDC, and is a professor of medicine and director
of the Division of Infectious Diseases at Emory University School
of Medicine. David has clinical appointments at Emory University
Hospital, the VA Medical Center, and Crawford Long Hospital, as
well as Grady Memorial Hospital here in Atlanta. David, thank you
for being with us today. David will talk to us today about clinical
anthrax.
Dr. David Stephens:
Thank you very much, Ed. I think we have all learned a lot
the last several weeks about anthrax. Let me present to you the
basics. Anthrax is caused by the spore-forming bacterium Bacillus
anthracis. It has historically been a zoonotic disease seen
in sheep, goats, cattle, and follows the ingestion of spores in
the soil. It is often seen now in developing countries. Anthrax
has been rare in the United States. Infections are acquired through
contact with anthrax-infected animals or animal products, or through
(as in the case in Florida) intentional exposure. There are 3 clinical
forms: cutaneous, inhalational, and gastrointestinal. This slide
shows the etiology of anthrax, Bacillus anthracis. It is
a gram-positive, spore-forming, nonmotile bacillus. It is seen on
your left with the characteristic spores, and on your right, in
a Gram stain of clinical material, the vegetative form of the organism
is shown. Again, a gram-positive, spore-forming, nonmotile bacillus.
Anthrax comes in several clinical forms. First is the cutaneous
form, which begins as a papule, progresses through a vesicular stage
to a depressed black necrotic ulcer or eschar. Edema, redness and
a necrosis without ulceration may occur. It’s the form most commonly
encountered in naturally occurring cases. These lesions are often
painless. They may be pussy. They often develop in exposed sites
on the hands, fingers and face.
The next form is inhalational anthrax. This is a clinical syndrome
characterized by a brief prodrome resembling a viral-like illness
occurring over a 2-3 day period, but sometimes longer. It is characterized
by myalgias, fatigue, fever, with or without respiratory symptoms.
This is followed by the development of hypoxia and dyspnea often
with radiographic evidence of mediastinal widening. Meningitis occurs
in 50% of patients. Inhalational anthrax has been extremely rare
in the United States. There were only 20 or so reported cases in
the last century.
The third form of anthrax is gastrointestinal anthrax. This is associated
with abdominal distress, often followed by bloody vomiting or diarrhea
and fever and signs of septicemia. It can present as oropharyngeal
ulcerations with cervical adenopathy and fever. It develops after
the ingestion of contaminated and poorly cooked meat.
This slide shows the virulence factors associated with Bacillus
anthracis. Three important virulence factors are encoded by
a plasmid, the pX01 plasmid, edema factor, protective antigen, and
lethal factor. A second plasmid, pX02, encodes a capsule which inhibits
phagocytosis.
The pathogenesis of anthrax is illustrated in this drawing. This
illustration is by Drs. Dixon and colleagues and was published in
the New England Journal of Medicine in 1999 and is a good
source and good reference for information about anthrax. Spores
may enter the skin, may enter the gastrointestinal tract, may enter
the pulmonary alveoli. They are taken up by macrophages. These spores
vegetate into bacilli. Bacilli then are spread either by lymphatic
spread or hematogenous spread to multiple sites. This organism through
its toxins produces edema. It also produces a proinflammatory cytokine
release characterized by the release of TNF Alpha and other cytokines
leading to shock and ultimately, in some instances, to death. And
as we mentioned earlier, meningitis is also a prominent feature
of—may be a feature of inhalational anthrax.
Now I want to illustrate some of the manifestations of cutaneous
anthrax. The vesicle may develop as early as Day 2. This progresses
to a blackened eschar between Days 4-10 of cutaneous anthrax.
Again, another illustration of cutaneous anthrax from the Armed
Forces Institute of Pathology’s collection showing a vesicle on
your left and ultimately the ulcer and eschar formation on your
right.
This is also a series of pictures from the New England Journal
of Medicine article I mentioned earlier showing cutaneous anthrax
on the face and on the hand in different presentations. Again, for
the purposes of recognition, this is another illustration of cutaneous
anthrax to remind us—to remind you that this often occurs
on exposed areas of the skin. The ulcer often has a heaped-up border
or vesicular ring and progresses to this black eschar during its
clinical course. Sometimes the lesions can be multiple, as seen
here, with a considerable amount of edema.
Now let me turn to inhalational anthrax. This is due to inhalation
of spores. It is felt that the number of spores required to produce
inhalational anthrax (and this is supported by animal data) is between
8,000 and 40,000 spores. The incubation period is 2-3 days with
a range of possibly up to 60 days. Spores are engulfed by macrophages
and transported to mediastinal and peribronchial lymph nodes. The
onset is insidious, with malaise, low-grade fever, non-productive
cough. There is an abrupt development after this prodrome period
of respiratory distress often accompanied by hemorrhagic mediastinitis.
Bacilli are hematogenously spread, and as we mentioned earlier,
in 50% of patients meningitis develops, which is often fatal.
This slide illustrates from an article in the Journal of the
American Medical Association by Inglesby and D.A. Henderson,
et al., looking at mediastinal widening associated with inhalational
anthrax. This is a second illustration of a chest X-ray of mediastinal
widening with pleural effusions.
Now, the differential diagnosis of cutaneous anthrax is long, as
was mentioned earlier—spider
bites or insect bites are often mentioned in the differential diagnosis.
There are a number of other conditions, including ecthyma gangrenosum,
ulceroglandular tularemia, plague, and even staphylococcal or streptococcal
cellulitis.
Now, the differential diagnosis of inhalational anthrax is also
long. It includes a variety of agents that cause pneumonia: Mycoplasma,
Legionella, psittacosis, Q fever, viral pneumonias. Histoplasmosis
with mediastinitis is sometimes mentioned in the differential diagnosis,
as is coccidioidomycosis. For patients who
present with acute sepsis or acute meningitis, we should be thinking
about anthrax in the differential as with down in the Florida case.
There are a number of other causes of pneumonia which probably should
be included in this list as shown.
Now the diagnosis of cutaneous anthrax is made by the characteristic
eschar, in addition culture and Gram stain of vesicular fluid or
exudates, blood cultures, biopsy. PCR is available, as is immunofluorescence
and immunohistochemistry, which have been used in the diagnosis
of the current cases.
Inhalational anthrax is associated with widened mediastinum, but not in all cases. Pleural effusions and blood or
CSF cultures may be positive and Gram stains can be an important
early clue. Again, PCR, immunofluorescence, and immunohistochemistry
are important in establishing the diagnosis.
I have listed the current MMWR guidelines regarding postexposure
prophylaxis to prevent inhalational anthrax. In adults these are
ciprofloxacin or doxycycline, 500 mg po b.i.d. of ciprofloxacin,
100 mg po b.i.d. of doxycycline. The current recommended duration
is 60 days. In children, again, the current recommendations are
ciprofloxacin 10-15 mg/kg po q. 12 hours or doxycycline in the doses
listed. I will comment that this dosing schedule is available on
the CDC Web site.
I want to emphasize that cephalosporins should not be used in the
treatment of Bacillus anthracis infection as Bacillus
anthracis is resistant to cephalosporins. Additional recommendations
concerning prophylaxis to prevent inhalational anthrax will be forthcoming
as additional data is developed.
Now, the recommendations for initial anthrax treatment regarding
inhalational or cutaneous exposure are listed on this slide. Again,
they include ciprofloxacin or doxycycline; ciprofloxacin, 500 mg.
po b.i.d. in adults, or doxycycline, 100 mg. po b.i.d. for 14 days.
Inhalational anthrax is again intravenous ciprofloxacin or doxycycline.
Ciprofloxacin and doxycycline are also currently recommended as
initial therapy for children in appropriate doses. As more information
becomes available on antimicrobial susceptibility these recommendations
may be modified.
I want to end by emphasizing these points. I think it is very important
that we do not panic. We must remain vigilant. Individuals must
be—to develop anthrax—must be exposed to B. anthracis
spores. To cause disease the spores must enter the skin, they must
be swallowed, or they must be inhaled. Disease can be prevented
after exposure to anthrax spores by early treatment with appropriate
antibiotics. And lastly, anthrax is not spread from person to person.
Dr. Baker (moderator):
David, thank you very much for that very comprehensive and
very useful discussion.
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