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Anthrax in a BioWar Environment
by Sheldon Campbell, MD
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ANTHRAX IN A BIOWAR ENVIRONMENT
Sheldon Campbell MD, PhD 12/2/90
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The following document is derived entirely from the open medical
literature and my clinical (and to a certain extent, tactical and
political) judgement. There are two important limitations to the
following data. First, I am a medical microbiologist, not a clinical
infectious disease specialist. Although the information is derived
from an exhaustive review of the available medical literature, and I
doubt that an ID person would significantly modify my
conclusions, there's a limit to the usefulness of knowledge derived
entirely from the literature. I've tried to indicate places where this
might be important. Second, I have no access to any classified
information, nor even to much of the open military literature.
Information on the nature of the potential biological threat might
supersede anything I say here.
DISSEMINATION AND INFECTION
It is expected that anthrax spores will be disseminated by the
aerosol route, causing inhalation anthrax. Because atmospheric
stability is important to efficient spread, and because sunlight is
highly toxic to biological agents, they are most likely to be
delivered at night. Particles from 1 to 5 microns in size are most
efficient in causing infection, and can be present in clinically
significant quantities more than 20 km downwind. The inhaled
infectious dose in man is quite high (est >3,000) -- nonimmunized
workers in animal-hair mills have been shown to inhale 150-700
infected particles/hour <=5 microns, but are rarely affected. The
addition of detergents, irritants, or immunosupressives to the
aerosol may decrease the infective dose needed by up to 10-fold.
It's likely that heavy smokers would be more susceptible, and to
larger particle sizes. There is no data available on this, however.
CLINICAL PRESENTATION AND DIAGNOSIS
Inhalation anthrax (also known as Woolsorter's disease) is a
biphasic illness. The first phase occurs when the spores are carried
to the mediastinal lymph nodes by pulmonary macrophages and
cause a suppurative infection with edema and hemorrhage. This
phase is characterized by nonspecific flu-like symptoms; mild
fever, malaise, fatigue, myalgia, nonproductive cough, and at times
a sensation of chest oppression or pressure. Rhonchi may be heard
with a stethoscope. The presence of such symptoms in a large
number of personnel at once should raise the suspicion of anthrax.
This phase can last for several days, or for as little as 24 hours in
heavy infections, and can be followed by an asymptomatic period.
A helpful radiographic sign is symmetrical enlargement of the
superior mediastinum due to lymph node enlargement. The disease
is treatable in this stage, but blood cultures are probably negative
(no data on this). Sputum cultures might have a higher yield,
particularly if anthrax is specifically looked for.
The second phase develops suddenly with the development of
severe shortness of breath and cyanosis. Hypotension and shock
occur. The temperature may be elevated or subnormal due to shock,
and perspiration is often profuse. Stridor may be present due to
enlargement of the lymph nodes near the trachea. Chest exam
shows moist, crepitant rales and signs of pleural effusion. Blood
cultures are positive, and the bacteremia may be high enough for
organisms to be visible on a Gram stained smear. The second, acute
phase typically lasts less than 24 hours and usually ends in death
despite therapy, due to the high number of toxin-producing
organisms present by this stage in the illness.
RECOMMENDATIONS FOR THERAPY
The standard therapy for inhalation anthrax is intravenous
penicillin G by continuous infusion, 50 mg/kg or 80,000 U/kg in
the first hour, followed by 200 mg/kg or 320,000 U/kg over the
following 24h. No data are available on the value on penicillin IM,
but it would likely be less effective and larger doses might be
required. Streptomycin, 1-2 g/24h IM has been described to be
synergistic in combination with penicillin. An alternative regimen
is erythromycin, 4g/24h by continuous infusion. In a biological
warfare situation, however, I would recommend that vancomycin be
a part of any regimen, in a dose of 500 mg every 6 hours.
Intramuscular injection of vancomycin is painful. An inferior but
possibly useful substitute for vancomycin would be oxacillin,
methicillin, or nafcillin in appropriate dosages (use the PDR).
Other drugs to which B. anthracis is generally considered
susceptible include the first-generation cephalosporins,
tetracycline, and chloramphenicol. Adjuvant therapy with
hydrocortisone, 100-200 mg/day may be helpful in the case of
malignant chest-wall and neck edema. As soon as in vitro
susceptibility data are available, therapy should be adjusted to
include effective drugs, and drugs to which the isolate is resistant
should be eliminated.
In animal models, therapy for less than 2 weeks was ineffective due
to persistence of infective spores in the lungs -- no data are
available in humans. If antibiotics are present in limited quantities,
the least ill patients should be treated first, as patients in the
second phase of the illness have a poor prognosis even with
effective therapy. I do not agree with the recommendation of Col.
Wiener (see below) of creating test groups to be treated each with
only one drug to see which works. Unless communications and
support services degenerate to a point of complete chaos, in vitro
susceptibility testing will provide equivalent data more rapidly. It
is, however, appropriate to treat as many people as possible with
whatever antibiotics if limited quantities are available.
RATIONALE FOR THERAPEUTIC RECOMMENDATIONS
Some discussion of these recommendations is in order. Most
clinical isolates of anthrax are penicillin-susceptible. Virulent
strains resistant to penicillin have been described at least since
1970, however. Because penicillin is cheap, it is likely that any
strain used for biological warfare will be penicillin-resistant. Most
penicillin-resistant organisms do so by producing beta-lactamases.
The oxacillin group of semisynthetic penicillins are resistant to
many beta-lactamases, thus the recommendation of these drugs as
an alternative to vancomycin.
On the other hand, vancomycin resistance, except for a few strains
of enterococcus, is primarily a rare laboratory phenomenon. In
addition, vancomycin is an expensive compound and it would be
prohibitive to produce industrial quantities of resistant organisms.
Thus vancomycin should be considered the gold standard of
empirical therapy in a biowar environment. Similarly, developing
and producing a strain resistant to both erythromycin and penicillin
would more than double the cost and difficulty of producing the
bugs unless fairly sophisticated molecular techniques were
employed. If I were running things for the Iraqis, I'd be using a
penicillin-resistant strain without any other modifications, since
each piece of genetic baggage the organism has to carry will have
unpredictable effects on virulence, and it's a very effective weapon
already.
EARLY WARNING, IMMUNIZATION, AND REFERENCES
REQUEST FOR INFORMATION:
Early warning is possible to biological attacks. Radar can detect
aircraft flying suspicious attack patterns. There are descriptions in
the literature of air-sampling arrangements which can be combined
with microculture or immunoassays to provide rapid identification
of an attacking organism. I have no idea what's currently being done
-- can anyone help out here without betraying secrets?
REQUEST FOR INFORMATION:
Anthrax vaccines are available and have been given to high-risk
groups such as textile workers. I have no data about what's going on
in Desert Shield -- surely this at least is open information (it'd be
hard to hide).
REFERENCES
Manchee RJ et al (1981), Bacillus Anthracis on Gruinard Island, Nature 294, 254-255.
Manchee RJ et al (1983), Decontamination of Bacillus Anthracis on Gruinard Island?, Nature 303, 239-240.
Wiener SL (1987), Strategies of Biowarfare Defense, Military Medicine 152, 25-28.
Brachman PS (1980), Inhalation Anthrax, Proc. NY. Acad. Sci., 83-93.
Knudson GB (1986), Treatment of Anthrax in Man: History and
Current Concepts, Military Medicine 151, 71-77.
Multiple Authors (1963), Defense Against Biological Warfare -- A
Symposium, Military Medicine 128, 81-146.
Health Aspects of Chemical and Biological Weapons, Report of a WHO Group of Consultants, World Health Organization, Geneva, Switzerland, 1970.
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