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Transcript
To: Alma College Community
From: Tim Keeton, Assistant Professor of Biology, [email protected]
Re: Current anthrax terror campaign, October 24, 2001
Alma College community,
With the recent terrorist campaign have come numerous and often conflicting reports and uncertain hype regarding the
nature of anthrax. Recently the mass media has done quite a bit to correct some of the initial confusion and perhaps panic,
but many of you no doubt still have many questions regarding this ‘bioterrorist’ weapon.
What follows is a short and certainly not all-inclusive list of frequently asked questions regarding this disease and its
potential as a weapon of mass destruction. Not being an expert on anthrax itself, I refer everyone to definitive sites and
files listed by the Centers for Disease Control and the American Medical Association. I will be glad to field any specific
questions anyone may have to the best of my ability. I also refer you to one of the sites below:
Centers for Disease Control (infectious disease ‘A to Z’)
The American Medical Association
Nature science journal (for the scientists in the crowd)
http://www.cdc.gov/health/disease.htm
http://www.ama-assn.org
http://www.nature.com/nature/anthrax/
1. What is ‘anthrax’?
The term refers to a soil bacterium called Bacillus anthracis, or, more recently, to the illness the organism can cause if
it infects your body. The illness is caused by a protein toxin manufactured by the bacterium, so it is technically correct
to call it a bacterial poisoning. This means that if bacterial growth occurs in a sensitive area (in this case the lungs),
death from the toxin can occur before any major, easily recognized symptoms appear. Other examples of bacterial toxin
poisonings you may have heard of would be tetanus (Clostridium tetani) or botulism (Clostridium botulinum).
B. anthracis is also capable of forming a ‘spore’ as a normal part of its life in the wild. This is a protective mechanism
that allows the bacterium to survive harsh environments. This is also what makes this bacterium a candidate for biological
warfare, as the spore can survive conditions (desiccation, heat, long-term storage, mild explosions, and some disinfectants)
which would kill the living bacterium. In general it is the spores which are worrisome, and indeed it is the spores which are
being used to contaminate certain items of mail sent to government officials and the press.
Anthrax infections are troublesome as the symptoms of infection can be extremely vague. The symptoms of the most
dangerous respiratory infections appear to be like those seen with many other common infections such as the flu or the
common cold (both caused by viruses). Proper treatment almost requires that the person have some knowledge of their
exposure, as by the time respiratory symptoms show it may be too late to treat the illness, as is being confirmed now
with postal worker deaths (more below).
Anthrax used to be a common disease of many domesticated farm animals, particularly sheep, and in fact
this infection (along with tuberculosis) was used by the microbiologist Robert Koch in the late 1800’s to
prove that certain diseases were in fact caused by bacteria. Our understanding of the infectious disease
process, combined with excellent veterinary systems, has all but wiped out this disease in North America.
2. Does the same bacterium cause all three ‘forms’ or ‘types’ of the disease?
Yes! The three forms of anthrax differ only in their site of entry into your body. The most common environmental (natural)
form of the disease is the cutaneous form. This occurs when spores gain access to the lower layers of your skin through
abraded skin or an open wound. This was at one time called ‘Wool Sorter’s Disease’ as individuals working in the wool
industry could obtain an infection by handling sheep hides and/or wool.
Cutaneous anthrax is 10-20% fatal if untreated. Once an infection is diagnosed (it may take weeks for the characteristic
black ulcer to show at the site of infection) it is easily treated by any number of antibiotics that kill Gram Positive
bacteria, such as several of the penicillins, and of course by ‘Cipro’, ciprofloxacin. To date several cases of cutaneous
anthrax have been reported (the youngest being a seven-month old infant), and according to reports all of the cases
are responding to treatment.
Gastrointestinal anthrax is rare in humans but can be fatal if not treated. To date no cases of this form have been
diagnosed due to terrorism. It requires a heavy load of spores directly into the digestive system to cause this form of
the disease, and historically this rare form of the illness has been caused by the consumption of under-cooked meat
from an infected animal.
Inhalation (or pulmonary) anthrax is the third and most deadly form. If enough spores gain access to the deepest passages
of your lungs the bacterium will grow quickly and you can be fatally poisoned before the obvious signs of a bacterial
infection in this part of your body (a bacterial pneumonia) can make themselves apparent. The best estimation regarding
the number of spores required to cause a dangerous infection range from a few thousand to tens of thousands per person.
However, remember this is a microorganism, and this number of spores can appear to be a few particles of dust. If
a victim knows of his/her exposure, immediate antibiotic therapy in most cases prevents the bacterium from growing
and causing illness. But if exposure is not noticed immediately, even aggressive intravenous antibiotic therapy may not
save the exposed individual once clear symptoms appear. As of this date (10/23) we have seen one confirmed and two
probable fatalities, and at least two additional patients undergoing antibiotic treatment for this form of the disease.
3. Is the infection treatable?
In general, yes. Most cutaneous cases can be easily treated with one of several antibiotics and the patient saved, even if
the infection appears to have gained the upper hand. Cutaneous infection causes alarmingly large black ulcers composed of
dead and decaying skin. The toxin however appears to remain fairly localized or diluted. Again, if untreated even this form
of the disease can be fatal. Inhalation infections are much more difficult to treat, but these individuals can still be saved
by aggressive intravenous antibiotic therapy if it is initiated early enough.
To date, all isolates have been responding to the common antibiotic Ciprofloxacin and/or the penicillins.
See CDC page www.bt.cdc.gov/DocumentsApp/Anthrax/10222001Advisory/10222001Advisory.asp for details. A major
worry is the possible use of antibiotic-resistant strains of the bacterium (which we know were
developed by the Soviet Union prior to its collapse). These strains would be extremely worrisome
initially, but even they would most likely be responsive to at least one modern antibiotic.
4. Is anthrax contagious?
In short, no. Cutaneous anthrax could conceivably be transmitted from an active ulcer if it were rubbed directly against an
open wound in your skin. The bacterium does not fare well out on its own, and any bacteria shed by an infected individual
which did happen to form a spore effectively would be few and far between. Inhalation anthrax is potentially more difficult
to transmit from person-to-person, as it is difficult for an infected individual to aerosolize enough organisms and spores
(via coughing) to infect a healthy person. Remember, an active inhalation infection will kill you due to poisoning from the
bacterium’s toxin before you have an easily-diagnosed, phlegm and fever and cough producing pneumonia.
Certain other potential biological warfare agents are in fact extremely contagious. Smallpox is caused by a virus which
can cause extremely contagious fatal illness in humans. Smallpox vaccination programs ended in the U.S. in the early
1970’s following the eradication of the disease, and it is likely anyone vaccinated prior to that date no longer is
immune. Smallpox weapons would truly be dangerous, and renewed vaccination campaigns are likely if this agent is
ever used. Production of smallpox virus is much more complicated than bacteria such as B. anthracis, and generally
it is considered unlikely that it could be produced outside of a large government-funded research lab. The only
known stocks of smallpox virus exist at the CDC in Atlanta and a similar lab facility in the former Soviet Union.
5. What are these different ‘strains’ of the bacterium,
and what does it mean when I read about a ‘man-made’ strain?
Any population of bacteria is bound to contain individuals who differ slightly in their genetic makeup, just like the human
species contains many different races. Most strains of the bacterium found in the wild are capable of causing disease in
humans. Bioport in Lansing manufactures our country’s only anthrax vaccine using a weakened strain that would not likely
be used to make a bioweapon. Strains may differ in their antibiotic sensitivity also.
The ‘man-made’ bacteria which have been mentioned in the press more than likely refer to antibiotic-resistant
strains generated via genetic engineering, which we have NOT seen to date. This terminology could
also refer to various innocuous genetic markers present within the organism’s chromosome. To date no
definitive information regarding these matters has been released and confirmed by the CDC or the FBI.
6. What is done for individuals who are exposed?
If exposure is strongly suspected, antibiotic treatment is started immediately and the suspicious source is shipped to one
of a few labs capable of identification of anthrax. Also, blood samples are taken, and a nasal swab performed. From the
samples technicians will try to grow the bacterium and positively identify it as B. anthracis. The bacterium’s growth could
be evident in a lab within 24 hours, and the genetic I.D. complete in approximately another day. Further fingerprinting
of the strain may take considerably more time.
An important aspect of the initial culturing is antibiotic sensitivity testing. The bacteria grown from the patient’s blood
sample is grown in the presence of paper disks soaked with a variety of antibiotics. Effective antibiotics will prevent bacterial growth around the disk containing that antibiotic. This confirmation can be complete within two days if all goes well.
7. If there is a vaccine, why aren’t we all being vaccinated?
Bioport in Lansing is the only maker of anthrax vaccine in this country. Technically the vaccine is known as a ‘cell-free
extract’ produced by a weakened strain of the bacterium. Like all vaccines, it is not without its side-effects and risks,
so it has not been given to the general public. Your chances of exposure are still extremely low - far far lower than
your chances of negative side effects from the vaccination (ALL vaccinations carry some risk that must be weighed
against the benefits).
Add to this the fact that Bioport cannot currently manufacture enough for everyone if we wanted! The company has had
many run-ins with the FDA over quality control issues, and this has hampered the Federal government’s desire to have all
Armed Forces personnel vaccinated. For several years only Armed Forces personnel serving overseas have been vaccinated.
Ultimately, assuming the risks of exposure increase dramatically, we may all begin being vaccinated, but this has not
even been discussed seriously that I know of. The vaccine is believed to be about 80% effective in establishing some
degree of immunity to the bacterium and its toxin. Its effectiveness against serious inhalation anthrax is not well known.
8. Why don’t we all simply start taking Cipro? Several reasons:
a. Chronic antibiotic use can lead to opportunistic infections. A fairly common side-effect of chronic long-term antibiotic
use is something called ‘antibiotic-associated colitis’. This is an infection within the intestines caused by a bacterium
which normally resides within our guts but does not normally cause problems. The trick is, our bodies are (like it or not)
complicated habitats for all sorts of bacteria, both within our bodies (the digestive tract, and genitourinary systems in
particular), and it is possible to upset the normal balance by taking antibiotics. Cipro is not specific to B. anthracis. It
kills many types of bacteria, including normally harmless or beneficial ones. Vitamin K for example, is produced within
our guts by beneficial bacteria.
b. Chronic antibiotic use can lead to the production of antibiotic-resistant bacteria. Antibiotic resistance is becoming
a severe problem in our hospitals, in part because of the fact that so many people take so many antibiotics. A given
population of bacteria will contain a few individuals which are somewhat better than others at shrugging off an antibiotic.
With less competition, these resistant bacteria now may be able to establish a harmful antibiotic-resistant infection.
c. Incorrect dosages of antibiotics can lead to resistance. See 7b., above. The reason antibiotic resistant strains of
tuberculosis have popped up is largely due to the fact that many individuals who have been treated for the disease
did not take their full regimen of drugs. Often drug side-effects, or a patient’s own ‘I feel better already’ attitude,
lead people to stop taking their medications or to take them at a lower dose. This combination can be deadly, as
it encourages the development of resistance. Please consult with your physician regarding any antibiotic use, and be
suspicious of any physician who prescribes antibiotics for you to keep around the house for your own use. Antibiotics
require prescriptions for a reason!
d. It has been shown in accidental human exposures and in monkey trials that the spores of B. anthracis can reside in
your lungs for some time before they ‘germinate’, becoming active toxin-producing bacteria. For this reason, antibiotic
therapy for a known exposure is unusually long (up to sixty days). So how long would you need to take antibiotics to
feel safe? Much longer than is healthy for you!
e. A Cipro-resistant genetically engineered strain may be in use, in which case taking Cipro won’t
help. Double and triple all the above problems if you plan on taking two or three antibiotics
together. To date there has been no mention of antibiotic resistance, but it is a real possibility.
9. It has been mentioned (in the media) that the letter sent to Senate Majority Leader Daschle contained ‘high
grade material’. What does this mean?
This is a report that I have not seen substantiated by the CDC or the FBI (etc.). If true, it is an indication that the
material being used may have originated at a large, relatively complex laboratory, such as one financed by a government.
While it is relatively easy to grow these bacteria, and relatively easy to produce spores, it can be extremely difficult
to produce an effective bioweapon. The spores must be treated properly to assure a high degree of viability (a large
percentage must be capable of germinating into growing, toxin-producing bacteria), and the spores must be ground into
a very fine powder or suspended well in a liquid.
To date the dried form has been used. The particles must be small enough to be able to gain access
to the smallest passages of your lungs, but not so small that the spores will be ground up and killed.
Apparently there is a fine line that is not easy to achieve. The composition of the materials used will no
doubt aid the government in its search for a source. Little information is being released by reliable sources.
10. Has anthrax been used before as a weapon?
The doomsday cult Aum Shinrikyo in Japan attempted anthrax release many times in Tokyo in the early 1990’s (it
was discovered after the fact), but for some reason it was not successful. It is possible that they were trying to use a
vaccine (weakened) strain of the bacterium. This same cult was convicted of the Sarin nerve gas attack in the Tokyo
subway system.
During World War II the Japanese Army had an active bioweapons research unit, in some cases testing
weapons on human subjects, namely Chinese prisoners. The United States and Britain worked with anthrax
as a weapon in order to better develop defenses against these weapons. Neither country has ever used
Biological Warfare Agents. Since then many countries have dabbled in bioweapons; in fact, they have been
referred to as ‘the poor man’s atom bomb’. In 1995 Iraq admitted developing anthrax bioweapons, and facilities
to produce such weapons were being targeted by the United Nations when Iraq expelled the UN monitors.
11. Do I have to worry about getting anthrax?
Obviously to date John and Jane Doe of Anytown USA do not have to panic. If you are a mail sorter/opener in a
government office in Washington D.C., you have reason for concern. In fact, this morning it was announced that all
postal service employees in the area will start taking antibiotics, a risky move. But remember, as the Postmaster General of
the United States mentioned this morning, the Post Office alone has handled a mind-boggling 20 BILLION packages since
September 11, and only a handful have been proven to contain anthrax. To date they have all been addressed to individuals in the press or government. Considering the number of people who handle each piece of mail, and the small number
of people infected, it appears that the letters are not shedding enough spores during transit to cause concern, at least
not to date. We do not yet know how well anthrax letters can contaminate other ‘clean’ mail in the same mailbox (etc.).
12. Can’t we sterilize the mail?
Many packages, especially envelopes, could conceivably be sterilized by gamma radiation much as certain foods are today.
But remember, 20 billion packages! It seems unlikely that the Postal Service would be able to effectively irradiate all mail.
Among numerous other hurdles, packages of different sizes and composition would require different exposures to ensure
sterility. Your mail would not however become radioactive. Ultraviolet light (common ‘black lights’) will NOT sterilize the
inside of packages, at best only their surfaces. Infrared light has no mail sterilizing ability at all.
It is certainly prudent to remain alert, and to educate yourself. I strongly encourage everyone to visit the above websites,
and to turn to a health care professional with your questions. Spreading the ‘urban legends’ often seen in the media
does nothing to help anyone, except possibly the terrorists themselves. Trust only the definitive answers provided by the
Centers for Disease Control or state health departments. Few physicians in this country have ever seen anthrax, and most
hospitals are not capable of definitive identification of the organism in a timely fashion. This is new territory for our
public health system, but we do have the best health care available in the world, so we are as prepared as we can be.