[BIOWAR] anthrax preparedness - my thoughts (fwd)

[Eugene Leitl]

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---------- Forwarded message ----------
Date: Mon, 15 Oct 2001 00:31:19 -0400
From: mnass at netquarters.net
Cc: biowar at topica.com
Subject: [BIOWAR]  anthrax preparedness - my thoughts


Response to two reported anthrax attacks suboptimal.  What can be
improved?

Coming up with more effective responses to the anthrax threat requires a
solid understanding of the unique characteristics of anthrax, how it is
like, and unlike other pathogens for which we have very effective
answers.
This is important both to save lives, but also to avoid panic.  People
are afraid when they do not know what to expect, and do not know how to
properly protect themselves.  The public and the doctors caring for them
have to be educated on anthrax asap.  These are my suggestions for
expediting the evaluation of anthrax "events" and the prophylactic
treatment of those exposed.
I do not wish to be alarmist, but now that the anthrax genie is out of
the bottle, we could be seeing a very large number of anthrax scares
ahead.   I have composed the following very quickly in hopes that it
will help us to be optimally prepared.
1.   It takes the inhalation of hundreds of thousands to millions of
spores of anthrax to cause the disease inhalation anthrax, with the
possible exception of people with immune deficiencies, for whom less
spores might lead to illness.  Fewer spores do not cause illness; the
immune system seems to readily defend against them.  This is presumably
why 5 others in Florida have now been found with anti-anthrax
antibodies, but were not ill.  In goat hair mills, where workers were
daily exposed to anthrax spores, some developed antibodies and some did
not.  (Our antibody (ELISA) tests may not detect all antibodies to
anthrax.)
2.   If there were enough spores inhaled in Florida to kill one worker,
then there must have been millions more in the office.  Other workers
would have therefore had spores on clothes, shoes, hair.  At this time,
I would suggest these items be washed (see comments on washing below) or
brushed out, outdoors.  There would have been spores on the desks,
floors, and in the indoor air.  Proper sampling of the environment
should have detected these spores, and should have provided an estimate
of the magnitude of the exposure.  This would have permitted an
extrapolation of the risk to individuals working in the office,
elsewhere in the building, and in the neighborhood of the building.  It
would have allowed appropriate antibiotic prescribing for those at risk,
who could have been observed carefully and received additional
investigations that would be appropriate to their risk.
3.      Instead, workers with only gloves on did some environmental
sampling
when the first case was diagnosed, and employees were allowed to remain
in the building for an additional week, where they would have received
further exposure to anthrax spores.  The environmental samples and nasal
swabs were all said to be negative, apart from one person and one
computer keyboard.  This is simply not possible.  Almost fifty years
ago, an electrician at Fort Detrick died after doing some work in a
building where anthrax research was conducted.  Samples taken then
(1950s) showed that the building was grossly contaminated, with anthrax
spores all over.  Why was the Florida sampling so much less sensitive
than the sampling that took place in the 1950s?  Why did it take
authorities a week to figure out that the other employees were also
exposed, and that the building was contaminated?
4.      At NBC New York, the FBI was notified of a suspicious letter on
September 25, but did not test it "until at least two weeks later, when
a private doctor city public health officials
" (Steinhauer J and Dwyer
J. FBI Did Not Test Letter to NBC or Immediately Notify City Hall. NY
Times October 13, 2001. Page A1.)  I'm guessing that the spate of hoaxes
has rapidly overwhelmed the FBI's ability to deal with each, and
overwhelmed their forensic lab's capability.  Hoaxes may also be a
strategy of a terrorist.  Remember how the anti-ballistic missile
program has been criticized for its inability to deal with thousands of
dummy missiles which could provide cover for a small number of "real"
missiles?  We may be seeing the same thing now.  There is one simple
answer:  the techniques for doing forensic investigation of suspect
materials need to be shared with state and local laboratories, so that
these efforts can be decentralized.  Then sufficient personnel can be
made available to do adequate testing.  It may be that of the billions
now allotted for terrorism, money should be spent training lab
technicians in these techniques, and in training more lab technicians,
since we do not know for how long US citizens will be at risk of
bioterrorism exposures.
5.      How do you test for anthrax, when a variety of tests are
available
with varying specificities and sensitivities?  Well, first of all, you
do not allow human beings to be the canaries in the mineshaft, which
happened in NYC.  Tests of environmental samples can be performed in
hours, not days, which is how long cultures take to identify an
organism.  Cultures are needed for antibiotic sensitivity testing, but
the diagnosis of exposure in cases of anthrax needs to be made more
quickly, in order to avoid loss of lives.
6.      The first test to be done should be extremely sensitive; it does
not
need to have extreme specificity.  The follow-on tests can be more
specific.  PCR testing fits this bill.  If PCR is positive, then
aggressive environmental samples, nasal swabs, sputum, blood,
cerebrospinal fluid in suspected meningitis cases can be obtained.  If a
massive exposure has occurred, case-finding is done to identify all
those potentially exposed.  All are treated with antibiotics prior to
any signs of illness.  I would propose consideration of bronchoalveolar
lavage in highly exposed patients.  This procedure has never been
reported in anthrax exposures, because there have been no reported
exposures since the technique came into clinical practice.  However, it
might be capable of removing large numbers of spores, and it might also
provide an estimate of the risk for the patient and others who had
similar levels of exposure, based on the amount of spores recovered from
the lungs.  We should learn whether this procedure is likely to be
helpful.
7.      Additional tests could be done as well.  One described in the
October
13 NY Times page B8 quoted Tom O'Brien of Tetracore, in Gaithersburg, MD
is an antigen test which is supplied to federal and local authorities,
and can be performed in 15 minutes.  Four groups described different
prototype anthrax identification systems for air and other environmental
samples at the 1998 international anthrax meeting in the UK.  Someone
needs to review all these devices and determine their sensitivity and
specificity for environmental samples, and make the most promising
devices available to local authorities for widespread air/environmental
sampling asap.  It may be that the US will have to live with biosensors
in public places, now that the anthrax genie is out of the bottle.  Not
a pleasing option, but one that might provide the lead time needed to
treat people during that important window: after exposure, but before
serious illness has developed.
8.      Treatment: not so simple as popping a cipro tablet twice a day.
First off, the risks involved in taking an antibiotic that you don't
need for a few days or weeks are really not that large.  However, if
everyone starts taking antibiotics in advance of any known exposures,
there will not be enough available in 6 or 12 months, and then the
terrorists can play havoc with us.  If it makes you feel more secure,
keep a week or two of any antibiotic on hand.  The Florida anthrax
strain was reported to be sensitive to just about every oral antibiotic,
including penicillins, tetracyclines and quinolones such as
ciprofloxiacin.  The problem is this: we do not know how long you will
need to take them, and we do not know if all the anthrax held by
terrorists will be antibiotic sensitive, as the Florida strain
apparently was.  Monkey experiments showed that the animals survived
lethal anthrax exposures when antibiotics were provided within 24 hours
following exposure, but that some died when antibiotics were stopped,
after a month or more.  So how long do you take them for?  Personally, I
would take them for at least six months, if that were the only treatment
I had.  I would only know which to take after antibiotic sensitivity
testing had been done.  I might start with doxycycline, since I am pen
allergic and it is inexpensive, and saved 9 out of 10 monkeys.  Cipro
saved 8 out of 10, if memory serves.  Given the small number of animals
tested, there is no difference in effectiveness between these two.
Neither drug is ideal for children or pregnant women, who should receive
a macrolide, penicillin or sulfa drug.  The environmental sampling, if
done properly, should alert you to your own level of exposure, and
therefore your risk.  If I inhaled 100 spores, I would not take
anything.  The data are that good on chronic occupational exposures in
contaminated environments, that I am assured I would not become ill.
9.      Methods for inactivating spores in the environment need to be
provided to the public.  On Scotland's Gruinard Island, contaminated
with anthrax for 45 years after experiments performed with anthrax
during World War Two, anthrax was killed after contaminated areas were
defoliated, and a dilute solution of formaldehyde in seawater was
sprayed on the land.  Bleach has also been used, but I do not know the
concentration needed or the amount of time required in which the
solution must be in contact with the spores.
10.     Detergents can increase the virulence of anthrax spores, and
thereby
decrease the number needed to cause disease.  It may be that the
addition of detergents at the Manchester NH goat hair mill where the US'
only epidemic of inhalation anthrax occurred (5 cases in 1957), was the
cause of the epidemic.  This increasing of spore virulence by detergent
was described in a paper by JM Barnes: "The development of anthrax
following the administration of spores by inhalation." British J
Experimental Pathology 1947, vol 28, pp385-94.  I would therefore not
wash contaminated clothes or surfaces with detergents, until we have
been informed exactly what to use and what not to use, by those who have
done the appropriate experiments at Fort Detrick Maryland or Porton Down
in the UK.
11.     What about masks?  What about envelopes?  What about opening
packages?  Obviously, if you are concerned, open things in such a way as
to prevent widespread dissemination of contents, like opening with
scissors instead of ripping.  Better yet, give it to the authorities.
Open things so that you are upwind of them.  Don't inhale while opening,
if you feel you need to go to these lengths.  Besides gas masks, there
are other medical masks which are cheap and easy and might be helpful.
Again, we need the information from authorities who have tested the
masks to learn exactly what types of protection they provide.  Do they
keep out 98% of particulates of the one to five micron size?  If so,
that would be a good mask for opening letters that might contain anthrax
spores, if you work in the media or a mailroom/post office.
12.     New treatment methodologies need to be put into place asap.
Antiserum needs to be produced in the US now, as a potentially
life-saving treatment for late-diagnosed cases.  Existing stocks should
be sought from China and possibly Russia. (See the October 14, 2001
Chicago Tribune: US Speeds Vaccine Creation, Research by Peter Gorner.)
Monoclonal antibodies, which are actively being researched, need to be
made available for experimental use, in the event they are needed for
life-threatening cases of anthrax. (See the October 12, 2001 Reuters
article: University of Texas Team Works on Anthrax Treatment.)

Bottom Line:
1.      Environmental sampling needs to be made more accurate, using
known
techniques, and more widespread.  Forensic testing of samples needs to
be decentralized, so it can be done in a timely manner, and so the
federal authorities are not overwhelmed.  The federal government should
pay the salaries of additional technicians in every state and possibly
in large hospitals, who would be trained as forensic experts, and
provide the materials and methodologies used by our federal experts at
Fort Detrick, CDC and the FBI, among others.
2.      Methods which go from most highly sensitive to most highly
specific
need to be used, in the proper order, so potential anthrax cases can be
identified and treated in a timely manner.  This means that existing
tests that take hours, not days, need to be the primary ones used.
3.      All questionable materials must be tested using sensitive
techniques.  We do not yet know how to select those which can be
ignored.
4.      The public needs to be reassured that in fact, the government
will
address these incidents promptly and effectively, so that the public is
not responsible for its own antibiotics and treatment strategies.
5.      Biosensors in development need to be assessed now, and the best
ones
need to be put into mass production.
6.      Pharmaceutical companies should increase production of a variety
of
antibiotics, and government stockpiles of these materials should
increase.
7.      Novel approaches to treatment should be investigated and
prepared or
obtained in advance. This might include antiserum, monoclonal
antibodies, and other materials currently being developed.  The utility
of bronchoalveolar lavage in monkeys should be investigated.  The
sensitivity of nasal swab testing, sputum, urine and blood antigen
tests, stains and cultures should be assessed in animal models
immediately.
8.      Information on safe methods for inactivating spores found in or
on
contaminated clothes, surfaces and other environmental materials should
be provided to the public immediately.
9.      Information on cheap masks, like those worn by lab techs working
under hoods, that have high efficacy for anthrax, should be provided to
the public.  Production should be increased.

Meryl Nass, MD

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