-- Eugen* Leitl <a href="http://www.lrz.de/~ui22204/">leitl</a> ______________________________________________________________ ICBMTO: N48 04'14.8'' E11 36'41.2'' http://www.lrz.de/~ui22204 57F9CFD3: ED90 0433 EB74 E4A9 537F CFF5 86E7 629B 57F9 CFD3 ---------- Forwarded message ---------- Date: Mon, 15 Oct 2001 00:31:19 -0400 From: mnass@netquarters.net Cc: biowar@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 officialsÂ…" (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 Post to: biowar@topica.com. Unsubscribe to: biowar-unsubscribe@topica.com. List info: www.topica.com/lists/biowar ==^================================================================ EASY UNSUBSCRIBE click here: http://topica.com/u/?bz8Q0W.a9I0on Or send an email To: biowar-unsubscribe@topica.com This email was sent to: Eugene.Leitl@lrz.uni-muenchen.de T O P I C A -- Register now to manage your mail! http://www.topica.com/partner/tag02/register ==^================================================================