by Merrryl Nass, MD

Issues that need to be addressed regarding the bioterrorism response include the following:

1. Are the anthrax-containing envelopes an initial tease, or warning? They are a good way to disseminate small quantities, while avoiding identification of the sender.

But what may be ahead?

Spores in ventilation systems? Spores at sports events or where there are dense population concentrations? Thousands or millions of letters containing anthrax? How will we know in time, and how will we decontaminate ventilation systems, electronics, sports arenas, soil, etc.?

2. At the present time, public health authorities have continued to use (primarily cutaneous) human anthrax cases as the harbingers of anthrax dissemination. Cutaneous infections require many fewer spores to induce illness, compared to inhalation anthrax.

The infected individuals are serving as the "canaries in the mineshaft" who warn that anthrax is present. If the extent of spore dissemination increases (higher concentrations in ambient air from envelopes, or through other means) then the inhalation cases will serve as the canaries, and there will be many fatalities.

3. I will continue to harp on the need for accurate and rapid sampling of the environment as the most important (by far) technology needed to deal with the offensive use of anthrax.

There are likely to be many more envelopes that have already dispersed anthrax spores, but have not been identified yet, because there have (so far) been no cases of illness related to those envelopes, and spores were not seen by the person(s) handling the mail.

This means that anthrax spores may be contaminating a number of environments in which they have not been detected. We may not see cases until small animals, children, or people with immune system impairment become exposed in those environments.

4. Only by identifying an environment contaminated with anthrax before illness appears are we likely to effectively treat inhalation cases.

5. Only by identifying these environments can we remove people from the environment and protect them from further exposure.

6. It is possible that we will not be able to do a complete clean up of contaminated environments, for the time being. There has not been a great deal of research into how to clean up homes and offices, for example.

Gruinard Island, off the coast of Scotland, was decontaminated 45 years after it was used as a test area for anthrax during World War II. During those 45 years, humans and animals were barred from the island.

Ten acres were decontaminated: this required defoliating the area, using 200 tons of 37% formaldehyde, diluted in seawater, that was sprayed over the area, and then additional formaldehyde was re-sprayed after deep soil sampling revealed persistent organisms.

7. What else works to kill anthrax spores, which can remain viable for decades or hundreds or years? Bleach, which must be in contact with spores for at least 2 minutes. Paraformaldehyde gas, glutaraldehyde, hydrogen peroxide and peracetic acid also work, and need to be in contact with spores for at least as long.

But these materials can be corrosive and are not appropriate for homes and offices, though they can be used to decontaminate most laboratories. Spores can be boiled; the standard recommendation has been to keep the water at a rolling boil at least 10 minutes to kill spores of any pathogen.

Steam also kills spores in from 1 to 10 minutes. In goat hair mills, the goat hair was treated at 170 degrees Fahrenheit for 15 minutes, but many spores retained their viability after this treatment. Moist heat works much better than dry heat. Fumigation can be performed with ethylene or propylene oxides, or paraformaldehyde gas.

8. I hope you can tell from this that I do not know a completely safe and effective way to perform decontamination. This needs to be an area of intensive investigation now.

Dr. Alibek has suggested that methods used for decontamination in Sverdlovsk in 1979 (washing trees and houses, and paving dirt roads), may have re-aerosolized anthrax spores, and that this may have increased the number of cases of inhalation anthrax.

9. Dr. Ken Alibek suggested steam ironing letters before opening, which sounds like a good idea. Put a cloth between the iron and the letter. We need to know more about the temperature setting and how long the iron needs to be in contact with the letter.

10. The bottom line is that spores are odorless, tasteless, and invisible, individually. In a worst case scenario, up to one trillion spores (1,000,000,000,000) might be present in one gram of material. One gram can be contained easily within a one-ounce (28 gram) letter.

It theoretically could contain a million lethal doses, if the majority of the spores were viable, of the right size, and dispersed easily without clumping.

11. What is a lethal dose of spores? The reason why you may read a variety of different estimates for this number is because

a) there are no human-derived data, and
b) there are a variety of factors that impact the answer.

There are many animal experiments, and those results are surprising at times. It also depends on the virulence of the anthrax strain used, the amount of air you inhale (during exercise, you breathe in several times as much air as you do at rest), the % of viable spores, the distribution of size of spores, whether the spores easily separate from each other, and your own inherent immune system function.

Thus the number might range from 10,000 spores to many millions. Animal tests of a sample from a letter should give us a rough idea of how virulent the potion is, and what a lethal dose might be.

12. Here are some animal data for lethal doses (LD50) of anthrax spores by subcutaneous injection and inhalation (from JM Barnes). This shows why there are so many cutaneous cases, compared to inhalation cases.

13. Another experiment in pigs: each of 50 pigs was fed from 10 million to 10 billion Ames strain spores (C Redmond et al.) Only 2 of the pigs died (4% of the total) and two others had anthrax isolated from blood, but survived.

By 21 days after feeding the spores, the majority of pigs had developed antibodies to anthrax, indicating that they became infected and recovered. Humans, like pigs, are probably relatively resistant to anthrax, compared to many other species.

14. How do we know antiserum is likely to be protective? Mice, which are notoriously hard to protect against anthrax with vaccines, were given antiserum and then exposed to anthrax. The survival of mice given two different antisera was 80% at two weeks post exposure for both groups, while those given control sera had a 0% or 10% survival rate (RJ Beedham et al).

15. It remains very important to keep one's exposure to anthrax spores to a minimum, particularly if you work in a high risk industry, such as the postal service, UPS, Fedex, media or politics. Although I earlier advised against gas masks, I have come to believe there is a role for appropriate, well-fitted masks that have demonstrated efficacy in preventing inhalation of particles of the 0.5 to 5.0 micron size.

My hope is that once environmental sensors are used widely, we will be able to discard masks. For now, if you feel there has been an exposure, or if you are trying to avoid exposure at a high risk occupation, HEPA dust masks (such as 3M Corp has sold for tuberculosis prophylaxis) may be useful. The more HEPA sheets in the mask, the better it will filter.

These masks have not been tested for anthrax or other bioterrorism exposures, so 3M cannot market them for this purpose. However, such masks ought to keep out 95-99% of particles in the desired size range, and could be used for "high risk" activities such as opening mail.

Gloves would also decrease one's exposure to spores, but must be discarded after use, or washed after use in order to reuse them.

16. Again, let me emphasize that a variety of soaps and detergents have been tested and were found to increase spore virulence by up to a factor of 16. That means the spores could be made 16 times as virulent, because soaps may make them easier to disperse as individual particles.

For now, wash only in water first to remove spores; you can then use soap when the spores are down the drain.

17. There are many methodologies for identifying spores in the environment. I have collected a large number of articles on this subject, and will discuss what looks promising, and the differences between the methods, in a subsequent update.

I continue to believe that PCR testing, because of its sensitivity and rapidity, should be the initial test done, with the understanding that some false positives will result, but no anthrax exposures will be missed, as long as sampling is adequate. I have spoken at length to Tom O'Brien of Tetracore, in Gaithersburg, MD.

His company has some very promising PCR and immunoassays for anthrax that can be completed in under 12 hours, and can detect as few as 100 cfu (viable spores) per milliliter of material.

18. Diagnosing exposure in people is not that easy.

Although obtaining nasal swabs is a simple procedure to perform, one study shows that the spores rapidly disappear from the nose after exposure, suggesting that swabs are only likely to be positive within 24 hours of contact. Thus sensitivity may be very low, and swabs will give you many false negative results.

19. Treatment is another question. I have suggested that many other antibiotics are as good or better than ciprofloxacin.

Doxycycline, for instance, will also work for plague, tularemia and brucella, and effectiveness for all these other potential biowarfare pathogens has not been established for cipro.

20. The duration of antibiotic treatment needed remains uncertain. It is not clear if those currently being treated are being helped by antibiotics, or would not have become ill anyway. Antibody titers will tell if you successfully fought off anthrax.

Although CDC Deputy Director David Fleming said that a four-fold rise in antibody titer is needed to confirm recent anthrax infection, this is not necessarily the case. Because anthrax is so rare, one positive antibody titer (by ELISA) should be adequate to make the diagnosis, as long as the ELISA test is accurate.

21. A pathologist called me today regarding an autopsy of a possible anthrax case. Autopsies can be a problem; in animals, when the animal is opened, spores form and are released. This could contaminate the autopsy suite.

There may be temperatures in which this does not occur, but I don't know that for sure. I recommended instead, that blood, CSF and mediastinal fluid be sampled for the presence of the relatively unique-appearing gram positive fat rods of anthrax. This might save you from having to do a whole autopsy.

22. How to protect pets? The animal vaccine works quite well though it may require yearly boosters (there is little data on how frequently they must be given).

23. I guess my take home message is that, unlike other pathogens, which live in the environment for minutes to, at most, days, these spores last nearly forever. Contamination does not resolve with time, although if spores are kicked up inside buildings, they may disperse to less infectious levels. Outdoors, the spores tend to stick to the soil components and do not easily re-aerosolize.

However, that may not be the case for indoor spore accumulations. First responders, affected workers, and others who may be in the vicinity of an anthrax event should behave as if there are invisible, potentially lethal spores everywhere: on surfaces, floors, your computer and desk, your person, walls and ceilings.

This requires an entirely new mindset for dealing with infectious emergencies.

Meryl Nass, MD
http://www.anthraxvaccine.org/

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