November 1 Update: Anthrax Bioterrorism

• More anthrax cases identified, with four deaths. More than half the cases are inhalation, less than half cutaneous anthrax.
• Lab results still slow, with a number of "possible" cases
• Clean up of buildings is taking place. Chlorine dioxide (if I remember correctly) is being used per the EPA. No report yet on its usefulness and possible problems using it.
• Private companies are being hired to perform remediation of post offices and media buildings
• Confusing media reports suggest that a) both the anthrax strain used (Ames) and the excipient mixed with it to promote aerosolization, derive from the old US biowarfare program (Debora MacKenzie, New Scientist) or b) come from Iraq (ABC says four labs found bentonite in the Daschle envelope)
• The US' two most knowledgeable people regarding preparation of anthrax for biowarfare, Dr. Ken Alibek and William Patrick, are quoted as saying that no one in the government has asked them for assistance
• Media and medical personnel are exploring how doctors can distinguish between anthrax and other infections, after one person, now deceased from inhalation anthrax, was sent home by a physician with the diagnosis of flu.
• Will anthrax vaccine be used? First, CDC said it was for those who are allergic to all antibiotics. Then it was to be given to first responders and lab technicians. Later still, its use for postal workers and others is mentioned. If no one is pressuring FDA, why do other agencies seem so sure that vaccine will be released for use by FDA by November 22, which, after performing a series of inspections, has refused to license the plant for the past 2.5 years?
• I've seen three articles discussing testing for anthrax:
• "The Most Precise Anthrax Tests Take Time and Money" NY Times, Oct 13
• "Diagnostic Tests Offer Few Certainties" Boston Globe, October 16
• "Anthrax Testing Can Be Difficult" Associated Press, October 20

It is time for better answers regarding testing.

1. The prevalence of inhalation cases suggests to me that indeed, this anthrax is very potent, and the infectious dose by inhalation is much lower than I originally thought. The factors that likely contribute to this were mentioned in an earlier update. This means that relatively more people will be at risk when spores disperse. It also means that tiny (invisible) quantities of anthrax could contaminate letters, and still be enough to kill.

2. The confusion about the origin of the anthrax, and the fact that the two most knowledgeable experts on weaponized anthrax haven't been consulted, makes me wonder if the powers that be are honestly seeking an answer for where it came from.

3. Dr. Fukuda at CDC suggests that flu causes nasal congestion and runny nose; anthrax does not cause nasal symptoms. But bacterial pneumonia doesn't cause nasal congestion and is also not anthrax, yet they share nearly all of the same symptoms, at the onset of illness. And many people happen to have stuffy noses from allergies much of the time, which could complicate using nasal symptoms to rule out anthrax. In order to make the correct diagnosis, we are going to need rapid diagnostic tests, and every hospital lab will need to have staff trained to perform them.

Using flu vaccine to help distinguish between flu and anthrax is not a bad idea. However, there is not enough flu vaccine to go around. And we still do not know whether this winter's flu strain(s) will be covered by the vaccine. Finally, the vaccine is not 100% effective, so having been vaccinated will still be no guarantee you don't have flu, instead of anthrax.

I suspect that this winter, most doctors will play it safe and treat anyone with an illness that might be anthrax with antibiotics. However, this still begs the question: how long should treatment continue? One animal study showed 15% of spores remained in the lungs 30 days after exposure, but only 1% were left after 75 days. IF this holds true in humans, you should be safe after 75 days with a small exposure. But what if you got a large exposure?

4. The NY Times, whose anthrax coverage has been quite good overall, has missed the ball on anthrax vaccine. No, it is not an issue of FDA not yet approving the manufacturing plant and new vaccine lots. FDA has inspected the factory (now Bioport, formerly Michigan Department of Public Health) many times and each time found them lacking. The inspection reports are linked to this website, and you can read them for yourself. That is why Canadian troops have been sent to West Asia, unvaccinated, although Canada still has some vaccine stocks.

(A Canadian reporter told me the US DOD had sold Canada anthrax vaccine a couple of years ago, and included plague vaccine as well in the deal, for prophylaxis of biological warfare. What we neglected to tell our northern neighbor was that the plague vaccine had been shown to be ineffective against plague delivered via inhalation. Our troops do not get it, and in fact, it is no longer made.)

Personally, I would guess that the US anthrax vaccine provides some, limited protection against anthrax, based on extrapolations from the animal data. If you go to my review article on anthrax vaccines (found in the same box on my Home Page as this update), you can see the survival rates for guinea pigs given the MDPH/Bioport vaccine, then exposed to the Ames strain of spores.

I think that antibiotics clearly offer more reliable protection, as long as they are taken soon enough. The fact that so far, the fatality rate from inhalation anthrax is under 50%, not 90%, tells us that early antibiotics do work. Prophylactic antibiotics are probably preventing many additional cases in postal workers and others.

If the vaccine offered partial protection and was safe, I'd recommend taking it. The problem is that it is simply not safe, and the odds of getting sick as a result of vaccination may be 10% - 35%, based on a considerable amount of anecdotal evidence, a study from the UK published in 2000 (J Royal Army Med Corps) and the five studies of Gulf War Illnesses and vaccination discussed elsewhere on this website.

The final vaccine issues to be considered are the state of the existing lots of vaccine, and the status of those who may receive vaccine from these lots. All 6-7 million vaccine doses now held by Bioport have up till now been unapproved for human use. They fall into one of the following three categories:

1. Lots which the FDA quarantined because of significant manufacturing lapses, which include among others inadequate potency, contamination by gasket material and lack of sterility (and they may be up to eleven years old, having expired several times and been redated with only cursory testing)
2. Lots for which former Secretary of Defense Cohen ordered 'supplemental testing' to assure potency, purity, safety and sterility--and which failed this test battery on at least two occasions. These lots also may be up to eleven years old.
3. Lots which were produced by the pilot plant after it was rebuilt, but during a period when FDA did not approve the procedures used. This led to some vaccine being sent to Washington State for bottling, as Bioport's bottling suite could not assure sterility. But some lots were bottled in Bioport's unacceptable suite. These lots are up to two years old.

Where in FDA's regulations is it permitted for them to a) release vaccine with these problems, and b) do it as part of an experiment? If you are experimenting to learn the effectiveness and safety of the vaccine, you should use "good" vaccine, properly manufactured and tested, should you not? If something happens to the volunteer who takes the vaccine, is there any legal remedy? Or is the volunteer "on his own" because he chose to participate and accepted a risk?

4. I am not well versed in the field of testing environmental samples, or patient samples for anthrax. I am a full-time practicing physician. But I have collected a variety of information and would like to provide the references, so that those who are interested will be helped in their search for details. Hopefully, those in the field of environmental testing, and laboratory pathologists, will be able to assess the different methodologies, and select or develop those that will work well to affordably, rapidly, accurately, and sensitively diagnose anthrax spores in the environment, and spores or vegetative cells in the patient.

Titball RW et al. The monitoring and detection of Bacillus anthracis in the environment. J Appl Bacteriology Symposium Supplement 1991;70:8S-18S. Discusses an E12 monoclonal antibody specific for whole Ames strain spores, gene probes, etc.

Phillips AP et al. Monoclonal antibodies against spore antigens of Bacillus anthracis. FEMS Microbiology Immunology 1988;47:169-178. This work is discussed in the preceding paper as well.

Modern Methodologies Discussed at the 3d International Conference on Anthrax, Plymouth UK, September 1998. Brief description of presentations by 4 groups: Society for Applied Microbiology Newsletter, December 1998, page 25.

More detailed descriptions of these presentations can be found in the Journal of Applied Microbiology 1999;87:214-269.

With respect to testing of human specimens, Bergey's chapters on Anthrax and Bacillus should be consulted. The M'Fadyean stain may be most accurate. These chapters and the other reports above discuss sample preparation to inactivate other microorganisms in samples, additional stains and culture techniques, and provide a wealth of information on anthrax.

"Bioweapon Test Makers Race to Meet Demand" by Alicia Ault, October 19, 2001 (Reuters) tells us a bit about what is already out there.

Finally, the article "Biological Warfare Canaries" by Christopher Aston in the October 2001 issue of IEEE Spectrum, discusses the variety of state of the art biosensor devices for biological warfare organisms and toxins. Well worth a read.

5. Private companies are being advised to hire other private companies to test their facilities for anthrax. But shouldn't the government be advising us of what tests should be done, how accurate they are, and whether any of the private testing companies have demonstrated proficiency in this area?