CIVIL DEFENSE PERSPECTIVES

November 2001 (vol. 18, #1)
1601 N Tucson Blvd #9, Tucson AZ 85716
c 2001 Physicians for Civil Defense

After four deaths from anthrax, the situation is, of course, dramatically different. Lawyers at a major Phoenix law firm have to open their own mail because employees refuse to do it. Some airlines serve only sugar for your coffee, no powders. Information and speculations on anthrax are found everywhere. Mexican pharmacies are running out of Cipro.

Delivering anthrax spores by mail-possibly the work of a home-grown, Unabomber-style terrorist-has been remarkably effective at causing panic, hindering commerce, wreaking financial damage, and driving Congress off Capitol Hill. It has not, so far, caused very many actual casualties (and the ultimate toll in sickness may owe more to excessive long-term use of Cipro than to the disease itself). We must not, however, be complacent about the very serious dangers of biological warfare agents, including anthrax. We have actual experience with the effective delivery of aerosols, not mere theory.

Creating an aerosol with particles between 1 and 5 microns in diameter, the proper size to lodge in the lungs, is not a trivial exercise. An uneducated would-be terrorist couldn't do it in his kitchen, or a cave. But in 1950, one of more than 200 experiments by the U.S. government caused nearly everyone in San Francisco to inhale 5,000 or more particles contaminated with supposedly harmless bacteria (JAMA 1989;262:644-648).

Although President Nixon ordered the destruction of U.S. stockpiles of biowarfare agents in 1969, other nations have toiled for more than 30 years to advance the technology, arms control agreements notwithstanding. The U.S. response: denial.

At DDP meetings in 1996 and 1998, the late Conrad Chester of Oak Ridge National Laboratory and intelligence analyst Joseph Douglass discussed the Soviet biowarfare program (lectures are available on CD- ROM). Key points are:

• Massive construction was undertaken by Biopreparat in 1972, in defiance of international agreements. Information from defectors indicated that the effort was ten times larger than the most pessimistic estimates, employing many thousands of scientists. The number was recently stated to be 65,000, of whom 7,000 were considered to be ``critical'' (Boston Globe 10/28/01). Douglass stated that fewer than 10 American officials were involved in monitoring this enormous enterprise.

• In 1979, about 100 people in Sverdlovsk, Russia, were infected with anthrax and nearly 70 died. For a long time, the U.S. officially accepted the Soviet explanation of a natural outbreak due to ``tainted meat,'' as did biochemist Matthew Meselson, author of the bee feces theory of yellow rain. Autopsy evidence proved conclusively that victims died of inhalation anthrax. And in 1998, genetic studies proved that multiple strains of the bacterium were involved, related to escape from a germ-warfare plant (Nature 2001;413:657- 658).

• Based on reasonable assumptions, there was a one-time release of approximately 1 gm of anthrax spores. Human casualties occurred as far as 4 km downwind, and sheep died as far as 50 km downwind. Onset of symptoms was as late as 6 weeks after the release. The late casualties may have resulted from secondary aerosols created by hosing down buildings in a clean-up effort (Wall St J 10/11/01).

• The spores were released on a sunny day. Though ozone generators and ultraviolet bulbs are quite effective at killing bacteria in aerosols, Dr. Chester estimated that a dose of UV sufficient to cause an early sunburn in a fair- skinned person would be required to kill anthrax spores.

• Dr. Chester said the Soviets admitted to immunizing 80% of the 59,000 persons at risk from the plume, using live nonencapsulated organisms. In a lecture recently posted at www.wml.com, Dr. Meselson stated that the Soviets managed to save 25% of the victims of inhalation anthrax, which is said to be nearly 100% fatal, using passive immunization with horse serum. The U.S. at the present time has no antitoxins or anti-anthrax immunoglobulin. The controversial American vaccine, made from a sterile filtrate from an attenuated strain of B. anthracis, has not previously been available to civilians. It requires 18 months to become maximally effective.

• Dr. Meselson said there is no reason to believe in a threshold and that very small numbers of spores have been infective. Dr. Chester noted, however, that anthrax can probably be found in any soil that has supported cattle-no doubt in higher concentrations than in the Hart Senate Office Building, which will never be free of the last spore, if indeed it ever was. Preventing exposure is obviously best but cannot be achieved unless one knows the threat is present. Better detectors are urgently needed. Masks serve the purpose, in Meselson's view, of keeping fingers out of the nose; a full-face mask with positive pressure to keep unfiltered air from entering has been recommended. A HEPA filter should be able to exclude all spores. Many vacuum cleaners now have such filters and are a much better choice for cleaning mail-sorting equipment than the blowers used previously. Dr. Chester recommended them as an improvement on his expedient filter in the air intake for a sealed room: the partly filled dust bag of a vacuum cleaner.

If no new cases emerge, momentum for needed actions may be lost. The U.S. may forget that the Soviets once made tons of anthrax each day and also taught 40 scientists a year from Libya, Cuba, Iran, Iraq, and other nations. U.N. inspectors verified that Saddam Hussein has actually deployed missiles and artillery shells loaded with anthrax (Wall St J 10/29/01). The U.S. looked the other way and is 30 years behind in researching numerous critical questions-to which Russians may know the answers. Can we learn from them (see DDP Newsletter)?

Basic Facts about Anthrax

Causative Agent: Anthrax is caused by Bacillus anthracis, an aerobic Gram positive, encapsulated, chain-forming rod that forms oval, centrally located spores under adverse environmental conditions. The spores are resistant to extremes of temperature, dryness, and flooding, and can persist in the soil for decades.

Occurrence: There are about 5,000 human cases of anthrax worldwide each year, according to Martin Hugh-Jones of Louisiana State University in Baton Rouge (Wall St J 10/10/01). Harrison's Principles of Internal Medicine, ed. 13, places the incidence as high as 100,000, with most cases unreported. It is primarily a veterinary disease, most common in poorer countries, and most exposures are occupational. It is not transmitted person-to-person, but by contact with infected hides, wool, hair, or meat. Because sporulation occurs only in the presence of oxygen, infected animals should not be butchered or autopsied. Hugh-Jones states that the disease can be eradicated by prompt identification, cremation of infected carcasses, and vaccination of the stock for at least 3 years.

Types: The most common form is cutaneous, acquired by contact with abraded skin or possibly from biting flies. It presents with a small red spot that progresses to a blister, a pustule, then a painless necrotic ulcer with a black eschar and local, expanding brawny swelling. The differential diagnosis includes staphylococcal skin infections, plague, tularemia, and orf. Untreated, up to 20% of cases are fatal, but early, effective treatment reduces fatalities to about 5%.

Oropharyngeal and gastrointestinal disease result from eating infected meat. Necrotic ulcers and edema of the palate and throat can cause airway obstruction. Vague initial G.I. symptoms of loss of appetite, fever, nausea, and vomiting are followed by abdominal pain, bloody vomiting and diarrhea, and possibly massive abdominal swelling (ascites). Septic shock and death are common.

Inhalation anthrax begins with nonspecific symptoms of fever and malaise, possibly with a nonproductive cough and vague chest discomfort. Early improvement lasting hours to 3 days is followed by the abrupt onset of difficulty breathing, with death occurring within 24 to 36 hours. Chest x-ray shows hilar adenopathy, a widened mediastinum, and pleural effusions. Metastatic infections, such as bloody meningitis, often occur.

Diagnosis: B. anthracis can be demonstrated in cutaneous lesions by Gram stain or fluorescent antibody staining, or cultured (unless the patient has been taking antibiotics). Nasal swabs may be useful to indicate exposure if positive, but negative results are not reliable. Antibody tests are useful in confirming the diagnosis. A polymerase chain reaction can detect spores in potentially contaminated material.

Treatment: Antibiotic prophylaxis is critical, immediately after exposure. The strains seen to date are sensitive to a wide range of antibiotics, but are resistant to cephalosporins (especially second- and third-generation) and sulfonamides (e.g. Septra, or Bactrim). Some experts suggest a combination of antibiotics to guard against resistance, and as noted, post-exposure immunization is recommended by many (including the military textbook linked to www.oism.org/ddp). Unfortunately, the currently available vaccines are ``impure and chemically complex, elicit only slow-onset protective immunity, provide incomplete protection, and cause significant adverse reactions''(Harrison's).

In critical cases, glucocorticoids may be tried. A small number of in vitro or animal experiments suggest that some toxin-mediated effects might be ameliorated with certain compounds, though the dosage is based on guesswork and there are no reported studies in human beings. Suggestions include: N-acetyl-L-cysteine, methionine, glutathione, intravenous vitamin C, and mepacrine (Hanna PC et al, Role of macrophage oxidative burst in the action of anthrax lethal toxin, Molecular Medicine 1994;1(1):7-18), and DHEA and melatonin (Shin S et al, Cell Biology and Toxicology 2000;16:165-174).

Sterilization and Disinfection: Spores are destroyed by autoclaving or by boiling in water for 10 minutes. Some have suggested ironing the mail; wet heat is more effective, as by putting a wet cloth between the iron and the letter, but the required iron temperature and time of exposure are not known. (Steam kills spores in from one to ten minutes.) For disinfecting surfaces, some say it is best to use copious quantities of soap and water. Formaldehyde, oxidizing agents such as potassium permanganate or hydrogen peroxide, cobalt irradiation, and 5% hypochlorite have been used.

Why Cipro?

Harold Koenig, M.D., a member of the small committee that made the decision, told A.L.E.C. in Austin this month that Cipro was chosen as anthrax protection for troops deployed in the Gulf War, not because of superior effectiveness but because doxycycline is photosensitizing and has an adverse effect on the developing fetus. But aside from its very high cost, Cipro has many side effects, which may become very apparent after long- term use. It can weaken cartilage and cause joint damage; lead to tendon rupture (especially of the Achilles tendon in runners); or cause chronic stomach problems, drowsiness, insomnia, irritability, hallucinations, seizures, or even brain damage.

Folklore

More Information

See past issues: Jan, July, Nov 1992; July 1993; January 1996 (www.oism.org/cdp), or the DDP Newsletter for March and Nov 1998, and Jan and Mar 1999 (www.oism.org/ddp).

Free e-mail subscriptions are available from the Program for Monitoring Emerging Diseases (www.promedmail.org). The CDC's Mortality and Morbidity Weekly Reports are online at www.cdc.gov/mmwr (Oct 19 or 26 and Nov 2 concern anthrax); also see www.bt.cdc.gov. The classic Sanford Guide to Antimicrobial Therapy, in a pocket-size or Internet version, may be ordered at www.sanfordguide.com.