Biological and Chemical Warfare Agents

Anthrax

Bacillus anthracis derives from the Greek word for coal, anthrakis, because the disease causes black, coal-like skin lesions. Bacillus anthracis is an aerobic, gram-positive, spore-forming, nonmotile Bacillus species. The nonflagellated vegetative cell is large (1-8 µm in length, 1-1.5 µm in breadth). Spore size is approximately 1 µm. Spores grow readily on all ordinary laboratory media at 37°C, with a "jointed bamboo-rod" cellular appearance and a unique "curled-hair" colonial appearance, and display no hemolysis on sheep agar.

This cellular and colonial morphology theoretically should make its identification by an experienced microbiologist straightforward, although few practicing microbiologists outside the veterinary community have seen anthrax colonies other than in textbooks.³⁰

Anthrax spores germinate when they enter an environment rich in amino acids, nucleosides, and glucose, such as that found in the blood or tissues of an animal or human host. The rapidly multiplying vegetative anthrax bacilli, on the contrary, will only form spores after local nutrients are exhausted, such as when anthrax-infected body fluids are exposed to ambient air.^{16, 17} Full virulence requires the presence of both an antiphagocytic capsule and 3 toxin components (ie, protective antigen, lethal factor, and edema factor).³⁰ Vegetative bacteria have poor survival outside of an animal or human host; colony counts decline to undetectable within 24 hours following inoculation into water.¹⁷ This contrasts with the environmentally hardy properties of the B anthracis spore, which can survive for decades

Anthrax is a zoonotic disease caused by the spore-forming bacterium B. anthracis. Human disease usually occurs through cutaneous exposure to infected animal tissue or products. Rarely, inhalation or ingestion of B. anthracis spores also leads to anthrax. In the United States during the early part of the 20th century, approximately 130 human cases occurred annually (1); two cutaneous infections have been reported since 1992.

Before this exposure, no animal anthrax cases had been reported in northern Minnesota since recordkeeping began in 1909. However, in adjacent areas of North Dakota during 2000, 120--150 cattle have died of anthrax (L. Schuler, North Dakota state veterinarian, personal communication, 2000), and 11 farms have reported anthrax-related cattle deaths in nearby Manitoba, Canada  (J.G. Spearman, Manitoba Department of Agriculture, personal communication, 2000).

Gastrointestinal anthrax in humans occurs 1--7 days after eating raw or undercooked meat from infected animals (2), and two forms of gastrointestinal disease have been reported (3). Disease affecting the distal gastrointestinal tract results in nausea, anorexia, and fever followed by abdominal pain and bloody stool. The case fatality rate among reported cases ranges from 25%--60% (2). Gastrointestinal anthrax never has been documented in the United States because livestock are vaccinated for anthrax in areas where the disease is endemic; animals routinely are inspected by federal and state meat inspectors before, during, and after slaughter; and raw meat is eaten infrequently. Anthrax has not been documented among the persons exposed to B. anthracis-contaminated meat described in this report; however, a serologic test to determine presence of infection is pending.

Limited experience with gastrointestinal anthrax complicates recommendations for use of postexposure prophylaxis. An extended duration of therapy is recommended for inhalational exposure because of the persistence of spores resistant to the action of antimicrobial agents (4,5). Upon cessation of chemoprophylaxis, such spores can cause disease several weeks after exposure. No evidence supports the existence of persistent spores associated with gastrointestinal forms of the disease; however, the meat consumed by the family in this report was highly contaminated with B. anthracis. Although possible interventions range from close observation to antibiotics alone to antibiotics with vaccination, because the family was at high risk for anthrax infection, management consisted of an extended course of ciprofloxacin combined with administration of anthrax vaccine.

Federal-inspected and state-inspected animal processing facilities are required to perform intensive cleaning after contact with an anthrax-infected carcasses^† ; veterinary inspection is not provided at custom meat processors. Slaughter house workers who may be exposed to an anthrax-contaminated carcass should receive medical evaluation for symptoms and for possible treatment. Management of anthrax in livestock should include 1) quarantine of the herd; 2) removal of the herd from the contaminated pasture, if possible; 3) vaccination of healthy livestock; 4) treatment of symptomatic livestock; and 5) disposal of infected carcasses, preferably by burning. Bedding and other material found around the carcass (e.g., soil) should be incinerated with the carcass and buried (6).

Veterinarians notified of sudden death in an animal or of an animal unable to rise should consider anthrax as a diagnosis, especially in areas where anthrax is endemic (6). However the potential risk for animal anthrax exists in all areas of the United States. Vaccination of livestock in areas where anthrax is endemic is the most effective method of prevention in animals and humans. Cases of anthrax in animals and cases of suspected human exposure should be reported immediately to the state health department, federal animal heath officials, and to CDC's National Center for Infectious Diseases, Meningitis and Special Pathogens Branch, telephone (404) 639-3158.

Bacillus of Anthracis (Gram Stain)

Robert Koch's original micrographs of the anthrax bacillus

References

1. Brachman P, Friedlander A. Anthrax. In: Plotkin S, Mortimer E, eds. Vaccines. 2nd ed. Philadelphia, Pennsylvania: WB Saunders Co., 1994:792--39.
2. Brachman P, Kaufmann A. Anthrax. In: Evans A, Brachman P, eds. Bacterial infections of humans. New York, New York: Plenum Medical Book Company, 1998.
3. Sirisanthana T, Navachareon N, Tharavichitkul P, Sirisanthana V, Brown AE. Outbreak of oral-oropharyngeal anthrax: an unusual manifestation of human infection with Bacillus anthracis. Am J Trop Med Hyg 1984;33:144--50.
4. CDC. Bioterrorism alleging use of anthrax and interim guidelines for management---United States, 1998. MMWR 1999;48:69--74.
5. Friedlander AM, Welkos SL, Pitt ML, et al. Post-exposure prophylaxis against experimental inhalation anthrax. J Infect Dis 1993;167:1239--43.
6. Animal Plant Health Inspection Service. Washington, DC: US Department of Agriculture Veterinary Services, US Department of Agriculture. September 1999. Available at http://www.aphis.usda.gov/oa/pubs/anthrax.html. Accessed September 2000.
   
   

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Smallpox

Ramses V c.1000bce
Spots on mummified remains of face believed to be smallpox.

What is smallpox?
Smallpox is an acute infectious disease caused by a virus. Smallpox infects only humans, and the last naturally acquired case of smallpox in the world occurred in 1977.

Who gets smallpox?
No one has naturally contracted smallpox since 1977. (There have been a limited number
of cases since 1977 where researchers have become infected from exposures that took place
in a laboratory setting.)

When smallpox naturally occurred, the disease was highly contagious. People became infected from being exposed to the respiratory secretions of people with smallpox, through direct contact with smallpox lesions of the skin and mucous membranes, or through contact with materials (e.g., bedding, clothing) which had been contaminated by such lesions or scabs.

People who developed a cough when they had smallpox could spread the disease by coughing and were considered at very high risk of transmitting their disease to others.

What were the symptoms of smallpox?
The initial symptoms of smallpox included the acute onset of fever, chills, headache, nausea, vomiting and severe muscle aches. This stage would usually last for two to four days and was, at times, accompanied by flushing of the skin. By the fourth day of illness, the fever dropped and the characteristic smallpox rash appeared. The rash started out as flat or slightly thickened spots (known as macules) and quickly progressed to raised spots (known as papules). These papules continued to enlarge and became filled with a clear fluid, and were then referred to as vesicles. The fluid in the vesicles would gradually change from clear to pus-like, and the lesions were then referred to as pustules. During the pustule stage, a fever would again be common and the pustules would start to form into scabs. Over time, the dried scab material would fall off of the skin. This entire process took three to four weeks, and the areas affected by the rash were often permanently scarred.

There were two types of smallpox: variola major and variola minor. Variola major was the more severe form and would usually kill 30-50% of persons infected with it who were unvaccinated (3% of those vaccinated), typically between the 5th and 7th day of their illness. Variola minor would usually kill 1-2% of persons infected with it who were unvaccinated. There were two rare and more serious forms of smallpox. In the most severe form, known as purpura variolosa or hemorrhagic-type smallpox, the initial stage of the illness (before the rash appeared) would be accompanied by a dark, purplish, blotchy flushing of the skin. People who developed purpura variolosa usually had a severe loss of blood into the skin and internal organs (hemorrhage), and died before the typical smallpox rash would appear. About 3% of the persons with variola major would develop purpura variolosa. Another rare and deadly form of smallpox was referred to as flat-type smallpox that affected about 5% of the persons with variola major. Persons with this
form of the disease would have lesions that developed more slowly, never raised above the
surface of the skin, and felt soft to the touch. If people with flat smallpox survived, they rarely experienced severe scarring. Both purpura variolosa and flat smallpox were virtually never seen in persons infected with variola minor.

Smallpox was sometimes confused with chickenpox, but several features of these diseases
were significantly different: The initial symptoms of smallpox were much more severe than those of chickenpox (i.e., high fever, severe muscle aches, etc.). Smallpox rash was most common on exposed portions of the body: face, forearms, wrists, palms, lower legs, feet, and soles. (Chickenpox is most common on covered areas of the body.)

Smallpox rash lesions tended to be at the same stage of development, and there was only one eruption of pox lesions. (With chickenpox, it is common to have more than one eruption of pox lesions and the lesions may be in different stages of maturation.) Smallpox lesions tended to be deeper in the skin than chickenpox lesions, hard to the touch, and the vesicles were tough to break.

How soon after exposure did symptoms appear?
The first symptoms of smallpox usually occurred within 10 to 12 days after exposure, with the rash appearing two to four days later. The first symptoms could appear, however,
as early as six days after exposure, or as late as 22 days.

How was smallpox diagnosed?
Smallpox was often diagnosed based on the patient’s clinical signs and symptoms; however, the disease could be definitively diagnosed by isolation of the virus from the blood or lesions, or by identification of antibodies in the blood that were made in response to the virus.

What was the treatment for smallpox?
There were no medicines available to treat smallpox once the lesions began to develop. Antiviral medicines were sometimes useful at preventing the development of smallpox if they were given to a person immediately after they were exposed to the disease. Antibiotics might have been offered if the pustules of the rash appeared to be infected with a bacteria, but supportive nursing care was the primary therapy available. Vaccinia immune globulin (VIG) was used primarily to treat complications of smallpox vaccination. VIG could also have been offered to persons exposed to smallpox as a prophylaxis. However, VIG needed to be given before their lesions began to develop, and it was most effective when given with smallpox vaccination.

How was smallpox prevented (and ultimately eradicated)?
There is a vaccine to prevent smallpox that was routinely administered in the United States until the early 1970s. It is effective at preventing smallpox, and was used to eradicate the disease. The last case of smallpox was diagnosed in Somalia in 1977 and, in 1980, the World Health Organization declared that smallpox had been eradicated from the face of the earth.

While the smallpox vaccine is effective, it was associated with a significant risk of adverse events in vaccinees. This risk of adverse events, accompanied by the rapid decrease in smallpox around the world in the 1970s, was part of the justification for the U.S. to discontinue routine vaccination against smallpox before the disease was eradicated in 1977.

Very limited stockpiles of smallpox vaccine and VIG are maintained by the CDC. Routine
vaccination of the civilian population for this disease is not recommended, nor is smallpox vaccination required for international travel to any country. The only persons currently recommended to receive smallpox vaccine are persons working in a laboratory setting with smallpox or closely related viruses.

Smallpox lesions on skin of trunk. Picture taken in Bangladesh, 1973.

Chemical Agents

The most common chemical agents include:

Sarin is a colorless, odorless nerve gas the Aum Shinrikyo cult used on a Tokyo subway in March 1995, killing 12 people and injuring more than 5,500. Sarin, which has been produced by the United States, Russia (and the Soviet Union) and Iraq, is a member of the organophosphate chemical family, as are many modern pesticides. It can be difficult to mix properly and safely, and can also be highly unstable.

Soman: With Sarin and another chemical weapon known as Lewisite — a blistering agent — the nerve agent Soman is said to have made up much of the former Soviet Union's chemical arsenal. It is considered a volatile substance effective mainly through inhalation.

VX, or O-ethyl S-diisopropylaminomethyl methylphosphonothiolate, is brownish in liquid form, and its vapors are odorless. The United States began producing VX in April 1961, but its composition was not widely known for another decade.

VX agents are among the most toxic substances known. Mere droplets can kill. It can remain on material, equipment and terrain for long periods. Uptake is mainly through the skin but also through inhalation of the substance as a gas or aerosol.

Tabun, invented by a German chemist, Gerhard Schrader, in the mid-1930s, is colorless or brownish as a liquid, and odorless as a vapor. Schrader worked for IG Farben, a company that later used slave labor from the Birkenau concentration camp to produce its products. Another one of Farben's inventions was Zyklon-B, a type of hydrogen cyanide used by the Nazis to gas victims in those same camps during World War II. Tabun, also an organophosphate like many pesticides, is considered among the easiest of nerve gases to manufacture, even in the non-industrialized world.

Hydrogen cyanide is a commercially produced "blood agent" used in plastic and organic chemical products in many parts of the world. It is a colorless vapor at normal temperatures with a smell likened to bitter almonds.There is no confirmed information on this substance being used in chemical warfare. However, it has been reported that hydrogen cyanide was used by Iraq in the war against Iran and against the Kurds in northern Iraq during the 1980s. Hydrogen cyanide has high toxicity and in sufficient concentrations rapidly leads to death.

Mustard Agents

First used toward the end of World War I, mustard agents — among the most commonly produced chemical weapons by those nations that have had them — cause severe eye and lung damage. They are often called "blister agents" since their injuries usually resemble burns or blisters. They United States, Germany, Russia and Iraq are all said to have produced mustard agents during the 20th century.