The threat of anthrax as a biological weapon has become a real concern for everyone. Anthrax is a disease caused not by a virus, but rather by bacteria. There aren't any known cases of anthrax passing from one person to another, so it is considered to be noncontagious. It is still a large threat, however, because if it isn't recognized and treated quickly enough it can be deadly. Bacillus anthracis is the bacterium that causes the disease anthrax. It has historically affected herbivores like cattle, sheep or other grazing herds, but has also been a threat to humans who work with these animals and their by-products.

While in the ground or on a surface, anthrax spores are relatively harmless, but once they come into contact with the right environment they begin to germinate. They need an environment that is rich in amino acids, nucleosides and glucose -- like those elements found in blood and other tissues in humans or animals. Once there, a series of changes takes place that can make these bacteria deadly to its host.

In this edition of HowStuffWorks, we'll look at what anthrax is and how it affects the body. We'll also discuss new research and ideas for treatment and prevention of the anthrax disease.

Where Does it Come From?
Anthrax is found all over the world. It contaminates the ground when an affected animal dies. It spreads when grazing animals pick it up from contaminated dirt or through contaminated food sources such as bone meal that may have been made from contaminated carcasses. There appears to be an increase in the cases of anthrax among grazing animals during droughts, when they tend to graze closer to the ground and consume more dirt with the grass.

Anthrax may also spread when carnivorous animals, such as vultures or even insects, feed on affected herbivores. The bacteria are then transferred to other areas by the host and contaminate the ground when that animal dies. As the animal decays, the bacteria are exposed to oxygen and turn back into the spores that contaminate the soil. The anthrax spores have a very tough outer casing and can remain viable in the ground for decades.


Anthrax cycle

Many diagnostic laboratories around the world have anthrax samples for use in research and for the identification of anthrax. Anthrax can be grown in laboratories from these existing spores. In the wrong hands, these spores can be grown, dried and milled for use in biological weapons.

How Does it Spread?
Anthrax spores can enter the body through:

  • Inhalation into the lungs (inhalation anthrax) - The spores can be inhaled in contaminated soil or other particles containing the spores. The spores have no smell, taste or color, so a person would not notice anything had happened unless the spores had been mixed into a substance that could be readily seen, smelled or tasted. In order to enter the lungs, where they can germinate, the spores have to be very small -- from 1 to 5 microns (millionths of a meter). According to an anthrax report published by the American Medical Association, at least 2,500 spores have to be inhaled to cause an infection.


Inhaled anthrax

  • Entry into a cut or opening in the skin (cutaneous or skin anthrax) - Open cuts and scrapes can allow entry of the spores into the body to an environment in which they can germinate. This type of anthrax may also be spread by biting insects that have fed on infected hosts. The head, arms and hands are most often affected. People who handle contaminated animal products such as leather, hair (particularly goat hair) and wool are often exposed to the anthrax bacteria. Cutaneous anthrax accounts for about 95 percent of cases worldwide. If untreated, it has a fatality rate of five to 20 percent. If treated with antibiotics, it rarely leads to death.


Cutaneous anthrax

  • Entry through the gastrointestinal tract (gastrointestinal anthrax) - Eating undercooked meat that is infected with the anthrax bacteria, or drinking unchlorinated water that harbors the spores, can introduce the bacteria into the gastrointestinal tract. Infection can occur in either the upper or lower GI tract. This form of anthrax is rare.


Gastrointestinal anthrax

What Happens When it Enters the Body?
When viewed at the cellular level, an anthrax bacterium looks like a jointed bamboo rod. When it enters the body and finds the environment it needs, it moves to the lymph nodes. From there it begins to multiply and produce a toxin that attacks human cells resulting in hemorrhaging, swelling, a drop in blood pressure and ultimately death.


Photo courtesy Public Health Image Library
Anthrax bacteria (Bacillus anthracis), stained

The way it attacks the cells and exactly what it does was in question for many years. Research that began in the mid 1980s has revealed some interesting facts about the behavior of the anthrax bacterium when it finds a host.

Researchers found that there are three proteins that are created by the anthrax bacteria. These proteins are harmless individually, but together can be deadly. These proteins are referred to as:

  • Protective antigen (PA)
  • Edema factor (EF)
  • Lethal factor (LF)
When these proteins are released, the protective antigen binds to the cell surface and forms a type of channel in the cell membrane that allows the edema factor and lethal factor to enter the cell. The edema factor, when combined with the protective antigen, forms a toxin known as the edema toxin. The lethal factor, when combined with the protective antigen, forms a toxin known as the lethal toxin. It is the lethal toxin that does the most damage within the cell.

Research in 1998, by George Vande Woude at the National Cancer Institute in Frederick, MD, revealed clues to what the lethal toxin does to the cells. He found that the lethal factor cuts enzymes in two -- the enzymes that are responsible for transmitting signals within the cells. He also identified the enzyme in question. He was studying the mitogen-activated protein kinase (MAPK) pathway, which helps control cell growth, embryonic development and the way oocytes (eggs) mature. He was specifically looking for information about what the pathway actually did in the oocyte maturation cycle, so he searched for compounds that blocked the activity of the MAPK. A database search lead him to the lethal factor.

It is still not completely understood why disrupting the signal transmission within the cell results in the symptoms anthrax generates, but research continues. Research is also being done to find ways to alter the protective antigen to disable its ability to allow the entry of the lethal and edema toxins into cells.

The Symptoms of Anthrax
In its bacterial state, anthrax survives outside of a proper host environment for only about 24 hours. But inside the body, where it gets the nutrients it needs to grow, anthrax germinates and spreads rapidly.

Inhalation Anthrax
Inhaled anthrax typically begins showing symptoms in seven to 10 days, although it could be as early as two to three days. It can take as long as 60 days after exposure to the anthrax spores for the disease to surface, however, and once the germination begins, the disease progresses very rapidly. It appears to come in two stages:

  1. It begins with fever, cough, headache, vomiting, chills, weakness, abdominal pain, shortness of breath and chest pain. This first stage may last from a few hours to a few days. Then there may be a brief break in symptoms.
  2. The second stage of the disease lasts anywhere from two to four days. The symptoms for the second stage include fever, difficulty breathing, sweating, a bluish discoloration of the skin, shock, and finally death.

Cutaneous Anthrax
Cutaneous anthrax, which occurs when the anthrax spore is deposited into a break in the skin, may occur as late as 12 days after exposure. The germination of the bacteria results in local swelling of the skin -- a small papule (bump) will appear. The following day the bump will enlarge into an ulcer and begin discharging a clear fluid. Then, a painless, depressed black scab will form that will dry and fall off within one to two weeks. Treatment with antibiotics may not change the appearance or formation of the bumps, but they decrease the chances that the disease will become systemic.

Gastrointestinal Anthrax
The gastrointestinal form of anthrax, which occurs from eating or drinking infected meats or water, brings about symptoms that include nausea, vomiting blood, abdominal pain, bloody diarrhea, and weakness. Death occurs in 25 to 60 percent of these cases.

Diagnosis and Treatment
According to an article in the Journal of the American Medical Association, a blood sample is taken from the patient and cultured for six to 24 hours. At this point, a "Gram stain" can be done. The Gram stain highlights the bacteria.


Photo courtesy Public Health Image Library
Anthrax bacteria in Gram stain

The Gram stain takes about 10 to 15 minutes and can identify whether the bacteria come from the anthrax category. At that point, biochemical testing can be done to find the specific anthrax bacteria, which takes another 12 to 24 hours. Usually, the specimens have to be sent to national reference laboratories for comparison with stock anthrax samples.

Treatment
Anthrax is treated with the antibiotics penicillin, ciprofloxacin or doxycylcine. The antibiotic most often used is ciprofloxacin, partly because of rumors that the Soviet Union had developed a penicillin-resistant form of anthrax for use in biological warfare. It is also specifically recommended by the U.S. Food and Drug Administration (FDA) for use in treating anthrax.

Treatment of inhaled anthrax has to start very early in the progression of symptoms. If treatment is begun after the symptoms have progressed too far, then the bacteria may be killed but the toxins remain in the body.

Vaccine and Treatment Research
The vaccine that was developed in the 1950s (licensed in 1970), is currently only given to military personnel, people who work directly with anthrax in research labs, and those who work with animals and animal by-products that may be infected with anthrax. The vaccine uses the anthrax protective antigen to make the body create immunity to the disease. It is created from a strain of anthrax that does not cause the disease, and doesn't use any live or dead whole bacteria. There is a separate vaccine for use in animals. (That vaccine can't be used in humans.)

The side effects of the anthrax vaccine include:

  • Mild local reactions at the site of the injection (like with many other vaccinations)
  • Occasional, moderate local reactions that include redness, swelling and tenderness, often at the site of the injection and extending up to 5 inches (13 cm) across the area
  • Large local reactions larger than 5 inches, including swelling of the forearm and at the injection site
  • Muscle aches, joint aches, headaches, rash, chills, fever, nausea, loss of appetite, and weakness for a few days after the vaccination (experienced in up to 35 percent of people who get the vaccine)
  • A severe allergic reaction (appears once in every 100,000 doses)
  • A severe reaction that requires hospitalization (appears once in every 200,000 doses)

Research
Studies by R. John Collier and his colleagues at the Harvard Medical School have uncovered a possible therapy that can be used both as a vaccine and as a treatment for anthrax after the fact (particularly when antibiotics were not administered quickly enough).

This research was based on the previous findings by George Vande Woude and others at the National Cancer Institute in Frederick, MD, that identified the role of the protective antigen in allowing the lethal factor and the edema factor to enter the cell and begin wreaking havoc. Collier's research involved mutating the protective antigen to prevent this transfer. Experiments have suggested that even a single protective antigen mutant can disrupt the entire process. This treatment has worked in rats exposed to anthrax, but it is still not known how long after exposure the treatment could be given and still be effective in stopping the disease.

Because mutant protective antigen also appears to bring about an immune response (at least in rats), it has the potential to be a vaccine as well as a treatment. If successful, this approach could also be used for other diseases.

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