Anthrax, Then and Now

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DOCTOR'S ARCHIVE

Medical Author: Michael C. Fishbein, MD
Previous Medical Editor: Leslie J. Schoenfield, MD, PhD
Revising Medical Editor: Jay W. Marks, MD

Introduction

Experts have said that it is a matter of when, not if, a large scale act of bioterrorism is carried out in the U.S. Why "bio" terrorism? Biologic weapons are cheaper and more devastating than chemical weapons and maybe even nuclear weapons. Deadly quantities of infectious agents are easy to hide, transport, and spread throughout the population. Indeed, the U.S. already experienced a bioterrorism attack. In 2001, powder containing the bacterium called anthrax was distributed through the U.S. mail. All together, 22 people became infected with anthrax. These people lived in South Florida, New York City, New Jersey, Maryland, Connecticut, Pennsylvania, Virginia, and Washington, DC. Eleven people seem to have inhaled the anthrax, and 11 others were infected through the skin. The FBI and CDC (Center for Disease Control) are still investigating this outbreak.

Because of this outbreak, most Americans are now aware of the infectious disease called anthrax. Most are also aware that it is usually a disease of animals and that it is a rare cause of disease or death in humans. Prior to the outbreak in 2001, the last case of fatal anthrax in the United States was in 1976. Moreover, no fatal cases occurred in the preceding 10 years. What may not be as widely known, however, is that the 1976 case occurred in California. This was not a case of bioterrorism. The patient did die of the infection, and the autopsy was performed at UCLA Medical Center. The details of this case have been described in a medical journal called Human Pathology (Volume 9, pages 594-597, September, 1978).

The California case--1976

The patient was a 32-year-old artistic weaver who worked at home. He purchased his yarns from commercial suppliers. Investigations later revealed that the source of his infection was imported wool from Pakistan. The patient had been well until he developed a fever and sore throat, six days before his death. The illness progressed to include chest pain, headache, nausea, and loss of appetite. During the illness, his major difficulties were trouble breathing, mental problems such as an inability to carry out simple commands, and involuntary eye and limb movements.

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cinenet.com/lumbar_puncture/article.htm" rel="proc" onclick="wmdTrack('embd-lnk');">spinal tap (removal of some spinal fluid for analysis) revealed spinal fluid bacteria that looked very much like anthrax. All of these findings indicated involvement of the lungs and central nervous system (spinal cord and brain). The bacterial organism was eventually confirmed at the CDC to be anthrax. In spite of antibiotic therapy, the patient died. In this case, the antibiotics were begun late in the course of the disease, after the anthrax had spread throughout the body.

Several medical examiner's offices and university hospitals in California declined to do the autopsy, presumably for fear of contracting or spreading the anthrax infection. When the UCLA Department of Pathology was asked to perform the autopsy, the faculty agreed for several reasons:

  • As part of a teaching and research institution, they felt obligated to society to do the autopsy.
  • They had the appropriate facilities, namely, an isolation room to limit exposure.
  • They had experts in the pathology of infectious diseases and neuropathology on the faculty.
  • For forewarned and prepared pathologists, the risk of getting infected during the autopsy was actually quite small.

The deceased was transported to UCLA in a sealed plastic body bag within a sealed metal container. The major findings at the autopsy were heavy lungs that were congested with blood and fluid, as well as bleeding into the central chest cavity (mediastinum) and the surface (meninges) of the brain (see Figure I below). These findings are characteristic of patients who die of anthrax. Finally, scientists from the CDC flew out to California to collect specimens and confirmed that the victim died of anthrax.

Figure I

What is anthrax?

Anthrax is a disease caused by a type of bacteria, or germ, (bacillus anthracis) that was discovered in 1850. Notably, it is actually the first bacterium to be shown to cause a disease. In fact, it was the well-known German physician Robert Koch who discovered this. He grew the anthrax bacteria in culture plates, injected them into animals, and thereby demonstrated that the bacteria produced the disease. Then, the famous French scientist Louis Pasteur (known for pasteurizing milk) used anthrax bacteria that he damaged to develop a vaccine for anthrax. His idea was that the damaged bacteria would not cause the disease but would still protect (produce immunity) against anthrax. Indeed, he showed that this vaccine protected animals from getting the disease when they were subsequently injected with healthy, virulent (disease-causing) anthrax bacteria.

Anthrax differs from most b

acteria in that they exist in an inactive (dormant) state called spores. The spores are found in soil, animal carcasses and feces (including sheep, goats, cattle, bison, horses, and deer), and animal products (for example, hides and wool). Some animals (cats, dogs, rats, and swine) are very resistant to anthrax. Remarkably, anthrax spores can remain dormant in soil for many years, perhaps decades. Likened somewhat to eggs that have the ability to hatch, spores can transform (germinate) into active bacteria under appropriate conditions. The spores themselves do not cause any significant damage to tissue. However, they can lead to disease by (1) entering broken skin (cutaneous anthrax), (2) being inhaled (inhalation anthrax), or (3) being eaten (gastrointestinal anthrax). Once in the body, the spores germinate to form the virulent (disease-causing) bacteria.

What symptoms does anthrax cause?

Cutaneous anthrax results in a large, relatively painless, ugly skin sore referred to as a malignant pustule. Death is rare with treatment; and 80% of untreated patients survive as well. In the other 20%, death occurs because the infection spreads to other parts of the body or the patients succumb to a poison (toxin) that the bacteria produce.

Gastrointestinal anthrax is rare and appears to follow ingestion of contaminated raw meat containing the spores. Symptoms caused by this type of anthrax can include nausea, vomiting, abdominal pain, and diarrhea. As with cutaneous anthrax, most people having gastrointestinal anthrax survive, with or without antibiotic treatment.

The most dangerous form of anthrax, and the greatest bioterrorism threat, is inhalation anthrax. It has also been called wool sorter's disease because it is an occupational hazard for people who sort wool. Inhaling spore-bearing dust is the usual way that inhalation anthrax is contracted. To cause the disease, spores must be inhaled and transported through the air passages into the tiny air sacs (alveoli) in the lungs. The spores are then picked up by scavenger cells (macrophages) in the lungs and are transported through small vessels (lymphatics) to the glands (lymph nodes) in the central chest cavity (mediastinum). In the glands, the spores transform (germinate) into active, multiplying (reproducing) bacteria. Damage to the central chest cavity and lungs can cause chest pain and difficulty breathing.

From the chest, the bacteri

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a can spread, by way of the blood stream, to other organs (for example, the brain). Most importantly, the anthrax bacteria anywhere in the body produce poisons (toxins) that are the primary agents of tissue destruction, bleeding, and death. We know that the toxins are lethal because experiments in animals have shown that injection of the toxins alone can cause most of the findings of the disease. Furthermore, in humans, even if antibiotics eradicate the bacteria, some individuals still will die because the toxins remain in their system.

As with other infectious diseases, there is a lag-time (incubation period) between exposure to the spores and the first symptoms and signs (manifestations) of anthrax. The incubation period is usually one to six days, but it can be much longer, even up to several weeks. This lag time is helpful to health-care providers during natural or terrorism-related epidemics, since it allows time for early institution of antibiotic therapy. On the other hand, the organism may spread through the population undetected for some time. Antibiotics are quite effective and almost always curative if used before the illness causes severe symptoms and becomes life-threatening.

How do we diagnose anthrax?

Most hospital laboratories should be able to make a tentative diagnosis of anthrax. Material is collected from presumed sites of infection: skin sores for cutaneous anthrax, stool samples for gastrointestinal anthrax, and sputum from patients with inhalation anthrax. If the organism has spread to the nervous system, spinal fluid may demonstrate the organism. If the anthrax bacteria have spread throughout the body, they can be demonstrated in a blood sample. Also, it is important to know that nasal swabs can be used to determine if someone has been exposed to anthrax by inhalation. Finding spores in the nose, however, does not mean that the individual has, or will develop, the disease. (Remember that the spores have to get all the way to the lungs before damage occurs.)

To make the diagnosis of anthrax, the laboratory personnel make slide preparations of the collected material. Then, after applying special dyes (gram stain) to the slide preparations, they can visualize the bacteria under the microscope. Samples of the collected material are also transferred to special plates containing growth media (culture plates) that enhance multiplication of the bacterial organisms. The idea is to make more bacteria available for microscopic and other studies. Classically, from the size and shape and the growth characteristics of the bacteria, one can be fairly certain of the type of bacteria causing the infection. In addition, laboratory testing of the cultured bacteria can determine which antibiotics will be most effective in killing the bacteria (called sensitivity testing). Finally, specialized centers, such as the CDC, do more sophisticated genetic and molecular diagnostic studies to verify the diagnosis of anthrax. These centers also can identify more detailed characteristics (for example, the strain, virulence, and type of toxin) of the bacteria.

How easy is it to get an

anthrax infection?

Not very easy! Since only the spores can spread (transmit) the disease and anthrax does not form spores in living tissues, the disease is not transmitted from person to person. That is to say, anthrax is not contagious. The most common way people get infected with anthrax is by working with animal carcasses or hides that contain spores. These people usually contract cutaneous anthrax.

Inhalation anthrax is exceedingly rare. This is because, as previously mentioned, the spores have to travel all the way to the tiny air sacs (alveoli) in the lungs. Thus, the spores must be small (less than 5 microns) and able to get past many protective barriers (such as mucus, body chemicals, and microscopic hairs) in the mouth, nose, throat, and air passages. What's more, the spores must overcome obstacles presented by the body's immune (defense) system. So, it is estimated that many thousands of spores (perhaps 10,000-20,000) are needed to establish an infection in humans. All things considered, most forms of anthrax bacteria are probably not that dangerous. Sadly, however, some governments and terrorist groups are spending millions of dollars to try to develop more deadly anthrax bacteria for use as biologic weapons. Anthrax is easy to grow. Anthrax bacteria are very resistant to destruction. Thus, when released into the air, they can spread over large distances and affect many people. It is not surprising, and it is somewhat reassuring, that major efforts are ongoing to find the best ways to prevent, detect, and treat future bioterrorist attacks using anthrax.


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Reviewed on 4/10/2007

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