Anthrax pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Bacillus anthracis is a rod-shaped Gram-positive bacterium, about 1 by 9 micrometers in size which normally rests in endospore form in the soil. There are 3 routes by which a person can become infected: Inhalation, ingestion and skin exposure. Once Antrhax spores are inhaled they are 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). Damage to the lungs causes chest pain and difficulty breathing. Once in the lymph glands, the spores germinate into active bacillus, that multiplies, and eventually bursts the macrophage cell, releasing many more bacilli into the bloodstream which are transferred to the entire body. Once in the blood stream these bacilli release a tripartite toxin (composed of lethal factor, edema factor and protective antigen) which is known to be the primary agents of tissue destruction, bleeding, and death. If antibiotics are given too late, even if the antibiotics eradicate the bacteria, some people still will die because the toxins produced by the bacilli still remain in their system at lethal dose levels. Eating anthrax infected meat is another mode of infection and is characterized by vomiting of blood, severe diarrhea, acute inflammation of the intestinal tract, and loss of appetite. Gastrointestinal infections can be treated but usually result in fatality rates of 25% to 60%, depending upon how soon treatment commences. Cutaneous (on the skin) anthrax infection causes a boil-like skin lesion that eventually forms an ulcer with a black center (i.e., eschar). The black eschar often shows up as a large, painless necrotic ulcers (beginning as an irritating and itchy skin lesion or blister that is dark and usually concentrated as a black dot, somewhat resembling bread mold) at the site of infection. Cutaneous infection is the least fatal form of anthrax infection if treated. But without treatment, approximately 20% of all cutaneous skin infection cases may progress to toxemia and death. Treated cutaneous anthrax is rarely fatal.

Pathogenesis

B. anthracis, the causative agent of anthrax, is a spore-forming bacterium. The spores of B. anthracis, which can remain dormant in the environment for decades, are the infectious form, but vegetative B. anthracis rarely causes disease. The bacterium causes disease through 2 mechanisms: toxemia and bacterial infection. Spores introduced through the skin lead to cutaneous or injection anthrax; those introduced through the gastrointestinal tract lead to gastrointestinal anthrax; and those introduced through the lungs lead to inhalation anthrax. After entering a human or animal, B. anthracis spores are believed to germinate locally or be transported by phagocytic cells to the lymphatics and regional lymph nodes, where they germinate; or both. B. anthracis begins producing toxins within hours of germination. Protective antigen (PA) and edema factor (EF) combine to form edema toxin (ET) and PA and lethal factor (LF) combine to form lethal toxin (LT). After binding to surface receptors, the PA portion of the complexes facilitates translocation of the toxins to the cytosol, in which EF and LF exert their toxic effects.

Gross Pathology

Inhalation Anthrax

Gross pathologic lesions observed in non-human primates used in aerosol challenge models of inhalation anthrax include edema, congestion, hemorrhage and necrosis in the lungs and mediastinum. Splenitis and necrotizing or hemorrhagic lymphadenitis involving the mediastinal, tracheobronchial, and other lymph nodes are common. Primary pulmonary lesions, including those of pneumonia, are occasionally observed. Meningeal involvement ranging from edema, congestion, hemorrhage, and necrosis to suppurative or hemorrhagic meningitis, usually secondary to hematogenous spread from other types of anthrax, occurs in ≤77% of animals studied. Autopsy findings for persons who died from inhalation anthrax in Sverdlovsk and in the United States are consistent with findings from the non-human primates studies. Persons who died had extensive amounts of serosanguinous fluid in pleural cavities and edema and hemorrhage of the mediastinum and surrounding soft tissues, and 48% had cerebral edema, 21% had ascites, 17% had pericardial effusions, and 14% had petechial rash. Mediastinal lymph nodes and spleen also showed hemorrhage and necrosis (11,12).

Exposure

Occupational exposure to infected animals or their products (such as skin wool and meat) is the usual pathway of exposure for humans. Workers who are exposed to dead animals and animal products are at the highest risk, especially in countries where anthrax is more common. Anthrax in livestock grazing on open range where they mix with wild animals still occasionally occurs in the United States and elsewhere. Many workers who deal with wool and animal hides are routinely exposed to low levels of anthrax spores but most exposures are not sufficient to develop anthrax infections. Presumably, the body’s natural defenses can destroy low levels of exposure. These people usually contract cutaneous anthrax if they catch anything. Historically, the most dangerous form of inhalation anthrax was called Woolsorters' disease because it was an occupational hazard for people who sorted wool. Fortunately this is now a very rare form of infection because of the much reduced incidence of anthrax disease in animals. The last fatal case of natural inhalation anthrax in the United States occurred in California in 1976, when a home weaver died after working with infected wool imported from Pakistan. The autopsy was done at UCLA hospital. To minimize the chance of spreading the disease, the deceased was transported to UCLA in a sealed plastic body bag within a sealed metal container. The details of this case have been described in a medical journal Human Pathology (Volume 9, pages 594-597, September, 1978).

In July 2006 an artist who worked with untreated animal skins became the first person in more than 30 years to die in the United Kingdom from anthrax.

Mode of infection

Anthrax can enter the human body through the intestines (ingestion), lungs (inhalation), or skin (cutaneous) and causes distinct clinical symptoms based on its site of entry. An infected human will generally be quarantined. However, anthrax does not usually spread from an infected human to a noninfected human. But if the disease is fatal the person’s body and its mass of anthrax bacilli becomes a potential source of infection to others and special precautions should be used to prevent more contamination. Unfortunately inhalation anthrax, if left untreated until obvious symptoms occur, will usually result in death if treatment is started too late.

Anthrax is usually contracted by handling infected animals or their wool, germ warfare/terrorism or laboratory accidents.

1) Pulmonary (pneumonic, respiratory, or inhalation) anthrax Respiratory infection initially presents with cold or flu-like symptoms for several days, followed by severe (and often fatal) respiratory collapse. If not treated promptly soon after exposure, before symptoms appear, inhalational anthrax is highly fatal, with near 100% mortality. A lethal dose of anthrax is reported to result from inhalation of about 10,000–20,000 spores. Like all diseases there is probably a wide variation to susceptibility with evidence that some people may die from much lower exposures; there is little documented evidence to verify the exact or average number of spores need for infection. Inhalation anthrax is also known as Woolsorters' disease or as Ragpickers' disease since these people often caught it. Other practices associated with exposure include the slicing up of animal horns for the manufacture of buttons, the handling of hair bristles used for the manufacturing of brushes, and the handling of animal skins. Whether these animal skins came from animals that died of the disease or from animals that had simply laid on ground that had spores on it is unknown. Anthrax is a very hard disease to eliminate since Anthrax spores are devilishly hard to kill and have been known to have reinfected animals over 70 years after burial sites of anthrax infected animals were disturbed.

2) Gastrointestinal (gastroenteric) anthrax Gastrointestinal infection is most often caused by eating anthrax infected meat and is characterized by serious gastrointestinal difficulty, vomiting of blood, severe diarrhea, acute inflammation of the intestinal tract, and loss of appetite. Gastrointestinal infections can be treated but usually result in fatality rates of 25% to 60%, depending upon how soon treatment commences.

3) Cutaneous (skin) anthrax

Anthrax skin lesion.

Cutaneous (on the skin) anthrax infection shows up as a boil-like skin lesion that eventually forms an ulcer with a black center (i.e., eschar). The black eschar often shows up as a large, painless necrotic ulcers (beginning as an irritating and itchy skin lesion or blister that is dark and usually concentrated as a black dot, somewhat resembling bread mold) at the site of infection. Cutaneous infections generally form within the site of spore penetration within 2 to 5 days after exposure. Unlike bruises or most other lesions, cutaneous anthrax infections normally do not cause pain. Cutaneous infection is the least fatal form of anthrax infection if treated. But without treatment, approximately 20% of all cutaneous skin infection cases may progress to toxemia and death. Treated cutaneous anthrax is rarely fatal.