Anthrax is a potentially fatal zoonosis caused by a toxin-producing bacillus, Bacillus anthracis. Also known as Siberian plague, malignant pustule, ragpicker's disease, and woolsorter's disease, anthrax is primarily a disease of animals, both livestock (cattle, goats, sheep, camels, and horses) and wildlife (hippos, antelope, buffalo, deer, and elephants); it is rare in humans. The English name of the disease comes from the Greek word for coal, because anthrax infections of the skin typically form ulcers with coal-black centers known as eschars. Humans and animals are only incidental hosts of the bacillus, as anthrax organisms form endospores that can be found in soil and survive there. Herbivores (animals whose primary diet is grass or other plant material) become infected when they breathe in or ingest the anthrax spores from contaminated soil, water, or plants. Humans become infected by handling wool, hides, or other products from infected animals; by inhaling anthrax spores; by consuming contaminated food or water; or by injecting drugs of abuse contaminated with anthrax spores.
Anthrax in humans takes one of four major forms: cutaneous, inhalational, gastrointestinal, and injection-related. Cutaneous anthrax, the most common form in ordinary circumstances, occurs when anthrax endospores enter the body through the skin. Although an open cut or abrasion makes it easier for the spores to gain entrance, they can also produce infection when the skin is intact. Although person-to-person transmission of anthrax is rare, it can occur through direct contact with another person's skin lesion. The first symptom of cutaneous anthrax is an itchy raised papule resembling an insect bite, usually on the face, neck, or hands. Within a few days, the papule enlarges into a skin ulcer surrounded by small fluid-filled blisters. A crusty black eschar develops over the ulcerated area later, and then falls off after a few weeks, leaving a scar on the skin.
Inhalation anthrax is the most lethal form of anthrax infection, but unlike cutaneous anthrax, it cannot be transmitted from one person to another. It occurs when a person breathes in anthrax spores from infected animal material or accidentally released in a laboratory. The first symptoms of inhalation anthrax include two or three days of low-grade fever and other flu-like symptoms. The patient typically experiences an aching sensation of heaviness in the chest. Later symptoms include high fever, dyspnea (painful or difficult breathing), heavy sweating, a rapid pulse, and rapid breathing.
Gastrointestinal anthrax is most likely to occur when a person eats undercooked meat from an infected animal. It is, however, the rarest form of anthrax in humans. The person may experience symptoms in the lining of the throat and esophagus as well as intestinal symptoms: nausea, vomiting, abdominal pain, loss of appetite, severe diarrhea, and eventually blood in the vomitus. The skin and mucous membranes may develop a bluish tinge known as cyanosis. The lymph nodes in the mesentery (the fold of tissue attaching the small intestine to the abdomen) may become inflamed by the toxins released by the anthrax bacilli, leading to intestinal blockage, bleeding, or perforation.
Injection-related anthrax has been reported only since 2009; it is thought to have appeared in Europe when heroin contaminated by bone meal from infected sheep was imported from Afghanistan. The symptoms of injection-related anthrax are similar to those of cutaneous anthrax, except that the infection lies deep within the skin and underlying muscle. It spreads more rapidly to other tissues than cutaneous anthrax and is more difficult to treat.
Anthrax in animals occurs only in the inhalational and gastrointestinal forms. Symptoms include fever, difficulty breathing, agitated behavior followed by depression, loss of coordination, diarrhea, bloody vomiting, convulsions, and death.
Risk factors for anthrax in humans are primarily related to occupation. The following are categories of persons who are at increased risk:
According to studies of the 2001 anthrax attack in the United States, other risk factors for developing anthrax after exposure to endospores include underlying lung disease and alcoholism.
Anthrax acquired naturally is rare in developed countries because of the widespread vaccination of livestock against the disease. Although anthrax is a notifiable disease in Australia, the United Kingdom, and the United States, relatively few cases are reported to the public health authorities in those countries. In the United States, the average number of cases prior to October 2001 was less than one per year; between 1955 and 1994, only 235 cases of anthrax were reported to the Centers for Disease Control and Prevention (CDC). Of these cases, 95% were cutaneous (skin-related) anthrax; slightly less than 4% were inhalational anthrax; and less than 1% were gastrointestinal anthrax. The October 2001 terrorist attack, in which a series of letters containing anthrax spores were mailed to several U.S. news media outlets and U.S. Congressional offices, killed five people by inhalational anthrax and infected 17 others. As of 2018, most cases of anthrax associated with contaminated heroin have occurred in the European Union and the United Kingdom, specifically Scotland, Denmark, France, and Germany.
Anthrax in humans is most common in the developing countries of Africa, India, Central Asia, the Caribbean, and southern Asia, with occasional cases reported in southern Europe. These are countries that do not have universal livestock vaccination programs. According to the World Health Organization (WHO), about 2,000 cases of human anthrax are reported worldwide each year. Some public health experts, however, believe that the true number is higher because many cases in Africa are not reported. WHO considers anthrax to be endemic in Africa and Asia in spite of local livestock vaccination programs.
People of both sexes and all race or age groups are equally susceptible to anthrax. Because most cases of the disease as of 2018 are related to occupation, however, most patients are young or middle-aged adults.
All forms of anthrax are caused by Bacillus anthracis, an anaerobic organism that readily forms endospores in order to survive unfavorable conditions. The endospores are essentially dehydrated cells with thick protective walls (capsules) that are resistant to heat, drying, ultraviolet radiation, and most disinfectants; they can survive in the soil for decades or even centuries. The endospores' resistance to drying makes them ideal biological weapons in either a powdered or an aerosol form.
When the anthrax endospores gain entrance into an animal or human body, they germinate at the entrance site and multiply within the skin, mucous membranes of the nose and throat or digestive tract. They germinate within macrophages (a type of white blood cell) and migrate into the lymphatic system. Anthrax bacilli are particularly virulent because of the external capsule that protects them from destruction by the macrophages and because of the toxic factors they secrete. The bacilli secrete three proteins: 1) the protein protective antigen (PA), which binds to cells and allows the other two factors to enter the cells; 2) edema factor (EF), which causes massive local swelling; and 3) lethal factor (LF), whose specific actions are not well understood but which is the cause of death from anthrax in fatal cases. The three protein factors combine to form anthrax toxins; PA plus EF forms edema toxin, and PA plus LF forms lethal toxin.
In cutaneous anthrax, the bacilli gain entrance to the skin either through an open cut or wound or through microscopic breaks in the skin. In addition to forming the initial papule and ulcer followed by the characteristic eschar, B. anthracis may spread into the bloodstream, causing bacteremia, or to such other organs as the liver, spleen, or kidneys via the lymphatic system. The bacilli remain within the smaller blood vessels of the affected organs, where the organisms can cause massive bleeding as well as tissue damage.
Inhalational anthrax is thought to require as many as 4,000–8,000 spores to cause infection of the respiratory tract. After an incubation period (usually 1–6 days), the spores are carried by the lymphatic system to the lungs, where they germinate, multiply, and cause swelling of and bleeding in the lung tissue. Anthrax does not cause pneumonia in the strict sense, but it does cause coughing, chest pain, difficult breathing, dizziness, and heavy sweating. The person may also develop anthrax-related meningitis from inhalational anthrax, with such changes in mental status as confusion or disorientation. It is common in inhalational anthrax for the bacteria to spread into the bloodstream and cause overwhelming infection or bleeding lesions elsewhere in the body.
In gastrointestinal anthrax, the cecum (a blind pouch at the beginning of the large intestine) is the most common location of the initial lesion produced by anthrax spores. The spores then invade the mucous lining of the intestines; in some cases, intestinal hemorrhage results. The anthrax spores are transported by the lymphatic system to lymph nodes in the mesentery, the membranous tissue that attaches the small intestine to the abdominal wall. As the bacilli multiply, they block the passages in the lymphatic system, leading to a buildup of fluid in the abdomen (ascites), intestinal paralysis (ileus), and swelling (edema) of the stomach and other nearby tissues. In some cases, the initial lesion of this form of anthrax is located in the pharynx, the part of the throat behind the mouth and above the esophagus. Pharyngeal anthrax is characterized by pain in the throat, difficulty in swallowing, and possible airway obstruction.
In injection anthrax, the initial lesion is often below the surface of the skin or in muscle tissue and may form an abscess followed by necrosis of the surrounding tissue extending to the entire limb. There may or may not be an ulcer on the surface of the skin at the site of the drug injection. In one case from Denmark, a large area of skin surrounding the injection site turned black. The anthrax bacilli may invade the bloodstream if treatment is delayed; as of 2018, all the European fatalities associated with injection anthrax died of sepsis.
In developed countries, the diagnosis of anthrax depends partly on a high index of suspicion on the doctor's part. The patient's occupation or history of recent exposure to anthrax may suggest the diagnosis. Although the papule and ulcer of cutaneous anthrax may be obvious during an office examination, gastrointestinal anthrax is particularly difficult to diagnose on the basis of early physical symptoms alone.
Accurate diagnosis depends on obtaining samples taken from skin lesions or throat lesions; cerebrospinal fluid; bloody fluid from the lungs; ascites fluid; or stool. B. anthracis can usually be visualized either by culturing the organisms on 5% sheep blood agar or peptone agar or by Gram stain. Anthrax bacilli are large for bacteria (3–4 microns); typically form long chains; and stain gram-positive. If cultured, they will usually grow on the medium within 24 hours. Laboratory personnel should be advised that anthrax is suspected so that they can take appropriate precautions.
Anthrax can also be diagnosed by testing blood samples by enzyme-linked immunosorbent assay (ELISA) for antibodies to the anthrax bacillus or for the presence of edema toxin and lethal toxin.
Nasal swabs or sputum samples are not helpful in identifying inhalation anthrax because the airway is not usually affected in that form of the disease. A chest x ray or CT scan is recommended for diagnosing inhalational anthrax; CT is useful in distinguishing inhalational anthrax from sarcoidosis, lymphoma, and tuberculosis.
A lumbar puncture should be performed if there is a change in the patient's mental status or evidence that the patient has anthrax-related meningitis.
Anthrax is treated with antibiotics. Patients with cutaneous anthrax without significant swelling or systemic symptoms can be treated as outpatients with a 7–10-day course of antibiotics, usually ciprofloxacin, doxycycline, or levofloxacin. Antibiotic therapy should, however, be extended to 60 days if there is any chance that the patient was exposed to inhalational anthrax.
Gastrointestinal anthrax, inhalational anthrax, and cutaneous anthrax with systemic symptoms are treated with a combination of antibiotics: one that is bactericidal and a second that inhibits protein synthesis. Bactericidal antibiotics include penicillin G, ampicillin, ciprofloxacin, levofloxacin, imipenem, and vancomycin. Antibiotics that inhibit protein synthesis include clindamycin, doxycycline, linezolid, and chloramphenicol. The patient is admitted to the hospital, with the antibiotics given intravenously initially for two weeks or until the patient is stable, after which the patient can be given a single antibiotic by mouth. Antibiotic therapy should be continued for 60 days if the patient may have been exposed to inhalational anthrax. Treatment with penicillin alone is not recommended because of the possibility that the patient has been exposed to genetically engineered strains of anthrax that are resistant to penicillin.
Patients with sepsis or who are hemorrhaging should be admitted to an intensive care unit for monitoring and ventilator support; however, their prognosis is very poor.
Anthrax is rare in humans in developed countries because of routine vaccination of livestock. The U.S. Department of Agriculture (USDA) and the American Veterinary Medical Association (AVMA) provide farmers, livestock producers, veterinarians, and pet owners with information about animal vaccination against anthrax. The first effective vaccine—for sheep—was developed by Louis Pasteur in 1881. Austrian immunologist Max Sterne (1905–1997) developed an improved animal vaccine against anthrax in 1935 that became the basis of almost all veterinary vaccines used after that.
A more pressing public health concern in the twenty-first century is the possible use of aerosolized anthrax spores as a weapon of bioterrorism. The October 2001 incident in the United States demonstrated the relative ease of disseminating a dangerous bacterium in its most lethal form through a means as ordinary as mail delivery. As of 2018, the anthrax bacillus is considered a Tier 1 select agent by the CDC, which is the highest rating possible under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002. The CDC defines Tier 1 agents as those that “present the greatest risk of deliberate misuse with significant potential for mass casualties or devastating effect to the economy, critical infrastructure, or public confidence, and pose a severe threat to public health and safety.” The CDC has the responsibility to regulate all laboratories that possess, transfer, or use any select agents and to work with local and state health agencies to ensure adequate supplies of medicines and needed equipment in the event of a bioterrorist attack using anthrax. The CDC also develops guidelines to protect the health of first responders and healthcare workers involved in treating victims of an anthrax attack.
The World Health Organization (WHO) has not posted any warning about outbreaks of anthrax in humans or updates about past outbreaks since late 2001. Most international efforts in regard to anthrax are directed toward improving safety standards in research laboratories that make use of the anthrax bacillus and toward preventing bioterrorist attacks using anthrax endospores. These efforts are based on the past history of using anthrax as a biological agent in warfare, beginning with World War I, when the German General Staff assisted rebels in Finland in using anthrax against the Russian army in 1916. In the 1930s, the Japanese army in Manchuria deliberately infected thousands of Chinese prisoners of war with anthrax; most of the prisoners died. During World War II, the Royal Air Force was preparing to drop cattle feed laced with anthrax on Germany in 1944 in order to kill off the country's livestock, but the raid was never carried out. The United States maintained stockpiles of weaponized anthrax until 1972, when it signed the Biological Weapons Convention, and President Nixon ordered the destruction of the anthrax stockpile as well as other biological weapons.
Accidental releases of anthrax from laboratories are an additional international concern. In April 1979, anthrax spores were leaked from a military research facility in Sverdlovsk (later called Ekaterinburg) in Russia and caused the deaths of at least 105 workers in the laboratory itself and a ceramics factory across the street. As the possession of weaponized anthrax indicated that the then-Soviet Union was in violation of the Biological Weapons Convention, evidence of the accident was hidden by the Soviet secret police. It was not until 1992 that Boris Yeltsin, then president of the Russian Federation, admitted that rumors of a Russian so-called biological Chernobyl were true.
Another laboratory accident involving anthrax occurred in June 2014 in three of the CDC laboratories in Atlanta, Georgia. A technician in a biosafety level 3 laboratory was preparing anthrax spores to be sent to two lower-level (biosafety level 2) labs on June 5 but failed to completely inactivate the bacteria. The technicians in the two lower-level labs assumed the spores had been completely inactivated and failed to wear adequate protective equipment. It was not until June 13 that laboratory staff members discovered that the anthrax spores were still active. All three laboratories required decontamination, and staff members were sent to a local hospital for preventive care; however, no one in the affected laboratories developed anthrax. The director of the CDC was required to testify before U.S. Congress in July 2014 regarding lapses in the agency's safety culture and measures taken to improve it.
Untreated anthrax has a high mortality rate: 100% in inhalational anthrax; 50–60% in gastrointestinal anthrax; 10–20% in cutaneous anthrax; and 60% in injection-related anthrax.
Prevention of anthrax requires several different approaches:
See also Zoonoses .
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Carol A. Turkington
Revised by Rebecca J. Frey, PhD