Disease
B. anthracis causes anthrax (Figure 1), which is common in animals but rare in humans. Human disease occurs in three main forms: cutaneous, pulmonary (inhalation), and gastrointestinal. In 2001, an outbreak of both inhalation and cutaneous anthrax occurred in the United States. The outbreak was caused by sending spores of the organism through the mail. There were 18 cases, causing five deaths in this outbreak.
Fig1. Skin lesion of anthrax. Note the black eschar, a necrotic lesion covered by a crust, caused by lethal factor, an exotoxin produced by Bacillus anthracis. Note the area of edema surrounding the eschar, which is caused by another exotoxin called edema factor. (Used with permission from Dr. James H. Steele, Centers for Disease Control and Prevention. CDC #2033.)
Important Properties
B. anthracis is a large gram-positive rod with square ends, frequently found in chains (Figure 2). Its antiphagocytic capsule is composed of D-glutamate. (This is unique—capsules of other bacteria are polysaccharides.) It is nonmotile, whereas other members of the genus are motile. Anthrax toxin is encoded on one plasmid, and the enzymes that synthesize the polyglutamate capsule are encoded on a different plasmid.
Transmission
Spores of the organism persist in soil for years. Humans are most often infected cutaneously at the time of trauma to the skin, which allows the spores on animal products, such as hides, bristles, and wool, to enter. Spores can also be inhaled into the respiratory tract. Pulmonary (inhalation) anthrax occurs when spores are inhaled into the lungs. Gastrointestinal anthrax occurs when contaminated meat is ingested.
Inhalation
anthrax is not communicable from person to person, despite the severity of the infection. After being inhaled into the lung, the organism moves rapidly to the mediastinal lymph nodes, where it causes hemorrhagic mediastinitis. Because it leaves the lung so rapidly, it is not transmitted by the respiratory route to others.
Pathogenesis
Pathogenesis is based primarily on the production of two exotoxins, collectively known as anthrax toxin. The two exotoxins, edema factor and lethal factor, each consists of two proteins in an A–B subunit configuration. The B, or binding, subunit in each of the two exotoxins is protective antigen. The A, or active, subunit has enzymatic activity.
Edema factor, an exotoxin, is an adenylate cyclase that causes an increase in the intracellular concentration of cyclic adenosine monophosphate (AMP). This causes an outpouring of fluid from the cell into the extracellular space, which manifests as edema. (Note the similarity of action to that of cholera toxin.)
Lethal factor is a protease that cleaves the phosphokinase that activates the mitogen-activated protein kinase (MAPK) signal transduction pathway. This pathway controls the growth of human cells, and cleavage of the phosphokinase inhibits cell growth, leading to apoptosis, cell death, and the necrotic skin lesion (black eschar). Protective antigen forms pores in the human cell membrane that allows edema factor and lethal factor to enter the cell. The name protective antigen refers to the fact that antibody against this protein protects against disease.
Clinical Findings
The typical lesion of cutaneous anthrax is a painless ulcer with a black eschar (crust, scab) (see Figure 1). Local edema is striking. Untreated cases progress to bacteremia and death.
Pulmonary (inhalation) anthrax, also known as “wool-sorter’s disease,” begins with nonspecific respiratory tract symptoms resembling influenza, especially a dry cough and substernal pressure. This rapidly progresses to hemorrhagic mediastinitis, bloody pleural effusions, septic shock, and death. Although the lungs are infected, the classic features and X-ray picture of pneumonia are not present. Mediastinal widening seen on chest X-ray is an important diagnostic criterion. Hemorrhagic mediastinitis and hemorrhagic meningitis are severe life-threatening complications. The symptoms of gastrointestinal anthrax include vomiting, abdominal pain, and bloody diarrhea.
Laboratory Diagnosis
Smears show large, gram-positive rods in chains (see Figure 2). Spores are usually not seen in smears of exudate because spores form when nutrients are insufficient, and nutrients are plentiful in infected tissue. Nonhemolytic colonies form on blood agar aerobically. Colonies on blood agar typically have a characteristic flared “comet’s tail” appearance.
In case of a bioterror attack, rapid diagnosis can be per formed in special laboratories using polymerase chain reaction (PCR)-based assays. Another rapid diagnostic procedure is the direct fluorescent antibody test that detects antigens of the organism in the lesion. Serologic tests, such as an enzyme-linked immunosorbent assay (ELISA) test for antibodies, require acute and convalescent serum samples and can only be used to make a diagnosis retrospectively.
Treatment
Ciprofloxacin is the drug of choice. Doxycycline is an alternative drug. No resistant strains have been isolated clinically.
Prevention
Ciprofloxacin or doxycycline was used as prophylaxis in those exposed during the outbreak in the United States in 2001. People at high risk can be immunized with cell-free vaccine containing purified protective antigen as an immunogen. The vaccine is weakly immunogenic, and six doses of vaccine over a 6-month period are given. Annual boosters are also given to maintain protection. An immune globulin preparation containing a monoclonal antibody against protective antigen (raxibacumab) is available for prevention in people at risk of inhalational anthrax. Incinerating animals that die of anthrax, rather than burying them, will prevent the soil from becoming contaminated with spores.
