Anthrax infection

Abstract

Bacillus anthracis infection is rare in developed countries. However, recent outbreaks in the United States and Europe and the potential use of the bacteria for bioterrorism have focused interest on it. Furthermore, although anthrax was known to typically occur as one of three syndromes related to entry site of (i.e., cutaneous, gastrointestinal, or inhalational), a fourth syndrome including severe soft tissue infection in injectional drug users is emerging. Although shock has been described with cutaneous anthrax, it appears much more common with gastrointestinal, inhalational (5 of 11 patients in the 2001 outbreak in the United States), and injectional anthrax. Based in part on case series, the estimated mortalities of cutaneous, gastrointestinal, inhalational, and injectional anthrax are 1%, 25 to 60%, 46%, and 33%, respectively. Nonspecific early symptomatology makes initial identification of anthrax cases difficult. Clues to anthrax infection include history of exposure to herbivore animal products, heroin use, or clustering of patients with similar respiratory symptoms concerning for a bioterrorist event. Once anthrax is suspected, the diagnosis can usually be made with Gram stain and culture from blood or surgical specimens followed by confirmatory testing (e.g., PCR or immunohistochemistry). Although antibiotic therapy (largely quinolone-based) is the mainstay of anthrax treatment, the use of adjunctive therapies such as anthrax toxin antagonists is a consideration.

Figure 1.

Key events in the uptake of edema or lethal toxin by host cells as well as the potential effects of edema and lethal factor. During infection, circulating protective antigen (PA) binds to one of at least two host cellular receptors, anthrax tumor receptor (ATR) encoded by the tumor endothelial marker 8 gene or another receptor encoded by the capillary morphogenesis gene 2 (CMG2), both of which are present on many tissues. The bound PA precursor molecule undergoes furin cleavage with release of an unbound subunit. Bound PA subunits form a heptamer that one to three circulating lethal factor (LF) or edema factor (EF) proteins competitively bind to. This complex undergoes endocytosis, and the toxic factors are then released into the cytoplasm. Edema factor has calmodulin-dependent adenyl cyclase activity and increases intracellular cAMP levels, whereas LF inhibits mitogen activated protein kinase kinase 1 to 4, 6, and 7. These factors have been shown to influence the function of several different types of host cells, as summarized by Moayeri and Leppla (9).

Figure 2.

Cutaneous anthrax. These lesions appeared on the arms of a man who 6 days earlier had handled ill cattle. The extensive edema and hemorrhagic vesicles and bullae are typical of cutaneous anthrax and appear before the formation of a black eschar (15).

Figure 3.

Gastrointestinal anthrax. Coronal reconstruction images from a CT scan of the abdomen and pelvis after the administration of intravenous contrast material show a large amount of ascites and concentric wall thickening of a long segment of the distal small bowel (A, arrows). Numerous slightly enlarged lymph nodes are enhanced with intravenous contrast material and are seen at the root of the small bowel mesentery (A, arrowheads) and in the retroperitoneum (B, arrowheads) (19).

Figure 4.

Inhalational anthrax. (A and B) The contrast-enhanced chest CT scans from a patient with inhalational anthrax shows perihilar parenchymal lung disease (A, arrow), widening mediastinum, hilar adenopathy, pleural effusions, and peribronchial infiltrates as well as patchy peribronchial air-space disease, especially on the right (B, arrow). (C–E) Photomicrographs of histopathologic specimens of hilar soft tissue from the same patient at autopsy shows perivascular and peribronchial hemorrhage (C, arrow; H&E; original magnification: ×10), hemorrhage and necrosis (D, arrow; H&E; original magnification: ×20), and abundant gram-positive bacilli (E, arrow; Brown-Brenn; original magnification: ×100) (84).

Figure 5.

Injectional anthrax. Preoperative photographs of a woman (A) with skin necrosis involving the medial aspect of her left thigh and labia majora and a man (B) with swelling of his scrotum and skin necrosis involving his buttock (85). (C) Surgical debridement of necrotic skin and fascia of a patient with injectional anthrax and compartment syndrome of the right arm (76).