Quantitative Pathology of Inhalational Anthrax I: Quantitative Microscopic Findings

Abstract

Forty-one cases of documented inhalational anthrax from the Sverdlovsk epidemic of 1979 traced to release of aerosols of Bacillus anthracis at a secret biologic-agent production facility were evaluated by semiquantitative histopathologic analysis of tissue concentrations of organisms, inflammation, hemorrhage, and other lesions in the mediastinum, mediastinal lymph nodes, bronchi, lungs, heart, spleen, liver, intestines, kidneys, adrenal glands, and central nervous system. These data were correlated with clinical, epidemiologic, and demographic data.The patients' courses, with a variable incubation period and short nonspecific course (4 days before hospitalization) with rapid demise (1 day of hospitalization before death), correlated with systemic bacterial infection and lesions. Bacillus anthracis were identified in all cases in which there was no antibiotic treatment or there was treatment for fewer than 21 hours. The lesions that were the most severe and apparently of longest duration were in the mediastinal lymph nodes and mediastinum. There and elsewhere, peripheral transudate surrounded fibrin-rich edema; necrosis of arteries and veins was the most likely source of large hemorrhages displacing tissue or infiltrating tissue, respectively; and apoptosis of lymphocytes was observed. Respiratory function was compromised by mediastinal expansion, large pleural effusions, and hematogenous and retrograde lymphatic vessel spread of B. anthracis to the lung with consequent pneumonia. The central nervous system and intestines manifested similar hematogenous spread, vasculitis, hemorrhages, and edema. These pathologic findings are consistent with previous experimental studies showing transport of inhaled spores to mediastinal lymph nodes, where germination and growth lead to local lesions and systemic spread, with resulting edema and cell death, owing to the effects of edema toxin and lethal toxin. The identification of the vascular lesions as a basis for the prominent hemorrhages is a novel observation for human inhalational anthrax.

Targeted Silencing of Anthrax Toxin Receptors Protects against Anthrax Toxins

“…We evaluated protection following ANTXR silencing in the AD293 human embryonic kidney cell line. The kidneys are targets of anthrax pathogenesis during human inhalational anthrax; capillaritis, intratubular bleeding, and tubular necrosis are observed by histopathology (21). Hemorrhaging in the kidney is also observed in animal models of gastrointestinal anthrax (25).…”

“…The kidneys are among the organs that are harmed in human cases of inhalational anthrax, with evidence of intratubular bleeding and tubular necrosis found by histopathology (21). Based on a previous study, we knew that human embryonic kidney 293 (HEK293) cells were susceptible to cleavage of MEK1 by LeTx and, thus, deduced that these cells had to express at least one of two ANTXRs.…”

Anthrax Lethal Toxin Enhances IκB Kinase Activation and Differentially Regulates Pro-inflammatory Genes in Human Endothelium

“…In addition, we showed that LT enhances vascular cell adhesion molecule-1 (VCAM-1) expression and monocyte adhesion on the surface of tumor necrosis factor-␣ (TNF)-activated primary human endothelial cells, suggesting a possible link between LT and the vasculitis associated with anthrax (9,22,23). The enhanced expression of VCAM-1 was found to be transcriptionally driven by the cooperative activation of the VCAM1-regulating transcription factors, interferon regulatory factor-1 (IRF-1), and NF-B (24).…”

“…The high mortality resulting from systemic anthrax infection is generally associated with profound vascular pathologies, including vascular leakage, edema, hemorrhage, vasculitis, and a poor immune response (7)(8)(9). Importantly, many of these symptoms are also observed in animals treated with purified LT (10 -14).…”

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

“…18 Various types of liver damage induced hemostatic abnormalities and hemorrhage. 19 Previous studies have revealed that anthrax induces liver damage; invasions of bacterium B. anthracis have been observed frequently in the liver of infected patients [20][21][22] and animals. 15,23,24 These results prompted us to investigate whether coagulant factor defects are associated with LT-induced liver damage.…”