The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax

• Published in: Journal of cellular and molecular medicine 2013-07, Vol.17 (7), p.914-920
• Main Authors: Coggeshall, Kenneth Mark, Lupu, Florea, Ballard, Jimmy, Metcalf, Jordan P., James, Judith A., Farris, Darise, Kurosawa, Shinichiro
• Format: Article
• Language: English
• Subjects: Animals; Anthrax; Anthrax - immunology; Anthrax - mortality; Anthrax - physiopathology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Bacillus anthracis - immunology; Bacteremia; Bacteria; Complications; disseminated intravascular coagulation; Disseminated Intravascular Coagulation - microbiology; Edema; Epidemics; Fatalities; Gram-Positive Bacteria - metabolism; Gram‐positive; Humans; Hypotheses; Immune System - immunology; Infections; Inflammation; Inhalation; lethal factor; Lethality; Lymphatic system; Mortality; oedema factor; Pathology; Patients; Point of View; Pre-eclampsia; Proteins; Respiration; Respiratory Tract Infections - immunology; Respiratory Tract Infections - mortality; Respiratory Tract Infections - physiopathology; Sepsis; Sepsis - physiopathology; Shock, Septic - microbiology; Toxins; Viper Venoms - metabolism
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12075

Inhalation anthrax is often described as a toxin‐mediated disease. However, the toxaemia model does not account for the high mortality of inhalation anthrax relative to other forms of the disease or for the pathology present in inhalation anthrax. Patients with inhalation anthrax consistently show extreme bacteraemia and, in contrast to animals challenged with toxin, signs of sepsis. Rather than toxaemia, we propose that death in inhalation anthrax results from an overwhelming bacteraemia that leads to severe sepsis. According to our model, the central role of anthrax toxin is to permit the vegetative bacteria to escape immune detection. Other forms of B. anthracis infection have lower mortality because their overt symptoms early in the course of disease cause patients to seek medical care at a time when the infection and its sequelae can still be reversed by antibiotics. Thus, the sepsis model explains key features of inhalation anthrax and may offer a more complete understanding of disease pathology for researchers as well as those involved in the care of patients.