title: The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax.
abstract: 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.
authors.affiliation: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. mark-coggeshall@omrf.org
authors.forename: Kenneth Mark
authors.initials: KM
authors.lastname: Coggeshall
authors.forename: Florea
authors.initials: F
authors.lastname: Lupu
authors.forename: Jimmy
authors.initials: J
authors.lastname: Ballard
authors.forename: Jordan P
authors.initials: JP
authors.lastname: Metcalf
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.forename: Darise
authors.initials: D
authors.lastname: Farris
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kurosawa
mesh_terms: D000881:Anthrax / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001408:Bacillus anthracis / Q000276:immunology; D004211:Disseminated Intravascular Coagulation / Q000382:microbiology; D006094:Gram-Positive Bacteria / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology*; D018805:Sepsis / Q000503:physiopathology*; D012772:Shock, Septic / Q000382:microbiology; D014757:Viper Venoms / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D014757:Viper Venoms; C416405:edema factor
keywords: Gram-positive; Sepsis; anthrax; disseminated intravascular coagulation; lethal factor; oedema factor