Sepsis and pathophysiology of anthrax in a nonhuman primate model.
Studies that define natural responses to bacterial sepsis assumed new relevance after the lethal bioterrorist attacks with Bacillus anthracis (anthrax), a spore-forming, toxigenic gram-positive bacillus. Considerable effort has focused on identifying adjunctive therapeutics and vaccines to prevent future deaths, but translation of promising compounds into the clinical setting necessitates an animal model that recapitulates responses observed in humans. Here we describe a nonhuman primate (Papio c. cynocephalus) model of B. anthracis infection using infusion of toxigenic B. anthracis Sterne 34F2 bacteria (5 x 10(5) to 6.5 x 10(9) CFU/kg). Similar to that seen in human patients, we observed changes in vascular permeability, disseminated intravascular coagulation, and systemic inflammation. The lung was a primary target organ with serosanguinous pleural effusions, intra-alveolar edema, and hemorrhagic lesions. This animal model reveals that a fatal outcome is dominated by the host septic response, thereby providing important insights into approaches for treatment and prevention of anthrax in humans.
Stearns-Kurosawa
Deborah J
DJ
Department of Free Radical Biology and Aging Research, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA.
Lupu
Florea
F
Taylor
Fletcher B
FB
Kinasewitz
Gary
G
Kurosawa
Shinichiro
S
D000818:Animals; D000881:Anthrax / Q000503:physiopathology*; D001408:Bacillus anthracis / Q000737:chemistry; D001773:Blood Cells / Q000473:pathology; D001778:Blood Coagulation Disorders; D002199:Capillary Permeability; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007262:Infusions, Intravenous; D008168:Lung / Q000166:cytology / Q000473:pathology; D009026:Mortality; D048548:Papio cynocephalus / Q000276:immunology*; D011486:Protein C / Q000378:metabolism; D018805:Sepsis / Q000473:pathology*; D014115:Toxemia / Q000097:blood
D011486:Protein C