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Sepsis and pathophysiology of anthrax in a nonhuman primate model
Deborah J Stearns-Kurosawa1, Florea Lupu, Fletcher B Taylor
1Department of Free Radical Biology and Aging Research, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA.
Abstract:
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.
Insights
A new nonhuman primate model effectively mimics human responses to Bacillus anthracis (anthrax) infection. This model highlights the host septic response as critical for fatal outcomes, aiding anthrax treatment and prevention strategies.
Area of Science:
- Microbiology
- Pathology
- Immunology
Background:
- Bacterial sepsis studies gained importance following Bacillus anthracis bioterrorism.
- Developing effective anthrax therapeutics and vaccines requires accurate human response models.
- Existing models often fail to fully recapitulate human sepsis pathophysiology.
Purpose of the Study:
- To establish a nonhuman primate model for Bacillus anthracis infection.
- To characterize the host response to B. anthracis infection in a primate model.
- To provide insights into anthrax pathogenesis and potential treatments.
Main Methods:
- Infusion of toxigenic Bacillus anthracis Sterne 34F2 bacteria into Papio c. cynocephalus (baboons).
- Dosage ranged from 5 x 10^5 to 6.5 x 10^9 CFU/kg.
- Monitoring of physiological and pathological changes mimicking human anthrax.
Main Results:
- The primate model exhibited vascular permeability, disseminated intravascular coagulation, and systemic inflammation.
- Primary target organ was the lung, showing pleural effusions, edema, and hemorrhagic lesions.
- Fatal outcomes were predominantly driven by the host's septic response.
Conclusions:
- The baboon model accurately recapitulates key features of human anthrax infection.
- This model is valuable for evaluating adjunctive therapeutics and vaccines.
- Understanding the host septic response is crucial for effective anthrax management.
