G M Zaucha1, L M Pitt, J Estep, B E Ivins, A M Friedlander. 1. Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
Abstract
OBJECTIVE: Although rhesus monkeys are considered to be an appropriate model for inhalational anthrax in humans, an alternative for vaccine and therapeutic efficacy studies is desirable. This study characterized the pathology of lethal anthrax in rabbits challenged by subcutaneous inoculation and aerosol exposure. MATERIALS AND METHODS: New Zealand white rabbits were exposed by subcutaneous inoculation or aerosol to lethal doses of Bacillus anthracis spores. RESULTS: The pathology of anthrax in rabbits exposed by either route was similar, with principal findings occurring in the spleen, lymph nodes, lungs, gastrointestinal tract, and adrenal glands. The cardinal changes were hemorrhage, edema, and necrosis, with bacilli and limited leukocytic infiltration. Features that depended on the route of exposure included mediastinitis in aerosol-exposed rabbits, a primary dermal lesion after subcutaneous inoculation, and differences in the pattern of lymph node involvement. Lesions observed in rabbits were comparable to those of inhalational anthrax in humans and rhesus monkeys. Noteworthy differences included the lack of leukocytic infiltration in brain and meningeal lesions, the relatively mild mediastinal lesions, and a lower incidence of anthrax-related pneumonia in rabbits compared with humans. These differences may be attributed to the greater susceptibility of rabbits to anthrax. Increased susceptibility is associated with both reduced leukocytic response to the bacilli and a more rapid progression to death, which further limits development of leukocytic infiltrates in response to the basic lesions of hemorrhage and necrosis. Primary pneumonic foci of inhalational anthrax, which may be influenced by preexisting pulmonary lesions in humans, were not observed in our rabbits, which were free of preexisting pulmonary disease. CONCLUSION: Anthrax in rabbits may provide a useful model for evaluating prophylaxis and therapy against inhalational anthrax in humans.
OBJECTIVE: Although rhesus monkeys are considered to be an appropriate model for inhalational anthrax in humans, an alternative for vaccine and therapeutic efficacy studies is desirable. This study characterized the pathology of lethal anthrax in rabbits challenged by subcutaneous inoculation and aerosol exposure. MATERIALS AND METHODS: New Zealand white rabbits were exposed by subcutaneous inoculation or aerosol to lethal doses of Bacillus anthracis spores. RESULTS: The pathology of anthrax in rabbits exposed by either route was similar, with principal findings occurring in the spleen, lymph nodes, lungs, gastrointestinal tract, and adrenal glands. The cardinal changes were hemorrhage, edema, and necrosis, with bacilli and limited leukocytic infiltration. Features that depended on the route of exposure included mediastinitis in aerosol-exposed rabbits, a primary dermal lesion after subcutaneous inoculation, and differences in the pattern of lymph node involvement. Lesions observed in rabbits were comparable to those of inhalational anthrax in humans and rhesus monkeys. Noteworthy differences included the lack of leukocytic infiltration in brain and meningeal lesions, the relatively mild mediastinal lesions, and a lower incidence of anthrax-related pneumonia in rabbits compared with humans. These differences may be attributed to the greater susceptibility of rabbits to anthrax. Increased susceptibility is associated with both reduced leukocytic response to the bacilli and a more rapid progression to death, which further limits development of leukocytic infiltrates in response to the basic lesions of hemorrhage and necrosis. Primary pneumonic foci of inhalational anthrax, which may be influenced by preexisting pulmonary lesions in humans, were not observed in our rabbits, which were free of preexisting pulmonary disease. CONCLUSION:Anthrax in rabbits may provide a useful model for evaluating prophylaxis and therapy against inhalational anthrax in humans.
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