Abstract
BackgroundPneumonic tularemia is caused by inhalation of the gram negative bacterium, Francisella tularensis. Because of concerns that tularemia could be used as a bioterrorism agent, vaccines and therapeutics are urgently needed. Animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures.Principal FindingsRabbits exposed to aerosols containing Francisella tularensis strain SCHU S4 developed a rapidly progressive fatal pneumonic disease. Clinical signs became evident on the third day after exposure with development of a fever (>40.5°C) and a sharp decline in both food and water intake. Blood samples collected on day 4 found lymphopenia and a decrease in platelet counts coupled with elevations in erythrocyte sedimentation rate, alanine aminotransferase, cholesterol, granulocytes and monocytes. Radiographs demonstrated the development of pneumonia and abnormalities of intestinal gas consistent with ileus. On average, rabbits were moribund 5.1 days after exposure; no rabbits survived exposure at any dose (190–54,000 cfu). Gross evaluation of tissues taken at necropsy showed evidence of pathology in the lungs, spleen, liver, kidney and intestines. Bacterial counts confirmed bacterial dissemination from the lungs to the liver and spleen.Conclusions/SignificanceThe pathophysiology of pneumonic tularemia in rabbits resembles what has been reported for humans. Rabbits therefore are a relevant model of the human disease caused by type A strains of F. tularensis.
Highlights
Francisella tularensis, a gram negative coccobacillus that can cause disease in a number of animals including amoeba, is the causative agent of tularemia [1,2]
It is difficult to elicit good protection in mouse models against aerosol challenge virulent F. tularensis strains at robust challenge doses. These findings suggest that different mechanisms may be involved both in the pathogenesis of F. tularensis infection in mice and the protection elicited by vaccines compared to what occurs in humans
To develop a rabbit model of pneumonic tularemia, 20 young female New Zealand White (NZW) rabbits were exposed to aerosols of F. tularensis strain SCHU S4 at doses ranging from 190 cfu up to 5.46104 cfu (Table 1)
Summary
Francisella tularensis, a gram negative coccobacillus that can cause disease in a number of animals including amoeba, is the causative agent of tularemia [1,2]. Prior to the introduction of a live, attenuated vaccine, F. tularensis was among the most common laboratory-acquired infections [4]. Both the United States (prior to 1969) and the former Soviet Union developed F. tularensis as a biological weapon [1,2]. For these reasons, F. tularensis is considered a Category A select agent by the U.S Department of Health & Human Services [5]. Animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures
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