Pathology case of the month - Mountain Cottontail

Gross Findings: On external exam, the fur around the nose is mildly blood stained. The inner pinnae are reddened. Internally, there is scant subcutaneous, visceral, and epicardial fat indicating a poor body condition. The lungs are dark red, wet, and float in formalin. The abdominal cavity contains approximately 4 ml of serosanguinous fluid with few fine fibrinous strands. Disseminated throughout the liver parenchyma are numerous white pinpoint foci. The spleen is enlarged, and numerous white pinpoint foci are scattered within the parenchyma. The caecum has multifocal-confluent, transmural, thickened white areas up to 4 mm in diameter. The mesenteric lymph node is enlarged (1.0 x 0.8 x 0.8 cm), diffusely white, and dense. All tissues not described are within normal limits.

Histopathological Findings: In the liver are multifocal random areas of lytic necrosis characterized by accumulations of nuclear and cellular debris containing colonies of small coccoid bacteria (Fig. 1A). The architecture of the spleen is distorted by multifocal, confluent, lytic necrosis with severe accumulation of nuclear and cellular debris, fibrin exudation, and hemorrhages associated with multiple colonies of small coccoid bacteria (Fig. 1B). The lung has marked alveolar edema. Multifocally, affecting alveolar walls, are small to moderate-sized areas of necrosis comprised of accumulations of cellular and nuclear debris which fill the lumen (Fig. 1C). Renal glomeruli often exhibit large thrombi within the capillary network. The Peyer's patches of the caecum exhibit massive lymphoid depletion and necrosis (Fig. 1D). In the mesenteric lymph nodes there are large areas of lytic necrosis with severe lymphoid necrosis of the follicles.

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Morphologic Diagnosis/es:

1. Liver: necrosuppurative hepatitis, severe, multifocal random, acute with intralesional coccobacilli
2. Spleen: necrosuppurative splenitis, severe, multifocal to coalescing, acute with intralesional coccobacilli
3. Lung: necrosuppurative interstitial pneumonia, mild to moderate, multifocal, acute with generalized severe alveolar edema
4. Caecum: Peyer patches lymphoid depletion and necrosis, severe, diffuse, acute
5. Mesentery lymph node: Lymphoid depletion and necrosis, severe, multifocal, acute
6. Kidney: glomerular thrombosis, severe, multifocal, acute

Disease: Tularemia (OIE reportable disease)

Etiology: Francisella tularensis, is an intracellular, gram-negative, small, short rod to coccoid bacterium. There are two major biovars: Type A (F. tularensis subspecies tularensis) and the less virulent type B (F. tularensis subspecies holarctica).

Distribution: Tularemia is a zoonotic disease of the Northern Hemisphere, with rare occurence in the Southern Hemisphere. Type A is found predominantly in North America, whereby Type B is common in Europe and Asia and less in North America.

Seasonality: Outbreaks occur at any time of the year, but typically late spring through early fall.

Host range: Francisella tularensis has a broad host range affecting over 300 vertebrate species, especially rodents and lagomorphs. However, infections of birds, amphibians, and reptiles have been reported.

Ecology: The persistence of tularemia within a habitat largely depends upon the composition and interaction of animals and vector populations. This includes reservoirs (ticks), donors (mainly lagomorphs and rodents with subclinical or clinical infections), recipients (highly susceptible species that facilitate bacterial transfer to reservoirs/vectors), and non-contributors (dead-end hosts).

Transmission: Francisella tularensis is highly infectious with an extremely low aerosol infective dose of 25 bacteria. Infection can occur via direct contact, arthropod bites, inhalation, or ingestion of contaminated water or food.

Clinical signs: The course of the disease is approximalely 2 to 10 days, whereas severe depression with fever is followed by a fatal septicemia. Usually animals are found dead with no prior clinical signs reported.

Pathology: Infection is characterized by hepato-, spleno-, and lymphadenomegaly with pinpoint white foci of necrosis predominantly found throughout the liver, spleen, lymph nodes, and less commonly in the kidney, heart, lung, and bone marrow. By histology, affected organs show random areas of multifocal confluent lytic necrosis admixed with variable types of inflammation ranging from suppurative to granulomatous depending on the chronicity of the disease. Vasculitis and thrombosis might occur. Colonies of small rod-shaped to coccoid bacteria can be found intralesional or intrahistiocytic.

Diagnosis: Francisella tularensis is a Biosafety level-3 agent and appropriate containment measures must be taken into account when handling suspicious material. Culture, PCR, and immunohistochemistry can be used for diagnosis (see WHO guidelines).

Public health concerns: Tularemia is a highly infectious zoonotic disease and is even considered as a potential Bioterrorist agent. Handling of suspicious carcasses and samples requires adherence to appropriate biosafety measures (see WHO guidelines).

Wildlife population impacts: Outbreaks can occur in lagomorphs (rabbits, hares, pikas) and rodents (mice, voles, lemmings, muskrat, beaver, etc.) leading to declines in local populations.

Management: Monitoring and surveillance of wildlife for tularemia activity is useful for advisories and guidance of the public in enzootic areas to reduce the risk of human exposure.

References:

WHO Guidelines on Tularaemia. 2007. WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland ISBN 978 92 4 154737 6 (NLM classification: WC 380).

Feldman KA. 2003. Tularemia. JAVMA; 222:725-730. 

Friend M. 2006. Tularemia. In: U.S. Geological Survey, Circular 1297: Reston, Va. Available online: https://pubs.usgs.gov/circ/1297/report.pdf. Accessed August 2020. 

Gyuranecz M, Szeredi L, Makrai L, Fodor L, Mészáros ÁR, Szépe B, Füleki M, Erdélyi K. 2010. Tularemia of European Brown Hare (Lepus europaeus): A Pathological, Histopathological, and Immunohistochemical Study.  Vet Pathol; 47: 958. 

Delaney MA, Treuting PM, Rothenburger JL. 2018. Lagomorpha. In: Pathology of Wildlife and Zoo Animals, Terio KA, McAloose D, St. Leger J, editors. Academic Press, pp. 481-498