History
A 14-day-old sexually intact male scimitar oryx (Oryx dammah) was received for necropsy by the Oregon State University Veterinary Diagnostic Laboratory, Corvallis, Ore. This oryx was born into a privately owned captive herd in Oregon during inclement weather. The owner reported difficulty in providing consistent shelter for this animal (which insisted on roaming into exposed areas). At 2 weeks of age, the oryx was found dead. There was a lack of observed clinical signs or evidence of injury.
Clinical and Gross Findings
On initial examination, the oryx was in thin body condition with minimal body fat reserves, pale pink mucous membranes, and sunken eyes. On opening the body cavities, the most remarkable lesion was in the liver. Disseminated throughout the parenchyma were hundreds of 1-mm-diameter, slightly depressed red foci surrounded by pale-yellow to white halos (Figure 1). The stomach contained coagulated white ingesta (consistent with milk), and the large intestine contained mucus-covered fecal pellets. No evidence of scouring was present. The lungs were diffusely reddened, wet, and heavy with rib impressions visible on the caudal lung lobes.
Photograph of the liver of a 14-day-old sexually intact male scimitar oryx (Oryx dammah) that was found dead by its owner. There had been no observed clinical signs of illness prior to death. On the capsular surface of the liver, notice numerous 1-mm-diameter darker red foci, each surrounded by a pale-yellow halo.
Citation: Journal of the American Veterinary Medical Association 242, 6; 10.2460/javma.242.6.765
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histologic and Microbiological Findings
Samples of brain (cerebrum, cerebellum, and brainstem), thyroid gland, heart, lungs, thymus, liver, kidneys, spleen, rumen, abomasum, intestines (duodenum, jejunum, ileum, and cecum), adrenal glands, diaphragm, bone marrow, and sciatic nerve were collected and processed for histologic examination. The liver tissue contained numerous large, random, coalescing foci of necrosis and fibrin, surrounded by a margin of degenerate cells and neutrophils (Figure 2). Scattered lymphocytes, plasma cells, and histiocytes were also present at the interface between necrotic and non-necrotic parenchyma. Only faint, fine gray intracellular filaments were visible in hepatocytes with H&E staining, but a Warthin-Starry silver impregnation of a recut of the slide revealed prominent bundles of filamentous bacteria, which had a haystack appearance within hepatocytes at the margins of the necrotic foci (Figure 3). Additional histologic abnormalities found were diffuse thyroid follicular hyperplasia (although the thyroid tissue was not grossly enlarged); mild, multifocal cerebral cortical neuronal necrosis (but lacking Alzheimer type II astrocytes); moderate, diffuse acute pulmonary congestion and edema; and serous atrophy of fat in the bone marrow. No abnormalities were identified in the sections of cerebellum, brainstem, heart, thymus, kidney, spleen, rumen, abomasum, intestine, diaphragm, adrenal gland, and sciatic nerve.
Photomicrographs of a section of liver tissue obtained from the oryx in Figure 1. A—Foci of necrosis (asterisks) with loss of cellular detail are surrounded by a more basophilic margin of inflammatory cells. H&E stain; bar = 200 μm. B—Higher magnification view of the section in panel A. Notice the infiltrates of degenerate inflammatory cells at the interface between necrotic and spared hepatocytes (asterisk), patches of coagulation necrosis (arrows), and aggregates of fibrin (arrowheads). H&E stain; bar = 80 μm.
Citation: Journal of the American Veterinary Medical Association 242, 6; 10.2460/javma.242.6.765
Photomicrographs of a section of liver tissue obtained from the oryx in Figure 1. A—Hepatocytes near the interface between necrotic and non-necrotic parenchyma contain very faint, gray filaments (black arrows). H&E stain; bar = 5 μm. B—Following silver impregnation, prominent, black filamentous intracellular bacteria (arrows) are visible within hepatocytes. Warthin-Starry stain; bar = 5 μm.
Citation: Journal of the American Veterinary Medical Association 242, 6; 10.2460/javma.242.6.765
Bacterial culture of samples of the liver yielded 3+ growth of Aeromonas spp. No eggs or oocysts were detected via routine fecal floatation.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: severe, multifocal to coalescing, subacute, necrotizing hepatitis with intracellular bacilli, consistent with Clostridium piliforme.
Case summary: Tyzzer's disease in an oryx.
Comments
The case described in the present report involves a classic lesion in an unusual species. The histopathologic lesions in the liver were characterized by disseminated foci of hepatic necrosis, accompanied by intrahepatocytic filamentous bacteria at the interface between necrotic and non-necrotic parenchyma, which are pathognomonic for infection with C piliforme, or Tyzzer's disease.1 To our knowledge, this is the first report of Tyzzer's disease in an oryx. The causative agent is a motile, filamentous, spore-forming, gram-negative bacterium, and disease typically develops in young, stressed, or immunosuppressed animals following infection.2 Stressful situations, including cold weather, may have had an influence on the illness in the oryx of this report. Clostridium piliforme usually causes sporadic disease, which has been observed in many species of domestic, wild, and laboratory animals, including rodents, lagomorphs, dogs, cats, horses, birds, and primates.3–5 The pathogenesis of Tyzzer's disease is not completely understood; however, ingestion of infective spores from the environment is likely. Carrier animals are a possible source of infective spores, with transmission likely occurring through ingestion of feces-contaminated soil or feed.6,7
Tyzzer's disease can be rapidly fatal, and clinical signs, if present, may consist of anorexia, signs of depression, pyrexia, jaundice, diarrhea, recumbency, loss of suckle reflex, dehydration, convulsions, and death.4,5 Hematologic and biochemical alterations can comprise increases in activities of liver enzymes (eg, sorbitol dehydrogenase, lactate dehydrogenase, aspartate transaminase, alkaline phosphatase, and γ-glutamyl transpeptidase), hyperbilirubinemia, leukopenia, hemoconcentration, and, terminally, profound hypoglycemia.4 Hepatic changes may be severe enough to cause CNS damage (ie, hepatic encephalopathy). However, characteristic Alzheimer type II astrocytes (indicative of hepatic encephalopathy) were not detected in the oryx of this report. Other lesions commonly reported for animals with Tyzzer's disease, among which are paintbrush hemorrhages in the cecum, mucosal necrosis and edema of the intestine, and myocardial necrosis (particularly near the apex),5,8 were not present in this oryx.
The Aeromonas spp grown on the bacterial culture of samples of the oryx's liver were considered to be contaminants, especially given that the only hepatic lesions visible histologically were classic lesions of Tyzzer's disease. An alternative possibility could be Aeromonas septicemia in the debilitated animal of this report; however, isolation of the organism from multiple organs (from which samples were not collected for bacterial culture) would be needed to confirm this. Clostridium piliforme does not typically grow in cell-free media, and microscopic identification of the causative bacteria, typically observed in either a crisscross or parallel (haystack) pattern within hepatocytes, is routinely achieved through use of silver impregnation techniques.3 In affected tissue samples, C piliforme can be identified via a PCR assay that is targeted to a sequence within the 16S rRNA gene of the bacterium; however, this test is not routinely used for diagnosis.7,9 Polymerase chain reaction testing of fecal samples has also been suggested as a potential diagnostic tool but is only useful when bacteria are shed in the feces at a concentration of at least 2.5 × 103 organisms/mL of feces (ie, in vitro experimental concentrations).10
In addition to infection with C piliforme, differential diagnoses for random, multifocal hepatic necrosis in domestic animals include infections with other viral, bacterial, and protozoal agents. In ruminants in the United States, Fusobacterium necrophorum and adenoviral infections are common causes of this pattern of hepatic necrosis. Exotic diseases such as Rift Valley fever and Wesselsbron disease (in lambs) are causes of multifocal hepatic necrosis in Africa and, more recently, the Arabian Peninsula (Rift Valley fever only).11 Herpesviruses are potential causes of hepatic necrosis in young animals of multiple species, and adenoviruses may cause similar lesions in dogs. Salmonella spp, other Clostridium spp, and Brucella spp can cause this type of lesion in many species.12 Diagnosis of infections with these etiologic agents can be made on the basis of results of bacterial culture of or viral isolation from affected tissue samples and compatible clinical signs or necropsy findings. Often, the age of the affected animal assists in diagnosis of the disease because certain infections (eg, infections with C piliforme, herpesviruses, and adenoviruses) are more common in very young animals. Ingestion of toxins, such as pyrrolizidine alkaloids, microcystins, or aflatoxins, may also lead to hepatocellular degeneration and necrosis; however, these toxin-induced changes are typified by a zonal distribution rather than the random multifocal pattern of necrosis associated with Tyzzer's disease and usually affect older (weaned) animals that are more likely to be exposed to plant toxins.12 Tyzzer's disease most commonly develops in foals, and treatment (although not generally successful) may include aggressive administration of polyionic fluids, bicarbonate, antimicrobials, and hyperimmune plasma.6
References
1. Wobester G, Campbell GD, Dallaire A, et al. Tularemia, plague, yersinia, and Tyzzer's disease in wild rodents and lagomorphs in Canada: a review. Can Vet J 2009; 50: 1251–1256.
2. Raymond JT, Topham K, Shirota K, et al. Tyzzer's disease in a neonatal rainbow lorikeet (Trichoglossus haematodus). Vet Pathol 2001; 38: 326–327.
3. Niepceron A, Licois D. Development of a high sensitivity nested PCR assay for the detection of Clostridium piliforme in clinical samples. Vet J 2010; 185: 222–224.
4. Borchers A, Magdesian KG, Halland S, et al. Successful treatment and polymerase chain reaction (PCR) confirmation of Tyzzer's disease in a foal and clinical pathologic characteristics of 6 additional foals. J Vet Intern Med 2006; 20: 1212–1218.
5. Brooks JW, Whary MT, Hattel AL, et al. Clostridium piliforme infection in two farm-raised white-tailed deer fawns (Odocoileus virginianus) and association with copper toxicosis. Vet Pathol 2006; 43: 765–768.
6. Denis KA, Waddell-Parks N, Belanger M. Tyzzer's disease in an 11-day-old foal. Can Vet J 2000; 41: 491–492.
7. Ikegami T, Shirota K, Une Y, et al. Naturally occurring Tyzzer's disease in a calf. Vet Pathol 1999; 36: 253–255.
8. Headley SA, Shirota K, Baba T, et al. Diagnostic exercise: Tyzzer's disease, distemper, and coccidiosis in a pup. Vet Pathol 2009; 46: 151–154.
9. Pritt S, Henderson KS, Shrek WR. Evaluation of available diagnostic methods for Clostridium piliforme in laboratory rabbits (Oryctolagus cuniculus). Lab Anim 2010; 44: 14–19.
10. Furukawa T, Furumoto K, Fujieda M, et al. Detection by PCR of the Tyzzer's disease organism (Clostridium piliforme) in feces. Exp Anim 2002; 51: 513–516.
11. Al-Afaleq A, Hussein MF. The status of Rift Valley Fever in Animals in Saudi Arabia: a mini review. Vector Borne Zoonotic Dis 2011; 11: 1513–1520.
12. Stalker M, Hayes MA. Chapter 2: liver and biliary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer's pathology of domestic animals. 5th ed. Philadelphia: Elsevier Saunders, 2007; 297–388.
