Signalment:  

4-month-old male ferret (Mustela putorius furo).The ferret was lethargic, anorexic and had been losing weight. On physical examination the oral mucous membranes and ocular conjunctiva were yellow, indicative of jaundice.

Gross Description:  

The oral mucous membranes, ocular conjunctiva, mesentery and joints were yellow. The liver was enlarged and had a matted pattern. The gallbladder was distended and firm.

Histopathologic Description:

Throughout the liver, the biliary tract is dilated and hyperplasic. In the biliary epithelium, meronts of coccidian parasites are abundant. Bile ducts are markedly dilated and contain neutrophils, cellular debris and coccidian oocytes. Portal tracts are surrounded by fibrous connective tissue with infiltrates of neutrophils, lymphocytes, plasma cells and macrophages. The gallbladder wall is markedly thickened and the epithelium is similarly affected as the bile ducts. Meronts contain at least 12 merozoites that measure about 2 microns in width and 5-6 microns in length. Oocytes are present intracellularly and in the lumen they measure approximately 10-11 microns in diameter.

Small intestine (not submitted): In the villus epithelium, meronts containing merozoites identical to those observed in the liver are abundant. Release of the merozoites into the lumen is also observed.

Morphologic Diagnosis:  

Liver: Hepatobiliary coccidiosis with marked biliary hyperplasia, purulent cholangitis and portal fibrosis. Intestine: Intestinal coccidiosis.

Condition:  

Biliary coccidiosis

Contributor Comment:  

There is only one report in the literature of hepatic coccidiosis in ferrets.(4) In this report, the lesions were limited to the biliary tract and gallbladder with no involvement of the intestine. The organisms described in that report closely resemble those observed in this animal. This case is unique in that the coccidian organism was also observed in the intestinal tract. The morphologic features described for this organism suggest the coccidian is of the genus Eimeria. The hepatic coccidian in the ferret has not been classified, but it has been suggested that it appears morphologically similar to the intestinal E. furonis. The ferret in this case had both intestinal coccidia and hepatic coccidia. Whether these hepatic and intestinal coccidia are the same species that infected both organs or are different coccidian species is open to speculation.

JPC Diagnosis:  

1. Liver, biliary tract: Cholangitis and pericholangitis, chronic, neutrophilic and lymphoplasmacytic, diffuse, moderate to marked, with biliary hyperplasia, and numerous intraepithelial apicomplexan schizonts and gametes, and intraluminal apicomplexan oocysts.
2. Liver: Extramedullary hematopoiesis, multifocal, marked.

Conference Comment:  

Conference attendees found this to be an interesting case. Participants briefly discussed the Phylum Apicomplexa and the various Eimeria and Isospora species that affect animals, summarized in the table that follows.(1,3,4)

Eimeria and Isospora of Animals
Host	Coccidian	Organ(s) Affected
Cattle	E. zuernii E. bovis	Distal small intestine Distal small intestine
Sheep	E. ovinoidalis E. ashata E. bakuensis E. crandallis	Terminal ileum/ cecum and colon Distal small intestine Distal small intestine Distal small intestine
Goats	E. ninakohlyakimovae E. caprina E. christenseni	Cecum and colon Cecum and colon Distal small intestine
Pigs	Isospora suis (neonatal pigs) E. scabra (weaners, growers) E. debliecki (weaners, growers) E. spinosa (weaners, growers)	Distal small intestine Distal small intestine Distal small intestine Distal small intestine
Horses	E. leuckarti	Small intestine
Dogs	C. canis C. ohioensis complex = (C. burrowsi, C. ohioensis, C. neorivolta)	Distal small intestine, large intestine Distal small intestine, large intestine
Cats	C. felis C. rivolta	Small intestine, large intestine Small intestine, large intestine
Mice	E. falciformis	Colon
Rabbits	E. stiedae E. intestinalis E. flavescens	Bile ducts Ileum, cecum Ileum, cecum
Guinea Pig	E. caviae	Large intestine
Ferret	E. furonis1,4 E. ictidea1,4	Small intestine, Bile ducts Small intestine
Chickens	E. acervulina E. necatrix E. tenella	Small intestine Small intestine Cecum

Morphologic features used to distinguish the various coccidia, such as Cryptosporidium, Besnoitia, Sarcocystis, Toxoplasma, Eimeria, and Isospora were also discussed. The primary characteristic used to differentiate the various genera of coccidia is the structure of the sporulated oocyst, particularly the number of sporocysts and sporozoites present, as summarized below.(2)

Apicomplexa Sporocyst and Sporozoite Numbers
Coccidian	Sporocysts	Sporozoites
Cryptosporidium	0	4
Besnoitia Isospora Sarcocystis Toxplasma	2	8
Eimeria	4	8

Additional differentiating characteristics, such as the host affected, location of the parasite within the host, and organism size and shape, were also mentioned as criteria to be considered when speciating coccidia. The moderator noted that Eimeria and Isospora may be also differentiated by their location of replication; Eimeria spp. replicate within the epithelium while Isospora spp. replicate within the lamina propria.

Attendees briefly reviewed the coccidian life cycle using E. stiedae as an example. In short, oocysts are shed in feces and sporulate. Sporulated oocysts contain four sporozoites that hatch within the intestine and then enter the liver via the portal vein. Sporozoites then penetrate into the bile epithelium and form trophozoites that undergo asexual nuclear division (schizogony). Schizogony results in the formation of schizonts that contain merozoites. The schizonts rupture, damaging the cell, and release merozoites which infect additional cells. Eventually, merozoites form sexual stages (i.e. male microgametes and female macrogametes) which unite to form oocysts. Oocysts are released into the bile and shed into the feces and the cycle then repeats itself.

Participants discussed the similarities and dissimilarities between the coccidian in this case and Eimeria stiedae. Both replicate within the hepatobiliary epithelium and cause chronic cholangiohepatitis, with marked epithelial hyperplasia, bile duct reduplication, and portal fibrosis.(3) Additionally, E. stiedae produces long papillary fronds within the bile duct that are not present in the case of this ferret. The moderator noted that hepatobiliary coccidiosis is rare in ferrets and has only been reported in very young animals that are generally less than four months of age. The vacuolation of hepatocytes noted in this case by attendees is a very common finding in ferrets due to inanition and fatty mobilization.

References:

1. Abe N, Tanoue T, Ohta G, Iseki M: First record of Eimeria furonis infection in a ferret, Japan, with notes on the usefulness of partial small subunit ribosomal RNA gene sequencing analysis for discriminating among Eimeria species. Parasitol Res 103:976-970, 2008
2. Gardiner CH, Fayer R, Dubey JP: An Atlas of Protozoan Parasites in Animal Tissues, 2ne ed., p. 20, Armed Forces Institute of Pathology, Washington, D.C., 1998
3. Thompson, ME: Proceedings: Department of Veterinary Pathology Wednesday Slide Conference 2006-2007. Armed Forces Institute of Pathology, Washington, D.C., 2007
4. Williams BH, Chimes MJ, Gardiner CH: Biliary coccidiosis in a ferret (Mustela putorius furo). Vet Pathol 33:437-439, 1996

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2-1. Liver

2-2. Liver

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