March 2017

N-P05 (NP)


Signalment (JPC #1590828):  Mouse




HISTOPATHOLOGIC DESCRIPTION:  Cerebrum:  Multifocally within the grey matter there are several distinct, 500 um diameter, multilobulated, expansile protozoal cysts that have a 1-2 um eosinophilic wall and contain numerous crescentic 2x5 um basophilic bradyzoites.  Focally within the hippocampus there is a 500 um diameter granuloma with a central core of eosinophilic debris, surrounded by epithelioid macrophages and rare foreign-body type multinucleated giant cells, further bounded by low numbers of lymphocytes and plasma cells.  Multifocally, surrounding small vessels and expanding Virchow-Robin spaces are low numbers of lymphocytes and plasma cells.  Similar infiltrates surround meningeal vessels.  Focally there is a perivascular aggregate of moderate numbers of macrophages with abundant foamy cytoplasm.


MORPHOLOGIC DIAGNOSIS:  Brain, cerebrum:  Meningoencephalitis, lymphoplasmacytic, multifocal, mild, with multifocal multilobulated protozoal cysts and a focal granuloma, etiology consistent with Frenkelia sp., mouse, rodent.


ETIOLOGIC DIAGNOSIS:  Cerebral frenkeliosis


CAUSE:  Frenkelia sp.



·         Frenkelia is an apicomplexan, coccidian protozoon, which forms large tissue cysts within the central nervous system of small rodents (intermediate hosts) and forms oocysts within the intestines of the definitive hosts (hawks and buzzards)

·         Two species are identified, F. microti and F. glareoli

o   F. glareoli is found in Europe and is distinguished by its strict intermediate host specificity (bank voles) and its non-lobate cysts

o   F. microti occurs in many areas of the northern hemisphere; has a wide intermediate host range (various rodents and small mammals)

·         Differentiation of Frenkelia from Sarcocystis is based on location and morphology of asexual stages in the intermediate hosts; both genera share many similar phenotypical characteristics and genetic analysis does not support separate genera, some consider Frenkelia and Sarcocystis to be synonymous;  Frenkelia is phylogenetically related to Sarcocystis neurona




·         Indirect: intermediate hosts are rodents and small mammals, which are infected by ingestion of sporulated oocysts (sporocysts)

·         Schizogony, with formation of tachyzoites, occurs in hepatocytes and Kupffer’s cells, with subsequent formation of large, multilobulated cysts (filled with bradyzoites) in the CNS

·         The definitive hosts are buzzards and hawks (Buteo spp.)

·         Gametogony and sporontogony occur in the lamina propria of the definitive host small intestine

·         Sporulated oocysts are passed in the feces



·         There are typically no associated clinical signs



·         Pinpoint whitish foci in the brain



·         Lobulated, thin-walled cystswith thin septa up to 1mm in diameter packed with crescentic bradyzoites in the central nervous system

·         There is usually no host reaction to mature cysts

·         Focal hepatocellular necrosis and lymphoplasmacytic perivascular inflammation in many organs is associated with development of first generation meronts in the rodent host

·         Developing cysts compress the adjacent nervous tissuewith resulting pressure necrosis and lymphoplasmacytic perivascular and meningeal inflammation

·         Granulomatous reactions may occur with cyst rupture



·         Cysts contain three cell types:  Peripheral metrocytes (immature rounded zoites), intermediary cells, and bradyzoites (endodyocytes)



·         Sarcocystis:  These cysts very similar and are found in skeletal/cardiac muscle and occasionally brain.  The two genera are very closely related

·         Besnoitia :  Cysts similar in size, ovoid; usually in skin/subcutis

·         Toxoplasma :  Cysts are small (30-100 mm), spherical

·         Hammondia:  These cysts are ovoid, up to 100x300mm, and in skeletal and cardiac muscle; cysts are rarely seen in brain, where they are usually small (20-25mm)



·         Frenkelia cysts have been described in the brains of wild voles, rats, lemmings, muskrats, a porcupine, and chinchillas



1.     Gardiner CH, Fayer R, Dubey JP. An Atlas of Protozoal Parasites in Animal Tissues. 2nd ed. Washington, DC: Armed Forces Institute of Pathology;1998:47-48.

2.     Hoberg EP, Cawthorn RJ, Hedstrom OR. Enteric coccidian (Apicomplexa) in the small intestine of the northern spotted owl (Strix occidentalis caurina). J Wildl Dis. 1993;29(3):495-497.

3.     Jones TC. Diseases due to protozoa. In: Jones TC, Hunt RD, King NW, eds. Veterinary Pathology. 6th ed. Baltimore, MD: Williams & Wilkins;1997:569.

4.     Laakkonen J, Henttonen H. Ultrastructure of Frenkelia spp from a Norwegian lemming in Finland. J Wildl Dis. 2000;36(2):362-366.

5.     Mugridge NB, Morrison DA, Johnson AM, Luton K, Dubey JP, Votypka J, Tenter AM.  Phylogenetic relationships of the genus Frenkelia:  A review of its history and new knowledge gained from comparison of large subunit ribosomal ribonucleic acid gene sequences. Int J Parasitol. 1999;29:957-972.

6.     Upton SJ, McKown RD. The red-tailed hawk, Buteo jamaicensis, a native definitive host of Frenkelia microti (Apicomplexa) in North America. J Wildl Dis. 1992;28(1):85-90.



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