JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
APRIL 2022
M-P04

Signalment (JPC #ACVP 75-33):  Rhesus monkey (Macaca mulatta)

 

HISTORY:  This wild-caught adult, male monkey was necropsied at the end of a 90-day drug toxicity study.  At necropsy, muscles of the hind limbs and intercostal spaces were pale and had numerous longitudinal white streaks.

 

HISTOPATHOLOGIC DESCRIPTION:  Skeletal muscle:  Multifocally and randomly comprising 50% of the section, the sarcoplasm of myocytes is expanded and replaced by cross and tangential sections of protozoal cysts that are up to 500um in diameter, lined by a thin, hyalinized wall, and are filled by innumerable 7 x 2um, crescent-shaped bradyzoites. There are occasional multifocal random foci of inflammatory cells that expand the epimysium, perimysium, and endomysium, and surround and separate individual myocytes, composed primarily of eosinophils and histiocytes with few neutrophils, lymphocytes, and plasma cells. Multifocally throughout the tissue section, myocytes demonstrate one of four changes: swollen, vacuolated sarcoplasm (degeneration); shrunken, hypereosinophilic sarcoplasm with pyknotic nucleus (necrosis); hypereosinophilic sarcoplasm with fragmentation (necrosis); or rarely lightly basophilic sarcoplasm and multiple central nuclei (regeneration). 

 

MORPHOLOGIC DIAGNOSIS:  Skeletal muscle:  Intrasarcoplasmic protozoal cysts, numerous, with multifocal mild eosinophilic and histiocytic myositis and myocyte degeneration, necrosis, and regeneration, etiology consistent with Sarcocystis sp., Rhesus monkey (Macaca mulatta), non-human primate.

 

ETIOLOGY:  Sarcocystis sp. (Most likely S. kortei)

 

ETIOLOGIC DIAGNOSIS:  Sarcocystic myositis

 

GENERAL DISCUSSION:

• Apicomplexan protozoan; more than 90 species reported in numerous mammals, reptiles, & birds; usually species specific but may be zoonotic
• Sarcocystis usually incidental finding of intracytoplasmic cysts in ruminant, porcine, or equine skeletal/cardiac muscle; although typically nonpathogenic, the schizogonous phase can cause disease
• Obligate two host life cycle; sexual stages (gametogony) in definitive (predator) host (carnivores and omnivores) and asexual stages (schizogony) in intermediate host (prey animals - herbivores, omnivores, and birds)
• Some marsupials, primates (including humans), and carnivores can act as both definitive and intermediate hosts, but usually not for the same species of Sarcocystis
• Sarcocysts usually occur in skeletal & cardiac muscle and rarely in the central nervous system
• Can also have fetal sarcocyst infection with abortion/neonatal mortality

 

LIFE CYCLE AND PATHOGENESIS:

• Carnivores (definitive hosts) become infected by preying on herbivores with mature sarcocysts in muscular or neural tissue> bradyzoites are released by digestion & invade intestinal epithelium of definitive host> develop into gamonts, micro- (male), macro- (female), are fertilized, and form infective oocysts> oocysts sporulate into intestinal lumen and are shed in feces (typical coccidian stage)
• Sporocysts from ruptured oocysts are ingested by susceptible herbivores (intermediate hosts)> excyst in intestine and undergo two generations of merogony (schizogony), first in endothelial cells of arterioles & then of capillaries> merozoites enter mononuclear cells in circulation, undergo endodyogeny, enter muscle fibers, and form noninfective sarcocysts containing metrocytes> metrocytes divide to produce infective bradyzoites
• Generally incidental unless protozoal cysts rupture and free bradyzoites are released> myositis, muscle degeneration and necrosis

 

TYPICAL CLINICAL FINDINGS:

• Clinical signs are typically rare, but variable and somewhat species dependent
• Fever, petechiation (clotting dysfunction), edema, icterus
• Lameness, abortion, salivation, lymphadenitis, diarrhea, anorexia, weight loss
• neurona (most commonly in horses and harbor seals) and S. calchasi (birds) cause severe neurological signs
• Definitive hosts are generally asymptomatic

 

TYPICAL GROSS FINDINGS:

• White cysts within muscle; considerable variation in size and shape
• Pale mottling and streaking of muscle
• Serous fat atrophy, edema, thoracic petechia, rarely generalized hemorrhage

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Large, thin walled cysts containing abundant bradyzoites
• Minimal muscular degeneration with variable, mixed inflammatory infiltrate
• Chronic lesions include muscular atrophy and myositis/myocarditis
• Organisms within endothelial cells cause few or no lesions
• Bradyzoites are PAS positive

 

ULTRASTRUCTURE:

• Apicomplexan: parasitophorous vacuoles (in mature cyst)
• Rhoptries, micronemes, conoid, nucleus (merozoites lack rhoptries)

 

ADDITIONAL DIAGNOSTIC TESTS:

• PCR, immunohistochemistry, antibodies can be detected by ELISA

 

DIFFERENTIAL DIAGNOSIS:

Other cyst-forming protozoa:

• Besnoitia : Larger cysts within epithelium, blood vessels, and connective tissue; often no inflammation
• Neospora caninum: Abortion/neonatal mortality; cattle, sheep, dogs, horses
• Trypanosoma cruzi: Thin-walled cyst, rod shaped kinetoplast
• Toxoplasma gondii: Small, thin-walled cyst; small, round bradyzoites
• Hammondia hammondia: Similar to Toxoplasma; rodent intermediate host; tachyzoites in lymphoid cells; cysts in skeletal/cardiac muscle
• Frenkelia: Thin-walled, lobulated cyst; liver and brain

 

COMPARATIVE PATHOLOGY:

• Generally, the Sarcocystis species transmitted by canids ( cruzi, S. tenella, S. miescheriana) are more pathogenic than those transmitted by felids (S. hirsute, S. fusiformis, S. gigantea, S. medusiformis, S. moulei, S. porcifelis)
• Eosinophilic myositis of cattle and sheep (M-M12): Dense infiltrate of eosinophils; tissue appears green grossly; thought to result from hypersensitivity to parasitic cyst rupture/degenerating sarcocysts
• Not recognized in goats
• cruzi typically result in subclinical myopathies; however, there is a recent report of severe and fatal eosinophilic, granulomatous, necrotizing myocarditis in a heifer infected with this species (Araoz et al, J Vet Diagn Invest, 2019)
• Cattle (U-P04):
  • S. cruzi (canid definitive host), S. hirsute (felid definitive host), S. hominis (human definitive host)
  • Dalmeny disease: Severe acute clinical syndrome of sarcosporidiosis in cattle; associated with the ingestion of a large inoculum of infectious sporocysts with resultant loss of microvasculature integrity; also reported in an alpaca that aborted (probably aucheniae)
  • Sheep: Sarcocystis gigantean (felid) large, grossly visible cysts in esophageal muscle; tenella (canid)- can be virulent in lambs if large infective dose & can cause encephalomyelitis in adults
• Horse:
  • S. bertrami (S. equicanis), S. fayeri, & S. asinus; non-pathogenic; canid definitive host
  • Equine protozoal myeloencephalitis (N-P01): Due to neurona within the central nervous system; opossum definitive host; bird intermediate host; destruction of white & gray matter; similar organism associated with neurologic disease in cattle, sheep, dogs, raccoons (common secondary infection to canine distemper virus (N-V11, U-V07)), minks, skunks, a zebra, and southern sea otters
  • Recent case report of gigantea (sheep-specific species) causing granulomatous eosinophilic myositis in a horse (Veronesi et al, J Vet Diagn Invest, 2020)
• Swine: S. miescheriana (canid)- Occasionally causes myositis, diarrhea
• Skunk: Case report of systemic neurona-like protozoal infection (brain, lung, liver, nasal tissue)- probably due to immunosuppression from canine distemper
• North American Waterfowl: rileyi; most frequently in dabbling ducks; definitive host is the skunk; grossly visible resembling rice-grains within skeletal muscle (“rice breast disease”); typically incidental
• Psittacines:
  • S. falcatula most significant species; opossum definitive host; grackles and cowbirds intermediate hosts, typically after eating an insect that has fed on opossum feces; asexual reproduction occurs in intermediate host’s endothelium à fatal disease in aberrant hosts; American or Neotropical psittacines (South, Central America and Mexico) typically resistant to disease; old world psittacines (Australia, Africa, Asia), particularly eclectus parrots, highly susceptible to fatal respiratory disease, +/- myocarditis; also results in systemic disease including severe muscular disease (lymphoplasmacytic myositis with cysts), neurologic disease (lymphoplasmacytic meningoencephalitis with schizonts in the cerebellum and brainstem), myocarditis, hepatitis, interstitial nephritis, splenitis, and encephalitis (encephalitis may also be due to S. calchasi).
  • S. calchasi recently reported in a captive Patagonian conure resulting in meningoencephalitis and numerous skeletal muscle and myocardial tissue cysts (Soderstrom, et al, J Comp Pathol, 2021)
• Domestic pigeons of Europe and North America: calchasi; severe encephalitis
• Galliformes: Recent report of calchasi in two captive vulturine guineafowls, resulting in nonsuppurative meningoencephalitis (Gadsby, et al, J Vet Diagn Invest. 2022)
• Raptors: may be intermediate or definitive hosts to many species ( falcatula, S. calchasi, S. glareoli, S. jaypeedubeyi); S. falcatula results in muscle tissue cysts as well as meronts and schizonts in endothelial cells of pulmonary capillaries, glial cells, and neurons (resulting in disease)
• Pacific Northwest cetaceans: neurona reported to cause nonsuppurative necrotizing meningoencephalitis in a Pacific white-sided dolphin and interstitial pneumonia in a harbor porpoise; skeletal and cardiac muscle cysts reported as incidental findings in Atlantic white-sided dolphins and beluga whales.
• North American Pacific pinnipeds:
  • Harbor seals- neurona; most common species to develop severe fatal disease; disease of subadults and adults; nonsuppurative meningoencephalitis (most severe in the cerebellum); increased severity in multiple marine mammal species associated with Type XIII
  • California sea lions: neurona; Severe polyphasic myositis in numerous muscles, including diaphragm and esophagus; disease may be result of immune-mediated pathogenesis
  • S. pinnipedi- closely related to S. canis; necrotizing hepatitis; Stellar sea lions, California sea lions, gray seals, monk seals
• Bears: Recent report of fatal encephalitis in a black bear (Greenfield, et al, J Vet Diagn Invest. 2022) and necrotizing hepatitis in a grizzly bear (Britton et al, J Vet Diagn Invest. 2019) due to canis; intramuscular S. ursusi and S. arctosi have also been described in healthy black and brown bears
• Camelid: Case report of necrotizing myositis associated with Sarcocystis
• Rhesus macaques: Disseminated Sarcocystis reported to cause chronic polymyositis & myocarditis
• Mice: Only intermediate host for muris; cats and SCID mice are definitive hosts; skeletal and cardiac muscle
• Rabbits: cuniculi; cats are definitive host; incidental findings in skeletal and cardiac muscle; very common in wild rabbits, but also incidental in domestic rabbits
• Rats: Sarcocystis; none overtly pathogenic under natural conditions.

 

Parasitic Myopathies of Domestic Species:

Agent	Type	Species affected
Sarcocystis spp.	Protozoan	Horses, ruminants, pigs, camelids
Trichinella spiralis (M-P02)	Nematode	Pigs
Neospora caninum	Protozoan	Dogs, cattle (fetal)
Trypanosoma cruzi (C-P06)	Protozoan	Dogs, primates
Cysticercus spp. (M-P03, C-P04)	Cestode (larval form)	Ruminants, pigs
Nematode larval migrans	Nematode	Dogs
Hepatozoon americanum (M-P01)	Protozoan	Dogs

 

REFERENCES:

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