Sarcocystis

The organism was first recognised in a mouse by Miescher in 1843.[1] His findings were not initially interpreted as involving a protist, and the literature referred to the structures he described as "Miescher's tubules". Incidentally, Miescher's son, Johann Friedrich Miescher, discovered DNA. Similar structures were found in pig muscle in 1865, but these remained unnamed until 1899, when the name Sarcocystis miescheriana was proposed for them.

Initially, whether these organisms were fungi or protozoa was unclear . This uncertainty was resolved in 1967 when electron microscopic studies showed that they were protozoa, related to Toxoplasma and Eimeria. The lifecycle remained unknown until 1970, when bradyzoites from sarcocysts in bird muscles were inoculated into cultured mammalian cells and seen to undergo development into sexual stages and oocysts. Transmission studies with Sarcocystis of cattle (then considered a single species, Sarcocystis fusiformis) in dogs, cats, and humans revealed three morphologically distinct species, which were named S. bovicanis, S. bovifelis, and S. bovihominis. This and post-1972 research on Sarcocystis was reviewed during the same decade; and that account is still a very useful source of information today.[2]

The heteroxenous (more than one obligatory host) lifecycle of these apicomplexan parasites remained obscure until 1972, when the prey-predator relationship of its definitive and intermediate hosts was recognised.[3] The lifecycles of about 60 of these species are now known.

In outline, gametogony and sporogony occur in the intestine of the definitive host, while both schizogony, which occurs in various tissues, and the formation of sarcocysts (containing bradyzoites and metrocytes) occurs principally in the muscles of the intermediate host. In some cases, a single species may act as both the definitive and intermediate host.

Oocysts are passed in the feces of an infected definitive host. The oocyst undergoes sporogony, creating two sporocysts. These sporocysts of Sarcocystis characteristically contain four sporozoites and measure approximately 15–19 by 8–10 μm. Oocysts of Sarcocystis are thin-walled and easily break open. The result is that sporocysts recovered from feces outnumber intact oocysts.

Intermediate hosts such as cattle or pigs then ingest sporocysts. Sporozoites are released in the body and migrate to vessels, where they undergo the first two generations of asexual reproduction. These rounds result in the development of meronts. This stage lasts about 15 to 16 days after ingestion of sporocysts. Merozoites emerge from the second-generation meronts and enter the mononucleated cells, where they develop by endodyogeny. Subsequent generations of merozoites develop downstream in the direction of blood flow to arterioles, capillaries, venules, and veins throughout the body, subsequently developing into the final asexual generation in muscles.

Merozoites entering muscle cells round up to form metrocytes and initiate sarcocyst formation. Sarcocysts begin as unicellular bodies containing a single metrocyte and through asexual multiplication numerous metrocytes accumulate and the sarcocyst increases in size. As the sarcocyst matures, the small, rounded, noninfectious metrocytes give rise to crescent-shaped bodies called bradyzoites (also known as "bradyzoic merozoites"[4]) that are infectious for the definitive host. The time required for maturation varies with the species and may take 2 months or more.

In species in which symptoms develop, these typically occur 20–40 days after ingestion of sporocysts and during the subsequent migration of sporozoites through the body vessels. Acute lesions (oedema, hemorrhages, and necrosis) develop in the affected tissues. The parasite has a predilection for skeletal muscle (myositis), cardiac muscle (petechial hemorrhages of cardiac muscle and serosae), and lymph nodes (oedema, necrosis, and hemorrhage). These lesions are associated with maturation of second generation of meronts within the endothelial and subendothelials cells. Occasionally mononuclear infiltration or hyperemia has been observed in the lamina propria of the small intestine. After the acute phase, cysts may be found in various muscular tissues, generally without pathology.

Once the intermediate host is eaten by the definitive host, such as a dog or human, the parasite undergoes sexual reproduction within the gut to create macrogamonts and microgamonts. Most definitive hosts do not show any clinical signs or symptoms. Fusion of a macrogamont and a microgamont creates a zygote, which develops into an oocyst. The oocyst is passed through the faeces, completing the lifecycle.

A second lifecycle has more recently been described whereby carnivores and omnivores pass the infectious stages in their faeces. Ingestion of this material may lead to successful infection of the ingesting animal.

The taxonomy of this genus and its relationship to other protozoal genera are currently under investigation.

Related genera include: Besnoitia, Caryospora, Cystoisospora, Frenkelia, Isospora, Hammondia, Hyaloklossia, Lankesterella, Neospora, and Toxoplasma.

Sarcocystis is the largest genus within the family Sarcocystidae and consists of species that infect a range of animals, including mammals, birds, and reptiles. Frenkelia, another genus within this family, consists of parasites that use rodents as intermediate hosts and birds of prey as definitive hosts.

Besnoitia, Hammondia, Neospora, and Toxoplasma apparently form a single clade. Within this clade, Toxoplasma and Neospora appear to be sister clades. Isospora also appears to belong to this clade and this clade is a sister to Sarcocystis. Frenkelia appears to be very closely related to Sarcocystis.

Several molecular studies have suggested that Frenkelia is actually a species of Sarcocystis. This genus was distinguished from Sarcocystis on the basis of its tendency to encyst within the brain rather than within muscle. This distinction may not be taxonomically valid.

Within the genus, a number of clades have been identified. These include one that contains S. dispersa, S. lacertae, S. mucosa, S. muris, S. neurona, and S. rodentifelis.[7] Frenkelia also groups with this clade.

These protozoa are being increasingly well studied in mammals, birds and reptiles. They do not appear to infect mammals of the superorder Afrotheria and infect only two species of the Xenarthra. Because of this pattern, the genus may have evolved in the Northern Hemisphere from a pre-existing protozoan species that infected mammals. Alternatively, because a number of Australian marsupials are also infected by this genus, marsupials may have been the original hosts of this genus and the parasites were spread to the Northern Hemisphere by birds. A third possibility is that the genus originally infected birds and was spread worldwide by these hosts. A final possibility because of the existence of lifecycles where both the intermediate and final hosts are reptiles, the genus may have originated in reptiles and spread from there to other genera. The resolution of this question awaits the outcome of further molecular studies.

Infection with Sarcocystis is known as sarcosporidiosis or sarcocystosis. Because of initial confusion over the nature of this parasite, the organism in the intestine was originally referred to as Isospora hominis .

Sarcocysts within pig skeletal muscle: Note the readily visible striated border.

Four recognised species infect cattle: S. bovifelis, S. bovihominis (S. hominis), S. cruzi (S. bovicanis), and S. hirsuta. S. cruzi is the only species known to be pathogenic in cattle. Several clinical syndromes have been reported in connection with this parasite: eosinophilic myositis; abortions, stillbirths, and deaths in pregnant cows; two cases of necrotic encephalitis in heifers have also been reported. Typical clinical signs of acute bovine sarcocystosis are: anorexia, pyrexia (42 °C or more), anemia, cachexia, enlarged palpable lymph nodes, excessive salivation, and loss of hair at the tip of the tail.[13]

Sheep may be infected by four recognized species of Sarcocystis: S. arieticanis and S. tenella (S. ovicanis) are pathogenic; S. gigantea (S. ovifelis) and S. medusiformis are nonpathogenic. Infection with these parasites is common in the US with over 80% of sheep examined showing evidence of infection.[14] S. arieticanis and S. tenella both produce extraintestinal disease. Anemia, anorexia, ataxia, and abortions are the chief clinical signs. Myositis with flaccid paralysis has been reported as a consequence of infection. Ovine protozoan myeloencephalitis is a recognised syndrome that may occur in outbreaks. The usual pathological findings in such cases are multifocal spinal cord white matter oedema and necrosis, glial nodules and mild to moderate nonsuppurative encephalomyelitis. The diagnosis may be established finding protozoan bodies (12.7–23.0 μm) that stain immunocytochemically for Sarcocystis epitopes.

Four recognised species infect pigs: S. medusiformis, S. meischeriana (S. suicanis), S. porcifelis, and S. suihominis. S. porcifelis is pathogenic for pigs causing diarrhea, myositis and lameness.

Five species infect horses: S. asinus, S. bertrami, S. equicanis, S. fayeri, and S. neurona (S. falcatula). All use canids as definitive hosts; transplacental infection has also been reported. S. neurona causes equine protozoal myeloencephalitis. Exposure to this parasite appears to be common in the United States, with serological surveys indicating that 50–60% percent of all horses in the Midwest United States have been exposed to it. Clinical signs include gait abnormalities including ataxia, knuckling, and crossing over. Muscle atrophy, usually unilateral, may occur. The lesions are typically focal. Brain stem involvement is common. Depression, weakness, head tilt, and dysphagia also occur. S. fayeri may cause myositis in horses.

Fatal infection of an alpaca (Lama pacos) with an unnamed species has been reported. Findings included disseminated eosinophilic myositis, abortion, and haemoabdomen. The myositis was associated with haemorrhage, necrosis, and degeneration.[15] Infection by S. tilopodi of muscle tissue in the guanaco has been reported.[16]

S. hemionilatrantis infects mule deer. Death from experimental inoculation has been reported.

These parasites can also infect birds, producing three different clinical forms: an acute pulmonary disease, muscular disease, and neurological disease. Symptoms include lethargy, shortness of breath, tail bobbing, yellow-tinted droppings, and sudden death. The presence of the cysts in the muscle of wild birds is known as "rice breast".

H&E micrograph showing Sarcocystis in a 3-year-old sheep cardiac muscle tissue (40X)

Infection with Sarcocystis is common. Rates in pigs vary: 18% in Iowa,[17] 27% in the Philippines,[18] 43% in Spain,[19] 57% in Uruguay,[20] and 68% in India [21] The infection rate in sheep is commonly above 90%.[19][22][23][24] Camels have a similarly high incidence of infection.[22][24] Rates above 80% are known in cattle and goats.[22][23] The incidence in water buffaloes, yak and hainag exceeds 80%[22][24] while the incidence in horses, donkeys, and chickens is lower.[23][24]

The diagnosis is usually made post mortem by examination of the skeletal muscle. In some species, the cysts may be visible to the naked eye (ducks, mice, rabbits and sheep), but in most, microscopic examination is required.

Ante mortem diagnosis may be made with the use of dermal sensitivity testing or complement fixation tests. Muscle biopsy is also diagnostic, but this is much less commonly used.

Current treatments are not entirely satisfactory. Amprolium (100 mg/kg, daily for 30 days), fed prophylactically, reduced illness in cattle inoculated with S. cruzi. Prophylactic administration of amprolium or salinomycin also protected experimentally infected sheep.

In horses, treatment has been confined to dihydrofolate reductase inhibitors such as the sulfonamides and pyrimethamine. Sulfadiazine (20 mg/kg orally) once or twice a day is a commonly used. Infected horses should also be placed on pyrimethamine at the dose of 1.0 mg/kg given once a day orally for 120 days or longer. Diclazuril and toltrazuril and other coccidiostats are being evaluated to treat EPM.

No vaccines are currently known. Experimentally inoculated pigs appear to develop a persistent immunity, so a vaccine may be possible.

The parasite's lifecycle typically involves a predator and a prey animal. A single species may infect multiple prey or predator animals. In at least 56 species, definitive and intermediate hosts are known. Many species are named after their recognised hosts.

A listing of the known host-parasite relations can be found on the page Sarcocystis: Host-parasite relations.

Hoareosporidium is now considered a synonym of Sarcocystis. The original type species was Sarcocystis miescheriana. Its description has since been considered less than satisfactory and S. muris has been proposed as the type species. S. turdi may not be a valid species.

Isospora bigemina has been reclassified as Sarcocystis bigemina. Isospora hominis has been reclassified as Sarcocystis hominis. S. bovihominis is a synonym of S. hominis. S. cruzi is a synonym of S. bovicanis. S. gigantea is a synonym of S. ovifelis. S. hirsuta is a synonym of S. bovifelis. S. idahoensis and S. roudabushi may be the same species. S. miescheriana is a synonym of S. suicanis. S. neurona is a junior synonym of S. falcatula. S. neuroma is the more commonly used name for this species. S. poephagi may be the same species as S. hirsuta. S. poephagicanis may be the same species as S. cruzi. S. tenella is a synonym of S. ovicanis.

• Equine protozoal myeloencephalitis

• Sarcocystis at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Sarcocystis genome project
• Review: Fayer R (2004). "Sarcocystis spp. in human infections". Clin. Microbiol. Rev. 17 (4): 894–902, table of contents. doi:10.1128/CMR.17.4.894-902.2004. PMC 523554. PMID 15489353.