Sarcocystis neurona

Sarcocystis neurona is an intracellular, apicomplexan protozoan that occurs in horses and other hosts in the Americas.  In horses S. neurona is the causative agent of equine protozoal myeloencephalitis (EPM), but infection is much more common than is clinical disease.  The parasite has also been associated with neurological disease in other intermediate host species.  The life cycle is indirect and involves the opossum as the definitive host and a variety of mammals and cowbirds as intermediate hosts.  Some of  these are potentially true intermediate hosts (with sarcocysts in their tissue), while others are likely "dead-end" or "aberrant" hosts (with no parasite development past the meront stage).  Among the mammals are cats, dogs, armadillos, seals, sea otters, skunks, and ferrets. Horses were thought to be "aberrant" hosts for S. neurona, but sarcocysts have recently been detected in a young horse, establishing this species as at least a potential true intermediate host.

The clinical signs of EPM depend on the  location(s) of parasite-associated lesions in the CNS, and include inco-ordination, stumbling, frequent interference, difficulty backing up, ataxia, head tilting, loss of reflexes, loss of sensation, muscle atrophy and sometimes sudden collapse.  Neurological deficits can be unilateral - the more frequent, or bilateral.  In some horses the clinical signs develop very rapidly, in others slowly.

Phylum: Apicomplexa
Class: Conoidasida
Subclass: Coccidiasina
Order: Eucoccidiarida
Suborder: Eimeriorina

The taxonomy of species within the genus Sarcocystis is somewhat uncertain, but a number of distinct species have been identified in domestic and free-ranging animals and birds, and in people.  Sarcocystis neurona is the cause of equine protozoal myeloencephalitis (EPM), a disease of horses in the Americas.  The species was first described only in 1991, its definitive host (the opossum) identified in 1995, and an intermediate host (the domestic cat) identified in 2000.

When a Sarcocystis was first associated with EPM there was some uncertainty as to whether the species was S. falcatula, which cycles between opossums and various birds.  It is now generally accepted that S. neurona and S. falcatula are both valid species, and that S. falcatula is not associated with EPM.

The life cycle stages of Sarcocystis neurona most often observed in horses are schizonts (meronts) and merozoites associated with asexual reproduction (merogony) in the central nervous system.  Sarcocysts have been seen very rarely in horses.  The schizonts of S. neurona in horses are microscopic, variable in shape and measure less than 100 µm in any direction.  The merozoites are crescent-shaped and measure 2 to 3 µm in length.  Individual host cells can contain several schizonts, and merozoites often occur in clusters.  Sarcocysts of S. neurona in horses also vary in shape and are microscopic, measuring up to 500 µm in length and 50 µm in diameter.

The sporocysts of S. neurona in the faeces of opossum definitive hosts are sub-spherical, measure approximately 10 to 12 µm by 6 to 8 µm, and each contains four sporozoites.

To date the only definitive host identified for Sarcocystis neurona is the opossum - Didelphis virginiana.  Extra-intestinal stages of the parasite have been found in several mammalian species and in cowbirds.  Some of  these are potentially true intermediate hosts (with sarcocysts in their tissue), while others are likely "dead-end" or "aberrant" hosts (with no parasite development past the meront stage).  Among the mammals are cats, dogs, armadillos, seals, sea otters, skunks, and ferrets.

Sarcocystis neurona in horses is restricted to the Americas and its geographic distribution matches that of the definitive hosts.  In the United States opossums are found in approximately the eastern half of the country and along the west coast.  In Canada they are present in areas of southern Ontario and southern British Columbia.  Only six cases of EPM have been reported in Canada, four in Ontario and two in Saskatchewan, where opossums do not occur.  All these cases were reported before S. neurona was identified as the cause of the disease and diagnosis was based on the presence of typical clinical signs and organisms and/or pathology.  The origins and travel histories of the horses are unknown.

Sarcocystis neurona, in common with other species of the genus, has an indirect life cycle.  The only known definitive host in North America is the opossum (Didelphis virginiana).  In this host the parasite undergoes development typical of the genus Sarcocystis, involving sexual reproduction (gametogony) in the enterocytes of the small intestine, which results in the production of oocysts.  These sporulate in the intestinal lumen  and the oocyst wall disintegrates, releasing  two sporocysts each containing four sporozoites.  These sporocysts leave the host in the faeces and are immediately infective. 

Infection of intermediate hosts is by ingestion of the sporocysts.  In these hosts the sporozoites are released and invade the intestinal mucosa, then blood vessels, where they enter the endothelial cells and undergo one or more cycles of asexual reproduction (merogony or schizogony), each resulting in the production of meronts containing merozoites.  Finally the merozoites enter muscle cells and form sarcocysts containing large numbers of bradyzoites.  Ingestion of the sarcocysts by opossums completes the life cycle.  Until recently it was believed that development of S. neurona in horses did not proceed beyond the meront stage and that meronts occurred only in the central nervous system (brain and spinal cord). Recently, however, sarcocysts have been reported in the skeletal muscle of a young horse, indicating that they can be true intermediate hosts. 

Several mammals and birds can become infected with non-intestinal S. neurona, including cats, dogs, raccoons, skunks, armadillos, sea otters, ferrets, and cowbirds.  Of these hosts species some develop sarcocysts in muscle tissues and can likely be a source of infection for opossums, and thus serve as true intermediate hosts, while others simply become infected without complete parasite development to sarcocysts, and can be considered as "dead-end" or "aberrant" hosts.  Neurological signs associated with S. neurona have been reported in most intermediate hosts species, although in horses, and likely in the other intermediate host species, clinical disease is much less common than is infection. Initially horses were thought to be aberrant hosts for S. neurona, but sarcocysts have recently been described in muscle tissues of a naturally infected horse.  Given the broadly based diet of opossums, it is probable that additional species of intermediate host will be identified. 

Transmission of Sarcocystis neurona within an ecosystem depends on sporocysts in the environment and a predator-prey link between opossums and the intermediate hosts.  While exposure to opossums and their faeces are established risk factors for the development of EPM in horses, little is known about the risk factors for infection with S. neurona or about maintenance of the parasite in intermediate host populations.

Infection with Sarcocystis neurona is not uncommon in horses in the United States, with seroprevalences of greater than 50% in some states.  Clinical disease (EPM) in horses is, however, much less common.  Although some sort of stress (for example, strenuous exercise, transport or disease) seems to be linked to disease, little is known of the reasons why some infected horses develop EPM while others do not.  There are no published data for the seroprevalence of S. neurona in horses in Canada, and only six reported cases of EPM, four in Ontario and two in Saskatchewan, where opossums do not occur (see Host Range and Geographic Distribution section).  In 2009 a case of EPM was described in a horse born and raised in Saskatchewan, but the causative organism was identified as Neospora hughesi which had been reported previously only in the United States. 

The key lesions associated with the parasite are in the central nervous system - meronts and free merozoites within neuron cytoplasm.  Parasite development can occur in any part of the CNS but the spinal cord is more frequently affected than the brain.  Typical pathology includes necrosis, haemorrhage, and inflammatory infiltrations surrounding neurons containing meronts and/or merozoites.  The parasites can also be found unassociated with lesions. 

The clinical signs of EPM depend on the  location(s) in the CNS affected and include inco-ordination, stumbling, frequent interference, difficulty backing up, ataxia, head tilting, loss of reflexes, loss of sensation, muscle atrophy and sometimes sudden collapse.  Neurological deficits can be unilateral - the more frequent, or bilateral.  In some horses the clinical signs develop very rapidly, in others slowly. .

The ante-mortem diagnosis of EPM in a horse is based primarily on history and clinical signs.  History should include information on any other horses on the premises and in the area, on on previous local cases of EPM or other neurological disease.  Serology for antibodies using Western Blot can be helpful, but because exposure to Sarcosystis neurona  does not invariably result in disease, a positive serological test alone is insufficient for a diagnosis of EPM.  The presence of antibodies to S. neurona in cerebro-spinal fluid (CSF) is more helpful, but there is a possibility of contamination with antibodies in serum resulting from the disease process or from the CSF sampling procedure.  PCR on CSF can also help and is very specific but the sensitivity is sub-optimal.

At post-mortem the diagnosis of EPM can be based on the presence of typical lesions and organisms, although the latter may be few and difficult to find, especially in H and E stained sections.  Immunohistochemistry is very useful in identifying Sarcocystis, and antibodies specific for S. neurona are available.  PCR can also be used on parasite DNA recovered from tissues.

Several drugs with anti-protozoal activity have been used to treat EPM.  Some of these drugs have been used with immunomodulators - to either stimulate or suppress the immune system, and some have potentially harmful side effects.  Treatment success has been variable.  An effective S. neurona vaccine for horses is not yet available.  Other approaches to control involve minimizing contact between horses and opossums and their faeces, including protecting feed and water from contamination.

Sarcocystis neurona is not known to be zoonotic.

MacKay R (2010) EPM: Pathogenesis, treatment and prevention. Proceedings OVMA Centennial Conference, Toronto. pp. 214-218.

Dubey, JP et al., (2001) A review of Sarcocystis neurona and equine protozoal myeloencephalitis. Veterinary Parasitology 95: 89-131.