Sarcocystis

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Sarcocystosis is caused by parasites of the Sarcocystis species, an intracellular protozoan parasite. It has a global distribution and is sporadically reported to cause human infections. Sarcocystosis is relatively rare as a majority of human infections tend to be asymptomatic and are detected incidentally. This article reviews the epidemiology, pathogenesis, evaluation, and treatment of sarcocystosis infection and highlights the role of an interprofessional team in identifying and treating this condition.

Objectives:

  • Describe the etiology and epidemiology of sarcocystosis.
  • Explain the evaluation and available investigations in patients with sarcocystosis.
  • Review the available therapeutic options in the treatment of sarcocystosis.
  • Summarize the importance of an inter-professional team to enhance the clinical outcomes in patients with sarcocystosis.

Introduction

Sarcocystis species are intracellular protozoan parasites. They were first reported by Miescher in 1843 as white threadlike cysts in striated muscles of a house mouse, and they were referred to as 'Miescher's tubules' for the next 20 years. For many decades it was unclear whether they were protozoa or fungi. Similar structures were found in 1865 in pig muscle. Subsequently, in 1967, these spindle or crescent-shaped bodies were studied under electron microscopy, and organelles were observed like those in apicomplexan protozoans of Toxoplasma and Eimeria.[1]

They have a heteroxenous (more than one obligatory host) life cycle based on a prey-predator host relationship of definitive and intermediate hosts, identified in 1972.[2] Over the years, about 150 symptomatic human cases have been reported with more than 100 Sarcocystis spp. known and most have been isolated from muscle tissues of various intermediate hosts, including mammals, birds, and reptiles.[3]

Etiology

Sarcocystosis caused by Sarcocystis species can occur in two forms in humans, the intestinal and the muscular type. Humans can be either definitive or intermediate hosts. Sarcocystis hominis (in cattle) and Sarcocystis suihominis (in pigs) use humans as definitive hosts and are known to cause intestinal Sarcocystosis. The definite host in some non-human species like Sarcocystis nesbitti is presumed to be reptiles, and humans acquire by ingestion of sporocysts through contaminated food and water. Undocumented species where humans can serve as a definitive host may be possible with the meat of domesticated animals, birds, wild animals, and birds being eaten across the world.[1][4][5]

Epidemiology

Sarcocystis species that infect humans are widely distributed across the world. Muscular sarcocystosis has been reported, with the highest incidence seen in Asia and Southeast Asia.[6] Sporadic cases have also been reported from Europe, Africa, North America, Central America, and South America.[1] A serology-based epidemiological survey in West Malaysia found Sarcocystis antibodies in 19.7% of the surveyed population.[7]

Intestinal sarcocystosis is reported from all regions of the world except Africa and the Middle East, which in humans tends to be more common in Europe compared to other continents. [1] Underdetection and underreporting are more likely as many cases can be asymptomatic. Signs and symptoms are usually limited to acute and rarely chronic gastrointestinal symptoms, which can be easily misdiagnosed.[8] 10.4% and 7.3% of fecal samples studied from children in Poland and Germany, respectively, were found to have Sarcocystis spp. Cases have also been found in a vast majority of countries, including Vietnam, Slovakia, Spain, Tibet, Cambodia, Iran, and Australia.[9][10][11][12][13]

Pathophysiology

In the infective form, sporocysts, when ingested by the intermediate host (cattle and pigs), rupture to release sporozoites. The sporozoites enter the endothelium of blood vessels to undergo schizogony and form first-generation schizonts. These further develop into merozoites and invade small capillaries and blood vessels to become second-generation schizonts. These merozoites invade the muscle cells to form sarcocysts made up of bradyzoites. Upon consumption of undercooked meat containing these sarcocysts, bradyzoites are released in the small intestine of humans, invading the intestinal epithelium, where they differentiate into macro- and microgametocytes. The fusion of these gametes results in oocyst formation, which is shed in the feces.  Humans may also become dead-end or accidental hosts for many non-human Sarcocystis spp. after the accidental ingestion of oocysts. The sporozoites ex-cyst and schizonts develop in the vascular endothelium of blood vessels, following which merozoites invade the muscle tissue causing muscular sarcocystosis.[4][8]

Histopathology

Most sporocysts of various species measure about 10 by 15 µm, contain four sporozoites and a residual body. The overall size, presence, or absence of septa and ultrastructural morphology of the wall are some of these features that help identify. However, it varies with the host cell type, the sarcocysts, and the method of fixation. The intact oocysts appear as two adjacent sporocysts with a thin oocyst wall. It often breaks to release the sporocysts, which are the most commonly found structures in the feces.[1]

The histopathological diagnosis is based on the part affected. Most sarcocysts in humans have been found in skeletal and cardiac muscle. Muscle biopsies will show sarcocysts within the muscle fibers. Sarcocysts of Sarcocystis hominis in cattle are microscopic, whereas those of Sarcocystis suihominis in pigs are macroscopic. Hematoxylin-and-eosin(H & E) stain can be used to detect sarcocysts in the muscles of the intermediate host. The walls of sarcocysts are positively stained by periodic acid-Schiff (PAS) reaction.[1][8] Many case reports have shown little or no inflammatory reaction in the adjacent muscle tissue surrounding the sarcocysts with some eosinophilic infiltration. Most infections go undetected due to the asymptomatic nature of the disease and the encysted nature of the parasite.[14][15]

History and Physical

A history of consuming undercooked or raw pork and beef should raise suspicion of sarcocystosis. Other meat, including meat from domesticated or wild mammals, birds, or reptiles, can potentially cause Sarcocystis infection if eaten undercooked.[4] The majority of Sarcocystis infections tend to be asymptomatic in humans.[4]

In symptomatic disease, the infection can present as two distinct syndromes or as a combination of both. Muscular sarcocystosis can present with fever, musculoskeletal pain, rashes, bronchospasms, cardiomyopathy, or subcutaneous swelling.[1] Intestinal sarcocystosis can present with nausea, anorexia, vomiting, abdominal pain, bloating, or diarrhea.[1] The physical examination can show lymphadenopathy, hepatomegaly, or tender muscles in case of disseminated disease or may be normal in localized muscular or intestinal disease.[3]

Evaluation

Blood investigations can show lymphocytosis or eosinophilia.[3][16] There have been reports of raised alanine aminotransferase, lactate dehydrogenase, slightly elevated C-reactive protein, and erythrocyte sedimentation rate.[8] In muscular disease, elevated creatine kinase or lactate dehydrogenase may be seen.[3][17] Definitive diagnosis may be made based on a history of gastroenteritis symptoms combined with epidemiological habits such as raw or undercooked meat consumption. Oocyst or sporocyst excretion happens during a small window. These pre-patent periods are 14 to 18 days for S. hominis and 11 to 13 days for S. suihominis. Oocyst/sporocyst excretion may last for around a month.[18]

Fecal studies can include different flotation techniques, modified Kato thick smear, formalin-ether technique, or direct smear.[1][19] Both oocysts and sporocysts can be detected in fecal samples from definitive hosts using stains such as periodic acid-Schiff stain.[18] The mature sarcocysts in each species tend to vary in size, length, and circumference with varying thickness of the sarcocyst wall, but all contain numerous bradyzoites. In muscular sarcocystosis, muscle biopsy light microscopy can show the sarcocyst, which may or may not show bradyzoites.[1] Imaging, including MRIs, may help detects muscle cysts and direct biopsies.[20]

Accurate and sensitive diagnostic tests do not currently exist for Sarcocyst infections. Immunofluorescence assays (IFAs), Enzyme-linked immunosorbent assays (ELISAs), and serological methods such as antibodies to Sarcocystis have been tried in the past but are not widely available.[18] Although it is known that human infection in susceptible individuals elicits a strong eosinophilic and T cell-mediated response due to a limited number of cases and the complex host-parasite interplay, little is known about the immunology in the infection. IgG detection is not reliable in assessing any seroconversion.[8]

Treatment / Management

Intestinal sarcocystosis: There are no effective prophylaxis or therapeutic options currently for intestinal sarcocystosis in either humans or animals.[4] Current recommendations are based on a handful of case reports and series which highlight the various treatment options that have been tried with varying degrees of success. Dithiazanine was tried in a patient, but Sarcocystis persisted.[21] Pyrimethamine with sulfisoxazole was also not effective.[22] Acetylspiramycin did not show adequate response either.[4] There have been reports of resection surgery of the affected ileum in certain cases.[23]

Muscular sarcocystosis: Albendazole therapy was trialed with steroid cover for muscular sarcocystosis, which was ineffective.[24] The role of co-trimoxazole remains unclear as there have been reports of improvement in symptoms as well as the absence of elevation of creatine kinase levels. Corticosteroids were demonstrated to ameliorate myositis.[17]  It is unknown whether immunosuppressive therapy for vasculitis or myositis reduces the severity of the inflammation or facilitates parasite proliferation.[1] In vitro studies have demonstrated that pyrimethamine and trimethoprim demonstrated activity against Sarcocystis, but no well-conducted clinical studies have been conducted.[25] 

Currently, no course of treatment can be recommended as superior or better than the other due to the lack of controlled studies and insufficient evidence of reported treatment protocols and clinical response.[1]

Differential Diagnosis

Sarcocystis may occasionally be misidentified as other cyst-forming coccidian parasites such as Toxoplasma or Neospora.[26] Other conditions that can be differentials for muscular sarcocystosis include autoimmune myositis, infective myositis due to leptospirosis, toxocariasis, trichinellosis, rickettsial disease, and toxoplasmosis, drugs including alcohol, cocaine, antimalarials, penicillamine, statin, toxin-induced myositis, including Haff disease.[3]

Prognosis

Infections are usually self-limiting, although long-lasting.[26] A vast majority of cases are incidentally found where humans acted as intermediate hosts of as yet unidentified Sarcocystis spp.[27] Occasionally, there can be a disseminated disease that can cause significant morbidity.[3]

Complications

Occasionally in intestinal sarcocystosis, segmental eosinophilic enteritis or necrotizing enteritis may be seen.[23] Some cases of muscular sarcocystosis can develop into severe myositis.[17] Very rarely, there can be a disseminated disease that can affect multiple organs.[3]

Consultations

Consultations in cases of suspected sarcocystosis should involve the microbiologist or tropical medicine physician trained in parasitology to identify the oocysts and sarcocysts in feces samples. In muscular sarcocystosis, a pathologist can identify the cyst with bradyzoites in the histopathology of a muscle biopsy. Treatment should be tailored, and patient-specific in the absence of standardized treatment regimens, and infectious diseases or tropical medicine clinicians may be consulted. Gastroenterologists and rheumatologists should keep the possibility of sarcocystosis in mind when treating gastroenteritis and myositis in patients with an unclear etiology.

Deterrence and Patient Education

Prevention of infection remains the best option in the absence of effective prophylaxis and therapeutic options. Patient education should be carried out to ensure thorough cooking or freezing of meat to kill the bradyzoites in the sarcocysts. Thorough cooking renders bradyzoites non-infectious. [4] Ensuring clean drinking water is important to avoid exposure to sporocysts. Boiling will provide disinfection. Chemical disinfection using chlorine or other similar agents is not effective in killing sporocysts. [28] It is also important to note that control of the parasite among the animal population with which patients frequently come in contact is an important aspect of preventing the infection. 

Pearls and Other Issues

Sarcocystosis is considered a zoonotic disease with a complex interplay between animals and humans. Only two species, including S. hominis and S. suihominis, have humans as definitive hosts in their life cycles. There may be multiple species that have humans as an intermediate host or as a dead-end host. Sarcocystosis is also considered an emerging disease, which, coupled with the zoonotic aspects of the disease, highlights the importance of a one health approach to treating, controlling, and preventing the disease.[29]

Enhancing Healthcare Team Outcomes

An inter-professional team approach is required for sarcocystosis for early diagnosis to improve clinical outcomes. The inter-professional team can involve physicians, pathologists, public health practitioners, and microbiologists. Given the global prevalence, a high index of suspicion is required in patients presenting with gastroenteritis or myositis. Increased education and awareness regarding disease prevention remain the most effective step in managing this infection.

Infection control should also involve attempts to eradicate the parasite from the animal population in domestic animals and other animal populations such as pets that patients frequently encounter. Hence, a one-health approach is paramount in combating this infection. [Level 5]



(Click Image to Enlarge)
From CDC, "this photomicrograph depicts a sporocyst of the parasite, Sarcocystis hominis, formerly known as Isospora hominis."
From CDC, "this photomicrograph depicts a sporocyst of the parasite, Sarcocystis hominis, formerly known as Isospora hominis."
From CDC PHIL; This image is in the public domain and free of any copyright restrictions.

(Click Image to Enlarge)
Illustration of life cycle of Sarcocystis hominis and S. suihominis through humans and animals.
Illustration of life cycle of Sarcocystis hominis and S. suihominis through humans and animals.
Created by CDC Department of Global Health, Division of Parasitic Diseases and Malaria.
Article Details

Article Author

Balram Rathish

Article Editor:

Raksha K

Updated:

9/18/2021 3:26:12 PM

PubMed Link:

Sarcocystis

References

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