REVIEW OF SARCOCYSTOSIS IN MALA YSIA

SP Kan and R Pathmanathan

Departments of Parasitology and Pathology, Faculty of Medicine,University of Malaya, 59100 Kuala Lumpur, Malaysia.

Abstract. Sarcocystis is a tissue coccidian with an obligatory two-host life cycle. The sexualgenerations of gametogony and sporogony occur in the lamina propria of the small intestine of definitivehosts which shed infective sporocysts in their stools and present with intestinal sarcocystosis. Asexualmultiplication occurs in the skeletal and cardiac muscles of intermediate hosts which harborSarcocystis cysts in their muscles and present with muscular sarcocystosis. In Malaysia, Sarcocystiscysts have been reported from many domestic and wild animals, including domestic and field rats,moonrats, bandicoots, slow loris, buffalo, and monkey, and man. The known definitive hosts forsome species of Sarcocystis are the domestic cat, dog and the reticulated python. Human muscularsarcocystosis in Malaysia is a zoonotic infection acquired by contamination of food or drink withsporocysts shed by definitive hosts. The cysts reported in human muscle resembled those seen inthe moonrat, Echinosorex gymnurus, and the long-tailed monkey, Macaca fascicularis. While humanintestinal sarcocystosis has not been reported in Malaysia so far, it can be assumed that such casesmay not be infrequent in view of the occurrence of Sarcocystis cysts in meat animals, such as buffalo.The overall seroprevalence of 19.8% reported among the main racial groups in Malaysia indicates thatsarcocystosis (both the intestinal and muscular forms) may be emerging as a significant food-bornezoonotic infection in the country.

INTRODUCTION

Sarcocystosis is caused by the tissue parasiteof the genus Sarcocystis belonging to the familySarcocystidae. The other medically importanttissue protozoan in this family is Toxoplasmagondii. Members of the family Sarcocystidae arecharacterised by an alteration of sexual andasexual generations in their respective definitiveand intermediate hosts. The two forms ofsarcocystosis affecting man are intestinal and mus-cular sarcocystosis.

LIFE CYCLE

Among Sarcocystis species, sexual generationsof gametogony and sporogony occur in the laminapropria of the intestine of definitive hosts whichare flesh-eating carnivores or omnivores, whileasexual generations occur in the muscles (both skel-etal and cardiac muscles) of intermediate hostswhich are usually herbivorous or prey animals.Thus, Sarcocystis has an obligatory two-host lifecycle in which definitive hosts present withintestinal sarcocystosis and intermediate hosts

present with muscular sarcocystosis. Definitivehosts shed sporocysts with their stool. These areimmediately infective when ingested by inter-mediate hosts. Rupture of sporocysts in theintestine of intermediate hosts releases sporo-zoites, which undergo an initial phase of schizo-gony in the vascular endothelium of internalorgans. Rupture of schizonts releases merozoiteswhich develop into cysts in skeletal or cardiacmuscles. These cysts, known as sarcocysts, areusually spindle-shaped and contain thousands ofzoites. Ingestion of raw or undercooked meatcontaining sarcocysts results in the initiation ofgametogony and sporogony in the intestinalepithelium with the appearance of sporocysts inthe stool.

TAXONOMIC RELATIONSHIPS

Ultrastructural features, such as the thicknessof the cyst wall, the absence or presence ofcytophaneres/projections and septa, and the sizeand appearance of zoites, together with infor-mation on the definitive and intermediate hosts,

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are of importance in deciding the taxonomicrelationships of Sarcocystis parasites. A total of93 species of Sarcocystis species have beenreported from a wide range of domestic andwild animals, but the final and intermediate hostsof only 29 species are known (Levine andTadros, 1980). Man is unique in that he canserve both as definitive and intermediate host forseveral known as well as unknown species ofSarcocystis. Among those species where man isthe known definitive host are Sarcocystis hominisand S. suihominis (Rommel and Heydom, 1972),whereas, among those cases of human muscularsarcocystosis reported so far, neither the originaldefinitive hosts nor the natural intermediate hostsare known.

SARCOCYSTOSIS AMONG ANIMALS INMALAYSIA

In Malaysia, the complete life cycles (withknown definitive and intermediate hosts) of onlyfive species of Sarcocystis are known. Theseinclude Sarcocystis levinei with a cat-buffalocycle, S. fusiformis 'with a dog-buffalo cycle(Dissanaike et ai, 1977; Dissanaike and Kan,1978) and S. singaporensis, S. villivillosus and S.zamani with a ratpython cycle (Beaver andMalecker, 1978). The ultrastructural features ofthese five species have been studied under theelectron microscope and the characteristics of thesporocysts shed by the definitive hosts are known.

In addition, Sarcocystis cysts have beenreported from a wide range of domestic andwild animals in Malaysia, including domesticrats such as Rattus norvigecus (Zaman andColley, 1975) and Rattus rattus diardii (Kanand Dissanaike, 1977); field rats such as R.annandalei, R. exulans and R. jolorensis (Lai,1977; Kan, 1979); the bandicoot, Bandicota indica(Kan, 1979); the moon rat Echinosorex gymnurus(Dissanaike and Poopalachelvam, 1975;Kan andDissanaike, 1976); the slow loris, Nycticebuscoucang (Zaman, 1970); the buffalo, Bubalusbubalis (Zaman and Colley, 1972; Dissanaike andKan, 1978; Kan and Dissanaike, 1978) and theMalaysian long-tailed macaque, Macaca fasi-cularis (Prathap, 1973; Kan et ai, 1979). Exceptfor the parasites found in R. norvegicus and B.babalis, the definitive hosts of all these species ofSarcocystis are unknown.

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HUMAN SARCOCYSTOSIS IN MALAYSIA

Muscular sarcocystosis

Only the muscular form of human sarco-cystosis has been reported in Malaysia with atotal of II cases documented from both males andfemales, ranging from 12-67 years of age, amongthe main ethnic groups (Malays, Chinese, Indiansand aborigines) from both East and WestMalaysia since 1975 (Pathmanathan and Kan,inpress.). As all these II cases were seen inparaffin sections of autopsied or biopsied mate-rials, ultrastructural studies of these human casescould not be carried out. Thus, the exact speciesof Sarcocystis causing human muscular sarco-cystosis in Malaysia are unknown. However, thelight microscopic features of these humansarcocysts resembled those seen in the moonrat and the Malaysian long-tailed macaque. Asnone of the subjects had ever left the country,it was assumed that these cases of muscularsarcocystosis were acquired locally and thedisease was endemic in the country, withperhaps isolated, but local, foci of infection. Inview of the occurrence of Sarcocystis in a rela-tively wide range of domestic and wild animalsin Malaysia, human muscular sarcocystosis isconsidered a zoonotic infection and probablya sylvatic zoonosis.

Despite the apparent zoonotic nature of theseinfections in Malaysia, human muscular sarco-cystosis has not been characterised by anysignificant cellular infiltration or inflammatoryresponses, as were cases of human muscularsarcocystosis reported in other parts of the world(Jeffrey, 1974; Beaver et ai, 1979). Among the 11cases reported in Malaysia, eight were associatedwith malignancies, four of which had carcinomaof the tongue. All the cases of lingual sarco-cystosis associated with carcinoma were reportedin elderly Indian patients who had commonhistories of chewing betal nut, a well-acceptedrisk factor for oral cancer. However, the apparentfrequent association of muscular sarcocystosiswith malignancies may also be due to the factthat excised malignant tissues were generallymore frequently and thoroughly examined thanother types of tissues, thus increasing the chancesof detection of Sarcocystis cysts in these tissues.While the inital phase of schizogony in thevascular endothelium preceding the later phase of

SARCOCYSTOSIS IN MALAYSIA

cyst formation in skeletal muscles was reportedto cause massive tissue destruction and evenabortions and death in naturally and experi-mentally-infected animal intermediate hosts(Heydorn and Mehlhorn, 1978; Leek and Fayer,1978; Zaman and Colley, 1975), all the cases ofhuman muscular sarcocystosis were not accom-panied by or associated with any history of pastor recent episodes of severe illness. This wasprobably due to the fact that Sarcocystis cystswere able to survive for many years in themuscles of intermediate hosts; it was observedthat some wild-caught, naturally-infected monkeysstill harbored sarcocysts after several years incaptivity (Karr and Wong, 1975). Thus, due tothe apparent mildness of muscular sarcocystosis,as well as the persistence of sarcocysts in inter-mediate hosts, it might be impossible for humansubjects to recall or relate an earlier episode ofillness (if any) during the acute phase ofschizogony, with the much later and milder,chronic phase of muscular involvement when thelatter was detected. Neither might these subjectsrecall retrospectively the causes or sources ofinfection, even if the onset of infection had beencharacterised by an episode of acute or severeillness.

While the exact sources of muscular sarco-cystosis is unknown, it is highly possible that thiscondition could be caused by the contaminationof food or drink with sporocysts shed with thefeces of domestic or wild animal definitive hosts,such as cats, dogs or pythons. These immediatelyinfective sporocysts could easily contaminate theenvironment (soil and water) and serve as areadily source of infection to suitable immediatehosts, including man. Sarcocystis sporocystsfound in dog feces have been shown to betransported in nature by flies (Markus, 1980),whereas several species of cockroaches wereexperimentally demonstrated to be able to serveas transport hosts of a murine Sarcocystis (Smithand Frenkel, 1978). As dogs and cats .are knowndefinitive hosts of several species of Sarcocystisin Malaysia, sporocysts shed by these animaldefinitive hosts could easily contaminate theenvironment which they share with their humanhosts. Toxoplasma oocysts shed by domestic catswere shown to be able to survive for severalmonths in shady, moist soil (Ruiz et ai, 1973;Coutinho et ai, 1982), and it is expected that

Sarcocystis sporocysts shed by canine or felinedefinitive hosts would be likewise viable insimilarly moist and shaded soil conditions. Astudy in South Germany revealed that approxi-mately two-thirds of Sarcocystis infections incattle were due to S. hominis caused by humanfecal contamination, another two-thirds were dueto S. bovicanis infections acquired from dogfeces, and about one third 'was due to S. bovifelisinfections acquired from. cat feces (Boch et ai,1978).

Intestinal sarcocystosisWhile muscular sarcocystosis has been re-

ported from the main ethnic groups in Malaysia,intestinal sarcocystosis is not yet documentedin the country. It is likely that such cases ofintestinal involvement may have been missedor misdiagnosed rather than absent. Sarcocystiscysts have been demonstrated in buffaloes andother herbivorous meat animals, such as cattle,goats and sheep (Kan, personal observation).While the exact prevalence rates and severity ofhuman intestinal sarcocystosis caused by eatingundercooked meat is not known among thehuman population in Malaysia, workers else-where have shown that experimental infectionsamong human volunteers were mild or subclinical(Rommel and Heydorn, 1972). Human subjectsingesting raw beef infected with cysts of S.hominis complained of nausea, abdominal pain,and diarrhea 3-6 hours after ingestion, whereasingestion of raw pork infected with cysts of S.suihominis gave rise to more pronounced nausea,bloating, anorexia, marked abdominal pain,unproductive retching, and diarrhea 6-8 hoursafter ingestion. Six other cases of intestinalsarcocystosis acquired naturally from ingestion ofundercooked beef were accompanied by fever,acute abdominal pain, nausea, vomiting, anddiarrhea (Bunyaratvej et ai, 1982). In view of thelack of specificity and the transient nature of thesymptoms in most cases of experimentally-induced or naturally-acquired human infection, itwould be expected that the majority of caseswould have been missed if there were nodeliberate effort to specifically detect sporocystsin the feces of human subjects.

Seroprevalence of Sarcocystis in Malaysia

A serological survey of 243 Malay, Chinese,Indian and aboriginal subjects in West Malaysia

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revealed an overall seroprevalence rate of 19.7%(Thomas and Dissanaike, 1978), with the highestprevalence rate reported among aborigines(39.7%), followed by Malays (17%), Indians(8.7%) and Chinese (3.6%). While seropositivityfor Sarcocystis antibodies could not differentiatebetwen muscular or intestinal sarcocystosis, thissurvey indicated that at least one in fiveindividuals examined had been exposed toSarcocystis parasites. The higher seroprevalencerates among certain. racial groups did not reflectany genetic predisposition or racial susceptibilityto infection, but was an indication of the life-styles, pastimes and socioeconomic status of aparticular community. Aborigines who lived inconditions of poor environmental sanitation andhad close contact with domestic animals (pets orbeasts of burden) and wild animals which theyhunted for meat or hide would have greaterexposure to the sources of infection, comparedto other ethnic groups who lived in highly urbanizedcommunities with better environmental sanitationand little or minimal contact with either domesticor wild animals.

PUBLIC HEALTH SIGNIFICANCE OFSARCOCYSTOSIS IN MALAYSIA

Sarcocystis has been reported from domesticand wild animals and humans in Malaysia. Sofar, human sarcocystosis reported in Malaysiaconsists of the muscular form only, with manserving as an accidental intermediate host. Thisinfection is probably zoonotic, acquired by theingestion of sporocysts shed by known andunknown definitive hosts. It is highly possiblethat the environment, especially soil and water,may be contaminated by sporocysts shed by de-finitive hosts, as reflected by an overall sero-prevalence rate of almost 20% among the mainethnic groups in the country. Because of themildness and chronicity of muscular sarcocystosisand the non-specificity and transient nature ofintestinal sarcocystosis, however, may such casesamong the human population may have beenmissed or misdiagnosed.

However, both forms of sarcocystosis, espe-cially intestinal sarcocystosis, can become apotentailly serious public health problem if thesources of infection (sporocysts and sarcocysts)are not controlled or monitored. This is partic-

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ularly so in view of the fact that seeminglyharmless or innocuous zoonotic infections causedby Toxoplasma gondii, Pneumocystis carinii, andthe intestinal protozoan, Cryptosporidium spp.,have been shown to be severe and even fatalamong immunosuppressed patients, especiallythose with the acquired immunodeficiencysyndrome (AIDS). It is highly possible for themild and transient form of intestinal sarcocystosisto become protracted, prolonged, and dissem-inated among immunosuppressed individualswho may not necessarily have AIDS but mayhave been subjected to immunosuppressivetherapy for other disease conditions. Similarly,the initial acute phase of schizogony in thevascular endothelial cells that preceded the laterchronic phase of cyst formation in the musclecells also has the potential to cause widespreadand massive tissue damage if this phase isprotracted or prolonged in immunocompromisedhosts. In view of the current frequent use ofimmunosuppressive therapy, it becomes man-datory to thoroughly screen all patients forsarcocysts in muscles or sporocysts in the fecesbefore initiating such chemotherapeutic regimes.

In addition to detection and surveillance ofhuman infection, it would be prudent to adoptmeasures to detect and prevent sarcocystosisamong domestic and wild animals. All animals,especially pets and livestock, should be period-ically screened for sarcocystosis, and infectedanimals should be treated. Animals slaughteredin abattoirs should be inspected for sarcocystsbefore being approved for human consumption.Both human and animal waste should be safelydisposed of to avoid contamination of theenvironment and infection of intermediate hosts.Health education should be given regardingproper food hygiene and the necessity ofthoroughly cooking meat.

While most of the above measures would, tosome extent, prevent exposure to and trans-mission of infection among domestic animals andman, very little can be done to reduce the sourcesof infection maintained by semi-domestic andwild animals. Public awareness of the existenceof this sylvatic zoonosis would reduce the risk ofexposure to infection, especially among thosepeople whose livelihood or pastimes (timber-logging, hunting, camping) predispose them toinfection with sylvatic parasites.

SARCOCYSTOSIS IN MALAYSIA

The occurrence of Sarcocystis among bothdomestic and wild animals poses a threat to bothrural and urban communities. Furthermore,intestinal sarcocystosis could easily occur where-ever there is unsanitary disposal of human andanimal waste. Such conditions of poor environ-mental sanitation prevails in all socioeconomicallydisadvantaged communities in both rural andurban areas, including among aborigines livingwithin or at the fringes of jungle settlements ofMalaysia. Lastly, man is capable of serving as adefinitive or intermediate host for both domesticor sylvatic species of Sarcocystis, therebyincreasing his chances of acquiring the infectionfrom either domestic or wild animals in urban orrural environments. The ease of transmission ofinfection, especially the muscular form (bycontamination of food or drink with imme-diately infective sporocysts), together with exoticculinary practices (such as eating raw orundercooked meat) further enhances the potentialof sarcocystosis to be a major food-borne zoo-notic infection in Malaysia.

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