Human Infections with Sarcocystis Species

17 Pages·2015·1.58 MB·English

crossmark
Human Infections with Sarcocystis Species
RonaldFayer,aDouglasH.Esposito,bJitenderP.Dubeya
U.S.DepartmentofAgriculture,AgriculturalResearchService,Beltsville,Maryland,USAa;DivisionofGlobalMigrationandQuarantine,NationalCenterforEmergingand
ZoonoticInfectiousDiseases,CentersforDiseaseControlandPrevention,Atlanta,Georgia,USAb
SUMMARY..................................................................................................................................................295
INTRODUCTION............................................................................................................................................295
LifeCycleStages..........................................................................................................................................296
SpeciesInfectingAnimals................................................................................................................................297
SpeciesInfectingHumans................................................................................................................................297
SourcesofIntestinalandMuscularSarcocystosis.........................................................................................................300
PREVALENCE,SYMPTOMS,ANDDIAGNOSISOFINFECTIONINHUMANS ...............................................................................301 D
IntestinalSarcocystosisSpeciesandSymptoms..........................................................................................................301 o
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IntestinalSarcocystosisinEurope........................................................................................................................301
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IntestinalSarcocystosisinAsia............................................................................................................................304 lo
IntestinalSarcocystosisinAustralia.......................................................................................................................305 a
IntestinalSarcocystosisinNorthandSouthAmerica.....................................................................................................305 d
DiagnosisofIntestinalSarcocystosis.....................................................................................................................305 e
d
ExtraintestinalSarcocystosis..............................................................................................................................305
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OutbreaksandCaseDescriptions........................................................................................................................306 r
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SarcocystosisandCardiomyopathy......................................................................................................................307 m
SarcocystosisandGlomerulonephritis...................................................................................................................307
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SarcocystosisandMalignancy............................................................................................................................307
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IMMUNITY,PROPHYLAXIS,ANDTREATMENT ............................................................................................................307 tp
IntestinalSarcocystosis...................................................................................................................................307 :/
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MuscularSarcocystosis...................................................................................................................................308 c
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PREVENTION................................................................................................................................................308
CONCLUSIONS.............................................................................................................................................309 r.
a
REFERENCES................................................................................................................................................309 s
AUTHORBIOS..............................................................................................................................................311 m
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SUMMARY INTRODUCTION o
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Recurrentoutbreaksofmuscularsarcocystosisamongtourists SarcocystisisclassifiedinthephylumApicomplexa,alongwith A
visiting islands in Malaysia have focused international atten- speciesofEimeria that cause coccidiosis in poultry and live- p
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tion on sarcocystosis, a disease once considered rare in hu- stock;Toxoplasmagondii,whichinfectsvirtuallyallwarm-blooded il
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mans.Sarcocystisspeciesrequiretwohosts,definitiveandinter- vertebrates;andspeciesofCystoisosporathatinfecthumansanda ,

mediate, to complete their life cycle. Humans can serve as varietyofanimals.Sarcocystisspeciesareubiquitousinnatureand 2
0
definitive hosts, with intestinal sarcocystosis for two species arefoundworldwide.Twohostsarerequiredtomaintainthelife 1
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acquired from eating undercooked meat: Sarcocystis hominis, cycle: an intermediate or prey host, in which cysts (sarcocysts)
b
from beef, and Sarcocystis suihominis, from pork. Symptoms containinginfectiouszoitesinfectthemuscles,andadefinitive, y

such as nausea, stomachache, and diarrhea vary widely de- final,orpredatorhostthatingeststhecysts,becomesinfectedwith g
u
pendingonthenumberofcystsingestedbutappearmorese- intestinal-stageparasites,andexcretesoocystsorsporocystsinto e
vere with pork than with beef. Humans serve as intermediate theenvironment.Forthe(cid:2)150speciesofSarcocystis,mostinter- st
hostsforSarcocystisnesbitti,aspecieswithareptiliandefinitive mediatehostsincludeherbivorousmammalsandhumansandother
primatesbutalsosomebirds,reptiles,andpossiblyfish.Definitive
host, and possibly other unidentified species, acquired by in-
hostsincludecarnivoresoromnivores,includinghumansandsome
gestingsporocystsfromfeces-contaminatedfoodorwaterand
reptilesandraptorialbirds(1).Althoughothersmayexist,onlySar-
the environment; infections have an early phase of develop-
cocystisnesbittihasbeenidentifiedinhumansandnonhumanprimates
ment in vascular endothelium, with illness that is difficult to
servingasintermediatehosts,withasnakepossiblyservingasthedefini-
diagnose; clinical signs include fever, headache, and myalgia.
Subsequent development of intramuscular cysts is character-
izedbymyositis.Presumptivediagnosisbasedontravelhistory
Published25February2015
totropicalregions,elevatedserumenzymelevels,andeosino-
CitationFayerR,EspositoDH,DubeyJP.25February2015.Humaninfectionswith
philiaisconfirmedbyfindingsarcocystsinmusclebiopsyspec- Sarcocystisspecies.ClinMicrobiolRevdoi:10.1128/CMR.00113-14.
imens.Thereisnovaccineorconfirmedeffectiveantiparasitic AddresscorrespondencetoRonaldFayer,[email protected].
drugformuscularsarcocystosis,butanti-inflammatorydrugs Copyright©2015,AmericanSocietyforMicrobiology.AllRightsReserved.
may reduce symptoms. Prevention strategies are also dis- doi:10.1128/CMR.00113-14
cussed.
April2015 Volume28 Number2 ClinicalMicrobiologyReviews cmr.asm.org 295
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FIG1Humansasdefinitive(final)hostsforSarcocystisspecies. a
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tivehost.However,thisidentificationisbasedonacomparisonofavail- riodestablishedtherequisiterelationshipofthetwo-host,prey- fr
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ablecongenersthatmostcloselymatchedthoseofspeciesinwhichsnakes predator(intermediatehost-definitivehost)lifecycleforallspe- m
werethefinalhostsandhasyettobeconfirmed.Twospecies,Sarcocystis ciesofSarcocystis. h
hominisandS.suihominis,havebeenidentifiedinhumansandnon- tt
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humanprimatesservingasdefinitivehosts(Fig.1). LifeCycleStages :
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Earlyknowledgeofinfectionsinhumansisscantbecausethe Inintermediatehosts,includinghumans,onlyasexual-stagepar- c
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relationship between infection and symptoms was not under- asitesarefound(Fig.2).Theinitialstagesofasexualdevelopment
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stood,tissuespecimenswererare,lightmicroscopy(LM)hadlim- areknownfromanimalstudiesbuthavenotbeenseeninhuman .a
s
itations, the life cycle was unknown, and other diagnostic tools tissues.ThefollowingdescriptionsarebasedonSarcocystiscruzi m
werenotdeveloped.Thefirstrecordofwhatwouldbecomerec- development in cattle. Infection begins when oocysts or sporo- .
o
ognized as Sarcocystis was in 1843 by Meischer, who observed cystsinfecesfromafinalhostbecomeingestedbyasusceptible r
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long,thin,whitecystsinmusclesofadeermouseinSwitzerland intermediatehost.Exposuretotrypsinandbilecausestheplates /

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(1). For the following 2 decades, this parasite with no scientific that form the sporocyst wall to disunite, liberating four motile n
name was called Meischer’s tubules. In 1865, a parasite with a sporozoites contained within. The sporozoites pass into or A
similar appearance in muscles of a pig was then described by throughthegutwallandarefirstfoundwithinendothelialcells p
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Kuhn,whoproposedthenameSynchytriummiescherianum(1). thatlinesmallarteriesinallpartsofthebody.Thisisthefirstof il
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However,thenameSynchytriumwasalreadyinuseforanother approximatelyfourcyclesofasexualdevelopment,calledmer- ,

organism.Thus,in1899,LabbechangedthenametoSarcocystis ogony or schizogony, the number and timing of which may 2
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meischeriana(1),anditbecamethetypespeciesofthegenus.In vary with the species. During each of the first three cycles, 1
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the following decades, many species of Sarcocystis were named nucleardivisioneventuallygivesrisetomerozoites,whichare

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basedonfindingintramuscularcystsinvariousanimals,andthese motile,crescent-shapedorganismswithastructuresimilarto y
werereferredtoassarcocysts.InsomereferencestoSarcocystis,the that of sporozoites. Subsequent generations are found down- g
u
termsarcosporidiumwasused.Thispossiblyresultedfromstud- stream,inarterioles,andthenincapillariesandinveinsinall e
iesinwhichsarcocystsinculturemediaappearedtodevelophy- partsofthebodyuntilthelastgenerationdevelopsinskeletal, s
t
phaeandmyceliaresultingfromcontamination,andSarcocystis smooth,andcardiacmuscles,andsometimesinneuraltissue,
thereforewasthoughttobeatypeoffungalorganism.In1967, wheresarcocystsareformed.
electron micrographs clearly demonstrated that the organisms ForS.cruzi,thefirstgenerationisfound(cid:3)2weeksafteringes-
containedwithinthesarcocystswerenotfungalsporesbutwere tionofsporocysts(Fig.3A),andthesecondgenerationisfoundas
zoites morphologically similar to those of other apicomplexan singlesorpairsofmerozoiteswithinmononuclearcellsinperiph-
protozoa(2),removinganyconsiderationthatSarcocystiswastax- eralbloodnearly4weeksafteringestionofsporocysts(Fig.3C).A
onomicallyrelatedtofungi.Otherlifecyclestagesremainedun- fewdaystoaweeklater,thethirdgenerationisseenasimmature
knownuntilthe1970s,whenzoitesfreedfromsarcocystsinthe multinucleateschizontsormatureschizontscontainingmerozo-
muscles of grackles (Quiscalus quiscula) developed into sexual- itesinendothelialcellsofcapillariesthroughoutthebody,butthey
stage parasites and oocysts in cultured mammalian cells (3, 4). areespeciallyprominentinrenalglomeruli(Fig.3B).Merozoites
Additionally, sarcocysts from cattle were fed to cats, dogs, and fromtheseschizontsentermusclecells,wheretheybeginsarcocyst
humans, establishing three distinct species, with the proposed formation, first differentiating into a single round cell, called a
namesSarcocystisbovifelis,S.bovicanis,andS.bovihominis,com- metrocyteormothercell.Aseriesofdivisionsgivesrisetonumer-
binations representing two hosts (5–7). Although these species ousmetrocytesasthesarcocystgrowswhile,concurrently,awall
nameswerelaterchanged,thecumulativefindingsfromthispe- develops, isolating the sarcocyst from the surrounding muscle
296 cmr.asm.org ClinicalMicrobiologyReviews April2015 Volume28 Number2
SarcocystosisinHumans
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FIG2HumansasaberrantintermediatehostsforSarcocystisspecies. d
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(Fig. 3D). At the time when metrocytes develop into infectious foursporozoitesandaclusterofresidualgranules(Fig.3I).Sporo- m
bradyzoites,alsoreferredtoascystozoitesorjustzoites,thesar- cystsofS.hominisandS.suihominishaveaveragesizesof9.3by h
cocystisconsideredmature(Fig.3EandF).Thematurationtime 14.7and10.5by13.5(cid:4)m,respectively,andareimmediatelyin- tt
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appearstodifferamongspeciesandcantake2monthsormoreto fectiouswhenexcreted(1). :
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complete,butthesarcocystcanthenpersistformonthsoryears. c
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Dependingonthespecies,sarcocystsdifferinsizeandshapefrom SpeciesInfectingAnimals
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microscopictomacroscopic.Theyrangefromafewmicrometers SomespeciesofSarcocystisthatinfectagriculturalandcompanion .a
to several millimeters in length, range from narrow to wide in animals,suchascattle,sheep,andhorses,areofeconomicimpor- sm
circumference, and have a great variety of wall structures that tancebecausetheycauseillnessthatresultsinfever,lethargy,poor .
o
differinthicknessandinpatternsofperipheralprotrusionscalled growth,poorfeeduse,reducedmilkproduction,lameness,wool r
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cytophaneres.Sevenmorphologicallyuniquewallstructureswere andhairloss,abortion,carcasscondemnationatmeatinspection, /

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describedinearlyreportsofsarcocystsfoundinhumanmuscles aswellasdeath.Informationobtainedfromsuchinfectionshas n
(8)(Table1),butmostsubsequentreportsofintramuscularsar- been helpful in understanding aspects of clinical disease in hu- A
cocystosis in humans did not identify wall morphology (9–31) mans. For example, data on hematology, serum enzyme level p
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(Table2).Somesarcocystshaveinternalseptathatformcompart- changes,theinflammatoryresponse,histopathology,thelocation il
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ments,whileinothers,noseptaareapparent.Theseptaandcyto- andtimingofdevelopmentalstages,thefebrileresponse,theneg- ,

phaneresmaybedifficulttodistinguishbylightmicroscopyand ativeimpactongrowth,abortion,andotherfactorshavebeenwell 2
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arebestseenbyelectronmicroscopy.Sarcocystscanbefoundin documentedfromexperimentalandoutbreakstudiesofsarcocys- 1
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the muscles of limbs, tongue, esophagus, diaphragm, and heart tosisinlivestockandhavebeenreviewed(1,32).

b
but also in neural tissue in the brain, spinal cord, and Purkinje y
fibers. SpeciesInfectingHumans g
u
Sexualstagesoccurindefinitivehosts.Afterasusceptiblehost Humanscanbeeitherfinalorintermediatehosts(Fig.1and2). e
haseatenmeatcontainingmaturesarcocysts,thewallofthesar- Humans can become final hosts after eating undercooked pork s
t
cocystbecomesdigestedorbroken.Bradyzoiteswithinthesarco- and beef harboring mature sarcocysts of S. suihominis and S.
cystsarereleasedandcansoonbefoundintracellularlyinvilliof hominis,respectively.Tissuesofmanyspeciesofdomesticatedan-
thesmallintestine.Eachbradyzoitetransformsintoeitherami- imals,wildmammals,birds,andreptilesthatareeatenformeat
crogamont (male) or a macrogamont (female) stage (Fig. 3G). throughouttheworldcontainsarcocystscapableofinfectingun-
Microgametocytes become multinucleate, and a sperm-like mi- identified final hosts, possibly including humans and with un-
crogamete forms around each nucleus. A single flagellated mi- knownhealthconsequences.Therefore,theremaybeadditional
crogametefindsandfuseswithamacrogamont.Theirnucleicom- undocumentedspeciesforwhichhumanscanserveasadefinitive
bine,andthefertilizedmacrogamontdevelopsintoanoocystthat host.AlthoughsporocystsinthefecesarediagnosticforSarcocystis
sporulatesinsitu,formingtwosporocyststhateachcontainfour infectionsofdefinitivehosts,theyaresomorphologicallysimilar
sporozoites(Fig.3H).Althoughoocystsareimmobile,theyreach thatspeciescannotbedifferentiatedsimplybythesizeandshape
thelumenoftheintestineandareexcretedwithfeces,sometimes ofsporocysts.
intactwithabarelyvisiblewall,appearingasapairofsporocysts, WithintheSarcocystislifecycle,humanswhoareinfectedwith
ormoreoften,thefragilewallbreaks,andindividualsporocysts muscular sarcocystosis are considered aberrant intermediate
arereleased.Sporocystsofvirtuallyallspeciesareindistinguish- hostsbecausetheyaccidentlysubstituteforthenaturalhoststhat
ablefromoneanother,measuring(cid:3)10by15(cid:4)mandcontaining routinelyserveaspreyforadefinitivepredatorhost.Thenum-
April2015 Volume28 Number2 ClinicalMicrobiologyReviews cmr.asm.org 297
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FIG3Sarcocystisstagesintissuesofintermediatehosts(AtoF)anddefinitivehosts(GtoI).PanelsAtoGshowhematoxylin-stainedimages.Allimagesareof 9
S.cruzi,exceptpanelE,whichisanimageofS.hominis.(A)Arterywithafirst-generationmultinucleateschizont(arrow)inanendothelialcell.(B)Kidney
b
glomeruluswithimmature(arrowhead)andmature(arrow)second-generationschizonts.(C)Bloodsmearwithamerozoiteinamononuclearcell.(D)Heart y
withanimmaturesarcocystcontainingglobularmetrocytes.(E)Skeletalmusclewithacrosssectionofamaturesarcocystwithathickstriatedwallsurrounded g
byamononuclearcellinfiltrate.(F)Skeletalmusclewithlongitudinalandcrosssectionsofsarcocysts.Thewasnoinflammatoryresponse.(G)Laminapropria u
e
ofsmallintestinewithamacrogametocyte(arrow).(H)Smallintestinewithsporulatedsporocysts(arrow)(Whipf’spolychromestain).(I)Phase-contrast
s
microscopyoftwosporocystsinafecalfloat. t
berofspeciesforwhichhumanscanserveasanintermediate cocystis nesbitti (26–28) based on 18S ribosomal DNA (rDNA)
hostisunknown,buttheremaybesevenormorespeciesbased sequencedata.Sarcocystisnesbitti,describedbyMandourin1969,
on differences in sarcocyst wall morphology observed in hu- wasoriginallydetectedinmusclesfromarhesusmonkeybasedon
mantissuespecimens(8).Sarcocystwallmorphologyhasalso LM,butitstaxonomicvalidityisquestionable,andtherearenei-
been used to differentiate species in animals (1). The use of ther transmission electron microscopy (TEM) morphological
sarcocystwallmorphologytodistinguishspecieshasbeencon- datanorLMphotographicsupportfortheoriginaldescription.
troversial because morphology can be difficult to discern by Nevertheless,thefirstreportofSarcocystisinnonhumanprimates
lightmicroscopy,canbeaffectedduringtheprocessingoftis- (Macacafascicularis)inChina,whichwassupportedbyLMand
sues,andcanchangewiththeageofthesarcocysts.Molecular TEMstudies(33),wasbasedontheperceivedresemblancetoS.
methods have been used but have been extremely limited. nesbitti,sothoseauthorsnamedtheorganismsthattheyfoundin
Greater use will extend and confirm species identity and im- M.fascicularismusclesS.nesbitti.Morphologicalsimilaritiessug-
provediagnosisofinfections. gestedthatonespeciesofSarcocystismightinfectMacacafascicu-
HumanshavebeenidentifiedasanintermediatehostforSar- laris,Macacamulatta,Papiopapionis,Cercocebusatys,aswellas
298 cmr.asm.org ClinicalMicrobiologyReviews April2015 Volume28 Number2
SarcocystosisinHumans
TABLE1Summarizationofearlyreportsofhumanswithsarcocystsc
Patientage(yr),
Countryorregion gender Sarcocystlocation(s) Biopsyorautopsy Sarcocysttypeb Originalauthor(s),yra
Sudan 36,M Abdomen A 2 Kartuli,1893
France Adult,M Larynx A 1 BarbaranandSt.Remy,1894
France Adult,unknown Skeletalmuscle A 1 Vuillemin,1902
Malaysia 30,M Tongue A 4 Darling,1919
UK Unknown Heart A 6 Manifold,1924
India 55,M Chest B 2 Vasudevan,1927
USAviaWestIndies 32,F Heart A 7 Lambert,1927
Indonesia 20,M Cheek B 4 BonneandSoewandi,1929
China Adult,M Leg B 1 Feng,1932
UK Adult,F Heart A 5 Hewett,1933
Panama 11,F Heart A 7 Gilmoreetal.,1942
Panama 48,F Heart A 7 KeanandGrocott,1943
Brazil 32,F Heart A 7 DeFreitas,1946 D
USAviaGermany 31,M Heart A 7 Arai,1949 o
w
USAviaPuertoRico 34,M Heart A 7 Arai,1949
n
India 37,M Leg B 2 DasturandIyer,1955 lo
India 20,M Leg B DasturandIyer,1955 a
Sudan 45,M Foot B 3 McKinnonandAbbott,1955 d
e
UKviaIndia 60,M Pectoral B 2 McGillandGoodbody,1957 d
Brazil 40,F Heart A 6 Koberle,1958 f
r
Italy 17,F Heart A 5 D’ArrigoandSquillaci,1962 o
m
Indonesia 51,M Pectoral B 4 VanThielandVandenBerg,1964

UKviaSoutheastAsia 51,M Leg B 4 Mandour,1965 h
t
Angola 30,F Chest B 2 LiuandRoberts,1965 tp
India 22,F Leg,arm B 2 Guptaetal.,1973 :/
/
SoutheastAsia 21,M Leg B 3 Jeffrey,1974 c
m
UKviaMalaysia 34,M Pectoral B 4 Jeffrey,1974
r
Malaysia 34,M Larynx B 4 KuttyandDissanaike,1975 .a
Malaysia 12,F Pharynx A 4 Kuttyetal.,1975 s
m
India 56,M Arm B 3 Agarwaletal.,1976
.
India 54,F Leg B 3 Thomas,1976 o
r
Malaysia 20,M Foot B 4 PrathapandDissanaike,1976 g
/
Malaysia 23,M Neck A 4 PrathapandDissanaike,1978 o
Unknown Unknown Skeletalmuscle A 4 Frenkel,1976 n

USAviaAsia 40,M Arm B 4 McLeodetal.,1979 A
p
Uganda 50,M Leg B 1 Beaver,1979 r
India 50,M Arm B 3 Beaver,1979 il
3
Singapore Unknown Skeletalmuscle B 4 Beaver,1979 ,

Singapore Unknown Skeletalmuscle B 4 Beaver,1979 2
0
CostaRica 9,M Heart A 6 Beaver,1979 1
9
aOriginalauthorsandyearscanbefoundinreference8,andnotalloftheseareincludedinthelistofreferencesinthisstudy.
bThesetypes,describedbyBeaveretal.(8),differfromthosedescribedbyDubeyetal.(1)andaredefinedasfollows:type1,thick,radiallystriatedwall,largezoitesoftensparsein b
y
thecenter,andmetrocytes;type2,generallylargesarcocysts,thinandsmoothwall,mediumzoites,andsepta;type3,smallandmediumsarcocysts,thinwall,mediumzoites,and
g
septa;type4,longandmediumsarcocysts,thinwall,smallzoites,andseptaevidentincenter;type5,smallsarcocysts,thinwall,mediumzoites,andinmyocardium;type6,smallto u
mediumsarcocysts,thinwall,largezoites,andinmyocardium;type7,smallsarcocysts,thinwall,smallzoites,andinmyocardium. e
cDatawerecompiledfromreference8.Abbreviations:A,autopsy;B,biopsy;F,female;M,male. st
humans(34).SarcocystsinmusclesfromM.fascicularisidentified TEM (26). The 18S rDNA sequences of Sarcocystis from these
asS.nesbittibyYangetal.(33)werelaterexaminedbymolecular patientsvaried1%fromeachother,andaBLASTanalysisfound
methods(34),and18SrDNAsequencedatafromtwosarcocysts thattheyshared99%homologywithS.nesbittifromthemuscleof
placedthisspeciesinaclusterwithS.atheridisandS.singaporensis, M.fascicularis(26).Anotherreportalsoidentifiedapatientwith
specieswithrodentintermediatehostsandsnakedefinitivehosts. sarcocystsinthetemporalismuscleandanotherwithsarcocystsin
This suggested that a final host for S. nesbitti might be a snake. alegmuscle,forwhichDNAsequencesmatched100%ofthosefor
PCRevidenceofSarcocystiswasfoundinfecesfromacobra(26); S.nesbittiinthecladewithS.atheridis(25).Stillanotherstudy(27)
the18SrDNAsequenceclusteredwithSarcocystissequencesfrom reportedthesame18SrDNAfindingsasthosereportedbyAbu-
othersnakesandwiththetwoS.nesbittisequencesobtainedfrom Bakaretal.(25)andTianetal.(34).The18SrDNAsequencefrom
M.fascicularisbyTianetal.(34).ThreereportsfromthePangkor themusclebiopsyspecimenofapatientwhohadvisitedTioman
IslandoutbreakinMalaysiareportedsimilarfindings.Musclebi- IslandinMalaysiaalsoshowed100%homologywiththeS.nesbitti
opsyspecimensfromtheswollenjawofonepatientandthelegof gene sequence reported under GenBank accession number
another showed intramuscular sarcocysts identified by LM and HF544323(28).
April2015 Volume28 Number2 ClinicalMicrobiologyReviews cmr.asm.org 299
Fayeretal.
TABLE2SummaryofreportsofmuscularsarcocystosisinhumansnotincludedinthereviewbyBeaveretal.andpresentedinchronologicalorder
ofpublication
Descriptionofhumansubject(s)or Reference,yrof
Countryorregion specimen(s) Sarcocystlocation Biopsyorautopsyc publication
Malaysia 58-yr-oldMa Tongue B 9,1981
India 2persons Leg B 10,1983
Gluteus B
Denmark? 4of112specimensb Muscle A? 11,1985
Malaysia 45-yr-oldMa Nasopharynx B 12,1987
53-yr-oldMa Nasopharynx B
Malaysia 1person Skeletalmuscle B 13,1988
D
AustraliaviaThailand 31-yr-oldM Skeletalmuscle B 14,1990
o
w
Egypt 1person Skeletalmuscle B 15,1990 n
lo
Malaysia 45-yr-oldMa Tongue B 16,1992 a
d
67-yr-oldFa Tongue B e
32-yr-oldFa Pectoralmuscle B d

f
r
o
Malaysia 21personsaged16to57yr Tongue A 17,1992
m

BelgiumviaBrazil,Kenya, 31-yr-oldM Thigh B 18,1995 h
t
andTanzania tp
:
/
/
India 40-yr-oldM Thigh B 19,1996 c
m
14-yr-oldF Arm B
r
52-yr-oldF Thigh B .a
23-yr-oldF Arm B s
m
.
Malaysia 44-yr-oldFa Thigh B 20,1998 o
r
19-yr-oldF Calf B g
/

o
Malaysia 7adults,M 1muscle B 21,1999 n

A
Thailand 66-yr-oldMa Larynx B 22,2011 p
r
il
India 20-yr-oldM Arm B 23,2012 3
,

2
India 50-yr-oldM Neck B 0
1
9
India 47-yr-oldM Leg B 24,2013
b
y
PangkorIsland,Malaysia 89people Leg B 25,2013 g
26,2014 u
e
27,2014 s
t
TiomanIsland,Malaysia 39Fand29Msubjects,aged4to72yr Skeletalmusclefrom15patients;1 B 28,2014
PCRpositive
29,2014
TiomanIsland,Malaysia 3Fand3Msubjects Febrilemyositissyndrome NTE 30,2014
TiomanIsland,Malaysia 26casesinGermanyreportedpreviously Symptomaticchanges;skeletalmuscle B 31,2014
aCancerpatients.
bTissuesexaminedbytrichinoscopy.
cNTE,notissueexamined.
SourcesofIntestinalandMuscularSarcocystosis animalsofmanyspecies.Althoughonlytwospeciesareknownto
The only source of intestinal sarcocystosis is ingestion of meat infect humans as definitive hosts, S. hominis from beef and S.
containingmaturesarcocysts.Therangeofmeatsandmeatprod- suihominis from pork, many others may exist throughout the
uctsconsumedbyhumansworldwideincludesdomesticandwild worldbutareasyetundefined.
300 cmr.asm.org ClinicalMicrobiologyReviews April2015 Volume28 Number2
SarcocystosisinHumans
Thesourceofmuscularsarcocystosisisingestionofsporocysts, quantityofmeatconsumed,thespeciesandnumberofsarcocysts
mostlikelythroughcontaminatedwaterorfreshproduceorpos- consumed,andwhetherapatientingestedrawmeatonceormul-
siblythroughexposuretoacontaminatedenvironment.Itisdif- tipletimes.Thelongestperiodofcontinuoussporocystexcretion
ficulttopredictforunnamedspeciesofSarcocystishowspecific (I.hominis)was21monthsormoreforapatientinTheNether-
eithertheintermediateorthefinalhostspeciesmustbe,butthere lands, while other patients excreted sporocysts for at least 6
aresomegeneralizedpatterns.Dogs,coyotes,andfoxes,butnot months(35).ApatientinPolandexcretedsporocystsforatleast
humansorcats,arefinalhostsforS.cruzi,withintermediatehosts 12months(36).However,themostreliableinformationonthe
beingrestrictedtocattleandbison,butnotsheep,monkeys,pigs, prepatentandpatentperiodsisfromhumanvolunteerstudies.In
orrats.IntermediatehostsofS.odocoileocanisincludewhite-tailed Germany,diaphragmsfromcattleandpigswereobtainedfroman
deer,sheep,andcattle.Thereareotherexamplesinwhichclusters abattoir,groundinameatgrinder,andfoundtocontainzoitesof
ofrelatedhostspeciesserveaseitherintermediateorfinalhosts. Sarcocystis.Thisgroundmeatwasthenfedtovolunteerswhowere
BasedonthelikelihoodthatonespeciesofSarcocystiscaninfect notexcretingoocystsorsporocystsintheirstools(6).Inthefirst
multiple closely related host species, some species of Sarcocystis experiment,twovolunteersate500gofrawbeefdiaphragmwith
thatinfectnonhumanprimatesmightalsobeexpectedtobeable onions and spices and began excreting sporocysts 9 days later,
to infect humans. This is true for S. nesbitti, a species found in continuingfor40daysorlonger.Inthesecondexperiment,four
D
musclesofmacaquesandrecentlyinhumans;snakesandpossibly volunteersateseasonedrawporkdiaphragmandbeganexcreting o
otherreptilesmayserveasdefinitivehosts(33,34).Becausemost sporocysts 9, 13, and 17 days later; the fourth person remained w
n
casesofhumanmuscularsarcocystosishavebeenfoundintropi- uninfected.Thepatentperiodforthethreevolunteerswasatleast lo
calareasinhabitedbymanyspeciesofnonhumanprimatesand 30 days. For a volunteer in China who ingested S. suihominis- a
d
reptiles,andbecausesomelocationscouldbesubjecttocontam- infected pork, the prepatent period was12 days, and the patent e
inationfromreptilianfeces,thecombinationofthesefactorsap- period was (cid:2)120 days (50). Another volunteer excreted sporo- d

pearsconducivetohumaninfection. cystsfromdays8to40aftereatingbeef(51).Twoothervolunteers fr
o
inChinawhoatebeefandthreewhoatewaterbuffalohadprepat- m
PREVALENCE,SYMPTOMS,ANDDIAGNOSISOFINFECTION entperiodsof10to12daysandpatentperiodsof11to29days h
INHUMANS (57). Another volunteer in China excreted sporocysts of S. ttp
suihominisforanestimated91daysbeginning10daysaftereating :
/
IntestinalSarcocystosisSpeciesandSymptoms pork(62).OfsevenvolunteersinBrazilwhoaterawkibbe(beef), /c
m
Humanswithintestinalsarcocystosis(Fig.1)havebeenidentified sixbegantoexcreteS.hominisoocysts/sporocysts10to14days
r
worldwide,withtheexceptionofAfricaandtheMiddleEast,al- laterandexcretedthemfor5to12days(58). .a
s
thoughsuchinfectionslikelyoccurtheregivencustomsofeating m
raworundercookedmeatinthoseareas.Locationswherecasesof IntestinalSarcocystosisinEurope .
o
intestinalsarcocystosishavebeenreportedarelistedinTable3, InTheNetherlands,oocystsandsporocystswereidentifiedasI. r
g
includinginfectionsthatresultedaftervolunteersingestednatu- hominisinstoolsamplesof17of72persons,somewithoutillness /

o
rallyinfectedorexperimentallyinfectedmeat(6,7,35–68).Early andotherssuspectedofsufferingfromchronicamoebiasis;addi- n
investigators,withnoknowledgeoftheSarcocystislifecycle,ob- tionally,in5of17subjects,intestinalmucosascrapingstakenat A
servedtwoparasiteswithcharacteristicsofapicomplexanoocysts autopsy contained sporocysts of I. hominis (35). Also, in The p
r
instoolsamplesofinfectedpersonsandnamedoneIsosporabelli, Netherlands and in various other countries between 1960 and il
3
whichwasexcretedasadistinctiveunsporulated(internallyun- 1970,severalsurveyswereconducted,inwhichstoolsamplesfrom ,
differentiated) oocyst, unique in size and shape and unlike any humans were examined (69). Ten percent to (cid:2)50% of persons 2
0
other apicomplexan parasite. The other coccidian parasite, ex- excretingsporocystswereincountrieswhererawmeatwasusually 1
9
cretedasasporulatedoocyst(containingsporocystswithsporo- consumed. In a subsequent survey in The Netherlands, babies

b
zoites) or as individual sporocysts, was named Isospora hominis borntomotherswhoexcretedsporocystsbeganexcretingsporo- y
(35,37,39,44)andrepresentedwhatisnowrecognizedasmulti- cystsat9to10monthsofage,correlatingwiththembeingfedraw g
u
plespeciesofSarcocystis,twoofwhichareknowntobeS.hominis or partially cooked, minced beef (69). In Poland, a 29-year-old e
(6,40,41,46–48,51,53,54,58,59)andS.suihominis(6,40,50,53, womanworkinginanorphanagehadsingleanddoublesporo- s
t
62).However,otherspeciesmayhavebeenpresentbecausethe cystsinherfecesfor12months(36),whichcouldhaveresulted
oocystsandsporocystsofSarcocystisspeciesaremorphologically fromrepeatedreinfection.Neitherherfamilynorhercoworkers
indistinguishable.MostreportsciteinfectionsinpersonsinEuro- werefoundtobepositive,butlater,7personsattheorphanage
pean countries, including The Netherlands, Germany, Poland, werefoundtobeinfected,andatotherlocationsinSzczecinProv-
Slovakia, France, and Spain (Table 3). In Asia, infections have ince,92additionalpersonswerefoundtobeinfected.
been reported in China, Tibet, Laos, and Thailand (Table 3). In Germany, of 150 stool samples examined, I. hominis was
OthercaseshavebeenreportedinAustralia,Argentina,andBrazil detectedin12personswhohadeatenrawbeeforpork(38).Sixof
(Table3). the12personshaddifferentgastricorintestinalsymptoms,and6
Asdefinitivehosts,humanscanexperiencenausea,vomiting, wereasymptomatic.AlsoinGermany,avolunteerconsumed100
acute and severe enteritis, or chronic enteritis, but many infec- to 200 g of raw beef naturally infected with S. hominis or meat
tionsappeartobemildorasymptomatic.Differencesdependon fromcattleexperimentallyinfectedwithS.hominisfor1to3days
thenumber,andperhapsthespecies,ofsarcocystsingested.Few onfourseparateoccasionsatintervalsofseveralmonths(40).The
accurate data are available on the duration of infection or the volunteerhadlow-gradeclinicalsymptomsofstomachache,nau-
numbers of oocysts and sporocysts excreted. Most case studies sea, and diarrhea beginning 3 to 6 h after meat consumption;
sufferfromnotknowingthetimeofonsetofinfection,thetypeor symptomslasted24to36h.Diarrheaandstomachachewereagain
April2015 Volume28 Number2 ClinicalMicrobiologyReviews cmr.asm.org 301
Fayeretal.
e
c
n
e
er
Ref 35 6 36 37 7 38 39 40 41 42 43 44 45 46 47 48
d
Clinicalsign(s) NI 1of6personshadsevereinfluenza-likesymptomsanmilddiarrhea Symptomsveryscant NI None;noinfectionresultedfromingestionofmacroscopiccystsfromsheep 6personshadgastricandintestinalproblems 10of22personshadgastricandintestinalproblems;12personshadnogastrointestinalsigns DiarrheaandstomachacheBloating,inappetence,nausea,vomiting,diarrhea NaturalinfectiontransmittedtocalfNI Intermittententeritiswithdiarrheaorrheumaticphenomenaorasymptomatic NI Asymptomatic Notinfectious,asymptomatic NaturalinfectionExperimentallyinfectedwith15,000sarcocysts NI All6subjectshadacutefeverandacuteabdominalpain,and5hadleukocytosis;bacterialinfectionmayhavecontributedtoseverityofillnesses Downloade
d
cysts fro
o m
c k
sar por h
bections Sourceof NI Beef Pork NI NI Sheep Beefand NI BeefPork NIBeef NI NI NI Beef BeefBeef Beef BeefBeef ttp://cm
nf
ali r.a
nt s
me m
eri .o
attemptedexp Species aI.hominis S.hominis S.suihominis Sarcocystissp.Sarcocystissp.Sarcocystissp. aI.hominis S.tenella Sarcocystissp. aI.hominis S.hominisS.suihominis S.hominisS.hominis NI NI aI.hominis S.cruzi S.hominisS.hominis S.hominis S.hominis S.hominisS.hominis on Aprg/
d r
inhumansan Naturalorexperimentalinfection N E N N E N N E NE N N N NE N N NN il 3, 2019
allyacquiredintestinalsarcocystosis Descriptionofhumansubject(s)and/orsamples 12of72persons5of17autopsyspecimens 2volunteers 4volunteers 29-yr-oldF7subjects(assumedtobechildren)92unidentifiedsubjects 200persons 1volunteer 12of150persons 22of300persons 1volunteer3volunteers 1child3volunteers 8of506persons 13of125children7to18yrold 12-yr-oldF 2persons 5persons1person 2%of3,500samples 30-yr-oldM 3-yr-oldF60-yr-oldF by guest
r
u
nat as
of are
TABLE3Reports Country Netherlands Germany Poland Poland Germany Germany Germany Germany Netherlands Germany Poland Slovakia UnitedStates Netherlands Franceviatropical Thailand
302 cmr.asm.org ClinicalMicrobiologyReviews April2015 Volume28 Number2
SarcocystosisinHumans
ge)
a
p
g
n
49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 owi
oll
f
Abdominaldistension,pain,diarrhea,constipation,stomachache,dyspneaNoinformation Asymptomatichumanwhoateporkexcretedsporocystsinfectiousforpigs;sarcocystsinpigmuscledidnotinfectmonkeys NI None AsymptomaticAsymptomatic NI Asymptomatic NI Allhadclinicalsymptomsincludingabdominalpain,distension,waterydiarrhea,andeosinophilia Diarrhea Abdominaldiscomfort,loosestools 8haddiarrheaandabdominalpain;1hadonlyabdominalpain NI Distension,diarrhea,fever,pain NINI Diarrhea Becameillbutdidnotexcretesporocysts (Continuedon Downloade
d
pork fro
or o m
BeefBeefBeef Pork Unknown Pork Beef Unknown BeefPork NI Possiblybeef NI Cattle Waterbuffal Beefkibbe Beef Pork(raw) Pork(raw) Pork NINI NI Buffalo http://c
m
cysts r.a
poro cted cted sm
S.hominisS.hominisS.hominis Sarcocystissp. Sarcocystissp. S.suihominis-likes S.hominis Sarcocystissp. S.hominisS.suihominis S.hominis Sarcocystissp. Sarcocystissp. Sarcocystissp. Sarcocystissp. S.hominis Sarcocystissp. S.suihominissuspe S.suihominissuspe S.suihominis Sarcocystissp.Sarcocystissp. Sarcocystissp. S.sinensis on Ap.org/
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il
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1
NNN N N N E EE N N N N N E E E N N N E NN N E 9

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9-yr-oldM19-yr-oldM70-yr-oldM 48-yr-oldM AdultM AdultM(naturallyinfected) 4monkeys 1volunteer2monkeys 14of1,228workers 20.5%–22.9%of926persons0.6%–7%of926persons (cid:2)10%of1,008persons 23.2%of362persons 2of385persons 3volunteers 2volunteers 6of7volunteers 35-yr-oldM 27of501persons 32of489persons 1volunteer 4.6%of479specimens8%of1,124specimens 31-yr-oldHIVpatient 2volunteers uest
m
China China(YunnanProvince) China SlovakiaviaNorthVietna Tibet Laos Thailand Australia China Brazil Spain China(Guangxi) China(Guangxi) China ThailandUbonRatchathaniKhonKaen Argentina China
April2015 Volume28 Number2 ClinicalMicrobiologyReviews cmr.asm.org 303
Fayeretal.
e presentwhenmostsporocystswereexcreted14to18daysafterthe
c
en meat was consumed. Again in Germany, three volunteers who
Refer 66 67 68 consumed 100 to 400 g of raw minced pork from pigs heavily
infectedwithS.suihominisbecamesymptomaticbeginning6to
8hlater,withdiarrhea,dyspnea,vomiting,bloat,nausea,stom-
achache,inappetence,andrapidpulse(40).Symptomscontinued
upto48h.Well-cookedporkfromthesamepigscausednoclin-
ng, icalsymptomsinnineothervolunteerswhoatethemeat.Basedon
miti these observations, S. suihominis was considered either patho-
o
v genicortoxicforhumans.Othersconcludedthatsuchpatholog-
ea, icaleffectswereduetotoxicity(69).
us
a IneasternSlovakia,a12-year-oldgirlhospitalizedfortubercu-
n
a, losiswasincidentallyfoundtobeexcretingoocystsandsporocysts
e
h
Clinicalsign(s) NI Abdominalpain,diarrintermittentfever NI onegIInnxafatcsmITetr.reshehottsaeoiiennidmlwataesinlnopsdStriois,kanrseiroanicrlxcsoyhspcwyseytamrhsstoisptoetotfnoiosmoStimssalm3r(sic4ni(ogt45ocrA)2ya.7sst)tIe0i.inadsycfoeoeavrnrestraroaamflpeSaealgroneivowoadkfioti4ahf9,1aod8cfaum1yts,e2o,e2nwn8tihttVehsr,iien1ttio4-s Downloade
andleukocytosisunderwentresectionsurgeryoftheileum(48). d
cysts Thehistopathologicaldiagnosisindicatedsegmentaleosinophilic fro
o a enteritisorsegmentalnecrotizingenteritis.Sexualstagesandde- m
c m
sar ar velopingoocystsresemblingthoseofSarcocystiswereobservedin h
Sourceof NI Beefshaw NI wereknown. rGoBetorshsaeemcirntse-d.pdiBcoutesicssitasciuuvaesetetslbesfar,aocraicmnloldicowytnhseteerseppwaaoettbirieeesnneprttrsv,eeaasdtneednirntasipwntiosblrsooeuceceafylssimnatsmcaahrpnkilldeeistdnbfiurseohmemfeesfr,rfioothuvmees ttp://cm
Species Sarcocystissp. S.hominis Sarcocystissp. opriabeforeSarcocystisspecies iSsRahStnoau.aoammrmthtKhccopaoaihomntcleareiyincsitsssnhtofwlPiiaarfssroanbtow(smhoi6vaPrar6iese1tnr)sro4rf.cpsoe0veO,opui,f8nnfonen3csmr4do.iet37braica%t9lnloehnesne2dfaotoa3con1fslr.oudt2,w1etl%dh1r2hsen0e4aodo2mimsTfnttmhhopsfetwaaolaoectillelstoetasirhlovpcneseoinedlamlclsc,mlai.aeam0gIctple.ntte4elrlesee%nsnd-s(2soh5ffwfrturr5rotoomeoh)mmr8.meea0Orn3nprKyfu6poeTh22rasaoah5riratlsn3aaisvUoisyKlsiefamttbaeanofoepogodSnne-rl., on Apr.asm.org/
Naturalorexperimentalinfection N N N stagesinlaminapr fiwisantrnoaeTdsoahilpnwasrgahielsmsaeearnpnendltdee,nis4no.tf6ter(cid:2)h%roiemc1ra0ssn1%a(dr,50c58o0o,%f8c6ysp6awse)tmeorsrsspueoilsgnepgissosefswseritnoteitrdmvheeeamepftoxeniarcroms.SroIatinnhrncseenord(cid:2)ecn,yig2saTth0nihbsdyao(ei6Srlaa3.irnn)hsg.dooTmLfihsaiaeonagssinees, ril 3, 2019
d
n b
subject(s) ystsinfecesamental. (afl5no4Idtn)a.tDTiouinbileomt,nesgttdhoeooqdlis,npagencdciomSu.enhntosiemfsrionwmiesrw9e2ae6sxdpaeemtresicnotenedsdfbirnoym2t0h.Le5inztoiznh2ci2,s.M9u%liflaiontef, y gues
man orocperi the specimens in the three counties (53). S. suihominis was de- t
Descriptionofhuand/orsamples 1of253persons 19-yr-oldM 1of269persons20-yr-oldF meusedtoidentifyspmale;N,natural;E,ex uawtennecIddrtneeiddsCucoilhsnuouibsn7ael.aled0l,y,sto0rpaf.eso6say,rttmooamnocpeyldtnsso0tptsm%.ewcaoitemifrctee,hnafeosnsuedpxneamdcmimoinisnetnesbpdse,efcrcraeiomsmmpeeenc1nts2ievfpgreaeolytrmisv(o5ent3was),fo.tsCeimrnasgaeelnnes
naM, (49).Noinformationwasprovidedforoneman,buttheother,48
TABLE3(Continued) Country NortheastThailand(KhonKaen) Jordan Malaysia aIsosporahominiswasanearlybNI,notindicated;F,female; ydhtcpimniyeiraoagasaedntrtrssitr,seeohhanaownaentcft.aeedearnIsaogebnpnfreeoada,YAcrswhaucossucaouncpadsnymnroessiaartesthbnskidcepdawbPaaotnteelormsintorooweobvinnhtieeSnaaeba.cntlndehsedduao,1oiciws3vCshcteaieoheatnomphonintftfdsiieaAnotSd,6oins.sa5cmaasaswvduranaoiiaicdsthvlyhhuioaspnaonmlcaibuhtdhiieetninefres,oaierafswdare.ndesdcidHoteeihhtvnsdoii,eosayfwltolnsohetepraexpevnrlaaeesnesmdiprnsaa,oui.tdfnitromHinhoazrgee-----
304 cmr.asm.org ClinicalMicrobiologyReviews April2015 Volume28 Number2