人体寄生虫学：机会致病寄生虫

机会致病寄生虫病为艾滋病病人的常见并发症或临终并发症约80%艾滋病病人死于机会致病性病原体感染机会致病寄生虫机会致病寄生虫：有些寄生虫在人体内通常处于隐性感染状态，当宿主免疫功能受损时则大量增殖并引起疾病，这些寄生虫称为机会致病寄生虫。Co-infectionwithHIVandparasitesiscommonandtheeffectsco-infectionontheoutcomeofbothparasiteandHIVinfectionarejustnowbeingdiscerned

Leishmaniasis---haveincreasingevidenceinHIV/AIDS

Giardiasis---commonparasiteinHIV-positivehomosexualmales

Trichomoniasis---theparasiteincreasingwomen’ssusceptibilitytoHIV

Trypanosomiasis---inHIV/AIDS,theCNSwasinvolvedwithhighT.cinfectionrate

Amebiasis---ithashighprevalencerateinhomosexualmalesFreelivingamebae---opportunisticamebae:Acanthamoeba&Balamuthia

Toxoplasmosis---comeintoitsownasamajorhumanpathogen

Cryptosporidiosis---hascometobealmostpathognomonicofHIVinfection

Cyclosporiasis---Microsporidiosis---isincreasinglyrecognizedinHIV/AIDSToxoplasmagondiiCatsaretheonlydefinitivehostsSomespeciesofbirdsandmammalsmayserveasintermediatehosts.HumansareintermediatehosttooToxoplasmagondiiisanobligateintracellularcoccidianparasiteThelifecycleofthisparasitebecameclearonlyin1970whenthedomesticcatwasidentifiedasitsdefinitivehostAllotherspeciesaremerelyintermediatehostsClinicaldiseasesisrelativerare,beingmostlyopportunisticinnatureMorphologyT.

gondii

occurs

in

three

forms----trohpozoite,tissue

cyst,oocyst

Thetrophozoiteiscrescent-shaped,withoneendpointedandtheotherendroundedDuringacuteinfection,theproliferatingtrophozoitedwithinahostcellmayappearroundedandenclosedbythehostcellmembrane.Thisappearance,calledthe‘pseudocyst’or‘colony’Thetrophozoitesaresusceptibletodrying,freeze-thawingandgastricdigestionThetissuecystformedduringthechronicphageoftheinfectionandcanbefoundinthemusclesandvariousothertissuesandorgans,includingthebrain.Thecystisroundoroval,10to200minsizeandcontainsnumerousbradyzoitesThecystcouldremainviableinthetissueforseveralyearsCystsaresusceptibletodesiccation,freeze-thawingandheatabove60℃

Oocystdeveloponlyindefinitivehost----intheintestinesofcatandotherfelinesCatsshedmillionsofoocystperdayinfaecesforabouttwoweeksduringtheprimaryinfectionThefreshlypassedoocystisnotinfection,itbecomeinfectiousonlyafterdevelopmentinsoilorwaterforafewdays(48-96hrs)Thematureoocystcontainingeightsporozoitesistheinfectiveform,andveryresistanttoenvironmentalconditionandremaininfectiveforaboutayearintermediatehosts:trophozoiteTachyzoite---pseudocyst(contain20ormore)Bradyzoite---cystLifecycleThelifecycleoftheparasiteconsistsof3stagesasfollows:a.Tachyzoitesb.Bradyzoitesc.SporozoitesinsideoocystsHumaninfectionisadeadendfortheparasite,humaninfectionisobtainedinthefollowingwaysa.Eatinguncookedorundercookedinfectedmeatcontainingtissuecystsb.Ingestionofmatureoocystthroughfood,waterorfingerscontaminatedwithcatfecesdirectlyorindirectlyc.Intrauterineinfectionfrominfectedmotherstobabiesd.RarelybybloodtransfusionortransplantationfrominfecteddonorsToxoplasmaoocystsincatfeces生活史

在中间宿主体内的肠外循环属无性生殖在终宿主体内为肠上皮细胞内循环，包括无性及有性生殖

特点：1.速殖子(假包囊)、包囊、囊合子均具感染性，中间宿主间可传播(假包囊,包囊)2.终宿主是猫，但猫也可作为中间宿主

3.中间宿主(哺乳类、鸟、爬虫、鱼类)与人的关系密切

4.对组织无严格选择性，除红细胞外，都能侵犯

OtheranimalsandbirdsMan

CongenitaltonewbornOtheranimalsandbirdsoocystSporocystartificialExo-entericcystinintermediatehostsEntericcycleincatsSchizogonySporogonyandClinicalFeaturesMosthumaninfectionareasymptomatic.ClinicaltoxoplasmosismaybecongenitaloracquiredCongenitaltoxoplasmosisCNSinflammatorylesionsbecomenecrotic&eventuallycalcify calcificationcommonwheninfectionduring1sttrimester

hydrocephalus(脑积水）mayoccur learningdeficitsifinfectedin2ndor3rdtrimestersfrequentretinochoroiditis(视网膜脉络膜炎): retinainflamed&necrotic

pigmentedlayerdisruptedbyinflammatorycellinfiltration granulationtissueforms&invadesvitreoushumorTheriskoffetalinfectionriseswiththeprogressofgestation,from25%whenthemotheracquiresprimaryinfectioninthefirsttrimester,to65%inthethirdtrimester.妊娠期胎儿感染率（%）胎儿损伤程度妊娠前三个月17-25最严重妊娠中三个月25中等严重妊娠末三个月65最轻，临床症状不明显不同妊娠期母体急性感染弓形虫后胎儿感染率与胎儿损伤程度美国由于先天性弓形虫病的每年经济负担总额高达77亿美元，英国则每年经济负担为1200万美元Conversely,theseverityoffetaldamageishighestwheninfectionistransmittedinearlypregnancyMotherswithchronicorlatenttoxoplasmainfectionacquiredearlierdonotordinarilyinfecttheirbabiesInfantbornwithhydrocephalis(abnormalCSFaccumulation)duetocongenitalToxoplasmainfection.Retinochoroiditis:inflammationofretina&choroid(vascularportionofeye)Insomewomenwithchronicorlatentoxoplasmainfection,thetissuecystmaybereactivatedduringpregnancyandliberatetrophozoiteswhichmayreachthefetusinuteroAfewarebornwithmaninfestationofacutetoxoplasmosis,whichincludefever,jaundice,diarrhoea,petechialrashes,hydrocephalus,microcephaly,cerebralcalcifications,microphthalmia,cataractglaucoma,chorioretinitis,opticatrophy,lymphadenitis,pneumonitis,myocarditisandhepatosplenomegaly先天性感染：母体原虫血症，50%可传给胎儿，引起广泛病变，导致流产、死胎或脑积水、小脑畸形、小眼畸形、白内障、青光眼、脉络膜视网膜炎、精神障碍、

心肌炎、婴儿出现智力发育不全、痴呆、癫痫

congenitaltransmission motherinfected(firstinfection)

tachyzoitescrossplacentatoinfectfetuslesionslessintensethancongenitalinfection inflammationaroundtachyzoites

inmuscle,spleen,liver&lymphnodes interstitialpneumonitismayaccompanyinfectionAIDSpatients

latentToxoplasma

re-activationofinfectionbradyzoitesreinitiatereplicationwithincysts

tachyzoites

spreadintotissuesToxoplasmaencephalitis:whenreactivationoccursinbrain

activationalsooccurs:lung,G.I.tract,heart,eye&liverAcquiredToxoplasmosistoxoplasmosismarkedlyreducedbyHIVHAARTtherapyMostlyasymptomatic,sometimelymphadenopathy,fever,headache,myalgia,splenomegalyToxoplasmosisisparticularlysevereintheimmunodeficient,particularlyinAIDSpatients----opportunityparasiteHostdefenceagainsttoxoplasmainfectioninvolvesbothhumoralandcellularresponses-----specificIgGantibodycanlyseextracellularparasites-----Tcell&NKcellsappearmorepreventingeffect

患恶性肿瘤、施行器官移植、长期接受放射治疗、应用免疫抑制剂以及细胞毒剂等或先天性、后天性免疫缺陷者，隐性感染状态转为急性或亚急性从而出现严重的全身性弓形虫病，其中多并发弓形虫脑炎而致死mostinfectionsareasymptomaticmostclinicallyapparentdiseaseismildgeneralizedlymphadenopathy

prominentenlargementofcervicalnodeslow-gradefever

raresevereacquiredtoxoplasmosis involvesmajorvitalorgans&systems maysuffermyocarditis&encephalitis spaceoccupyinglesionsofCNS(necroticmasses)

rareretinochoroiditisLymphadenopathy:swellingoflymphnodesMyocarditis:inflammationoftheheartmuscleEncephalitis:inflammationofthebrainDiagnosisMicroscopicdemonstration:lymphnodes,bonemarrow,spleenorbrain-----Giemasstainimpressionsmear---animal血液、骨髓、淋巴结、脑脊液—染色或动物接种、盲传3代。Tissuesection----cystSerologicaldiagnosis:themostcommonmethodoflabdiagnosisDyetest---baseonthespecificinhibitionbyantibodyofthestainingofthetrophozoitebyalkalinemethyleneblue---acutestageThestandardtestusednowisELISA,separatelyforIgM&IgGantibodies.ADyetestisaserologictesttodiagnosefortoxoplasmosisThetestisbasedonthepresenceofcertainantibodiesthatpreventmethylenebluedyefromenteringthecytoplasmofToxoplasmaorganisms.PatientserumistreatedwithToxoplasmatrophozoitesandcomplementsasactivator,andthenincubated.Afterincubation,methyleneblueisadded.Ifanti-Toxoantibodiesarepresentintheserum,becausetheseantibodiesareactivatedbycomplementsandlysetheparasitemembrane,parasitesloseitsaffinityformethyleneblueandwasbeennotstained(positiveresult);Iftherearenoantibodies,trophozoiteswithintactmembranearestainedandappearblueundermicroscope(negativeresult)黄白色瘢痕，小片状出血正常人眼底瘢痕色素增生卫星病灶黄斑区渗出灶内CNV呈绒球状ICGA:边界清晰黄斑区见边界清晰的瘢痕染色灶，周围因色素增殖呈遮蔽荧光EpidemiologyHumantoxoplasmosisisazoonosis.ItisacquiredthroughfoodorwatercontaminatedwithmatureoocystorbyingestionofraworundercookedmeatcontainingtissuecystsPork&beeffrequentlyhavetissuecystsFlies&cockroachesmayactasmechanicalvectorMaybetransmittedthroughbloodorleucocytetransfusionororgantransplantationAsoneofmajorfatalcomplicationinAIDS全世界抗体阳性率20-50%(93%)我国0.7-38.6%

广泛流行原因：生活史多期具感染性,抵抗力强中间宿主广泛，与人类关系密切终宿主可有可无，在中间宿主间可传播包囊在中间宿主体内存活的时间长在宿主体内存活的时间长，囊合子抵抗力强传染源：动物、人易感人群：婴儿、胎儿传播途径：经口传播经口、鼻、眼粘膜传播经输血、移植传播经胎盘传播1.Ingestionofbradyzoites:enclosedinapepsin-resistantcyst.SmallepidemicamongCornellmedicalstudentswhoateundercookedhamburgers.Cystsinmeatarekilledbyfreezingorheating.2.Ingestionofoocysts:3%hadanacutediseasewithretinitis&lymphadenopathy.Contaminationofreservoirwaterwithoocysts(cats&cougars).Oocystsnotalwayskilledbywaterchlorination3.Transplacentalinfection:Ifapregnantwomanisinfected,shecantransmitittoherunbornchild.~0.1%acquireinfectionthisway.ThreeModesofToxoplasmaTransmissionPreventionCombinedtreatmentwithpyrimethamineandsulphonamidesorcotrimoxazolemayleadtoclinicalcure,thoughtheparasitesmaynotbeeliminatedTreatmentiseffectiveonlyagainsttrophozoitesandnotagainstCystseatonlycookedmeats，rateofinfectioninFranceis>85%(rawlamb/beefservedassteaktartar)carewhenhandlingcatfeces(cleaningcatboxes)activitymustbeproscribedforpregnantwomenrarelyduetoinhalingdustordrinkingwaterwithoocytesnovaccinesMaybetransmittedthroughbloodorleucocytetransfusionororgantransplantationAsoneofmajorfatalcomplicationinAIDSBoththecystandoocystcanseverasthesourceofinfectionandwithhighresistantItcouldbetransmitbetweenintermediatehostCystsmaysettleinanytissueororganandcanremainviableformanyyearsOocystdonotbecomeinfectionfor48to96hrs,cleaningthecatlitterboxdailyisasimpleandeffectivepreventivemeasurePoint:防治原则1.避免与猫接触、不生吃肉类、蛋、奶品2.保护孕妇，查治3.治疗：磺胺+乙胺嘧啶螺旋霉素:孕妇Cryptosporidium

Thefirstcaseofhumaninfectionreportedon1976CryptosporidiahasassumedgreatimportanceasafrequentcauseofintractablediarrheainAIDSpatientsItcanleadtoacuteself-limiteddiarrheainhealthypersonandchroniclife-threateningdiarrheainimmunocompromisedsubjectsItsimportanceasapathogencausingdiarrheainanimalswasrecognizedin1971CryptosporidiawerefirstobservedinthegastricmucosalcryptsofLaboratorymicebyTyzzerin1907InfectionisacquiredbyingestingtheoocystincontaminatedfoodordrinkTheoocystcontainsfoursporozoiteswhicharereleasedintheintestineTheoocystcanremainviableintheenvironmentforlongperiods,asitisveryhardyandresistanttomostdisinfectionsandtemperatureupto60ºCInfectioninhealthypersonmaybeasymptomaticorcauseaself-limitedfebrileillnesswithwaterydiarrheaInHIVinfected&otherimmunodeficientperson,itwillbeseverediarrhea,feverandemaciation.Mayinvadethebronchialandbiliarytracts小儿腹泻或旅行者腹泻的原因之一，属于机会致病寄生虫形态和生活史：卵囊具感染性，椭圆形或圆形，直径4.5-5.5μm生活史简单，无需转换宿主薄壁卵囊20%——继续循环厚壁卵囊80%——体外hostingestssporulatedoocysts(eachwith4sporozoites)oocystsentersmallintestine

sporozoitesexcyst proteinplugincystwall exposureto37°Ciscuetoexcystsporozoitesattachtoepithelialcells microvilliadjacenttoparasiteelongate&fuse parasiteinintracellularbutextracytoplasmicspaceCryptosporidiumparvumLifeCycle易感人群：①免疫功能正常者②小儿③

免疫功能受损者在隐孢子虫病患者中也存在无症状携带者，而且是重要的传染源。正常人群中无症状的隐孢子虫病患者较少，而在HIV感染的人群中却相当高。致病隐孢子虫主要寄生在宿主肠上皮细胞的刷状缘层，由宿主细胞形成的纳虫空泡内虫数最多是空肠近端，严重者可扩散至整个消化道。肺、扁桃体、胰腺和胆囊等器官也可波及Cryptosporidiumparvumoocysts5

m.SmallintestineofAIDSpatientinfectedwithC.parvumCancerchemotherapypatients:(immunocompromised)protractedlife-threateningdiarrhea significantweightlossAIDS