機(jī)會(huì)致病寄生蟲病為艾滋病病人的常見并發(fā)癥或臨終并發(fā)癥約80%艾滋病病人死于機(jī)會(huì)致病性病原體感染機(jī)會(huì)致病寄生蟲機(jī)會(huì)致病寄生蟲：有些寄生蟲在人體內(nèi)通常處于隱性感染狀態(tài)，當(dāng)宿主免疫功能受損時(shí)則大量增殖并引起疾病，這些寄生蟲稱為機(jī)會(huì)致病寄生蟲。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

在中間宿主體內(nèi)的腸外循環(huán)屬無性生殖在終宿主體內(nèi)為腸上皮細(xì)胞內(nèi)循環(huán)，包括無性及有性生殖

特點(diǎn)：1.速殖子(假包囊)、包囊、囊合子均具感染性，中間宿主間可傳播(假包囊,包囊)2.終宿主是貓，但貓也可作為中間宿主

3.中間宿主(哺乳類、鳥、爬蟲、魚類)與人的關(guān)系密切

4.對組織無嚴(yán)格選擇性，除紅細(xì)胞外，都能侵犯

OtheranimalsandbirdsMan

CongenitaltonewbornOtheranimalsandbirdsoocystSporocystartificialExo-entericcystinintermediatehostsEntericcycleincatsSchizogonySporogonyandClinicalFeaturesMosthumaninfectionareasymptomatic.ClinicaltoxoplasmosismaybecongenitaloracquiredCongenitaltoxoplasmosisCNSinflammatorylesionsbecomenecrotic&eventuallycalcify calcificationcommonwheninfectionduring1sttrimester

hydrocephalus(腦積水）mayoccur learningdeficitsifinfectedin2ndor3rdtrimestersfrequentretinochoroiditis(視網(wǎng)膜脈絡(luò)膜炎): retinainflamed&necrotic

pigmentedlayerdisruptedbyinflammatorycellinfiltration granulationtissueforms&invadesvitreoushumorTheriskoffetalinfectionriseswiththeprogressofgestation,from25%whenthemotheracquiresprimaryinfectioninthefirsttrimester,to65%inthethirdtrimester.妊娠期胎兒感染率（%）胎兒損傷程度妊娠前三個(gè)月17-25最嚴(yán)重妊娠中三個(gè)月25中等嚴(yán)重妊娠末三個(gè)月65最輕，臨床癥狀不明顯不同妊娠期母體急性感染弓形蟲后胎兒感染率與胎兒損傷程度美國由于先天性弓形蟲病的每年經(jīng)濟(jì)負(fù)擔(dān)總額高達(dá)77億美元，英國則每年經(jīng)濟(jì)負(fù)擔(dān)為1200萬美元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：母體原蟲血癥，50%可傳給胎兒，引起廣泛病變，導(dǎo)致流產(chǎn)、死胎或腦積水、小腦畸形、小眼畸形、白內(nèi)障、青光眼、脈絡(luò)膜視網(wǎng)膜炎、精神障礙、

心肌炎、嬰兒出現(xiàn)智力發(fā)育不全、癡呆、癲癇

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

患惡性腫瘤、施行器官移植、長期接受放射治療、應(yīng)用免疫抑制劑以及細(xì)胞毒劑等或先天性、后天性免疫缺陷者，隱性感染狀態(tài)轉(zhuǎn)為急性或亞急性從而出現(xiàn)嚴(yán)重的全身性弓形蟲病，其中多并發(fā)弓形蟲腦炎而致死m(xù)ostinfectionsareasymptomaticmostclinicallyapparentdiseaseismildgeneralizedlymphadenopathy

prominentenlargementofcervicalnodeslow-gradefever

raresevereacquiredtoxoplasmosis involvesmajorvitalorgans&systems maysuffermyocarditis&encephalitis spaceoccupyinglesionsofCNS(necroticmasses)

rareretinochoroiditisLymphadenopathy:swellingoflymphnodesMyocarditis:inflammationoftheheartmuscleEncephalitis:inflammationofthebrainDiagnosisMicroscopicdemonstration:lymphnodes,bonemarrow,spleenorbrain-----Giemasstainimpressionsmear---animal血液、骨髓、淋巴結(jié)、腦脊液—染色或動(dòng)物接種、盲傳3代。Tissuesection----cystSerologicaldiagnosis:themostcommonmethodoflabdiagnosisDyetest---baseonthespecificinhibitionbyantibodyofthestainingofthetrophozoitebyalkalinemethyleneblue---acutestageThestandardtestusednowisELISA,separatelyforIgM&IgGantibodies.ADyetestisaserologictesttodiagnosefortoxoplasmosisThetestisbasedonthepresenceofcertainantibodiesthatpreventmethylenebluedyefromenteringthecytoplasmofToxoplasmaorganisms.PatientserumistreatedwithToxoplasmatrophozoitesandcomplementsasactivator,andthenincubated.Afterincubation,methyleneblueisadded.Ifanti-Toxoantibodiesarepresentintheserum,becausetheseantibodiesareactivatedbycomplementsandlysetheparasitemembrane,parasitesloseitsaffinityformethyleneblueandwasbeennotstained(positiveresult);Iftherearenoantibodies,trophozoiteswithintactmembranearestainedandappearblueundermicroscope(negativeresult)黃白色瘢痕，小片狀出血正常人眼底瘢痕色素增生衛(wèi)星病灶黃斑區(qū)滲出灶內(nèi)CNV呈絨球狀I(lǐng)CGA:邊界清晰黃斑區(qū)見邊界清晰的瘢痕染色灶，周圍因色素增殖呈遮蔽熒光EpidemiologyHumantoxoplasmosisisazoonosis.ItisacquiredthroughfoodorwatercontaminatedwithmatureoocystorbyingestionofraworundercookedmeatcontainingtissuecystsPork&beeffrequentlyhavetissuecystsFlies&cockroachesmayactasmechanicalvectorMaybetransmittedthroughbloodorleucocytetransfusionororgantransplantationAsoneofmajorfatalcomplicationinAIDS全世界抗體陽性率20-50%(93%)我國0.7-38.6%

廣泛流行原因：生活史多期具感染性,抵抗力強(qiáng)中間宿主廣泛，與人類關(guān)系密切終宿主可有可無，在中間宿主間可傳播包囊在中間宿主體內(nèi)存活的時(shí)間長在宿主體內(nèi)存活的時(shí)間長，囊合子抵抗力強(qiáng)傳染源：動(dòng)物、人易感人群：嬰兒、胎兒傳播途徑：經(jīng)口傳播經(jīng)口、鼻、眼粘膜傳播經(jīng)輸血、移植傳播經(jīng)胎盤傳播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:防治原則1.避免與貓接觸、不生吃肉類、蛋、奶品2.保護(hù)孕婦，查治3.治療：磺胺+乙胺嘧啶螺旋霉素:孕婦Cryptosporidium

Thefirstcaseofhumaninfectionreportedon1976CryptosporidiahasassumedgreatimportanceasafrequentcauseofintractablediarrheainAIDSpatientsItcanleadtoacuteself-limiteddiarrheainhealthypersonandchroniclife-threateningdiarrheainimmunocompromisedsubjectsItsimportanceasapathogencausingdiarrheainanimalswasrecognizedin1971CryptosporidiawerefirstobservedinthegastricmucosalcryptsofLaboratorymicebyTyzzerin1907InfectionisacquiredbyingestingtheoocystincontaminatedfoodordrinkTheoocystcontainsfoursporozoiteswhicharereleasedintheintestineTheoocystcanremainviableintheenvironmentforlongperiods,asitisveryhardyandresistanttomostdisinfectionsandtemperatureupto60oCInfectioninhealthypersonmaybeasymptomaticorcauseaself-limitedfebrileillnesswithwaterydiarrheaInHIVinfected&otherimmunodeficientperson,itwillbeseverediarrhea,feverandemaciation.Mayinvadethebronchialandbiliarytracts小兒腹瀉或旅行者腹瀉的原因之一，屬于機(jī)會(huì)致病寄生蟲形態(tài)和生活史：卵囊具感染性，橢圓形或圓形，直徑4.5-5.5μm生活史簡單，無需轉(zhuǎn)換宿主薄壁卵囊20%——繼續(xù)循環(huán)厚壁卵囊80%——體外hostingestssporulatedoocysts(eachwith4sporozoites)oocystsentersmallintestine

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

免疫功能受損者在隱孢子蟲病患者中也存在無癥狀攜帶者，而且是重要的傳染源。正常人群中無癥狀的隱孢子蟲病患者較少，而在HIV感染的人群中卻相當(dāng)高。致病隱孢子蟲主要寄生在宿主腸上皮細(xì)胞的刷狀緣層，由宿主細(xì)胞形成的納蟲空泡內(nèi)蟲數(shù)最多是空腸近端，嚴(yán)重者可擴(kuò)散至整個(gè)消化道。肺、扁桃體、胰腺和膽囊等器官也可波及Cryptosporidiumparvumoocysts5

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