人体寄生虫学：07 吸虫

1972年湖南省长沙市东郊一座汉朝墓葬的横空出世。相传2000多年前楚王马殷的墓地，故称“马王堆”。1号墓女尸经医学家临床检验：结缔组织、肌肉组织和软骨等细微结构保存完好，全身有柔软的弹性，皮肤细密而滑腻，部分关节可以转动，甚至手足上的纹路也清晰可见。病理解剖检查发现，死者生前患有冠心病、多发性胆石症、全身性动脉粥样硬化症，右上肺有结核病灶，右前臂曾经骨折，在直肠和肝脏内有鞭虫卵、蛲虫卵和日本血吸虫卵。送瘟神（二首）—毛泽东1958年7月1日读六月三十日人民日报，余江县消灭了血吸虫。浮想联翩，夜不能寐。微风拂煦，旭日临窗。遥望南天，欣然命笔。

其一绿水青山枉自多，华佗无奈小虫何？

千村薜苈人遗矢，万户萧疏鬼唱歌。

坐地日行八万里，巡天遥看一千河。

牛郎欲问瘟神事，一样悲欢逐逝波。

其二

春风杨柳万千条，六亿神州尽舜尧。

红雨随心翻作浪，青山着意化为桥。

天连五岭银锄落，地动三河铁臂摇。

借问瘟君欲何往？纸船明烛照天烧。ThebloodflukesFiveschistosomespeciespathogenictohumans:S.japonicum,S.mansoni,S.haematobium,S.mekongiandS.intercalatum.Despitethecontrolprogress,thediseaseremainsendemicin74countries.Of200millioninfectedpeople,20millionsuffersevereconsequencesfromthediseaseand120millionareasymptomatic.Globally,500-600millionpeopleareattheriskofinfection.候选疫苗：GST,Sm97,IrV-5,TPI,Sm23,Sm14……Schistosome

ThreespeciesofSchistosomesthatparasitizehumansaremaiorimportance:Schistosomajaponicum,S.mansoni,&S.haematobium.Lesscommonare

S.intercalatum

inAfricaandS.mekongiintheMekongBasin.TheSchistosomesdifferfromothertrematodeinthat(1)theadultwormsaredioecious

(2)theadultwormsparasitizebloodvessels(3)theyproducenon-operculateeggs(4)thecercaria,withabifurcatedtail,invadesthefinalhostpercutaneously血吸虫(Schistosoma)

又称裂体吸虫，寄生人体主要有五种虫种寄生部位虫卵分布日本血吸虫肠系膜V肠壁及肝、肠系膜曼氏血吸虫肠系膜小V、痔V丛肠壁、肝埃及血吸虫膀胱V丛膀胱、生殖器官间插血吸虫肠系膜V、门脉系统肠壁、肝湄公血吸虫肠系膜上V、门脉系统Schistosomamansoni-adultsoccurintheposteriormesentericveinsofthelargeintestineSchistosomajaponicum-adultsoccurintheanteriormesentericveinsofthesmallintestineSchistosomahaematobium-adultsoccurintheveinsoftheurinarybladder

-------------------------------------------------------------------------------SpeciesHabitatinhostMajororganinvolvement-------------------------------------------------------------------------------

S.japonicumSurperiormesentericveinintestines/liverS.mansoniInferiormesentericveinintestine/liverS.haematobiumVesical

venous

plexusbladder/ureters

S.intercalatumInferiormesentericveinintestine/liverS.mekongiSurperiormesentericveinintestines/liver

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DistinguishingofSchistosomeSpecies曼氏血吸虫埃及血吸虫日本血吸虫曼氏血吸虫卵埃及血吸虫卵日本血吸虫卵S.haematobiumS.mansoniS.japonicumMorphologyAdult:theadultwormsaredioeciousMaleworm:#white,short&widerthanfemaleworm,#7testesareusuallypresentonthedorselsidejustbelowtheventralsucker#thegynecophoralcanal#oralsuckerissmallerthanventral

Femaleworm:*heldinthegynecophoralcanal*theuterusisalongstraighttubeandopensbehindtheventralsucker

Egg:ovoid,non-operculate,containonemiracidium,knob

SchistosomajaponicumaThelifecycleofS.japonicumfollowsapathwayfromthesexualgenerationofadultwormwithintheportalsystemofthedefinitivehosttoasexualgenerationintheintermediatehostoffreshwatersnail---Oncomelaniahupensis,andareturntothedefinitivehostbyskin

penetrationofinfectivestage----cercariae

AdultEggfreshwater

MiracidiumSporocystDaughtersporocystparasitizeinthedischargedinfecesmesentericvein

penetratingtheskinlostthetailSchistosomulumCercariaEggofSchistosomajaponicum.Nospinecanbeseen.85

mx60

m.虫卵产出和发育(Deposition&developmentofeggs)adultinhabitinbranchesofportalsystem&mesentericveinseggsdepositioninsmallperivasculartissuesoftheintestineandliver(about24daysintotal)

take11daysfortheeggtomature&survivesintissueforanothertendays(21to22daysintotal)

thesubstancesecretedbymiracidium,theeosinophilicabscessformationinintestinemucosa,ulceration…eggsescapeanddischargedintointestinalcanal

毛蚴孵化(Hatchingofmiracidium,multiplicationinsnail)孵出因素：水清qualityofwater温度temperature<10℃or>37℃hatchingwillbeinhibited光线light

pH:7.5—7.8

含氯>0.3ppminhibit

miracidiumcanfree-livingfor3daysbeforeentertissueofsnail

miracidiahatchfromtheeggs,rapidlyswimbymeansofciliaandpenetratethebodyofsnail---intermediatehost‘miraxone’—吸引毛蚴在其头足部

毛蚴在螺体内的发育和繁殖尾蚴逸出的条件：水及pHpH6.6-7.8

温度20℃to25℃光线Thepeaktime:8am-12pmthousandsofcercariaefromasinglemiracidium尾蚴逸出后50%在螺附近，作尾部在前，体部在后运动一般寿命25.4hr，最长为50hr尾蚴侵入infectivestage

penetrateskinormucousmembranebypenetrationglands&mechamicalvibrationoftailMaturationofwormpenetrationthecercarialosestail,bodyformedschistosomulaperipheralvenulesrightheartlung

leftheartintrahepaticportalsystemmesentericvenulaEggsappearinfeces5-6weeksaftercercarialpenetration

Pathogenicity基本病变Schistosomiasismayoccurateachofthemajorstageparasitelifecycle1.

尾蚴所致病变cercariapenetration:dermatitisrepeatedexposureleadstosensitization

developmentofamaculopaularrashIgEorIgGantibodies&eosinophilicinfiltrate

Thighofachildwithamaculopapularrash(“swimmer’sitch”)fromcercariaeofschistosomespeciesthatnormallyinfectsbirds.2.

童虫所致病变schistosomulamigration&maturation:toxicreaction,pulmonarycongestionaccompaniedbyfever,vasculitis3.

成虫所致病变Adultworm:releaseimmunogensfromintestine,tegument,&excretorysystem-----immunopathologicalresponse,immuno-nephropathyeggs:profoundimmunopathogenicresponse

almostallpathology&symptomsofschistosomiasisS.japonicumeggdeposition incirculationofsmallintestine&liver

intestinal&hepaticfibrosisSchistosomeeggintissueofsmallintestine肉芽肿→组织增生纤维化肠：虫卵沉积→嗜酸性粒细胞浸润→嗜酸性脓肿

溃破→粘液血便、腹痛腹泻肝：虫卵沉积→嗜酸性粒细胞浸润→嗜酸性脓肿→肉芽肿→纤维组织增生腹水、脾肿大、静脉曲张←门静脉高压←肝纤维化

虫卵所致损害：是最主要和最重要的损害巨脾型腹水型

结肠增殖型侏儒型TheliverthesolubleantigeniceosinophiliceosinophilicgranulomasubstancesecretedbyinfiltrationabscessmiracidiumsplenomegalyfibrosiscirrhosisportalasciteshypertensionvenousvaricesesophagealvaricescaputmedusaehemorrhoidvenousvaricesInintestine

Thesolubleantigeniceosinophilic

eosinophilicsecretedbymiracidiuminfiltrationabscess

diarrhea

fibrosisBrainformepilepticseizuresDwarfismseveredisturbanceofgrowthinchildrenulcerationgranulomaAcuteinflammation---theantigenelicitresultfever,abdominalpain,enlargedtenderliverandspleen,ordischargeofeggsintointestinalcanalaccompaniedbydysenteryordiarrheaTheeggsolubleantigencaninducehostsensitizationofTcellandrecruitmentofmacrophages,lymphocytes,epitheliodcell,firoblasts,andnumerouseosinophilstoform

inflammatorygranulomaTheantigenicsecretionstopswhenthemiracidiumwithintheeggdies,granulomathenundergoahealingprocesswithdeposition

offibroustissue临床表现

1.急性血吸虫病：季节性，第一次感染而无免疫力人群多见

2.慢性血吸虫病：无症状者和有症状者之分

3.晚期血吸虫病：最严重、危害最大的损害

巨脾型腹水型结肠增殖型侏儒型巨脾型腹水型结肠增殖型侏儒型Acuteschistosomiasis(fever,syndrome) mostcommonlyinnewimmigrants intenseexposuretoS.japonicumcercariae~4-8weeksafterexposure(adultwormsreleaseeggs)symptomsareflu-like

cough&headache fever&eosinophilia hepatosplenomegaly lymphadenopathyChronicschistosomiasis manyyearsofprogressiveinjury(chroniceggdeposition)

granulomaformationintissues

extentofinjurydependsonchronicwormburden

S.japonicum

injuryfromeggsin intestinewall liverparenchyma

chronicintestinal&hepaticdysfunctionChronicchildhoodschistosomiasis

abdominalpain,diarrhea,bloodloss&intestineulceration maycauseirondeficiency&anemia

physicalgrowthretardation(likeintestinalnematodes)

stuntingreversiblewithanthelminthictherapy肝脾肿大肝硬化：贫血:成虫吞噬、脾功能亢进、毒性物质作用、自身免疫

水肿:肝功能下降、白蛋白下降、血浆胶体渗透压下降、血管内液体外漏血流受阻，血浆溢出激素降解减少、水钠储留肾小球受损，蛋白质滤过增加静脉曲张:

食道、痔上、腹壁侏儒症:垂体、肾上腺、性腺、甲状腺等萎缩、功能不足异位损害:脑血吸虫病、肺血吸虫病hepatomegalyduetoportalfibrosis

splenomegalyfollowsadvancedcases:spleenmayfillmuchofleftsideofabdomen

portalhypertension

developmentofcollateralcirculation

侧支循环

schistosomeeggswashedintolungs

inducegranulomatousinflammation

leadstoobstructivedisease

leadstocorpulmonale

（肺源性心脏病）long-standinginfectionscausesnephroticsyndrome

depositionofimmunecomplexesinkidney—血吸虫性肾病CNSschistosomiasis(schistosomescauseinflammationinCNS) rarecases:depositionofeggsinspinalcordorbrain

inflamation

focaltransversemyelitis&encephalopathy--血吸虫性脑病Immunity先天性免疫获得性免疫concomitantimmunity:hostscarryinganinitialinfectionofadultschistosomesshowpartialbutsignificantprotectiontoacercarialchallengeinfection.immuno-evasion:theschistosomescanevadethehostimmuneresponse------theadultwormacquirehostantigenonitssurface，

occludingantibody,membranemodificationDiagnosis病原诊断stoolspecimens---microscopeexamination---eggscannotbedetectedinstoolduringthewormmature,verylightandchronicinfection,eggmaybeverydifficulttodetectinstool---直接涂片法Sedimentationhatchingmethod-----recommended--沉淀孵化法Kata-katzmethod-recommended----定量透明法(Kata-katz)rectalbiopsy----直肠粘膜活检

免疫诊断皮内试验Circumovalpricipitintest(COPT)Antibodydetection---ELISA:crudeadultwormextracteggantigenImmunoblotFastdot-ELISAAntigendetection----循环抗原检测

IntegrationorCombinationofdiagnosticmethod---综合查病环卵沉淀试验

2009年7月16日国家人类基因组南方研究中心主持协同有关部门单位经过5年多的艰苦奋战，完成了日本血吸虫基因组测序和基因功能