1、1血吸蟲(裂體吸蟲) Schistosoma (Blood fluke)2Six species of schistosomes in the world曼氏血吸蟲（SMansoni 1907）埃及血吸蟲（Shaematobium1852）日本血吸蟲（SJaponicum 1904）間插血吸蟲（Sintercalatum1934）湄公血吸蟲（SMekongi 1978）馬來血吸蟲（SMalayensis 1988）Brief introduction3Global distribution of schistosomiasisInhabit the portal vascular system

2、 of a number of animals 4讀六月三十日人民日報，余江縣消滅了血吸蟲。浮想聯翩，夜不能寐。微風拂煦，旭日臨窗。遙望南天，欣然命筆。5Advanced Schistosomiasis晚期血吸蟲病67SchistosomesDisease: schistosomiasis Ubiquitous Inhabitats blood vessels of the definitive hostsSeparate sexes, male has gynecophoral canal(抱雌溝)Infected population: 200 million in Africa, Asi

3、a and S. AmericaSymptomatic population: 120 million Population at risk: 600 millionsMortality Unknown, but 20 million severely infected Brief introduction8Important SchistosomesSpeciesResident LocationLesion of tissueDistributionS.Japonicum日本血吸蟲Portal-mesenteric veinLiver, intestineAsia(Japan ,China

4、,Philippines et al)S.Mansoni曼氏血吸蟲Superior mesenteric veinLiver, intestineAfrica (52 countries), Latin AmericaS.Haematobium埃及血吸蟲Vesical veinUrinary bladder Reproductive organsAfrica (54 countries), Western AsiaBrief introduction9Only Schistosoma japonicum in ChinaThe most serious parasitic disease in

5、 ChinaA documented history of over 2100 years Termed potbelly diseaseor big bellyS. japonicum named by Katsurada in 1904 In 1905, first case found in Hunan Infective population：12 million Brief introduction10Adult 成蟲Gonochorism or dioecism (雌雄異體）Females resides in Gynaecophoric canal(抱雌溝) -Important

6、 for maturationCopulation(合抱） Oral suckerVentral suckerMorphology11Digestive and reproductive system gc. gynecophoral canal os. oral sucker Ov. Ovary Sp. spermatic gland ut, uterus vs. ventral sucker vt. vitelline glandReproductive tract differs in different species12Tegument: Poor in organelles; sy

7、ncytiumDiagram of the ultrastructure of the adult schistosome tegumentBasal lamina: mitrotubules體壁超微結構13 Egg (蟲卵)8967m OvalNo operculum a lateral spine(側棘) Miracidium（毛蚴）ShellSoluble egg antigen， SEALateral spine14Schistosoma mansoni （egg）Schistosoma hematobium （egg）S. japonicum eggs 15Furcocercous

8、cercaria 叉尾型尾蚴Continuous syncytial (合胞體) tegument： 0.5 m， 0.2 m plasma membrane and basement membrane ：outer surface of the tegument Glycocalyx糖萼 (highly antigenic) of 1-2 m Penatration gland(穿刺腺) -furcal tailHead gland5 pairs of penetration glandsVentral sucker尾部體部16Life cycle蟲卵毛蚴胞蚴尾蚴童蟲成蟲17AdultsLi

9、fe cyclePortal -mesenteric venous system門靜脈-腸系膜靜脈系統18Female releases eggFemale releases 3000 eggs/day， eggs pass into fecesLife cycle19Water ： low osmotic pressure Temperature 25-30Illumination (光照) pH ： 7.5-7.8 Scanning Electron Micrograph of miracidium newly hatched from egg (bottom left)Life cycl

10、eMiracidium ：hatching20Miracidium： Accumulate around the snailMiraxone(毛蚴松)Phototropic向光性Remain infective for 8-12 hoursSwim ceaselesslyLife cycle21Snail：Intermediate Host Oncomelania hupensis (湖北釘螺)Life cycle22Snail life span ：1-2years. Transmission season ： April to OctoberLife cycle23Intramollusc

11、an phase螺內發育期miracidium 1 mother sporocysts 1 daughter sporocysts 50 cercariae 200,000Life cycle6-7weeks24Cercaria water fresh water temperature 200C250C pH 7.0 illumination 1-2hourslife span ：1-3 days Active swimming Life cycle25Attachment： ventral suckerPenetration： penetration glands and head gla

12、nd Muscular movementsFurcal tailThe entry time ： 3 to 7 minutes 10 secondLife cycleCercariaPenetration 26From cercaria to schistosomula(童蟲)Formation of a new double-unit membrane on the syncytial surface.Loss of resistance to the hypoosmolar stressAerobic anaerobic metabolismLife cycle27Schistosomul

13、um 童蟲Cercariae penetrate skin schidtosomulum lymphatic or blood vessels(capillaries) right heart lungs pulmonary capillaries left heartcirculatory system mesenteric arteries intestinal capillary bed hepatoporal systempair up and grow mesenteric vein lay eggs Life cycle24 days28Penetrate into the ski

14、n24 daysmature eggs 11 daysEggs can be found in stool 45 daysLife cyclemature miracidium, SEA cause inflammation, Miracidium live 11 days in tissueLay eggs11 days later29Life cycle of schistosomesS.haematobium,S.mansoni, S.japonicum 30EggMiracidiumsnailSporocystAdult CercariaPortal -mesenteric veinD

15、efinitive hostReservoir hostInfective stageIntermediate hostDiagnostic stage Pathogenic stageLife cycle31Key points of life cycle Adults live in portal vein system, mainly in the inferior mesenteric vein for 20-30years Infective stage: cercariaInfective route: skin intermediate host: Oncomelania sna

16、il (釘螺) Reservoir ：mammals (buffalo, cattle, wild rodents, goat, monkey, pig, fox.)Egg ：no operculum； main pathogenic stage. 32ImmunitySchistosomal antigensADCC: antibody-dependent, cell-mediated-cytotoxicity (Attack target: Schistosoma)Concomitant immunityImmune evasion33Schistosomal antigens: 血吸蟲抗

17、原Secretions, waste products, metabolic products, integument shed of worm etc SEA :(soluble egg antigens)： Circulating antigens： diagnosis GAA(gut associated antigens) 34Concomitant immunity伴隨免疫Pre-infectionConcomitantimmunityAdult wormreinfectionAcquired immunity 獲得性免疫獲得性免疫的殺蟲機制：Antibody dependent c

18、ell-mediated cytotoxicity抗體依賴細胞介導的細胞毒性反應（ADCC）35IgG/IgMmacrophageeosinophilO2IgG/IgEIgE/IgMneutrophilplateletIgEAvailable in skin & lungs 36Antigenic disguise &Host molecular mimicry抗原偽裝和抗原模擬Shedding of surface antigensmembrane changesImmune toleranceImmune evasion免疫逃避 37Cercariae & schistosomulaAdu

19、lt wormEggI type hypersensitivityIII typehypersensitivityIV typehypersensitivityPathogenesis 38SEAIL-1T cellESP FSF MIFLymphocytes, eosinophils, macrophages & fibroblastsmacrophagesEgg-granulomaRepeated SEA stimulation39 Hoeppli phenomenon(何博禮現象）Egg granuloma (eosinophilic granuloma) 蟲卵肉芽腫(嗜酸性膿腫)Egg

20、: (SEA)eosinophils plasma cells lymphocytes macrophages40Egg granuloma (eosinophilic granuloma)eosinophilsneutrophils macrophageslymphocytes fibroblasts,multinucleated giant cellsmacrophages41Damage by eggs in tissue: liver and intestine/rectum42血吸蟲卵沉積在腸壁43Miracidium in egg diedEgg calcifiedFibrobla

21、sts cluster & synthesize collagenFibrous tissuePeriportal pipestem fibrosis (干線性纖維化）Fibrosis in intestinal wallCirrhosis Portal hypertension & splenomegaly門靜脈高壓 脾腫大Colonic polyposis結腸息肉44Eggs role predominantly in pathogenesis45Death of miracidium in egg calcificationGranulomatous formation fibrous

22、tissuePeriportal pipestem fibrosis and fibrosis in intestinal walls portal hypertension（門脈高壓） and splenomegaly（脾腫大） Pathogenesis46Most cases asymptomaticCercarial dermatitis尾蚴性皮炎Migration of the schistosomula童蟲移行 pneumonia：chills, fever, ， bloody cough, diarrhea, eosinophilosisClinical symptoms47Acu

23、te phase (Katayama fever釘螺熱):急性血吸蟲病 fever, chills, headache, gastrointestinal complaints, hepatomegaly, splenomegaly and eosinophilia eggs in feces？Chronic phase 慢性血吸蟲病 90% infected personsweakness, fatigue, abdominal pain, hepato-splenomegaly, anemia and emaciation（消瘦） eggs in feces？48Late phage(晚期

24、血吸蟲病) Four types:splenomegaly巨脾, ascites腹水 , colonic polyposis 結腸增殖 ， dwarfism侏儒Ectopic lesion（異位血吸蟲病） Cerebral & pulmonary schistosomiasis49Advanced schistosomiasis hepatosplenomegaly50Advanced schistosomiasisascites WeaknessAbdominal painDiarrhoea HepatomegalySplenomegaly51Advanced schistosomiasis

25、 abdominal collateral vein dilatation5220y32yNormal 5y childAdvanced schistosomiasisDwarfism 侏儒型53Detection of egg and miracidiumDetection of Special antibodyUltrasonographyDetection of circulating antigenDiagnosisDiagnosis 54Direct smears Thick smear (Kato-katzs method 改良加藤厚涂片法)Concentration techni

26、ques 濃集法Hatching of miracidium毛蚴孵化法Microscopic examination of rectal biopsyDetection of egg and miracidium55Hatching of miracidium毛蚴孵化法56ImmunodiagnosisInterdermal test(IDT) Antibody detection Circumoval preciptin test(COPT) 環卵沉淀試驗 antigens: viable eggs Indirect haemagglutination test(IHA) antigens:

27、 soluble egg antigen(SEA) Enzyme-linked immunosorbent assay(ELISA) antigens: SEA/AWA(adult worm antigen)Antigen detection Dot-ELISA/Sandwich ELISA5758Altrasound examination ALSO IMPORTANT: Clinical signs, symptoms and history59Epidemiology60Hubei, Hunan, Jiangxi, Anhui, Jiangsu, Sichuan & YunnanShan

28、ghai, Guangdong, Fujian, Guangxi & Zhejiang In China 12 provinces in the south part 427endemic counties61 Snail areas reduced 76 % Case number reduced 93% 62Global distribution and control of SchistosomiasisControl successfulControl unsuccessful63 Schistosomiasis Endemic areas: 110 counties in 7 pro

29、vinces Number of cases estimated: 843,000 Acute cases increased 22% than that of year 2002still a public health problemSituation in 200364Marshy type(江湖洲灘型): still serious 82.1% infested snail areasMountainous and hilly type(山丘型) Sichuan, Yunnan 10% Water-net type(水網型) controlled Shanghai, Guangdong

30、, Fujian, Guangxi & Zhejiang controlled 7.9% Endemic areas 65Marshy type(江湖洲灘型)Mountainous and hilly type (山丘型)Detection of Infested water by mice66Reservoirs : buffaloes & pigs , 42 species wild mammalsRoutes of transmission: contacting infested waterSusceptible population:Season : April to OctEpid

31、emiology6768SnailEpidemic factors Natural factors: Social factors69How to control Schistosomiasis ? EducationTreatment of the infected Control of the vector Protective vaccination if available查病治病 管水管糞查螺滅螺個人防護70to treat patients & livestock to control snailto reduce the frequency of water-contacting

32、to prevention by drug e.g., artemisininVaccine (not for a long time)2. Control measurements1. Control the sources71ChemotherapyPraziquantel(吡喹酮)Isoquinilone（異喹啉）Cure Rate: 70%-100% Main Side Effects: Diarrhea,Nausea Abdominal pain Mode of Action: Calcium Channel blocker?72Artemisia annua青蒿素（葉）Arteme

33、ther(蒿甲迷）Artesunate(青蒿琥酯 ) 73Excising the enlarged spleen from and advanced schistosomiasis patientFor late stage case-operation74caused by infection of genera Trichobilharzia（毛畢屬） and Orientobilharzia（東畢屬） Infected cattle and ducks are major reservoirs. rice-field dermatitis（稻田皮炎）swimmers itch （游泳癢

34、）initial tingling sensation, erythema, maculopapular rash（斑丘疹）, vesicles, and edemaCercarial Dermatitis75While, we are challenged. 767778Nature 460, 345-351 (16 July 2009) | The photomicrograph on the cover, by David Scharf (/), shows a mated pair of S. mansoni flukes atapproximately x265, with the

35、slender female emerging from the lower part of the male.79Schistosoma GenomicsSchistosoma Genome Network (SGN): (http:/www.nhm.ac.uk/hosted_sites/schisto/) Genome structure: 270 Mbp ( 1/10 human genome; C. elegans 100 Mbp; Drosophila melanogastor 123 Mbp; Anopheles gambiae 278 Mbp; Plasmodium falcip

36、arum 23 Mbp; E. coli 5 Mbp ) 40% repetitive sequencesDiploid, with 8 pairs of chromosomes Estimated to be 14,000 15,000 expressed genes(/tdb/tgi/smgi/)Mitochondrial genome analysis says Schistosoma genus has an Asian origin Transcriptome (microarrays) and proteome projects8081Adult worm: dioecious/d

37、imorphism male: gynecophoral canal, 7 testes female: ovary at the middle, uterus is longEgg: no operculum, with spine & a miracidiumCercaria: with forked tailLife cycle: egg, miracidium, mother sporocysts, daughter sporocysts, cercariae, schistosomula, adult wormSummary82Adult worm :portal-mesenteric venous systemCercariae : infective stageEgg:a major pathological cause, egg-granulomaIV type delay hypersens