医学(人体血吸虫)

1、Human Schistosome(人体血吸虫)2007-11-7Disease due to schistosomes is termed schistosomiasis or bilharzia after the shortlived German physician Theodor Bilharz (1825-1862)./dpdx/HTML/Schistosomiasis.htmKingdom: AnimaliaPhylum: PlatyhelminthesClass: TrematodaSubclass: DigeneaOrder: StringeiformesGenus: Sch

2、istosomaSpecies: Schistosoma haematobium, S. japonicum, S. mansoni and S. intercalatum/Schistosomiasis/Default.htmSchistosome: A parasitic trematode worm contracted from infested water that is capable of causing liver, gastrointestinal tract and bladder disease. There are three main species of these

3、 trematode worms (flukes) - Schistosoma haematobium, Schistosoma japonicum, Schistosoma mansoni and S. intercalatum that produce disease in humans. Endemic in 74 developing countries with more than 80% of infected people living in sub-Saharan Africa. S. haematobium is the most prevalent and widespre

4、ad species in Africa and the Middle EastS. intercalatum occurs in 10 countries in the rainforest belt of AfricaS. mansoni is found in Africa and is the only species seen in Latin AmericaS. japonicum is restricted to the Pacific region including China and the PhilippinesS. mekongi is found in limited

5、 areas of Laos and Cambodia. S.japonicum, S.haematobium, S.mansoni, S.intercalatum, S. mekongi Human Schistosomes:S.japonicum(日本血吸虫)S. mansoni(曼氏血吸虫)S. haematobium(埃及血吸虫)S.mekongi(湄公血吸虫)S. japonicum named by Katsurada in 1904In 1905, first case found in Human The discovery history of SchistosomesS.h

6、aematobium eggs were found in the kidneys of twentieth-dynasty Egyptian mummies (1250-1000 B.C) The first Europeans to record contact with S.haematobium were surgeons with Napoleons army in Egypt (1799-1801).In 1858 (or 1852), Weinland proposed the name Schistosoma haematobium.In 1905, Sir Patrick M

7、anson found another species of worm, named S. mansoni by Sanbon (1907)In 2005, 0.799 million cases Lake areas: human cases, snail infested areas, and number of infected bovines was accounting for 87.5%、94.4%、68.8%, respectivelyDistribution in China一定要消灭血吸虫病MorphologyLife cyclePathogenesis & clinical

8、 manifestationDiagnosisEpidemiologyPrevention & controlSchistosome: causative agent of schistosomiasis Life cycle: adult worm, egg, larvae ( miracidia , sporocysts ,cercariae ), schistosomulaDefinitive host: humanIntermediate host :snailThe rount of the infection: cercariae penetrating an individual

9、s unbroken skin while contacting infested water with cercariaeParasitized site: The adult worms live in the blood vessels Eggs: egg-granuloma Life cycleadult worm eggMiracidium sporocyst (mother and daughter sporocyst)Cercariaeschistosomula The life cycle : adult worm, egg, miracidium, sporocyst (mo

10、ther and daughter sporocyst), cercariae, and schistosomula (童虫) .It is completed in following hosts: a) definitive host: man domestic animals (pigs, cattle/buffalo) and wild animals; (S.japonicum) b) Intermediate host: SnailOncomelania species (Oncomelania hupensis湖北钉螺 in mainland of China). Dimorph

11、ism(雌雄异体）copulation(合抱）S.japonicumLife cycleFor exampleS. japonicum日本血吸虫intermediate host snails of the genus Onchomelania, hupensis spp. 3.病毒性肺炎 如冠状病毒、腺病毒、流感病毒、巨细胞病毒、单纯疱疹病毒等。 4.真菌性肺炎 如白念珠菌、曲霉、放射菌等。 5.其它病原体所致的肺炎 如立克次体、弓形虫、原虫、寄生虫如肺包虫、肺吸虫、肺血吸虫）等。机体免疫力低下者（如艾滋病患者）容易伴发肺部卡氏肺包子虫、军团菌、鸟形分支杆菌、结核菌、弓形体等感染。 6.理化

12、因素所致的肺炎 如放射性肺炎、胃酸吸入、药物等引起的化学性肺炎等。 7.支原体肺炎 由肺炎支气体引起。 编辑本段发病原因 肺炎患肺炎的原因可能是：接触到一些厉害的病菌或病毒身体抵抗力弱， 如长期吸烟。上呼吸道感染时，没有正确处理。例如是没有正确地看医生、没有正确地看服药，又或者是滥用止咳药止咳以至痰和菌愈积愈多（Sputum retention)。 如果一年内有多过一次真正的肺炎 （一些医生误看X光片或滥用了肺炎的诊断)，原因可能是：身体抵抗力弱 （先天性或后天性) 气管有异物。尤其是幼童。 心肺有其它病变：如癌病、气管扩张、肺尘埃沉着病、没有正确地看医生、没有正确地看服药，又或者是滥用止咳药

13、止咳以至痰和菌愈积愈多（Sputum retention) 工作环境有问题。注意改善空气流通、冷气系统。 打造最权威的专业课件医学精品课件本文档免费浏览阅读，下载后可以编辑修改。Life cycleFor exampleS. mansoni 曼氏血吸虫Intermediate host snails of the genus Biomphalaria (Planorbidae family)Life cycleFor exampleS.haematobium埃及血吸虫intermediate host :snails of the genus Bulinus Worm in veins aro

14、und the bladder (in the venus plexus of bladderlife cycle : a sexual stage in humans and an asexual stage in snails an asexual stage in snailsHatching (孵化) of miracidium in freshwater Development in snail miracidium,sporocyst (mother and daughter sporocyst), cercariaea sexual stage in humansPenetrat

15、ion of host ( skin)Migration and inhabiting Schistosomule migrate following circulatory systemimmature worms develop Male and female to Copulating(mating)adult worm inhabite in in veinsWorm lay eggs and egg-granuloma1. Penetration of the skin by cercariaeInfection occurs when cercariae penetrate the

16、 skin while in the water or shortly after leaving 2. Migration and maturation of immature wormsThe cercaria loses its tail becoming a schistosomule which moves through various tissues to the veins Schistosomule migrate following circulatory system Adult worm of S.japonicum: Portal -mesenteric venous

17、 system3. Adult worm inhabit in veinsAdults mature in the in the veins surrounding the intestines or bladder, depending on the species. Schistosoma haematobium matures in veins around the bladder (in the venus plexus of bladder or in the rectal venules )S. mansoni and S. japonicum mature in veins ar

18、ound the intestines. Schistosoma japonicum, S.mansoni S. haematobiumhttp:/www.wellcome.ac.uk/en/labnotes5/animation_popups/schisto.htmlPortal -mesenteric venous systemthe venus plexus of bladdercercariaeskinschistosomulaLymphatic & blood vessels (capillaries)heartlungsCirculatory systemMesenteric ar

19、tery and capillariesPortal -mesenteric venous systemCopulationadult wormlay eggs 24 days4. egg-granuloma (虫卵肉芽肿)the eggs laid by the females in the tissues are the cause of pathology egg-granulomafibrous tissue cirrhosis portal hypertension (门脉高压) and splenomegaly (脾肿大) 5. eggs pass through tissue t

20、o lumen of visceraegg granulomatous lesions in the wall of intestine or bladderLesions breakEggs pass through tissue to lumen of intestine or bladderthe eggs can be detected in faeces or urine Some eggs are flowed into liver or capillary beds cause egg-granulomaAdult worm in mesenteric venousPenetra

21、tion of the skin by cercariae to lay egg: 24 daysEggs develop to mature eggs: 11 daysEggs can be found in stool: 45 days(eggs pass through tissue to lumen of viscera)Schistosoma japonicumCercariae: lose tails, penetrate skin of host in 3-5 minutes and enter circulation via lymphaticsImmature schisto

22、somes: carried in circulation throughout body, generally only survive and mature in the venous Mature adults: copulated worm migrate to mesenteric venous and lay eggs in small venuleseggs: pass through tissue to intestine or bladder, ova may be found in faeces or urine directly or using rectal scrap

23、ing or biopsies (eggs pass through tissue to lumen of viscera)Penetration of the skin by cercariae to lay egg:24 daysEggs develop to mature eggs: 11 daysEggs can be found in stool: 45 daysQuestion for S.japonicumMORPHOLOGYAdult Worm ：The adult worm of S.japonicum have elongate and slender bodies, an

24、d is sexual dimorphism (dioecious).雌雄异体Clonorchis sinensisHermaphrodite (monoecism)雌雄同体Copulation合抱20-25 x 0.3 mm10-22 x 0.5-0.55 mm Gynecophoral canaluterusovaryvitellariacecaFemaleMale7 testescopulationAdulrt worm鸳鸯 mandarin duck “止则相耦，飞则成双”。千百年来，鸳鸯一直是夫妻和睦相处、相亲相爱的美好象征，也是中国文艺作品中坚贞不移的纯洁爱情的化身，备受赞颂。不过

25、根据科学研究，鸳鸯并不是终生不二配的。 89 x 67 umspineNo operculum华支睾吸虫miracidiumTope glandHead gland99 x 35 umHead gland5 pairs of penetration glandstailfurcacercariaS. japonicumS.mansoniS.haematobiumS. intercalatumS. mekongiSchistosoma japonicum eggs are smaller (68 to 100 m by 45 to 80 m) than those of the other sp

26、ecies S.mansoniS.haematobiumC. sinensisF. buskiS. japonicumP. westermaniCercaria of TrematodeCercariae & schistosomulaAdult wormEggI type hypersensitivityIII typehypersensitivityIV typehypersensitivityPathogenesis (发病机制)cercariaeSkin invasionsensitizationImmediate hypersensitivityCercarial dermatiti

27、sMigration(pass through)Venulitis, lymphangitis, giant cell, eosinophilsInflammation, hemorrhage schistosomulaAdult worm Adult wormMetabolic products & toxins productsWaste products & secretionsImmuno-complexIII type hypersensitivitySEAIL-1Treated & represent AgT cellIL-2T cell proliferationESP FSF

28、MIFLymphocytes, eosinophils, macrophages & fibroblasts infiltrate surrounding egg macrophagesEgg-granulomaThe mechanism of granulomatous formationT-cells are of major importance for the formation of large granuloma around the eggs of S.japonicum like S.mansoni, but modulation of size of granuloma is

29、 primarily antibody medicatedVI type delay hypersensitivityHoeppli phenomenon(何博礼现象）eosinophilseggEgg-granuloma in liver(inflammatory reaction)egg were surrounded by eosinophilisDamage by eggs in tissue: liver and intestine/retumAn inflammatory granuloma forms with epithelial ,giant,plasma and eosin

30、ophil cells and fibroblasts ( Hoeppli reaction)25% eggs are flowed into liver beds cause egg-granulomaAdult worm in mesenteric venousThe progress of egg-granuloma?Miracidium in egg diedEgg calcifiedFibroblasts cluster & synthesize collagenFibrous tissuePeriportal pipestem fibrosis (干线性纤维化）Fibrosis i

31、n intestinal wallClinical picture of cirrhosisPortal hypertension & splenomegalyColonic polyposisIndividuals with infection of schistosomePatients with schistosomiasisMain clinical finding:weakness, abdominal pain, diarrhoea, hepatomegaly & splenomegalyClinical presentationAcute stage: within a mont

32、h of infectionChronic stage: 90% infected personsLate stage(advanced): splenomegaly, ascites , colonic polyposis & dwarfismEctopic lesion: cerebral & pulmonary schistosomiasisascitesdwarfismConcomitant immunityImmune evasionImmunityADCC: antibody-dependent, cell-mediated-cytotoxicityAttack target: S

33、chistosomaConcomitant immunity(伴随免疫)caused by adult worm of pre- infection, which immunity can resist reinfection but the adult worms of pre- infection can survive by immune evasion. It is considered to be a common immune phenomena in helminthes infection”Pre-infectionConcomitantimmunityAdult wormre

34、infectionWorms from mouseBlood vessel of rabbitworms surviveRabbit immunized by blood cells of mouseworms diedAntigenic disguise1. Parasitological examinationFinding eggs/miracidium Direct smears: 35-48 days Kato-katzs method: quantitative examination Hatching of miracidium: as index of viable egg M

35、icroscopical examination of rectal biopsyDiagnosis Intradermal test(IDT) antigen-adult worm antigen(AWA) sensitivity95% false positive rate 2% two weeks after infection early diagnosis(or for new infection) screening test 2. Immunodiagnosis Antibody detection(in sera) sensitivity 95% specificity hig

36、her(false positive 2-3%) cant distinguish between past and active inf. Diagnosis for new infection & Epidemiology Methods: COP, IHA, ELISA 2. ImmunodiagnosisAntigen detection Cag, maybe distinguish current & past infection & evaluating the effect of drug Dot-ELISA/Sandwich ELISA monoclonal antibody(

37、McAb) sensitivity 84.5%( 29.0-85.0%) false positive rate 3.1% 2. Immunodiagnosis4. Altrasound examination for advanced case, e.g.hepatomegaly & splenomegalyNetwork pattern (网状结构) was found in elder cases with history of repetitive and long term infection of S. japonicumThickening of the portal vein

38、wall was also commonly found in S. japonicum infection. B Altrasound examination Distribution Mainland of China, Japan, the Philippians, Indonesia. Japan has controlled Schistosomiasis since 1978 In China 12 provinces in the south part391(381) endemic counties79 million people in endemic areas14.8 b

39、illion square meters snail riddenEpidemiology of S.japonicumHubei, Hunan, Jiangxi, Anhui, Jiangsu, Sichuan & YunnanShanghai, Guangdong, Fujian, Guangxi & ZhejiangTypes of endemic areas Marshy type(江湖洲滩型): still serious Hubei, Huana, Jiangxi, Anhui, Jiangsu 82.1% infested snail areas Mountainous and

40、hilly type(山丘型) Sichuan, Yunnan Water-net type(水网型) controlled Shanghai(1985), Guangdong(1985), Fujian, Guangxi & Zhejiang controlledDetection of Infested water by mice Epidemic features Main reservoirs of infection: water buffaloes & pigs 31 species wild mammals Ways to infection: contacting infest

41、ed water Susceptible population: Human a susceptible host, lower age people Transmission season: April to OctSnail: Oncomelania hupensis only intermediate of S.japonicum male & female female lay eggs in Spring, Baby snail grows under water, develop to be adult in Autumn, one years life span infected

42、 by miracidiae & release cercariaeMountainous areasWater-net & marshy areasEpidemic factors Natural factors: environment, temperature, level of water, natural of soil & vegetation Social factors: economic level, sanitary condition, medical care, way to produce in local & local costumes(water-contact

43、ing) So environment modification, development of economy, health education & national program of schistosomiasis control will impact on the transmission significantlyHow to control Schistosomiasis ?1. Control Objectivesto control morbidity due to schistosomiasis& to interrupt, in some areas, it tran

44、smissionHow to control疾病控制(mobility control)控制传播(transmission control)传播阻断(transmission interrupt/Elimination )2. Control measurementsto treat patients & livestock Chemotherapy: mass /selective treatmentto control snail Environment modification, molluscidingto reduce the frequency of water-contactin

45、g Health education to prevention by drug e.g., artemisinin Artemisia annua青蒿素（叶）Anti-malaria drugAnti-schistosomula (7 days old larva) drug Artemether(蒿甲迷） Artesunate(青蒿琥酯 ) 6 mg/kg /weekChemotherapy(化疗)Praziquantel(吡喹酮) high efficacy & low toxicitya single dose of 40 mg/kg(50 mg/kg) for chronic cas

46、es or mass treatment in China60 mg/kg in 2 divided doses give with a 4-hr interval on the same day (WHO recommends)120 mg/kg in 4-6 days for acute casesExcising the enlarged spleen from and advanced schistosomiasis patientFor late stage case疫苗发展(vaccine development for Schistosomiasis) Vaccine for A

47、nti-diseases (抗病疫苗) Vaccine for Anti-infection (抗感染疫苗)Schistosoma genome project 我国在血吸虫病防治基础研究方面取得了重要进展1、Schistosoma japonicum Genome ProjectChinese National Human Genome Center at Shanghai 2 、Vaccine developmentVaccine candidateField trial for demostical animal2001-2003年，国家自然科学基金，利用EST识别和克隆血吸虫疫苗候选抗

48、原基因的研究2003-2005年，国家自然科学基金，紫外线致弱日本血吸虫早期童虫的功能蛋白质组学研究2004-2006，广东省自然科学基金,虫源性免疫抑制因子Sj16对树状细胞作用的实验研究2005-2007年， 2005年博士学科点专项科研基金日本血吸虫和宿主相适应的相关信号分子的识别和鉴定2006-2008。广州市科技计划项目虫源性免疫抑制剂Sj16的开发及临床前期研究2008-2009。国家自然科学基金日本血吸虫致弱尾蚴差异表达蛋白的表达调控机制及其生物学意义Adult worm: dioecious/dimorphism male: gynecophoral canal, 7 test

49、es 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 wormSummaryAdult worm :portal-mesenteric venous systemCercariae : infective stageEg

50、g:a major pathological cause, egg-granulomaIV type delay hypersensitivity Acute, chronic & late(advance) caseLate stage: splenomegaly, ascites, colonic polyposis & dwarfism Concomitant immunity, immune evasion, antigenic disguiseADCC: antibody-dependent cell-mediated-cytotoxicity, IgE/IgG, eosinophi

51、lsAttack to schistosomula in lung stageDiagnosis: finding egg in stool detecting the specific antigens or cag Chemotherapy: Praziquantelway to infection: contacting infested waterReservoirs: water buffaloes and pigs, zoonosis Intermediate host: snail3.病毒性肺炎 如冠状病毒、腺病毒、流感病毒、巨细胞病毒、单纯疱疹病毒等。 多种 肺炎细菌均可引起大

52、叶性肺炎，但绝大多数为肺炎链球菌，其中以型致病力最强。肺炎链球菌为革兰阳性球菌，有荚膜，其致病力是由于高分子多糖体的荚膜对组织的侵袭作用。少数为肺炎杆菌、金黄*色葡萄球菌、溶血性链球菌、流感嗜血杆菌等。肺炎链球菌为口腔及鼻咽部的正常寄生菌群，若呼吸道的排菌自净功能及机体的抵抗力正常时，不引发肺炎。当机体受寒、过度疲劳、醉酒、感冒、糖尿病、免疫功能低下等使呼吸道防御功能被削弱，细菌侵入肺泡通过变态反应使肺泡壁毛细血管通透性增强，浆液及纤维素渗出，富含蛋白的渗出物中细菌迅速繁殖，并通过肺泡间孔或呼吸细支气管向邻近肺组织蔓延，波及一个肺段或整个肺叶。大叶间的蔓延系带菌的渗出液经叶支气管播散所致。编辑

53、本段临床表现多数起病急骤，常有受凉淋雨、劳累、病毒感染等诱因，约1/3患病前有上呼吸道感染。病程710天。 （一）寒战、高热：典型病例以突然寒战起病，继之高热，体温可高达3940，呈稽留热型，常伴有头痛、全身肌肉酸痛，食量减少。抗生素使用后热型可不典型，年老体弱者可仅有低热或不发热。 （二）咳嗽、咳痰：初期为刺激性干咳，继而咳出白色粘液痰或带血丝痰，经12天后，可咳出粘液血性痰或铁锈色痰，也可呈脓性痰，进入消散期痰量增多，痰黄而稀薄。 （三）胸痛：多有剧烈侧胸痛，常呈针刺样，随咳嗽或深呼吸而加剧，可放射至肩或腹部。如为下叶肺炎可刺激隔胸膜引起剧烈腹痛，易被误诊为急腹症。 （四）呼吸困难：由于肺实变通气不足、胸痛以及毒血症而引起呼吸困难、呼吸快而浅。病情严重时影响气体交换，使动脉血氧饱和度下降而出现紫绀。 打造最权威的专业课件本文档免费浏览阅读，下载后可以编辑修改。医学精品课件Controlling infective sources byChemotherapy dont contacting water by Health educationControlling snailsIndi