1、Human Schistosome (人体血吸虫),2007-11-7,Disease due to schistosomes is termed schistosomiasis or bilharzia after the shortlived German physician Theodor Bilharz (1825-1862). http:/www.dpd.cdc.gov/dpdx/HTML/Schistosomiasis.htm,Kingdom: Animalia Phylum: Platyhelminthes Class: Trematoda Subclass: Digenea O
2、rder: Stringeiformes Genus: Schistosoma Species: Schistosoma haematobium, S. japonicum, S. mansoni and S. intercalatum,http:/www.schisto.org/Schistosomiasis/Default.htm,Schistosome: A parasitic trematode worm contracted from infested water that is capable of causing liver, gastrointestinal tract and
3、 bladder disease. There are three main species of these 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 Af
4、rica. S. haematobium is the most prevalent and widespread species in Africa and the Middle East S. intercalatum occurs in 10 countries in the rainforest belt of Africa S. mansoni is found in Africa and is the only species seen in Latin America S. japonicum is restricted to the Pacific region includi
5、ng China and the Philippines S. mekongi is found in limited 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 1904 In 1905, f
6、irst case found in Human,The discovery history of SchistosomesS.haematobium 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
7、 proposed the name Schistosoma haematobium.In 1905, Sir Patrick Manson 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%, respectively,Distri
8、bution in China,一定要消灭血吸虫病,Morphology Life cycle Pathogenesis & clinical manifestation Diagnosis Epidemiology Prevention & control,Schistosome: causative agent of schistosomiasis Life cycle: adult worm, egg, larvae ( miracidia , sporocysts ,cercariae ), schistosomula Definitive host: human Intermedia
9、te host :snail The rount of the infection: cercariae penetrating an individuals unbroken skin while contacting infested water with cercariae Parasitized site: The adult worms live in the blood vessels Eggs: egg-granuloma,Life cycle adult wormegg Miracidiumsporocyst (mother and daughter sporocyst) Ce
10、rcariae schistosomula,The life cycle : adult worm, egg, miracidium, sporocyst (mother and daughter sporocyst), cercariae, and schistosomula (童虫) . It is completed in following hosts:a) definitive host: mandomestic animals (pigs, cattle/buffalo) and wild animals; (S.japonicum)b) Intermediate host: Sn
11、ail Oncomelania species (Oncomelania hupensis湖北钉螺 in mainland of China).,Dimorphism(雌雄异体）copulation(合抱）,S.japonicum,Life cycle For example S. japonicum 日本血吸虫intermediate host snails of the genus Onchomelania, hupensis spp.,Life cycle For example S. mansoni 曼氏血吸虫 Intermediate host snails of the genus
12、 Biomphalaria (Planorbidae family),Life cycle For example S.haematobium 埃及血吸虫 intermediate host : snails of the genus Bulinus,Worm in veins around the bladder (in the venus plexus of bladder,life cycle : a sexual stage in humans and an asexual stage in snails an asexual stage in snails Hatching (孵化)
13、 of miracidium in freshwater Development in snail,miracidium, sporocyst (mother and daughter sporocyst), cercariae,a sexual stage in humans Penetration of host ( skin) Migration and inhabiting Schistosomule migrate following circulatory system immature worms develop Male and female to Copulating(mat
14、ing) adult worm inhabite in in veins Worm lay eggs and egg-granuloma,1. Penetration of the skin by cercariaeInfection occurs when cercariae penetrate the skin while in the water or shortly after leaving,2. Migration and maturation of immature worms,The cercaria loses its tail becoming a schistosomul
15、e which moves through various tissues to the veins,Schistosomule migrate following circulatory system,Adult worm of S.japonicum: Portal -mesenteric venous system,3. Adult worm inhabit in veins Adults mature in the in the veins surrounding the intestines or bladder, depending on the species. Schistos
16、oma 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 around the intestines.,Schistosoma japonicum, S.mansoni S. haematobium,http:/www.wellcome.ac.uk/en/labnotes5/animation_popups/schisto.html,Portal
17、 -mesenteric venous system,the venus plexus of bladder,cercariae,skin,schistosomula,Lymphatic & blood vessels (capillaries),heart,lungs,Circulatory system,Mesenteric artery and capillaries,Portal -mesenteric venous system,Copulation adult worm lay eggs 24 days,4. egg-granuloma (虫卵肉芽肿),the eggs laid
18、by the females in the tissues are the cause of pathology,egg-granuloma fibrous tissue cirrhosis portal hypertension (门脉高压) and splenomegaly (脾肿大),5. eggs pass through tissue to lumen of viscera,egg granulomatous lesions in the wall of intestine or bladder Lesions break Eggs pass through tissue to lu
19、men of intestine or bladder the eggs can be detected in faeces or urine,Some eggs are flowedinto liver or capillary beds cause egg-granuloma,Adult worm in mesenteric venous,Penetration of the skin by cercariae to lay egg: 24 days Eggs develop to mature eggs: 11 days Eggs can be found in stool: 45 da
20、ys (eggs pass through tissue to lumen of viscera),Schistosoma japonicum,Cercariae: lose tails, penetrate skin of host in 3-5 minutes and enter circulation via lymphatics,Immature schistosomes: carried in circulation throughout body, generally only survive and mature in the venous,Mature adults: copu
21、lated worm migrate to mesenteric venous and lay eggs in small venules,eggs: pass through tissue to intestine or bladder, ova may be found in faeces or urine directly or using rectal scraping or biopsies,(eggs pass through tissue to lumen of viscera),Penetration of the skin by cercariae to lay egg:,2
22、4 days,Eggs develop to mature eggs:,11 days,Eggs can be found in stool:,45 days,Question for S.japonicum,MORPHOLOGY Adult Worm ： The adult worm of S.japonicum have elongate and slender bodies, and is sexual dimorphism (dioecious).雌雄异体,Clonorchis sinensis,Hermaphrodite (monoecism) 雌雄同体,Copulation 合抱,
23、20-25 x 0.3 mm,10-22 x 0.5-0.55 mm,Gynecophoral canal,uterus,ovary,vitellaria,ceca,Female,Male,7 testes,copulation,Adulrt 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。不过根据科学研究，鸳鸯并不是终生不二配的。,89 x 67 um,spine,No operculum,华支睾吸虫,miracidium,Tope gland,Head gland
24、,99 x 35 um,Head gland,5 pairs of penetration glands,tail,furca,cercaria,S. japonicum,S.mansoni,S.haematobium,S. intercalatum,S. mekongi,Schistosoma japonicum eggs are smaller (68 to 100 m by 45 to 80 m) than those of the other species,S.mansoni,S.haematobium,C. sinensis,F. buski,S. japonicum,P. wes
25、termani,Cercaria of Trematode,Cercariae & schistosomula,Adult worm,Egg,I type hypersensitivity,III type hypersensitivity,IV type hypersensitivity,Pathogenesis (发病机制),cercariae,Skin invasion,sensitization,Immediate hypersensitivity,Cercarial dermatitis,Migration (pass through),Venulitis, lymphangitis
26、, giant cell, eosinophils,Inflammation,hemorrhage,schistosomula,Adult worm,Adult worm,Metabolic products& toxins products,Waste products & secretions,Immuno-complex,III type hypersensitivity,SEA,IL-1,Treated & represent Ag,T cell,IL-2,T cell proliferation,ESP FSF MIF,Lymphocytes, eosinophils, macrop
27、hages & fibroblasts infiltrate surrounding egg,macrophages,Egg-granuloma,The mechanism of granulomatous formation,T-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 primarily antibody medicated VI
28、 type delay hypersensitivity Hoeppli phenomenon(何博礼现象）,eosinophils,egg,Egg-granuloma in liver(inflammatory reaction) egg were surrounded by eosinophilis,Damage by eggs in tissue: liver and intestine/retum An inflammatory granuloma forms with epithelial ,giant,plasma and eosinophil cells and fibrobla
29、sts ( Hoeppli reaction),25% eggs are flowedinto liver bedscause egg-granuloma,Adult worm in mesenteric venous,The progress of egg-granuloma,?,Miracidiumin egg died,Egg calcified,Fibroblasts cluster &synthesize collagen,Fibrous tissue,Periportal pipestemfibrosis (干线性纤维化）,Fibrosis inintestinal wall,Cl
30、inical picture of cirrhosis,Portal hypertension & splenomegaly,Colonic polyposis,Individuals with infection of schistosomePatients with schistosomiasis,Main clinical finding: weakness, abdominal pain, diarrhoea, hepatomegaly & splenomegaly,Clinical presentation,Acute stage: within a month of infecti
31、on,Chronic stage: 90% infected persons,Late stage(advanced): splenomegaly, ascites , colonic polyposis & dwarfism,Ectopic lesion: cerebral & pulmonary schistosomiasis,ascites,dwarfism,Concomitant immunity,Immune evasion,Immunity,ADCC: antibody-dependent, cell-mediated-cytotoxicity,Attack target: Sch
32、istosoma,Concomitant 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-infection,Concomitant immunity,Adult wo
33、rm,reinfection,Worms frommouse,Blood vessel of rabbit worms survive,Rabbit immunizedby blood cellsof mouse worms died,Antigenic disguise,1. Parasitologicalexamination,Finding eggs/miracidium,Direct smears: 35-48 daysKato-katzs method: quantitative examinationHatching of miracidium: as index of viabl
34、e eggMicroscopical examination of rectal biopsy,Diagnosis,Intradermal test(IDT)antigen-adult worm antigen(AWA)sensitivity95%false positive rate 2%two weeks after infectionearly diagnosis(or for new infection)screening test,2. Immunodiagnosis,Antibody detection(in sera)sensitivity 95%specificity high
35、er(false positive 2-3%)cant distinguish between past and active inf.Diagnosis for new infection & EpidemiologyMethods: COP, IHA, ELISA,2. Immunodiagnosis,Antigen detectionCag, maybe distinguish current & past infection & evaluating the effect of drugDot-ELISA/Sandwich ELISAmonoclonal antibody(McAb)s
36、ensitivity 84.5%( 29.0-85.0%)false positive rate 3.1%,2. Immunodiagnosis,4. Altrasound examination for advanced case, e.g. hepatomegaly& splenomegaly,Network 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 wall w
37、as also commonly found in S. japonicum infection.,B Altrasound examination,Distribution Mainland of China, Japan, the Philippians, Indonesia. Japan hascontrolled Schistosomiasis since 1978, In China 12 provinces in the south part 391(381) endemic counties 79 million people in endemic areas 14.8 bill
38、ion square meters snail ridden,Epidemiology of S.japonicum,Hubei, Hunan, Jiangxi, Anhui,Jiangsu, Sichuan & Yunnan,Shanghai, Guangdong, Fujian,Guangxi & Zhejiang,Types of endemic areasMarshy type(江湖洲滩型): still seriousHubei, Huana, Jiangxi, Anhui, Jiangsu82.1% infested snail areasMountainous and hilly
39、 type(山丘型)Sichuan, YunnanWater-net type(水网型) controlledShanghai(1985), Guangdong(1985), Fujian, Guangxi & Zhejiang controlled,Detection of Infested water by mice, Epidemic featuresMain reservoirs of infection: water buffaloes & pigs 31 species wild mammalsWays to infection: contacting infested water
40、Susceptible population: Human a susceptible host, lower age peopleTransmission season: April to Oct,Snail:Oncomelania hupensisonly intermediate of S.japonicummale & femalefemale lay eggs in Spring, Baby snail grows under water, develop to be adult in Autumn, one years life spaninfected by miracidiae
41、 & release cercariae,Mountainousareas,Water-net & marshy areas,Epidemic factorsNatural factors: environment, temperature, level of water, natural of soil & vegetationSocial factors: economic level, sanitary condition, medical care, way to produce in local & local costumes(water-contacting)So environ
42、ment modification, development of economy, health education & national program of schistosomiasis control will impact on the transmission significantly,How to controlSchistosomiasis ?,1. Control Objectives to control morbidity due to schistosomiasis & to interrupt, in some areas, it transmission,How
43、 to control,疾病控制(mobility control) 控制传播(transmission control) 传播阻断(transmission interrupt/Elimination ),2. Control measurements to treat patients & livestock Chemotherapy: mass /selective treatment to control snailEnvironment modification, mollusciding to reduce the frequency of water-contactingHeal
44、th education to prevention by drug e.g., artemisinin,Artemisia annua 青蒿素（叶） Anti-malaria drug Anti-schistosomula (7 days old larva) drugArtemether(蒿甲迷）Artesunate(青蒿琥酯 )6 mg/kg /week,Chemotherapy(化疗) Praziquantel(吡喹酮) high efficacy & low toxicitya single dose of 40 mg/kg(50 mg/kg) for chronic cases o
45、r mass treatment in China 60 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 cases,Excising the enlarged spleen from and advanced schistosomiasis patient,For late stage case,疫苗发展 (vaccine development for Schistosomiasis),Vaccine for
46、Anti-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 Project Chinese National Human Genome Center at Shanghai 2 、Vaccine development Vaccine candidate Field trial for demostical animal,2001-2003年，国家自然科学基金，利用EST识别和克隆血吸虫
47、疫苗候选抗原基因的研究 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/dimorphismmale: gynecophoral can
48、al, 7 testesfemale: ovary at the middle, uterus is long Egg: no operculum, with spine & a miracidium Cercaria: with forked tail Life cycle: egg, miracidium, mother sporocysts, daughter sporocysts, cercariae, schistosomula, adult worm,Summary,Adult worm :portal-mesenteric venous system Cercariae : in
49、fective stage Egg:a major pathological cause, egg-granuloma IV type delay hypersensitivityAcute, chronic & late(advance) case Late stage: splenomegaly, ascites, colonic polyposis & dwarfismConcomitant immunity, immune evasion,antigenic disguise,ADCC: antibody-dependent cell-mediated-cytotoxicity, IgE/IgG, eosinophils Attack to schistosomula in lung stage Diagnosis: finding egg in stooldetecting the specific antigens or cag Chemotherapy: Praziquantel way to infection: contacting infested water Reservoirs: water buffaloes and pigs, zoonosis Intermediate host: snail,
