医学寄生虫学：蓝氏贾第鞭毛虫（贾第虫）

1、GIARDIASIS （贾第虫病）Infection with the protozoan parasite Giardia duodenalis most common name used. also G. intestinales and G. lamblia. 蓝氏贾第鞭毛虫（贾第虫） Giardia lamblia 1681, van Leeuwenhoek 发现Giardia spp. can parasitize the intestinal tract of a wide range of vertebrates, including humans. The distributi

2、on is cosmopolitan 全球分布. GIARDIASISdiarria, 腹泻、营养不良CONCEPTIONThe trophozoite of Giardia duodenalisLives in the upper two-thirds of the small intestine (duodenum and jejunum) 12 to 15 m long, shaped like a pear Two nuclei: Equal DNA content Both transcriptionally active both divide at the same time F

3、our pairs of flagella= 8 flagella Ventral Adhesive Disc Reproduction by binary fission-asexual reproductionCross-section through a trophozoite of Giardia duodenalisVentral disk: most distinctive structure of the trophozoite. It is a large, rigid structure stabilized by numerous physical cross-links

4、between its components.Scanning electron micrographs of trophozoites of G. lamblia.Observe the typical pear-shaped body. a: Dorsal view of G. lamblia. Observe the lateral flange (arrowhead) and the caudal or posterior (P) and the anterior (A) flagella. b: Ventral view of the parasite. The arrowhead

5、indicates the presence of the lateral flange, which surrounds the whole cell. The ventral flagella (V) are seen in the region of the ventral groove and the adhesive or striated disk (SD) is clearly observable. Bars: a: 2.7 m and b: 2.0 m.Microscopy and Microanalysis (2004), 10: 513-527TEM of giardia

6、 cellsNote the impression left on the epithelia where a trophozoite has detached (upper left) and the interaction between the ventral disk of the parasite and the brush boarder cells of the intestines (lower right). Adhesion of the trophozoite to the epithelial cells of the small intestine.病理切片中的贾第虫

7、滋养体包囊粪便染色(生理盐水或2%碘液涂片）1 滋养体-铁苏木素染色滋养体-瑞氏染色TEM of a Giardia cystThe cyst wall is composed of filamentous丝状 and membranous portions and is separated from the cytoplasm of the trophozoite by a peritrophic space N: nucleus; f flagellum.Clinical Microbiology Reviews, 13, p. 35-54SEM illustrating the fila

8、mentous nature of the cyst wallLIFE CYCLEExcystation and Encystation（脱囊和成囊） Excystation: In vivo occurs in the stomach/small intestine. Motile trophozoites emerge in the small intestine.In vitro: can be induced by:Low pH Encystation In vivo occurs in the lumen of the small intestine. Trophozoites st

9、ars synthesizing cyst wall components and transport them to the outer surface. In vitro: can be induced by:High pHHigh bile salts concentration GIARDIA INTERACTION WITH THE HUMAN INTESTINEGIARDIASISPathophysiologyGiardia colonizes the upper small intestineVillous blunting 绒毛僵硬Lymphocytic infiltratio

10、nMalabsorption 吸收不良No tissue invasion-high number of trophozoites present in the duodenal cryptsDiarrhea may lasts for weeks- antigenic variation? 恶臭慢性腹泻病理切片患贾第虫病6岁男孩因严重吸收不良死亡尸体解剖小肠病理切片(H&E X400)The surface of the Giardia trophozoite is covered by the Variant Specific Protein (VSP) - only one is exp

11、ressed per trophozoite. Over 150 different VSP genes are encoded in the Giardia genome. Expression of different VSPs results in the phenomenon of Antigenic VariationMechanisms not known: may be changes in gene expression at the mRNA levelAntigenic VariationIs re-infection by Giardia due to antigenic

12、 switching after differentiation?VSP-1 expressedEncystationVSP changesRe-infectionNew VSP expressedColonizationGIARDIASISCLINICAL FEATURESIncubation period : 1-2 weeksMajority of infected individual are asymptomaticSYMPTOMS: Diarrhea with loose, fool-smelling stoolsFlatulence （胃肠胀气）Abdominal cramps

13、and bloating （腹部胀痛）Nausea anorexia （厌食）Malaise (不适）Weight lossProlonged symptomsMalabsorption （吸收不良）GIARDIASIS - DIAGNOSISIdentification of cysts or trophozoites in fecal specimensMay need to be repeatedDetection of Giardia antigens in feces.Serodiagnosis is not usefulThe Cypress Diagnostics Giardia

14、 kit is an enzyme linked immunosorbent assay (ELISA) intended for the detection of Giardia antigen in fecal specimen. A Giardia trophozoiteThree Giardia Cysts 由于包囊形成有间歇的特点，故检查时以隔天粪检并连续3次以上为宜GIARDIASIS - TREATMENTMetronidazole（灭滴灵）: not FDA approved but used (250 mg x 3 for 5-7 d)Tinidazole （替硝唑）- no

15、t approved in the US. Single dose of 2 g. Furazolidone（痢特灵）- approved by the FDA for giardiasisParanomycin（巴龙霉素）- used for pregnant womenNitazoxanide（硝唑尼特）: recently approved for giardiasis and cryptosporidosis in childrenGiardiasis cure rates with single-dose tinidazole therapy range from 80-100%.

16、EPIDEMIOLOGYWorldwide distributionCommon in areas with poor sanitary conditionsSeasonal with peak during late summer in UK, USA and MexicoPrevalence: 2-7% in developed countries 20-30% in most developing countries. 10% 中国Travelers, hikers, campers are at risk. Swallowing water while swimming, drinki

17、ng tap water, eating lettuce.Risk groups : travelers, children in day cares and homosexual menPREVENTIONCysts are resistant and are responsible for transmission. Both cysts and trophozoites can be found in the feces. (But trophozoite can not be survived outside.) The cysts can survive several months

18、 in cold water. In addition the domestic dog and certain wild animals serve as hosts. Most common protozoan disease in the United States.GIARDIASISTRANSMISSIONReservoir-human and possibly other mammalsInfective cysts in feces: 10-25 cysts sufficientFecal contamination of water Feces for fertilizer Defective piping Flyes Soiled handsttp:/index.asp?PageAction=VIEWPROD&ProdID=2209A GIARDIA VACCINE