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MICR 454L Emerging and Re-Emerging Infectious Diseases Lecture 9: Cryptosporidium, Schistosoma Dr. Nancy McQueen & Dr. Edith Porter NOT FINAL YET Slide 2 Cryptosporidium Slide 3 Protozoa Belongs to sporozoa Reservoir Mammals, birds, reptiles Waterborne infection Affects primarily intestinal tract Oocysts Sporozoites Water Sporozoites Invade intestinal epithelial cell Slide 4 Life Cycle of Cryptosporidium Slide 5 Cryptosporidiosis: Pathogenesis Formation of a unique intracellular compartment in the apical region of the host cell Involves rearrangement of the host cell cytoskeleton in intestinal epithelial cell Incorporates host cell actin and alpha- actinin into a host-parasite junctional complex Slide 6 Cryptosporidiosis: Disease Infectious dose ~ 10 oocysts Autoinfection Incubation time 2 10 days Massive diarrheae Up to 25 bowel movements Millions of oocysts are shed Up to 10 fluid loss Accompanied by fever Last about for 1-2 weeks Life threatening for immunocomprised patients Some may not develop symptoms Slide 7 Cryptosporidiosis: Diagnostic Modified acid fast stain from stool sample (Kinyoun) ELISA testing for Cryptosporidium antigen in stool samples Molecular (PCR) http://www.stanford.edu/class/humbio103/ParaSites2006/C ryptosporidiosis/Images/acid-fast%20crypto%20(2).jpg 5 m Slide 8 Cryptosporidiosis: Therapy Nitazoxanide in otherwise healthy patients Nitrothiazole benzamide Blocks anaerobic metabolism Inhibition of the ferredoxine reductase Also used in worm infections, some anaerobic bacterial infections Symptomatic Improve immune system Anti-retroviral therapy for AIDS patients Slide 9 Cryptosporidiosis: Prevention Requires special water treatment in municipal systems Routine chlorine does not inactivate oocysts Small size allows penetration through routine filter Home filtration Reverse osmosis 1 micron filters Slide 10 Threats by Cryptosporidium 1993 Milwaukee outbreak Contamination of the municipal water system C. parvum 100 deaths and 400,000 illnesses Critical Biological Agent for Public Health Preparedness Category B Some potential for large-scale dissemination, but generally cause less-severe illness than those in Category A Could be used to contaminate food or water sources, and many of them are relatively easy to obtain. Difficult to detect, high dose in fecal movements and low infectious dose Slide 11 The worms crawls in, the worms crawl out, in your belly, and out your snout. ANONYMOUS Slide 12 Overview Schistosoma Helminths Morphology Life cycles Vector Pathogenesis Diseases Diagnosis Therapy Prevention Threats Slide 13 Helminths: Classification Phylum: Platyhelminthes (flatworms) Class: Cestodes (tapeworms) Class: Trematodes (flukes) E.g., Schistosoma Phylum: Nematodes (roundworms) E.g., Filaria Animalia Multicellular Organs and biological systems* Circulatory Nervous Reproductive Hermaphrodites Dioecious Digestive Excretory * Depending on species some systems may be lacking or rudimentary Slide 14 Trematodes Flukes Oral sucker: food uptake Incomplete digestive tract Ventral Sucker: Attachment Mostly hermaphroditic (monoecious) Image 98601B Slide 15 Schistosoma Schistosoma japonicum Schistosoma mansoni Schistosoma haematobium Adult females size 7 to 20 mm; males slightly smaller Slide 16 Schistosoma: Life Cycle (1) Infection from contaminated fresh water in which certain types of snails that carry schistosomes are living Schistosoma can penetrate the skin Within several weeks, worms grow inside the blood vessels of the body and produce eggs. Some of these eggs travel to the bladder or intestines and are passed in the urine or stool Schistosoma eggs gain access to fresh water when infected people urinate or defecate in the water. Eggs Miracidia Sporocysts Cercariae Adults Snail Human Slide 17 Schistosoma: Life Cycle (2) Slide 18 Developmental Stages of Schistosoma Cercaria penetrating skin Adult male and female worms EggMiracidia Slide 19 Schistosoma and Affected Organs S. japonicum S. mansoni S. haematobium superior mesenteric veins of small intestine superior mesenteric veins draining of large intestine venous plexus of bladder Slide 20 Schistosoma: Pathogenicity Factors Soluble hypersensitivity antigen released by miracidia within the eggs. Local inflammation Tegument Unique double membrane structure Glycan rich surface Antioxidant enzymes Elastase-like IgE protease Excretory/secretory (ES) molecules from cercariae down-regulate the host's immune response Bind host defense molecules on their surface Slide 21 Schistosoma: Diseases Bilharzia Often asymptomatic Acute schistosomiasis (Katayama's fever) May occur weeks after the initial infection S. mansoni and S. japonicum Fever, cough, abdominal pain, diarrhea, hepatospenomegaly, and eosinophilia Occasionally central nervous system lesions occur granulomatous lesions around ectopic eggs Brain, spinal cord Chronic infection Granulomatous reactions and fibrosis in the affected organs Colonic polyposis with bloody diarrhea (Schistosoma mansoni mostly) Portal hypertension with hematemesis and splenomegaly (S. mansoni, S. japonicum) Cystitis and ureteritis (S. haematobium) with hematuria, which can progress to bladder cancer; Slide 22 Schistosoma and Cancer General: Chronic inflammation with chronic phagocytes at the inflammatory site Release reactive oxygen radicals and reactive nitrogen radicals Chronic inflammation leads to repeated cycles of cell damage and compensatory cell proliferation Promoting neoplasia Schistosoma specific Adult schistosomes liberate carcinogenic amines in urine Rised beta-glucuronidase levels originating from miracidia enclosed in the eggs Khurana S et al. (2005) Indian J Med Microbiol. 2005 Apr;23(2):74-9. Slide 23 Squamous Bladder Cancer Induced by Schistosoma Normal epitheliumSquamous bladder cancer Slide 24 Schistosoma: Diagnosis Microscopy Antibody detection ELISA and immunoblot Schistosomal adult microsomal antigen indicative only of schistosome infection at some time cannot be correlated with clinical status, worm burden, egg production, or prognosis Slide 25 Schistosoma: Identification of Eggs S. mansoniS. japonicum Spine S. haematobium In FecesIn Urine Slide 26 Schistosoma: Therapy Praziquantel for all species Slide 27 Schistosoma: Prevention No vaccine No drug Avoid wading, swimming or other fresh-water contact in endemic countries Avoid untreated piped water coming directly from canals, lakes, rivers, streams or springs that may contain cercariae Heating bathing water to 50C (122F) for 5 minutes or filtering water with fine-mesh filters Allow bathing water to stand for 2 days because cercariae rarely remain infective longer than 24 h Slide 28 Schistosoma: Epidemiology 200 million people infected world wide 50% endemic among the local population in high infested areas South America Caribbean Africa Middle East Far East Depends on species Slide 29 Schistosoma: Endemic Areas Slide 30 Threats by Schistosoma Mainly threat to population in endemic areas and to travelers Slide 31 Resources The Microbial Challenge, by Krasner, ASM Press, Washington DC, 2002. Brock Biology of Microorganisms, by Madigan and Martinko, Pearson Prentice Hall, Upper Saddle River, NJ, 11 th ed, 2006. Microbiology: An Introduction, by Tortora, Funke and Case; Pearson Prentice Hall; 9 th ed, 2007. www.asnom.org/.../nodule_oncho.jpg http://www.icp.ucl.ac.be/~opperd/parasites/images/man.jpg http://www.the-travel-doctor.com/filari9.gif http://www.payer.de/entwicklung/entw2029.gif http://emu.arsusda.gov/typesof/images/onchyo.jpg http://www.denniskunkel.com/product_info.php?products_id=1089 http://www.denniskunkel.com/product_info.php?products_id=592 http://www.cdc.gov/ncidod/dpd/parasites/schistosomiasis/default.htm http://www2.ncid.cdc.gov/travel/yb/utils/ybGet.asp?section=dis&obj=schisto.htm http://education.vetmed.vt.edu/curriculum/VM8054/Labs/Lab4/IMAGES/SIMPL%20COLM %202%20GALL.JPG http://education.vetmed.vt.edu/curriculum/VM8054/Labs/Lab4/IMAGES/SIMPL%20COLM %202%20GALL.JPG http://www.pathguy.com/lectures/bladder_cis.jpg