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Schistosomes and schistosomiasis Medical Parasitology, CBIO 4500 January 26, 2010

Schistosomes and schistosomiasis Medical Parasitology, CBIO 4500 January 26, 2010 Silvia N.J.Moreno. Glass of Worms Shown are 1,659 adult Schistosoma mansoni worms obtained by live surgical perfusion of an 18-year-old patient. Image: Dr. Daniel G. Colley. Turbellarians. Free-living worms.

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Schistosomes and schistosomiasis Medical Parasitology, CBIO 4500 January 26, 2010

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  1. Schistosomes and schistosomiasis Medical Parasitology, CBIO 4500 January 26, 2010 Silvia N.J.Moreno Glass of Worms Shown are 1,659 adult Schistosoma mansoni worms obtained by live surgical perfusion of an 18-year-old patient.Image: Dr. Daniel G. Colley

  2. Turbellarians Free-living worms Monogenea Monogenetic flukes Trematodes Digenetic flukes Cestodes Tapeworms Helminths (Parasitic worms) Phylum Platyhelminths Phylum Nematoda

  3. Trematodes • Flatworms: flat in cross section • Life cycle includes a snail as Intermediate Host • Solid/no cavity/no blood system • Have blind digestive tract • Possess suckers for attachment • Adult form covered by a tegument (skin) • Hermaphroditic except blood flukes This undergraduate student investigates trematode parasites emerging from an infected horn snail. The snail is in the vial, and the small white larvae are visible swimming in the water. Photograph by Kevin Lafferty, USGS. http://soundwaves.usgs.gov/2006/08/research2.html

  4. Schistosomes and schistosomiasis Theodor Bilharz -(1825-1862) Postal stamp released in Egypt, 1962 Issued on his 100th death anniversary • Disease: schistosomiasis or Bilharzia (in honor of Theodor Bilharz) • Infect 200 millions of the world’s population in Africa, Asia and S. America. Population at risk: 600 millions. 20 Million with severe disease • Live in blood vessels of the definitive hosts including humans. • Pathology is not due to host response against the worms but rather to eggs entrapped in tissues Theodor Bilharz Research Institute (TBRI) is a governmental medical research institution named after T. Bilharz who discovered, in autopsy material the causative agent of haematuria : Schistosoma worm, during his work in Egypt in 1851. Ascites due to portal hypertension, liver fibrosis. Bilharzia. Schistosomiasis. Schistosoma mansoni. Photo Dr Van den Enden

  5. Schistosome biologyimportant points • They live in the bloodstream • They live for a long time • The host can become resistant to infection • The parasites do not replicate in their definitive host • Have separate sexes-male has pouch which holds female www.icp.ucl.ac.be/~opperd/ parasites/schisto1.html

  6. Transmission • Pollution of fresh water with excreta containing Schistosome eggs • Presence of the snail host Snail from genus Biomphalaria http://www.cdfound.to.it/HTML/sch1.htm • Human contact with water infested with cercaria

  7. S. mansoni S. japonicum Geographic distribution • Schistosoma mansoni • Africa (52 countries) , Caribbean, Eastern Mediterranean, South America • Schistosoma japonicum • Asian countries and the Pacific region • Schistosoma haematobium • Africa (54 countries), Eastern Mediterranean • Schistosoma intercalatum • African Countries (10) S. hematobium

  8. Schistosome life cycle Eggs passed in feces or urine

  9. Schistosoma mansoni eggs These eggs are large (length 114 to 180 µm) and have a characteristic shape, with a prominent lateral spine near the posterior end.  The anterior end is tapered and slightly curved.  When the eggs are excreted, they contain a mature miracidium S. hematobium egg: In this species, the eggs are large and have a prominent terminal spine at the posterior end.  Length 112 to 170 µm.  S. japonicum egg the egg is typically oval and has a vestigial spine. Schistosoma japonicum eggs are smaller (68 to 100 µm by 45 to 80 µm) than those of the other species.

  10. Schistosome miracidium • Eggs hatch releasing miracidia.Temperature, light and osmotic pressure are important factors • 200 m length and 40  diameter • Swims at 2 mm/sec by beating of the cilia • Remain infective for 8-12 h • Infects the snail • They accumulate around the snail or in a drop of snail-conditioned water Miracidium Swimming towards Snail Intermediate Host Scanning Electron Micrograph of miracidium newly hatched from egg (bottom left)http://www.path.cam.ac.uk/~schisto/SchistoLife/Miracidium.html

  11. Main intermediate snail hosts that transmit human schistosomiasis S. Mansoni S. intercalatum S. hematobium S. japonicum S. mekongi (Biomphalaria) (Bulinus) (Bulinus) (Oncomelania) (Tricula) Africa B. Pfeifferi B. Alexandrina B. Sudanica Americas B. glabrata B. straminea B. tenagophila B. globosus B. forskalii B. truncatus B. glabosus B. forskalii B. africanus O. hupensis T. aperta Bulinus globosus, the intermediate host snail for Schistosoma haematobium (courtesy WHO/TDR) www.icp.ucl.ac.be/~opperd/ parasites/schisto1.html Biomphalaria glabrata

  12. Intramolluscan stages SPOROCYST • The miracidium penetrates the snail • It sheds the epithelium and remodel its surface (2 h approx.) • A new surface layer appears around the newly formed sporocyst • A newsyncytial tegument is formed • Primary sporocyst:hollow, fluid filled germinal sac • Daughter sporocysts in less than a week and secondary sporocysts (35-600) • Cercaria by 3-4 weeks after infection (1500/day for 18 days) http://www.personal.leeds.ac.uk/~bgy1mjt/sporocyst.html

  13. Cercaria in the water • First escape into the hemolynph and then through the snail’s integument • Swim into the surrounding water to find their definitive host • Swims by alternating side-to-side rhythmic contractions • It is composed of a body 125 m long by 25 m in diameter to which a 200 m long tail is attached • Covered by a single continuous syncytial tegument http://www.personal.leeds.ac.uk/~bgy1mjt/cercaria.html A cercaria of S. mansoni stained with CellTracker Green (Molecular Probes) to highlight the pre- and post-acetabular glands.

  14. Cercaria to schistosomula • Cercaria finds a host and penetrates skin • Tail is lost • Shedding of surface molecules • Penetration glands empty • Formation of a new double-unit membrane on the syncytial surface. • Loss of resistance to the hypoosmolar stress of fresh water • Change from aerobic to anaerobic metabolism

  15. Inside the human host: Schistosomula • 3-4 days in the subdermal layers • Bloodstream briefly passing through the right side of the heart into the pulmonary artery • Pulmonary capillaries around the 4th day and remain for 2-3 days • Schistosomula becomes resistant to the immune response • After passing through the lungs schistosomula come to rest in the hepatic portal vein http://www.cdfound.to.it/HTML/sch2.htm Schistosomulum penetrating the wall of a blood vessel

  16. Inside the human host: Schistosome adult worms • Male/female pair copulate throughout life-produce eggs • Females resides in canal-Important for maturation • Some differences among species • Worm pairs can live for more than 10 years in a host • Pair migrate back against the blood flow to the mesenteries around the intestine (mansoni). http://www.nhm.ac.uk/zoology/projects/project3.html http://www.med.sc.edu:85/parasitology/schis8.jpg

  17. Adult worm characteristics SEM head of male Schistosome (parasite) http://www.rhul.ac.uk/ElectronMicroscopy-Unit/Gallerybiological2.html • No body cavity or circulatory system. The internal organs are embedded within a solid cellular parenchyma • Covered by a tegument (skin) • Ventral and oral suckers • Reproductive tract differs in different species Digestive system of schistosomes is very simple: They have only one bifurcated digestive tract. Their digestion is performed by frame cells, and they seem to have no excretory pore. http://www2.ttcn.ne.jp/~akky/parasite/digest.htm

  18. The tegument • Adults worms are bounded by a 2-4 um thick syncytiun called tegument which covers the entire surface. • The pitted tegument provides a large surface area for nutrient uptake. • Males: • Warty tubercles with many spines which help to maintain the position of the pair against the blood flow • Female: • Wrinkled annularly and is smooth except for dense spination around the excretory pore. Diagram of the ultrastructure of the adult schistosome tegument. www.york.ac.uk/res/ schisto/proteomics.htm

  19. The egg • Surrounded by a biopolymer composed of proteins crosslinked to each other by quinone bridges • Contains pores to allow the influx of nutrients and efflux of macromolecules • The shell is a highly organized conglomerate • Eggs pass through the walls of the mesenteries and through the intestinal walls into the lumen of the intestine. The egg is eliminated with feces into the water to release miracidia that …… http://www.wellcome.ac.uk/en/labnotes5/animation_popups/schisto.html

  20. Pathogenesis of SchistosomiasisThe granuloma • Eggs that do not leave the body are swept to the pre-`sinusoidal capillaries of the liver and are trapped there (or in the bladder wall) • The immune system responds and walls off the eggs with a granuloma, the egg dies • Continuous stimulation of the immune system leads to regulation or fibrosis (less or more morbidity) • Periportal fibrosis leads to portal hypertension • Portal hypertension leads to collateral circulation, eosophageal varices, blood loss (Sm; Sj) • Continuous aggravation in the bladder wall leads to carcinoma of the bladder (Sh) Granuloma in a mouse liver formed around a Sepharose bead coupled with schistosome egg secreted proteins. http://www.york.ac.uk/res/schisto/proteomics.htm

  21. Clinical symptoms • Schistosomiasis is an immunologic disease. • Symptoms are rarely seen except in heavily infected individuals. • Skin penetration-local dermatitis: within 24 h • Migration of the schistosomula: chills, fever, sweating, cough, diarrhea, leukocytosis • Acute phase (Katayama diseases by S. japonicum) • fever, chills, headache, anorexia, urticaria, and diffuse megaly, lymphadenopathy and diffuse vasculitis lesions • 2-3 weeks after the infection and usually lasts 1-2 months (typhoid fever) • Chronic disease-most important • Fatigue, bowel and bladder symptoms, hepatic dysfunction • Hepatosplenomegaly because of portal obstruction • S. hematobium: urinary tract infection, Inflammation, squamous cell epithelioma, hydronephrosis and fibrosis of ureters

  22. The morbidity spectrum of schistosomiasis mansoni The 2 faces of schistosomiasis ‘Intestinal’ asymptomatic schistosomiasis at the Egyptian village level Egyptian boy with hepatosplenomegaly, ascites fluid build-up and superficial collateral circulation (NAMRU-3 clinical ward in Cairo)

  23. Then there is the North American schistosome-induced pathology --- Duck schistosomes Raccoon schisto;… etc. Sign on the door leading out of a resort to Lake Bemidji, in Minnesota (the advice can’t hurt, but may not help either Cercarial Dermatitis

  24. Diagnosis of Schistosomiasis Microscopic fecal or urine examinations Thick smear (Kato/Katz) Concentration techniques (sediment/filter) Polycarbonate filters (urine; S. haematobium) Antibody assays (measure exposure) Antigen assays (measure active infection & and quantify intensity) The standard is egg counts… but…. ALSO IMPORTANT: Clinical signs, symptoms and history of living in an endemic area

  25. Treatment of schistosomiasis PraziquantelOxamniquineMetrifonate Type of Isoquinilone Tetrahydroquinilone Organophosphorous Compound Active against All Species S. mansoni S. haematobium Dosage 40-60mg/kg 15-40mg/kg 7-10mg/kg Single dose 1-2 doses 3 doses/2 weeks Cure Rate 70%-100% 80%-100% 50%-90% Main Side Diarrhea,Nausea Dizziness Nausea Effects Abdominal pain Drowziness Price/adult $0.25 - $3 $2 - $5 $0.30 dose Mode of Calcium Channel Delayed action Energy Action blocker ? Alkylation ? Inhibition??? As with egg excretion Effective treatment also requires host responsiveness

  26. Factors Contributing to Transmission of Schistosomiasis • Water -- Uses & Abuses • Development (Dams; Irrigation), Socioeconomic (Sanitation) • Snail hosts • Habitat (geography & weather), Dams, Marshes • Adult worms -- Longevity & Fecundity • Human & animal (Sj) reservoir hosts • Contamination & Contact Patterns; Occupational aspects • Age/Prevalence & Age/Intensity Curves • Immunity? • New data on the topic -- if time permits • Focal Transmission sites • Rural -- and now Urban/peri-urban settings • Location, Location, Location…..

  27. The infection is age-related • S. haematobium and S. mansoni show age related patterns • Children are nonimmune • They become infected when old enough to play in open water • Adults gradually acquire immunity

  28. How do you get schistosomiasis ??? How about total body immersion …. In a canal off the Nile, just southwest of Cairo, Egypt In a storage reservoir just outside of Belo Horizonte, Brazil

  29. Washing Clothes or other jobs

  30. There is also no transmission without fecal contamination. So, how does fecal contamination happen???

  31. Control measures/ Possible Points of Attack • Sanitation, Water Supply & Community • Health education; Hygiene • Socioeconomic development ==> toilets & water systems • Snail Control • Molluscicides; Competitors/Predators; Habitat reduction/closed irrigation; Environmental modification • Chemotherapy • Target, Coverage -- Process & Outcome Indicators • Delivery options/Integration with other control programs • Prevalence/Intensity/Morbidity • Vaccine (not for a long time) • Discovery, Process development, Testing • Re-infection studies & immune correlates

  32. Has schistosomiasis control ever really worked? YES -- Japan

  33. Schistosomiasis Control Initiativehttp://www.schisto.org • 1.To encourage development of a sustainable schistosomiasis control programme in sub Saharan Africa. • 2.In the selected countries: • To reach at least 75% of school-age children and other high-risk groups with chemotherapy - praziquantel and albendazole. • Reduce schistosomiasis-related morbidity in high risk groups. • Reduce prevalence and intensity of schistosomiasis infections. • Reduce burdens due to intestinal helminths in the targeted populations. • 3.Create a demand for sustained schistosomiasis control. • 4.To promote access to anthelminthic drugs and good case management in the regular health system.

  34. Check on these movies http://animal.discovery.com/videos/monsters-inside-me-the-schistosomiasis-parasite.html http://animal.discovery.com/videos/monsters-inside-me-inside-a-snail-fever-lab.html

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