1. Schistosome

2. Introduction Schistosome (blood fluke) causes schistosomiasis
first discovered by the German parasitologist Theodor Bilharz in 1852 in Egypt
Dated back to ancient Egypt and about 2000 years ago in China
over 200 million people in the world infected
600 million people are at risk

3. Introduction Six species affecting human being Schistosoma japonicum
S.mansoni
S.haematobium
S.intercalatum
S.mekongi
S.malayensis : parasite of humans (rarely) and other animals. A recently described 'new' species

4. Introduction Three species of significant medical importance :
S. mansoni: Africa, Arabia, S. America, Caribbean
S. haematobium: Africa, Middle East
S. japonicum: China, the Philippines, southern Japan, Central Sulawesi (Indonesia)
Different homing orientation :
S. mansoni: Mesenteric veins
S. haematobium: Vesical plexus
S. japonicum: Superior mesenteric veins

5. Global Epidemiology Purple: S.mansoni Blue: S.intercalatum
Africa
South
America
Purple: S.mansoni
Blue: S.intercalatum
Asia
Africa
Orange: S. haematobium
Green: S. japonicum
Red: S. mekongi

6. S. japonicum still endemic in China
7 endemic provinces with 119 endemic counties

7. Morphology “schisto-” means “split”
Dioecious worms
Gynecophoral canal in male –
Pheromone from the male is necessary for the development of female worms
Incomplete digestive system: mouth, esophagus , gut
Some variations
between species
Hermaphroditic [hE:7mAfrC5ditik

8. Morphology
The male adult worm of S. japonicum is slightly larger than the other 2 species at ~ 1.2cm by 0.5mm
Two suckers
maintains its position in the blood vessels－－
the ventral, and larger oral suckers

9. Female adult worm Morphology
S.japonicum female parasite is about 2cm by 0.4mm
Eggs in the uterus
S. mansoni: a single egg is shown, usually 1 - 3
S. haematobium: many more are seen (between )
S. japonicum: 50 or more eggs
Dark grey color because of the metabolic RBC in the digestive duct

10. Eggs of S.japonicum Average size 89×67µm Oval or sub-spherical
Morphology
Average size 89×67µm
Oval or sub-spherical
Pale yellow or yellow brown
Small lateral spine
No operculum
Embryonated, contains mature miracidium when discharged

11. Eggs
Morphology

12. Miracidium A ciliated, swimming larva Size about 99×35µm
Morphology
A ciliated, swimming larva
Size about 99×35µm
The germinal cells will become sporocysts
Tropism – toward limpidity ; phototrophic

13. Cercaria
Morphology
Free- swimming
a forked tail
penetrating glands

14. Cercariae of trematodes
C. sinensis
F. buski
S. japonicum
P. westermani
Cercariae of trematodes

15. Life Cycle

16. Life Cycle Mode of infection: penetration of the skin
Migration: stay in skin(5-10h) convert to schistosomula  subcutaneous venules pulmonary circulation  heart  systemic circulation  portal vein  mesenteric vein
Diagnostic stage: egg
One intermediate host -- Oncomelania hupensis (S. japonicum)
Biomphalaria (S. mansoni )
Bulinus (S. haematobium )
Infective stage: Cercaria
Lack of metacercaria stage
no redia
two generations of sporocyst

17. Life Cycle
Reside in portal system, superior mesenteric vein or vesical plexus
Tissue-residing ova (the main result for pathology) – 15-63% in tissue (liver and intestine)
Instant hatching of the discharged egg in water
A variety of reservoir hosts -- zoonosis

18. Residing place (mesenteric vein )
Life Cycle
Residing place (mesenteric vein )
Intermediate host
Oncomelania hupensis
Eggs in the vein

19. Pathogenesis Schistosomiasis is an immune disease
All stages in host may be pathogenic: cercaria, schistosomulae, egg and adult
The main pathogenic factor is the egg
Deposit in important organs – liver, intestine,etc
Formation of egg granuloma
Accumulation of eggs (thousands of eggs per day)
Ectopic migration – brain, lung

20. Pathogenesis
Skin - “swimmer’s itch” just for a short period after cercaria penetration –type I & IV allergic reaction
Transient fever and coughing -- mechanically damage and allergic reaction to the metabolic materials of schistosomulae
Phlebitis caused by adult worm (rarely) and glomerulonephritis caused by the type III hypersensitivity to the metabolic materials to adult worms
The eggs induced granuloma formation is a Delayed Type Hypersensitivity (Type IV Hypersensitivity) reaction
Although eventually resulting in severe pathology, appears to be a necessary protective host response against hepatotoxic components of Soluble Egg Antigen (SEA).

21. Papules caused by the penetration of cercariae

22. Egg granuloma in liver Pathogenesis
The granuloma consists mainly T and B lymphocytes, macrophages, giant cells, epitheloid cells, mast cells, plasma cells, fibroblasts and Eosinophils
Fibroblasts mediate collagen deposition in the granuloma, leading to the fibrosis that will eventually result in the hepatosplenic disease associated with schistosome infections

23. Fibrosis of portal vein

24. Eggs of S. japonicum in brain

25. Clinical features Acute schistosmiasis
May occur 5-8 weeks after the initial infection
Allergic reaction to first release of the eggs called Katayamu fever
Enlarged spleen and tender liver

26. Clinical features
Chronic schistosomiasis – immune modulation period
Thickening of colon with tiny ulceration
Liver and spleen enlargement
Occasionally diarrhea, anemia,wizened

27. Clinical features
Advanced schistosomiasis – hepatosplenic schistosomiasis -- usually happens 5 years after infection
Irreversible liver and spleen enlargement with abnormal function of these organs
Increased pressure in veins that drain upper intestine with risk of bursting of these veins. upper gastrointestinal bleeding may cause death
Cerebral granulomatous disease may be caused by ectopic S. japonicum eggs in the brain
In child, it may cause nanoid

28. Advanced schistosomiasis patients
ascites
Splenomegaly

29. Immunity Non-sterilized immunity
Concomitant immunity: Concomitant immunity has long been considered a feature of schistosome infections and describes the phenomenon where by the adult worms can survive happily in the mesenteric veins where as the host seems to be resistant to secondary infection.
Age-related immunity in human
Concomitant Immunity
Concomitant immunity has long been considered a feature of schistosome infections and describes the phenomenon where by the adult worms can survive happily in the mesenteric veins where as the host seems to be resistant to secondary infection. What is responsible for this type of immunity?
Experimental evidence in the mouse-schistosome model suggested that concomitant immunity was due to non-immune processes. Wilson and co-workers suggested the. As previously mentioned, as an infection proceeds there is a gradual build up of eggs in the liver which clogs the intra-hepatic circulatory system. These workers found that as a result of this blockage both intra and extra hepatic astamosis occurred such that the blood flow was shunted around these obstructions. These by-passes usually occurred in vessels of larger diameter such that the schistosomula on leaving the lungs were swept past the liver, where they would normally be trapped by the capillary bed and complete their development, and instead passed to other sites and eventually died. The researchers demonstrated this by injecting polystyrene beads of known diameter and showing that they ended up in sites other than the liver, once a critical threshold number of eggs were deposited in the liver. However, whether this occurs in human infections, or is a peculiarity of the mouse model system, is not clear. Given the enormous size of the human liver in comparison to the mouse and therefore its greater capacity to sustain higher egg burdens it seems less likely that this would be the only mechanism resulting in the concomitant immunity.
Epidemiological studies have demonstrated a pattern of age related immunity to reinfection which is not consistent with that which would be observed with normal non-sterile immunity. The bell shaped curve on the age-prevalence curve shown below suggests resistance due to acquired immunity or as a result of a change in the pattern of water contact.(It is well known that in general, children tend to play in water and therefore have more frequent contact with infective stages than the adult population.)
                                                      
There is some evidence for age related resistance to schistosomiasis:
1. Some heavily infected individuals, after treatment do not become re-infected. Resistance is not demonstrable in children under 10 years but increases progressively with age.
2. Some studies have demonstrated an association between of high levels of eosinophilia and resistance to re-infection.
3. Children under the age of 10 are readily re-infected after treatment, demonstrating a lack of resistance. This is as a result of increased levels of circulating IgM antibody which bind to the schistosomula, and as a result, blocks or masks the binding site for IgG antibody. IgG is important for initiating antibody-dependant cell-mediated cytotoxicity by eosinophils and macrophages. The level of IgM production decreases as the child ages which coincides with increase resistance to infection.

30. Diagnosis Etiological diagnosis
Sedimentation hatching method – first choice
Kato’s smear method for EPG
Rectal biopsy – must distinguish live or dead egg
Immunological diagnosis
COPT – CircumOval Precipitation Test
Intracutaneous test
ELISA, IHA, etc

31. Man's arm showing positive skin test for schistosome
Intracutaneous test

32. Control methods
Treat both human and the reservoir animals, such as buffalo, swine etc ---praziquantel
Feces (egg) control—avoid being discharged into water
Snail control---molluscicides
Ask people to avoid contacting with water that contained the snails and cercariae