Schistosome

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

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

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

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

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

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

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

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 20 - 30) S. japonicum: 50 or more eggs Dark grey color because of the metabolic RBC in the digestive duct

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

Eggs Morphology

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

Cercaria Morphology Free- swimming a forked tail penetrating glands

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

Life Cycle

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

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

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

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

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).

Papules caused by the penetration of cercariae

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

Fibrosis of portal vein

Eggs of S. japonicum in brain

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

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

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

Advanced schistosomiasis patients ascites Splenomegaly

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.

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

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

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