S4 L5 SCHISTOSOMA

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S4 L5: Schistosoma (Blood Flukes) by Dr. Mary Antonette Madrid Bulinus sp.

Biomphalaria sp.

SCHISTOSOMIASIS Caused by digenetic blood trematodes. The three main species infecting humans are 1. Schistosoma haematobium ( bilharzia worm) 2. Schistosoma japonicum (Japanese blood fluke) 3. Schistosoma mansoni. (Manson’s blood fluke) Two other species, more localized geographically, are S. mekongi and S. intercalatum. In addition, other species of schistosomes, which parasitize birds and mammals, can cause cercarial dermatitis in humans. Schistosoma japonicum Oriental blood fluke Endemic in China, Philippines, Sulawesi and Indonesia In the Phil., the first report of schistosomiasis was made by Woolley in 1906 Strains from different geographic areas are distinct although ALL require Onchomelania snails as intermediate host Wide range of host o Dogs, pigs, cats, carabaos, cows, rodent, monkeys – found to be naturally infected Some hosts such as humans, monkey, rabbits, and mice are considered permissive hosts (S. japonicum matures and oviposits over extended periods) Adult and female worms are primarily parasites of the portal vein and its branches Females: lay up to 200 immature eggs in the branches of the portal vein which require 10-12 days to mature Eggs escape through ulcerations into the intestinal lumen  exported to feces Embryonated egg comes in contact with water  hatches  liberates miracidium Miracidia infect snail (intermediate host: Oncomelania hupensis quadrasi), and develop into sporocysts Sporocysts develop into cercariae Cercariae leave snail host and infect definitive hosts who come in contact with water by skin penetration 60-70 days from miracidial infection of the snail host to formation of cercariae Cercariae are transformed into schistosomula after skin penetration and find entry to the superficial lymphatic vessels or subcutanesous veins to reach the lungs From pulmonary circulation, schistosomulae migrates to the portal vein where they mature. Egg deposition begins from the 24th to the 27th day after cercarial penetration Intermediate hosts

Oncomelania sp.

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Eggs are eliminated with feces or urine; eggs hatch and release miracidia, which swim and penetrate specific snail intermedicate hosts. Stages in the snail include 2 generations of sporocysts and the production of cercariae. Upon release from the snail, the infective cercariae swim, penetrate the skin of the human host and shed their forked tail, becoming schistosomulae. Schistosomulae migrate through several tissues and stages to their target residence in the veins. Adult worms in the human reside in the mesenteric venules in various locations; females deposit eggs in the small venule of the portal and perivesical systems and are moved progressively toward the lumen of the small intestine (S. mansoni & S. japonicum) and of the bladder and ureters (S. haematobium) and are eliminated with feces or urine, respectively.

ADULT SCHISTOSOMES Adult worms in humans reside in the mesenteric venules in various locations, which at times seem to be specific for each species. S. japonicum is more frequently found in the superior mesenteric veins draining the small intestine S. mansoni occurs more often in the superior mesenteric veins draining the large intestine However, both species can occupy either location, and they are capable of moving between sites S. haematobium most often occurs in the venous plexus of bladder, but it can also be found in the rectal venules. Have separate sexes unlike other trematodes With large sucker capping the anterior end, a ventral sucker and a gonophore located posterior to the ventral sucker Suckers aid in movement; enables flukes to maintain position inside the veins Incomplete digestive systems; excretory system made up of flame cells. These internal structures are surrounded by circular and longitudinal muscles

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Male: shorter, sturdier; measures 12-20mm in length by 0.4 to 0.5mm diameter o Has a gynecophoral canal where the longer female is held o Testes arranged in one row above the ventral sucker Female: 15 -26 mm by 0.3mm o Single pyramidal ovary located in the midline Worms ingest RBC and possess a protease that breaks down globulin and hemoglobin Utilize glucose and are presumed to absorb nutrients through the body wall GEOGRAPHIC DISTRIBUTION S. mansoni is found in parts of South America and the Caribbean, Africa, and the Middle East; S. haematobium in Africa and the Middle East S. japonicum in the Far East. S. mekongi and S. intercalatum are found focally in Southeast Asia and central West Africa, respectively. In the Philippines, there are 24 endemic provinces o Includes Sorsogon, Oriental Mindoro, Samar, Leyte, Bohol and all provinces in Mindanao island except Misamis Oriental o Highest prevalence of infection is in children 5-15 years of age

2. 3.

period of early egg deposition and extrusion period of tissue proliferation

Early schistosomiasis Itching, chills, fever, cough Colonic schistosomiasis Ulceration caused by eggs result in dysentery or diarrhea Chronic stage: usually asymptomatic but occasional bouts of diarrhea may occur Occasionally chronic colonic schistosomiasis is associated with malignancies Hepatosplenic disease Hepatosplenomegaly, ascites, collateral circulation Pulmonary schistosomiasis Principal manifestation is cor pulmonale from obstruction of lung vasculature due to granuloma formation and fibrosis Cerebral schistosomiasis Acute stages present with fulminating meningoencephalitis with fever, headache, confusion, lethargy and coma Chronic cases: gives a clinical picture of a tumor with localizing signs and inc. intracranial pressure Among Filipinos, cerebral schistosomiasis is associated with pathology in other organs (liver and intestines)

PATHOLOGY OF SCHISTOSOMES CLINICAL FEATURES S. mansoni and S. japonicum schistosomiasis includes: Katayama fever, hepatic perisinusoidal egg granulomas, Symmers’ pipe stem periportal fibrosis, portal hypertension, and occasional embolic egg granulomas in brain or spinal cord. S. haematobium schistosomiasis includes: hematuria, scarring, calcification, squamous cell carcinoma, and occasional embolic egg granulomas in brain or spinal cord S. japonicum schistosomiasis includes: Main pathology: due to host granulomatous reaction to eggs deposited in the liver and other organs Quantity of cercariae determine severity of infection Cercarial penetration may result in dermatitis (cercarial dermatitis) Schistosomular migration causes superficial lung petechiae and pneumonitis After egg deposition, there is a granulomatous hypersensitivity reaction around it Most serious consequence of granuloma formation in liver is obstruction of the intrahepatic portal branches  portal hypertension, splenomegaly, ascites

Many infections are asymptomatic. Acute schistosomiasis (Katayama's fever) may occur weeks after the initial infection, especially by S. mansoni and S. japonicum. Manifestations: fever, cough, abdominal pain, diarrhea, hepatospenomegaly, and eosinophilia. Occasionall, central nervous system lesions occur. Continuing infection may cause granulomatous reactions and fibrosis in the affected organs, which may result in manifestations that include: o colonic polyposis with bloody diarrhea (Schistosoma mansoni mostly) o portal hypertension with hematemesis and splenomegaly (S. mansoni, S. japonicum, S. mansoni) o cystitis and ureteritis (S. haematobium) with hematuria, which can progress to bladder cancer o pulmonary hypertension (S. mansoni, S. japonicum, more rarely S. haematobium) o glomerulonephritis o central nervous system lesions.

CLINICAL ASPECTS S. japonicum Course of infection divided into 3 progressive stages 1. incubation: corresponds to period from cercarial penetration and schistosomular migration to maturation

The abdomen of an 11-year-old boy with intestinal schistosomiasis with the size and extent of the liver and spleen marked. Both are well below the midline, indicating the

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severity of infection. The disease has caused a stunting of the boy's growth, he is only 120cms tall and weighs 22 kg. WHO/TDR/Crump

Currently regarded as the method of choice for the definitive diagnosis of schistosomiasis in the Philippines COPT may take more than 2 years to become neg. LABORATORY DIAGNOSIS

(Left) A 13-year-old boy with schistosomiasis, hepatosplenomegaly, ascites, muscle atrophy, pyrexia, anaemia and haemorrhage from the gastrointestinal tract. (Right) Two boys, victims of schistosomiasis showing typical distension of the abdomen.

LABORATORY DIAGNOSIS Microscopic identification of eggs in stool or urine: most practical method for diagnosis Stool examination: S. mansoni or S. japonicum infection urine examination: S. haematobium Eggs can be present in the stool in infections with all Schistosoma species. The examination can be performed on a simple smear (1 to 2 mg of fecal material). Enhance detection of eggs by repeated examinations and/or concentration procedures (such as the formalin - ethyl acetate technique) field surveys and investigational purposes: quantify egg output by using the Kato-Katz technique (20 to 50 mg of fecal material) or the Ritchie technique. Eggs can be found in the urine in infections with S. haematobium (recommended time for collection: between noon and 3 PM) and with S. japonicum. Detection will be enhanced by centrifugation and examination of the sediment. Quantification is by using filtration through a Nucleopore® membrane of a standard volume of urine followed by egg counts on the membrane. Tissue biopsy (rectal biopsy for all species and biopsy of the bladder for S. haematobium) may demonstrate eggs when stool or urine examinations are negative.

ANTIBODY DETECTION Can be useful in both in clinical management (e.g., recent infections) and for epidemiologic surveys Can be useful to indicate schistosome infection: 1. Patients who have traveled in schistosomiasis endemic areas 2. Patients in whom eggs cannot be demonstrated in fecal or urine specimens Test sensitivity and specificity vary widely among the many tests reported for the serologic diagnosis of schistosomiasis and are dependent on both the type of antigen preparations used (crude, purified, adult worm, egg, cercarial) and the test procedure. At CDC, a combination of tests with purified adult worm antigens is used for antibody detection. All serum specimens are initially tested by FAST-ELISA using Schistosoma mansoni adult microsomal antigen (MAMA). A positive reaction (greater than 8 units/µl serum) indicates infection with Schistosoma species. o Sensitivity for S. mansoni infection: 99% o Sensitivity for S. haematobium infection: 95% o Sensitivity for S. japonicum infection: