TREMATODE DISEASES SCHISTOSOMIASIS AL-Abbasi A.M. PhD, FRCP, DCN, DTM&H Professor of Infectious Diseases and Clinical Immunology

TREMATODE OF MEDICAL IMPORTANCE LIVER FLUKE: Fasciola hepatica SCHISTOSOMIASIS ARE OF DIFFERENT SPECIES: Synom. Flat warms S. mansoni S. hematobium S. japonicum S. mathee, S. intercalatum, S. mekongi

EPIDEMIOLOGY RECENT WHO REPORTS ESTIMATED: 500-600 million people in 74 tropical& subtropical countries are at risk More than 200 million are infected Of these 120 million are symptomatic 20 million have sever clinical disease

No racial predilection exists. Sex Race No racial predilection exists. Sex Schistosomiasis is more common in males, most likely because of increased exposure to infected water via bathing, swimming, and agricultural activities. Age Exposure to infection can start shortly after birth. People aged 10-14 years are at the maximum risk of exposure. The lower prevalence in adults is possibly due to partial immunity (concomitant immunity). and decreased exposure to infected water.

PATHOPHYSIOLOGY Allergic dermatitis at the site of entry. Cercariae: Allergic dermatitis at the site of entry. With prior sensitization, a pruritic papular rash develops. This also is observed with nonhuman avian schistosomes. Schistosomula: The tailless cercariae transported through blood or lymphatic's to the right side of the heart and lungs. Heavy infection can cause symptoms of cough and fever Katayama fever

Eggs: ADULT WORM Adult worms do not multiply inside the human body. In the venous blood, adult male and female worms mate, and the female lays eggs 4-6 weeks after cercarial penetration. Adult worms are rarely pathogenic The female adult worm lives for approximately 3-8 years and lays eggs throughout her life span. Eggs: They cause Katayama fever and schistosomiasis.

LIFE CYCLE OF SCHISTOSOMIASIS

MALE& FEMALE SHISTOSOMULAE IN BLOOD VESSEL

Urinary tract schistosomiasis: Gastrointestinal schistosomiasis: Peri portal fibrosis (Simmers clay pipe stem fibrosis). portal hypertension and gastrointestinal hemorrhage. Liver failure is uncommon except in concomitant chronic hepatitis or cirrhosis. Co-infection with either hepatitis B or C and S mansoni rapid progression of liver disease. Urinary tract schistosomiasis: Obstructive uropathy Renal failure pyelonephritis, bladder carcinoma (occurring usually 10-20 y after the initial infection). Immune complexes that contain worm antigens glomeruli, glomerulonephritis amyloidosis.

BLADDER L I VER

Female genital schistosomiasis (FGS): S haematobium causes lesions in the female lower genital tract (i.e., cervix, vulva, vagina). Facilitate the spread of some sexually transmitted diseases as HIV and human papillomavirus (HPV). Schistosomal cor pulmonale: An important complication that develops in about 5% of patients with hepatosplenic S mansoni. CNS schistosomiasis: Mostly with S japonicum, 2-4% of all S japonicum infections. CNS schistosomiasis can also occur with other species. Spinal schistosomiasis usually presents as transverse myelitis, primarily due to S mansoni infection.

SHISTOSOMAL OVA &CERCARIA

CLINICAL MANIFESTATIONS Acute manifestations Cercarial dermatitis: Individuals exposed to fresh or salt water may develop a pruritic rash due to cercarial dermatitis (Swimmer's itch). Also elsewhere and in North America due to nonhuman avian schistosomes.

a serum sickness–like illness. Katayama fever The exact pathophysiology is not known. It occurs 4-6 weeks after infection, at the time of the initial egg release. Most commonly with S japonicum but also has been reported with S mansoni. KF due to the high worm and egg antigen stimuli, from immune complex formation and lead to: a serum sickness–like illness. Fever, malaise, shortness of breath. Hepato splenomegaly Eosinophilia This syndrome is not due to granuloma formation.

ACUTE MANIFESTATIONS Katayama syndrome: most common symptoms. Fever, lethargy, and myalgia are most common symptoms. Less common symptoms: cough, headache, anorexia, and rash. A travel history that includes exposure to fresh water in an endemic area is an important part of the medical history.

Chronic manifestations Typically, onset is insidious. S mansoni, S mekongi, S intercalatum, and S japonicum cause intestinal tract and liver disease. S hematobium only rarely causes intestinal or liver disease but characteristically causes urinary tract disease.

Acute schistosomiasis Generalized lymphadenopathy Hepatosplenomegaly PHYSICAL FINDINGS Acute schistosomiasis Generalized lymphadenopathy Hepatosplenomegaly Rash Fever

C o m p l i c a t I o n s GI bleeding GI obstruction Malnutrition Schistosomal nephropathy Renal failure Pyelonephritis Bladder cancer Sepsis (Salmonella) Pulmonary hypertension Cor pulmonale Neuroschistosomiasis

S C H I S T O S O M A L E G G S IN THE L I V E R Chronic Granuloma, Type IV Immune Reaction

Stool or urine analysis LABORATORY STUDIES Stool or urine analysis Quantification of the egg excretion is calculated by collecting 24-hour urine or stool, homogenizing the sample, and counting the eggs in a measured sample. Urine or stool egg count in a 24-hour collection quantitates the severity of the infection. Fewer than 100 eggs per gram indicates a light infection, 100-400 eggs per gram indicates a moderate infection, and more than 400 eggs per gram indicates a heavy infection.

Egg viability test This test is important for assessing the effectiveness of treatment. It requires mixing the stools or urine with room-temperature distilled water and observing for hatching miracidia. An active infection produces viable eggs, while treated or past infection results in nonviable eggs and an absence of miracidia.

Serology The antibody test is a useful epidemiological tool but cannot be used to differentiate active and past illness. It does not allow quantification of egg burden. Serology findings can be used to reach a diagnosis in a patient from a non endemic area because a negative antibody test result would be expected. Falcon assay screening test (FAST), Enzyme-linked immunoassay (ELISA), and immunoblot assays.

Imaging Studies. Urinary schistosomiasis (occurs with chronic disease) Plain abdominal radiographs may demonstrate bladder and ureteral calcifications. On a sonogram, hydronephrosis, hydroureters, and bladder wall irregularities may be visible. Urography may demonstrate abnormalities in the ureter and bladder wall. Liver and intestinal schistosomiasis (chronic disease) Ultrasonography of liver and spleen is used to reach an early and accurate diagnosis of periportal fibrosis and a diagnosis of hepatosplenomegaly and ascites. On CT scan of the liver, calcified capsules and septa are visible. Mucosal irregularities are revealed by contrast studies of the intestine. Lung schistosomiasis (chronic disease) CT scan of the lungs may demonstrate early interstitial fibrosis. Findings on echocardiogram reflect pulmonary hypertension due to egg emboli to pulmonary vasculature. CNS schistosomiasis also occurs with chronic disease, and a CT scan and MRI scan of the brain and spinal cord may show lesions.

MANAGEMENT

Praziquantel (Biltricide) Description Usually well tolerated. Mechanism of action is complex. Damages the tegument membrane (the natural covering of the worm body) and exposes the worm to the body's immune response, which leads to worm death. Cure rate is equal to or greater than 85%. In persons not cured, the egg burden is markedly decreased. Adult Dose S haematobium and S mansoni: 40 mg/kg/d PO divided bid for 1 d S japonicum and S mekongi: 60 mg/kg/d PO divided tid for 1 d Pediatric Dose Contraindications Documented hypersensitivity; ocular cysticercosis Interactions Hydantoins may reduce serum praziquantel concentrations, possibly leading to treatment failures Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals Precautions Destruction of parasite within the eyes can cause irreparable lesions (ocular cysticercosis should not be treated with praziquantel); caution while driving or performing other tasks requiring alertness on the day of and following treatment; minimal increases in liver enzyme levels reported; when schistosomiasis or fluke infection is associated with cerebral cysticercosis, hospitalize patient for duration of treatment

Oxamniquine (Vansil) Description Adult Dose Pediatric Dose No longer available in the United States. Mechanism of action is complex. Metabolized into an ester by schistosomes. Damages tegument surface of male schistosome worms so that the immune system is able to kill the worm. Stops female from producing eggs. Only effective against S mansoni. Cure rate is 60-90%. Adult Dose 15 mg/kg PO as single dose Pediatric Dose 20 mg/kg PO divided bid for 1 d Contraindications Documented hypersensitivity Interactions None reported; food may delay absorption Pregnancy D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus Precautions Use caution and closely monitor in patients with history of seizures because they may experience epileptiform convulsions; EEG abnormalities may develop in patients with normal pretreatment recordings

Early disease usually improves with treatment. Prognosis Early disease usually improves with treatment. Hepatic, renal, and intestinal pathology improves with treatment. Hepatosplenic schistosomiasis carries a relatively good prognosis because hepatic function is preserved until the end of the disease (unless variceal bleeding occurs). Cor pulmonale usually does not improve significantly with treatment. Depending on location and size, brain lesions usually improve with treatment. Spinal cord schistosomiasis carries a guarded prognosis. Praziquantel should be administered as soon as possible