CEREBRAL SCHISTOSOMIASIS SUBSEC A6 DRA. NAVARRA

1. Pathogenesis of hepato-splenic manifestations of Schistosoma infection CENTENO, Lisa Joy S.

Ova carried in the portal blood  embolize to the liver  lodge in the sinusoids  granuloma formation. Ova carried in the portal blood  embolize to the liver  lodge in the sinusoids  granuloma formation. Hemodynamic changes result Hemodynamic changes result Portal hypertension Portal hypertension Development of portosystemic collaterals at the esophagogastric junction and other sites. Development of portosystemic collaterals at the esophagogastric junction and other sites. Esophageal varices can rupture causing hematemesis Esophageal varices can rupture causing hematemesis

Compensatory arterialization of blood flow through the liver is established  retention of hepatic perfusion  maintenance of normal liver function for several years. Compensatory arterialization of blood flow through the liver is established  retention of hepatic perfusion  maintenance of normal liver function for several years.

Periportal (Symmers’ clay pipe-stem) fibrosis then ensues: Periportal (Symmers’ clay pipe-stem) fibrosis then ensues: In areas of egg deposition and granuloma formation but may also be in periportal areas. In areas of egg deposition and granuloma formation but may also be in periportal areas. It is a pure fibrosis vs. the cirrhosis involving other nutritional factors or infectious agents (i.e. Hepatitis B and C). It is a pure fibrosis vs. the cirrhosis involving other nutritional factors or infectious agents (i.e. Hepatitis B and C). Fibrinogenesis as a result of cytokine stimulation by IL2, IL4, IL1 and TGFβ. Fibrinogenesis as a result of cytokine stimulation by IL2, IL4, IL1 and TGFβ. Interaction of T lymphocytes and cells of the fibroblast series deposits fibrotic tissue in the extracellular matrix. Interaction of T lymphocytes and cells of the fibroblast series deposits fibrotic tissue in the extracellular matrix.

Hepatic splenic manifestations can occur early in the disease with liver enlargement due to granulomatous lesions. Hepatic splenic manifestations can occur early in the disease with liver enlargement due to granulomatous lesions. May be correlated roughly with intensity of infection, occurring more often in children and related to specific HLA haplotypes. May be correlated roughly with intensity of infection, occurring more often in children and related to specific HLA haplotypes.

Subsequent phases: Portal hypertension and splenomegaly due to presinusoidal blockage of blood flow. Subsequent phases: Portal hypertension and splenomegaly due to presinusoidal blockage of blood flow. Varices at the lower end of the esophagus and at other sites. Varices at the lower end of the esophagus and at other sites. Bleeding from esophageal varices may be first clinical manifestation of hepatosplenic phase. Bleeding from esophageal varices may be first clinical manifestation of hepatosplenic phase. RUQ “dragging” pain that may move to the LUQ as splenomegaly progresses RUQ “dragging” pain that may move to the LUQ as splenomegaly progresses

Late-stage disease: Late-stage disease: Fibrotic changes with deteriorating liver function Fibrotic changes with deteriorating liver function Onset of ascites, hypoalbuminemia and coagulation defects. Onset of ascites, hypoalbuminemia and coagulation defects. Accelerating or exacerbating factors to hepatic function deterioration: Accelerating or exacerbating factors to hepatic function deterioration: Concurrent viral infections of the liver (esp. hepatitis B and C) or nutritional deficiencies. Concurrent viral infections of the liver (esp. hepatitis B and C) or nutritional deficiencies. HCC risk can increase. HCC risk can increase.

Complications: Complications: Through portosystemic collaterals, or directly from the IVC in the case of bladder wall schistosomiasis, eggs can reach the pulmonary circulation leading to pulmonary granulomatosis and fibrosis, pulmonary hypertension, and cor pulmonale with a high mortality rate. Through portosystemic collaterals, or directly from the IVC in the case of bladder wall schistosomiasis, eggs can reach the pulmonary circulation leading to pulmonary granulomatosis and fibrosis, pulmonary hypertension, and cor pulmonale with a high mortality rate. Gallbladder cancer can also be associated. Gallbladder cancer can also be associated.

2. Differentiate the clinical features of schistosomal hepatomegaly from that of viral hepatitis, miliary tuberculosis, and malaria Rosalyn Chan

Schistosomal Hepatomegaly Ova are carried by portal blood embolize to the liver and lodge at presinusoidal sites, where granulomas are formed Ova are carried by portal blood embolize to the liver and lodge at presinusoidal sites, where granulomas are formed Class I and Class II human leukocyte antigen (HLA) haplotypes and markers – genetic basis appears to be multigenic Class I and Class II human leukocyte antigen (HLA) haplotypes and markers – genetic basis appears to be multigenic Presinusoidal blockage causes several hemodynamic changes, including portal hypertension and associated development of portosystemic collaterals at the esophagogastric junction and other sites Presinusoidal blockage causes several hemodynamic changes, including portal hypertension and associated development of portosystemic collaterals at the esophagogastric junction and other sites Esophageal varices are present and can lead to recurring hematemesis Esophageal varices are present and can lead to recurring hematemesis Since changes in hepatic portal blood flow occur slowly, compensatory arterialization of the blood flow through the liver is established – retention of hepatocyte perfusion permits maintenance of normal liver function for years Since changes in hepatic portal blood flow occur slowly, compensatory arterialization of the blood flow through the liver is established – retention of hepatocyte perfusion permits maintenance of normal liver function for years

Periportal fibrosis (Symmers’ clay pipe-stem fibrosis) but can also be diffuse Periportal fibrosis (Symmers’ clay pipe-stem fibrosis) but can also be diffuse Fibrosis, when diffuse, may be seen in areas of egg deposition and granuloma formation but is also see in distant locations such as portal tracts Fibrosis, when diffuse, may be seen in areas of egg deposition and granuloma formation but is also see in distant locations such as portal tracts Pure fibrosis lesions – deposition of fibrotic tissue in the extracellular matrix results from the interaction of T lymphocytes with cells of the fibroblast series; several cytokines such as IL-2, IL-4, IL-1, and transforming growth factor beta (TGF-B) are know to stimulate fibrogenesis Pure fibrosis lesions – deposition of fibrotic tissue in the extracellular matrix results from the interaction of T lymphocytes with cells of the fibroblast series; several cytokines such as IL-2, IL-4, IL-1, and transforming growth factor beta (TGF-B) are know to stimulate fibrogenesis

Viral Hepatitis Esophageal varices common as a result of portal hypertension Esophageal varices common as a result of portal hypertension Stigmata of liver cirrhosis due to viral hepatitis: Stigmata of liver cirrhosis due to viral hepatitis: Spider angioma Spider angioma Palmar erythema Palmar erythema Asterixis Asterixis Gynecomastia Gynecomastia

Acute Hepatitis Enlarged, reddened liver; greenish if cholestatic Enlarged, reddened liver; greenish if cholestatic Parenchymal changes: Parenchymal changes: Hepatocyte injury (swelling, ballooning degeneration) Hepatocyte injury (swelling, ballooning degeneration) Cholestasis: canalicular bile plugs Cholestasis: canalicular bile plugs HCV: mild focal fatty change of hepatocytes HCV: mild focal fatty change of hepatocytes Hepatocyte necrosis: isolated cells or clusters Hepatocyte necrosis: isolated cells or clusters Cytolysis (rupture) or apoptosis (shrinkage) Cytolysis (rupture) or apoptosis (shrinkage) If severe: bridging necrosis (portal-portal, central-central, portal- central) If severe: bridging necrosis (portal-portal, central-central, portal- central) Lobular disarray: loss of normal architecture Lobular disarray: loss of normal architecture Regenerative changes: hepatocyte proliferation Regenerative changes: hepatocyte proliferation Sinusoidal cell reactive changes: Sinusoidal cell reactive changes: Accumulation of phagocytosed cellular debris in Kupffer cells Accumulation of phagocytosed cellular debris in Kupffer cells Influx of mononuclear cells into sinusoids Influx of mononuclear cells into sinusoids Portal tracts: Portal tracts: Inflammation: predominantly mononuclear Inflammation: predominantly mononuclear Inflammatory spillover into adjacent parenchyma, with hepatocyte necrosis Inflammatory spillover into adjacent parenchyma, with hepatocyte necrosis

Chronic Hepatitis Changes shared with acute hepatitis Changes shared with acute hepatitis Hepatocyte injury, necrosis, and regeneration Hepatocyte injury, necrosis, and regeneration Sinusoidal cell reactive changes Sinusoidal cell reactive changes Portal Tracts Portal Tracts Inflammation: Inflammation: Confined to portal tracts Confined to portal tracts Spillover into adjacent parenchyma, with necrosis of hepatocytes (interface hepatitis) Spillover into adjacent parenchyma, with necrosis of hepatocytes (interface hepatitis) Bridging inflammation and necrosis Bridging inflammation and necrosis Fibrosis: Fibrosis: Portal deposition Portal deposition Portal and periportal deposition Portal and periportal deposition Formation of bridging fibrous septa Formation of bridging fibrous septa HBV: “ground glass ” hepatocytes, “sanded ” nuclei HBV: “ground glass ” hepatocytes, “sanded ” nuclei HCV: bile duct epithelial cell proliferation, lymphoid aggregate formation HCV: bile duct epithelial cell proliferation, lymphoid aggregate formation

Miliary Tuberculosis Hepatic granuloma and resulting hepatomegaly occurs in more than 90% of patients with military tuberculosis Hepatic granuloma and resulting hepatomegaly occurs in more than 90% of patients with military tuberculosis Clinical symptoms: fever, night sweat, fatigue, and weight loss. Jaundice is an unusual finding Clinical symptoms: fever, night sweat, fatigue, and weight loss. Jaundice is an unusual finding Granulomas are found randomly scattered in the parenchyma and also in the portal tracts, though therea re reports of granulomas in the portal area and caseation may be seen. Granulomas are found randomly scattered in the parenchyma and also in the portal tracts, though therea re reports of granulomas in the portal area and caseation may be seen. Acid-fast organisms are not usually found in liver smears but PCR for mycobacterium tuberculosis can be performed (Sp = 96%, Sn= 53%) Acid-fast organisms are not usually found in liver smears but PCR for mycobacterium tuberculosis can be performed (Sp = 96%, Sn= 53%)

Malaria Budd-Chiari Syndrome: the obstruction of two or more major hepatic veins produces liver enlargement, pain, and ascites due to increased intrahepatic blood pressure and an inability of the massie hepatic blood flow to shunt around the blocked outflow tract Budd-Chiari Syndrome: the obstruction of two or more major hepatic veins produces liver enlargement, pain, and ascites due to increased intrahepatic blood pressure and an inability of the massie hepatic blood flow to shunt around the blocked outflow tract Sequestration in the hepatic microvasculature and increased coaguation cascade activity through intrinsic pathway activation have been proposed as likely mechanisms. Antithrombin III depletion in severe falciparum malaria may produce a hypercoaguable state and hepatic vein thrombosis. Cytokine release is also procoagulant and may add to the mechanism of venous block. Disseminated intravascular coagulation is important in the pathogenesis of severe malaria. Thus, coagulopathy can play a major role in producing a complication like Budd-Chiari syndrome in falciparum malaria. Sequestration in the hepatic microvasculature and increased coaguation cascade activity through intrinsic pathway activation have been proposed as likely mechanisms. Antithrombin III depletion in severe falciparum malaria may produce a hypercoaguable state and hepatic vein thrombosis. Cytokine release is also procoagulant and may add to the mechanism of venous block. Disseminated intravascular coagulation is important in the pathogenesis of severe malaria. Thus, coagulopathy can play a major role in producing a complication like Budd-Chiari syndrome in falciparum malaria.

With acutely developing thrombosis of the hepatic veins the liver is swollen and red-purple and has a tense capsule. Microscopically the affected hepatic parenchyma reveals severe centrilobular congestion and necrosis. Centrilobular fibrosis develops in instances in which the thrombosis is more slowly developing. With acutely developing thrombosis of the hepatic veins the liver is swollen and red-purple and has a tense capsule. Microscopically the affected hepatic parenchyma reveals severe centrilobular congestion and necrosis. Centrilobular fibrosis develops in instances in which the thrombosis is more slowly developing. The major veins may contain totally occlusive fresh thrombi, subtotal occlusion, or, in chronic cases, organized adherent thrombi. The major veins may contain totally occlusive fresh thrombi, subtotal occlusion, or, in chronic cases, organized adherent thrombi.

3. Outline Instructions for a Person Planning to Travel to an Endemic Area Chavez, Justin Karlo B.

Prevention and Control It is prudent for travelers to avoid contact with all freshwater bodies. It is prudent for travelers to avoid contact with all freshwater bodies. If exposure occurs, a follow-up visit with a health care provider is strongly recommended. If exposure occurs, a follow-up visit with a health care provider is strongly recommended.

Usage of molluscicides, provision of sanitary water, sewage disposal, chemotherapy and health education may be a valuable tool to prevent schistosomiasis. Usage of molluscicides, provision of sanitary water, sewage disposal, chemotherapy and health education may be a valuable tool to prevent schistosomiasis.

Diagnosis The afflicted patient usually presents with: The afflicted patient usually presents with: Cercarial dermatitis Cercarial dermatitis Katayama Fever Katayama Fever High level peripheral blood eosinophilia, (+) serologic assay for schistosomal antibodies (FAST- ELISA, EITB). High level peripheral blood eosinophilia, (+) serologic assay for schistosomal antibodies (FAST- ELISA, EITB). * To make a correct diagnosis, it is important to note the recent travel history of the patient and exposure to freshwater bodies.

Geographic history, characteristic clinical presentation and presence of schistosome ova in excreta Geographic history, characteristic clinical presentation and presence of schistosome ova in excreta Serologic assays may be used to detect circulating schistosome antigen Serologic assays may be used to detect circulating schistosome antigen Kato thick smear of feces may be done to detect disease in a lightly infected individual Kato thick smear of feces may be done to detect disease in a lightly infected individual Nucleopore filter of urine may be done to check for S. Hematobium Nucleopore filter of urine may be done to check for S. Hematobium Tissue biopsy may also be done Tissue biopsy may also be done

Treatment S. mansoni, S. intercalatum, S. haematobium, S. japonicum, S. mekongi – Drug of choice: Praziquantel, 20/mgkg, 2 doses in a day and 3 doses for S. japonicum and mekongi S. mansoni, S. intercalatum, S. haematobium, S. japonicum, S. mekongi – Drug of choice: Praziquantel, 20/mgkg, 2 doses in a day and 3 doses for S. japonicum and mekongi Cure rate is 85%, reduces egg counts >90% Cure rate is 85%, reduces egg counts >90%

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