Fasciola Hepatica ECCMID LONDON ABRIL 2012 EDUARDO GOTUZZO,A M.D.FACP.FIDSA

TREMATODES: Fasciola hepatica ECCMID LONDON ABRIL 2012 EDUARDO GOTUZZO,A M.D.FACP.FIDSA

UNIVERSIDAD PERUANA CAYETANO HEREDIA HOSPITAL NACIONAL© by CAYETANO author HEREDIA

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia HERMAPHRODITIC TREMATODES

- BILIARY TRACT: • Fasciola hepatica • Clonorchis sinensis

- INTESTINAL CANAL: • Fasciolopsis buski

- LUNG: • Paragonimus© by westermani author

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia HERMAPHRODITIC TREMATODES CLASSIFICATION

- BILIARY TRACT: Liver flukes • Fasciola hepatica, F. gigantica • Clonorchis sinensis • Opistorchis felineus, O. viverrini • Dicrocoelium dendriticum © by author

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia HERMAPHRODITIC TREMATODES CLASSIFICATION

- INTESTINAL CANAL: Intestinal flukes • Fasciolopsis buski

• Heterophyes heterophyes • Metagonimus yokogawai • Echinostoma • Gastrodiscoides© by authorhominis

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia HERMAPHRODITIC TREMATODES CLASSIFICATION - LUNG : Lung flukes • Paragonimus westermani

• P. miyazakii, P. skrjabini, P. heterotremus • P. africanus, P. uterobilateralis • P. mexicanus, P. caliensis, P. amazonicus, P. inca © by author

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia

ESCMID Online Lecture Library HERMAPHRODITIC TREMATODES

LIFE CYCLE • Adult fluke: vertebrate host • Eggs water miracidium • Miracidium snail (1st. IH) sporocysts • Sporocyst 1st and 2nd generation rediae fish • Rediae cercariae water crustacean metacercariae plant (encyst) © by author(2nd IH )

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola hepatica

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola hepatica and F. gigantica • F. hepatica : Adult: 20-30 mm by 8-13 mm Worldwide Definitive Host: Sheep, cattle • F. gigantica : Adult: 20-75 mm by 8-20 mm Africa, western Asia, South America Definitive Host: Cattle, sheep

• 1st Int. Host : Lymnaea snails © by author

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola hepatica and F. gigantica

• Metacercariae in 2nd intermediate host: Watercress, alfalfa, lettuce (or water) → excyst (duodenum) → penetrate the intestinal wall → peritoneal cavity → penetrate Glisson's capsule → traverse liver parenchyma → large bile ducts → adults • Incubation period to adult flukes: 3-4 months • Life span: 9-13 years

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia FASCIOLA LIFE CYCLE

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola Hepatica Infection

• High prevalence – Bolivia (Altiplano) - Peru (Andean Valleys)

• New endemic area: South east Asia • (THAILAND.LAOS.CAMBODIA,VIETNAM)

• Endemic in some AREAS TURKEY ,IRAN

Mas-Coma 2010 © by author

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia FASCIOLA Egg Miracidium

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia FASCIOLA Redia Cercaria

Sym: - Abdominal pain (65%) in RUQ, epigastrium - Anorexia, nausea, vomiting, diarrhea - Fever (60%), headache, night sweats, weight loss (35%) PE: - Tender hepatomegaly, splenomegaly, jaundice unusual, ascites - Urticaria, wheezing - Cough, pleural effusion,© by pulmonary author infiltrates Lab: - Leukocytosis, marked eosinophilia (95%)

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola hepatica and F. gigantica PATHOLOGY • Migrating larva: - Liver parenchimal destruction and dilatation of bile ducts - Fibrosis and calcification with necrosis - Abscess formation and hemorrhage. • Adult flukes: - Hiperplasia, desquamation, thickening and dilatation of bile ducts - Fibrosis and calcification. • Granulomas and abscesses© aroundby author eggs trapped in the parenchimal tissue.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola hepatica-induced liver abscess

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Foreign body reaction against the ovum (pseudotubercle)

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fascioliasis NEJM 2002;346(16):1232-1239 7 cm lesion 1,5 months later

1,5 months later Serpiginous yellow nodules

ESCMID Online Lecture Library Fascioliasis Marcos LA et al. Am J Trop Med Hyg 2008;78(2):222-227.

Less 1 week of symptoms: Thickened 2 weeks of symptoms: Hypodense, tract- Glisson`s capsule and hypodense lesion. like, serpiginous lesion.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fascioliasis Marcos LA et al. Am J Trop Med Hyg 2008;78(2):222-227.

2 mo of symptoms: Subcapsular hematoma; 5 mo of symptoms: Lesions are more thickening and enhancing of Glisson`s capsule. central, nodular, serpiginous; splenomegaly.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola Hepatica Acute Phase Subcapsular Hematoma

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola hepatica and F. gigantica CLINICAL MANIFESTATIONS CHRONIC PHASE (LATENT or OBSTRUCTIVE) Asymptomatic or symptomatic Sym: - Intermittent abdominal pain in RUQ, epigastrium, biliary colic - Anorexia, nausea, vomiting - Cholangitis (fever, jaundice) - Calculous or acalculous cholecystitis PE: - Tender hepatomegaly - Severe: Ascites with© blood, by author severe anemia Lab: - Abnormal LFT, eosinophilia

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fascioliasis Palmer PES and Reeder MM. The Imaging of Tropical Diseases, Springer-Verlag 2001.

Gallbladder with sludge and vermiform Dilated comon duct nonshadowing images

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fascioliasis. Multiple linear, crescent-shaped lucencies in the distal common duct (flukes). Palmer PES and Reeder MM. The Imaging of Tropical Diseases, Springer-Verlag 2001.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola hepatica and F. gigantica COMPLICATIONS

CHRONIC PHASE - Hemobilia - Anemia - Hematemesis and melena - Bile duct and gallbladder stones - Sclerosing cholangitis - Biliary cirrhosis © by author

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fascioliasis-liver fluke (trematode) Hx: 62-year old female with 3m. of fever, severe general malaise, loss of appetite, 10 kg weight loss, right upper quadrant pain and initially some icterus. No meds. Evaluation 1 m. earlier had shown an eosinophil count of 7,500, Alk P. 8X normal, transaminases 2X normal, and 3 neg stools. CXR was normal and an abdominal ultrasound showed numerous small (<15mm) lesions throughout the liver. Empiric Rx with 7 days of praziquantel without effect. No past med Hx. Epi: Farmer. Her husband, who had a history of chronic alcoholic liver disease,© had by become author ill at the same time and died with icterus, ascites, and hypereosinophilia. Just prior to the illness the husband had heard of beneficial health effects of watercress which was consumed on only once. THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Case continued

PE: Pale. Afebrile. Liver non-tender 3 cm below costal margin. No splenomegaly. Lab: Hct 31. WBC 15,600 21 PMN, 18L, and 56 eos. Blood cultures neg. LFTs not repeated. Hepatitis A, B, C, negative. Stool O & P and serological tests were ordered. Available CT image is from 3 months later.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Clinical presentation and management of Fasciola hepatica infection: Single-center experience.

Mushin Kaya, Remzi Bestas and Sedat Cetin

World J Gastroenterol 2011, November 28;17(44):4899-4904

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Human Fasciolasis in Turkey

Jan. 2008 - Feb. 2011

30 patients (24 females) 22 hepatic lesions 5 Biliary tract 3 Biliary and pancreatitis © by author

OTHER LOCALIZATIONS • Blood vessels, lung, peritoneum, intestinal wall • Muscles, eyes, brain, testes

“HALZOUN” (Jtalzoun or Marrara): Suffocation • NOT due to Fasciola© by → authorPentastomids • Pharyngeal edema: Dysphagia, dyspnea, asphyxiation

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fascioliasis. Cutaneous migratory track in the patient. Am J Trop Med Hyg 2005;72(5):508–509.

Clinical picture removed on request of the author

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola hepatica and F. gigantica DIAGNOSIS ACUTE PHASE: Serology : • FAST-ELISA: 95% sens, ~100% spec • Fas2-ELISA: 95% sens, ~100% spec • Immunoblot: ~100% sens, ~100% spec • CIEF for copro-antigens (3-4 w before eggs)

CHRONIC PHASE: Eggs • Stools: Rapid sedimentation technique (Lumbreras) • Duodenal contents ("string© by test")author Rule out spurious infection

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola Hepatica Infection

1. Treatment a) Emetina Hydrocloride IM Bithionol 30-50mg/Kg in alternate days for 10 days b) New indication: Triclabendazole 10mg/Kg. one dose/day (1-2 days) -High efficacy >95% -Low side effect -Oral © by author IS THE DRUG OF CHOICE

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Massive Fasciola hepatica infection •Probable single exposure to contaminated watercress. •+ve for eggs of Fasciola hepatica. WB+. •Altiplano of Peru and Bolivia highly endemic. Prevalence up to 67% in some villages. •DDx of hypereosinophilia with destructive hepatic lesions is limited. Toxocariasis pathology due to granulomas around individual non-migrating larvae; non-destructive •Only trematode infection for which praziquantel is not the drug of choice. Triclabendazole (Novartis) is on WHO essential drugs list. •Destructive inflammatory tracks persist radiologically and histologically for months even© after by apparent author parasitic cure.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fascioliasis Marcos LA et al. Am J Trop Med Hyg 2008;78(2):222-227. 6 mo after treatment: Calcified, popcorn- like 11 months after treatment: Multiple lesions with a hypodense centre. calcified nodular foci.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Clonorchis sinensis

• Definitive host: Cats, dogs, fish-eating mammals.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Clonorchis sinensis and Opistorchis viverrini / felineus PATHOLOGY • Desquamation, adenomatous hyperplasia of bile duct epithelium. • Infiltration with lymphocytes, monocytes, eosinophils and plasma cells. • Biliary obstruction, bile retention, periductal fibrosis. • Inflammation, necrosis and atrophy of hepatocytes. • Worms and eggs act© as bya nidus author for stone formation.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Clonorchis in dilated bile ducts.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Clonorchiasis. Mild, uniform dilatation of bile ducts. Byung Ihn Choi et al. Clin Microbiol Rev 2004;17(3):540-552.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Clonorchiasis. Choi D et al. Korean J Parasitol 2007;45(2):77-85.

B. Periductal enhancement with thickened bile A. Mild dilatation of peripheral bile ducts. duct walls.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Clonorchis sinensis and Opistorchis viverrini / felineus COMPLICATIONS - Recurrent ascending cholangitis - Obstructive jaundice - Cholecystitis - Pancreatitis - Gallbladder or intrahepatic stones - Cholangiocarcinoma© by author

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Clonorchis. Well-differentiated adenocarcinoma of the bile duct.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Clonorchiasis Byung Ihn Choi et al. Clin Microbiol Rev 2004;17(3):540-552. Choi D et al. Korean J Parasitol 2007;45(2):77-85. A. Intrahepatic cholangiocarcinoma (T). B. Segmental and more severe dilatation around Dilated bile ducts peripheral to the tumor. the tumor caused by obstruction by the tumour.

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Cholangiocarcinoma in magnetic resonance cholangiopancreatography and fascioliasis in endoscopic ultrasonography

Amir Houshang Mohammad Alizadeh, Mohammad Roshani, Farhad Lahmi, Nasrin Ahangar Davoodi, et al

Case Rep. Gastroenterol 2011. Sep-Dec; 5(3):569-577

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia Fasciola hepatica:chronic impact

• In animal model ,dr Marcos showed excellent data about the liver fibrosis • In peruvian study in cirrhotic patients • 9.1% were positive toFas2 ELISA • CAN be associate to cancer of biliary tract?

THE UNIVERSITYESCMID OF Online Lecture LibraryUniversidad Peruana ALABAMA AT BIRMINGHAM The Gorgas Course Cayetano Heredia