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Gorgas Case 2010-08

History:  38 year-old female with 8 weeks of RUQ abdominal pain and fever with several days of self-limited watery diarrhea at the onset.  Progression of the unremitting pain led to an admission to another hospital where she was reportedly anemic, with leucocytosis and a 12% eosinophilia.  No history of trauma.  She was treated with blood transfusion and broad spectrum antibiotics at this and a subsequent hospital without effect on the RUQ pain but the fever eventually came down.

Epidemiology:  Born and lives in Chiclayo on the north coast.  Nocontact with animals, no household members with TB, no HIV risk factors.

Physical Examination: (on arrival at our hospital)  Afebrile,normal vital signs.  No pallor, jaundice or rash.  Normal chest andcardiovascular exam.  Marked RUQ pain on palpation, mild hepatomegaly.

Laboratory Results:  Hemoglobin 12.3 g/dl.  WBC 6780, 49% polys,11% eos.  Alk phosphatase 2 times normal; all other biochemical tests normal.  Normalchest x-ray.  PPD 10 mm.  CT scan is shown in Images A & B.

Discussion:  IgG Fas2 ELISA [Trans R Soc Trop Med Hyg. 1999 Jan-Feb;93(1):54-7] was positive for Fasciola hepatica.  This test is more specific than Western blot or Arc2 immunodiffusion.  Eggs of F. hepatica were observed in stool samples.

Fasciola hepatica is a trematode (fluke or flatworm) in which the mature adult parasites inhabit the large biliary ducts.  As with all other trematodes, Fasciola hepatica requires a snail intermediate host.  Eggs produced by the hermaphroditic adults pass with the feces and hatch, releasing larvae in fresh water.  After passing through a snail, mature cercariae emerge and rapidly encyst on various kinds of aquatic vegetation such as watercress.  After ingestion by a human or animal definitive host, the metacercariae excyst in the duodenum and larvae penetrate the intestinal wall and subsequently directly into the liver via Glisson’s capsule embarking on a destructive migratory process through the hepatic parenchyma [Image C] for 3-4 months until they reach large biliary ducts where they mature to adults.  As in this case, migration through a capsular vessel may result in significant hemorrhage.

The mature adults are from 1-3 cm long and attach to the biliary epithelium by a single ventral sucker [Image D from our case files shows an endoscopic view of an adult in the common bile duct use].  In the absence of direct visualization of adults, characteristic eggs can be seen on stool examination, but more often patients present in the early migratory phases of infection prior to maturation of the worm and the onset of egg-laying.  Specific serology is the test of choice.

The distribution of Fasciola hepatica is cosmopolitan, but is by far the most common in sheep-raising areas where herbivores are common definitive hosts.  Heavily infected sheep develop “sheep liver rot”.  Other important definitive hosts are goats, cattle, horses, llamas, vicunas, and camels.  The contiguous Altiplano regions of the Peruvian and Bolivian Andes are highly endemic, with human prevalence rates of as high as 67% in some villages.  Egypt, Cuba, and Northern Iran are also highly endemic and the parasite is emerging in Vietnam and Cambodia.  Cooking, which would kill the metacercariae, dramatically changes the flavor of watercress and the population is reluctant to adopt this simple measure.  Our patient regularly ingested emoliente, a local tea-like drink that uses drops of watercress juice to provide a bitter flavor.

Clinically, the disease can be divided into acute and chronic phases.  During the acute phase, migrating parenchymal larvae generally cause fever, eosinophilia, right upper quadrant pain and especially significant anorexia.  Vomiting and weight loss of 20 kg or more may develop, which usually abates when the larvae mature to adults.  The adult flukes in the biliary tree are generally asymptomatic but some patients develop chronic manifestations including right upper quadrant pain, nausea, vomiting, and hepatomegaly.  Eosinophilia and abnormal liver function may develop but are less common than with acute disease.  Adult flukes may cause hyperplasia, desquamation, thickening, and dilatation of the bile ducts.  Malignant degeneration and cholangiocarcinoma such as results from chronic infection with the oriental liver fluke Clonorchis sinensis has not been reported with Fasciola hepatica.  We have recently reported a case series with clinical findings and evolution of disease [Am J Trop Med Hyg. 2008;78:222-7].  Please see Gorgas Case 2005-02 for a CT image of the typical larval tracks seen in acute disease.

The differential diagnosis of eosinophilia with accompanying destructive hepatic lesions is limited.  Toxocariasis causes hypereosinophilia with hepatomegaly but the pathology results from small granulomas around individual non-migrating larvae and not the large destructive lesions seen in our patient.  Eosinophilia is common in Perú so it may be due to an unrelated event present concomitantly with a bacterial liver abscess; this had been the initial impression in this case.

Fasciola hepatica is the only trematode infection for which praziquantel is not the drug of choice.  WHO has put the anthelmintic triclabendazole (Egaten, Novartis) on its essential drugs list.  Egaten is registered in Perú (as in Mexico and Egypt) and is available via free donation from the WHO.  In the U.S. and many other countries Egaten can be obtained by special release from the manufacturer or it may be obtained directly from the World Health Organization in Geneva.  The usual dosage is 10mg/kg with a meal.  Many practitioners repeat the dosage 12-24 hours later.  In our institute the cure rate is 96% [A. Terashima, unpublished].