University of Alabama at Birmingham

Gorgas Case 2018-08

Universidad Peruana Cayetano Heredia

The following patient was seen in the Outpatient Department of the Hospital Cayetano Heredia.

Image for Case 2018-08
History: 41yo previously healthy female, presents with an 8-month history of oppressive right upper quadrant pain (up to 7/10), which is intermittent, without radiation, and associated with nausea and episodic diarrhea without mucus or blood. The pain has increased in the last two months and now radiates to the back with exacerbation with food intake with resulting anorexia. No fever, rash, jaundice, vomiting, or joint pain.

Epidemiology: Born and lives in Huaraz, in the Peruvian highlands. Non-smoker, no alcohol abuse, no known TB exposures. No HIV risk factors. Normal diet with ingestion of lettuce, spinach and other vegetables. Occasional contact with Guinea pigs. Denies any travels for the past year.

Physical Examination on Admission: BP: 110/60mmHg.  HR: 70. RR 19. Weight 55kg. Height 1.46m. Afebrile with no lymphadenopathy. Skin: No jaundice or rash. Chest: Clear. Abdomen: Mild tenderness and pain to deep palpation in the right upper quadrant and a liver span approx. 14cm with a palpable edge. Negative Murphy's sign. No splenomegaly. Rectal exam is normal.

Laboratory Examination and Imaging:  WBC 9 110 (0 bands, 31% segmented neutrophils, 35 eosinophils, 7 monos, 27 lymphs). Hb 14.2g/dl, Hct 40%. Platelets 321 000. Glucose 95 mg/dl. Urea 27 mg/dl. Creatinine 0.4 mg/dl. Total protein 6.9 g/dl. Albumin 3.3 g/dl. Total Bilirubin 0.5 mg/dl. ALT/AST 38/57 UI/L. Gamma-glutamyltransferase 104 UI/L. Alkaline phosphatase: 274U/L (N<104). Serological tests for Hepatitis B and C, HTLV-1 and HIV were negative. Abdominal CT-Scan is shown in Image A.

UPCH Case Editors: Carlos Seas, Course  Director / Karen Luhmann, Associate Coordinator
UAB Case Editor: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director
Diagnosis:  Fasciola hepatica infection
Images for Case 2018-08
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Discussion: IgG Fas2-ELISA for Fasciola hepatica was positive at UPCH, a stool sample was positive for eggs of Fasciola hepatica (Image B).  The abdominal CT scan (Image A1) shows ill-defined areas of low attenuation (blue arrow), and tunnel-like branching hypodense areas (red arrow) inside the liver. The rounded lesions are non-specific and cannot be distinguished from neoplasms or either pyogenic or amebic liver abscesses, the presence of tortuous channels make fascioliasis the leading diagnosis. Hepatic calcifications as a sequelae of massive hepatic infestation have been reported (See Gorgas Case 2005-02).

The differential diagnosis of eosinophilia with accompanying destructive hepatic lesions is very limited. Toxocariasis causes hypereosinophilia with hepatomegaly but it is more common in children, acute schistosomiasis is another option, but is not endemic in Peru. Amebic liver abscess tends to be a single lesion and is not associated with eosinophilia. Recent advances in the diagnosis of chronic infection using molecular methods on stool samples show potential benefit for implementation in developing countries [Am J Trop Med Hyg 2017;96:341].

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 or alfalfa. Recent data, however, also suggests waterborne transmission. Our patient denies ingestion of watercress or alfalfa, but did admit to eating salads with lettuce. After ingestion by a human or animal definitive host, the metacercariae excyst in the duodenum and larvae penetrate the intestinal wall and subsequently migrate directly into the liver via Glisson’s capsule and embark on a destructive migratory process through the hepatic parenchyma for 3 to 4 months until they reach large biliary ducts, where they then mature into adults.

The mature adults are from 1 to 3 cm long and attach to the biliary epithelium by a single ventral sucker. 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 F. hepatica is cosmopolitan, but is by far the most common in cattle-raising areas where herbivores are common definitive hosts. Other important definitive hosts are goats, sheep, horses, llamas, vicunas, and camels. The contiguous Altiplano regions of the Peruvian and Bolivian Andes are highly endemic, with human prevalence rates as high as 67% in some villages. In the agricultural areas near Cusco, the prevalence in children 3 to 12 years old is 11% by stool microscopy and Fas2 ELISA [Am J Trop Med Hyg. 2014 Nov;91(5):989-93]. Fascioliasis has been also found in the jungle of Peru [Am J Trop Med Hyg 2015;94:1309]. 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. Emoliente, a local tea-like drink that uses drops of watercress juice to provide a bitter flavor is a frequent vehicle of infection.

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 F. hepatica. However, liver fibrosis and liver cirrhosis have been reported with chronic Fasciola infection [Plos Negl Trop Dis 2016;10:e0004962]. We have reported a case series with clinical findings and evolution of disease [Am J Trop Med Hyg. 2008 Feb;78(2):222-7]. Please see Gorgas Case 2005-02 and Gorgas Case 2015-05 for CT images of other examples with the typical larval tracks seen in acute disease.

Fasciola hepatica is the only trematode infection for which praziquantel is not the drug of choice. The 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. the drug is available from the CDC Parasitic Drug Service. The usual dosage is 10 mg/kg with a meal. Many practitioners repeat the dosage 12 to 24 hours later. In initial studies at our institute, the cure rate was 96%, but it has been lower in recent experience suggesting resistance to triclabendazole [PloS Negl Trop Dis 2016;10:e0004361].

Treatment with triclabendazole 10 mg/kg in a single dose was provided to the patient with resolution of her symptoms within one week. An abdominal CT scan taken almost two years after finishing treatment shows complete resolution of the tract lesions in the liver (Image C).

We would like to thank Dr. Eduardo Gotuzzo for presenting this case.