Fasciola hepatica Infection in the United States

CE Update
Fasciola hepatica Infection in the United States
Adnan Alatoom, MD, PhD, Dominick Cavuoti, DO, Paul Southern, MD, Rita Gander, PhD
(Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX)
DOI: 10.1309/MLFFXA77UBBFH4GP
Abstract
Enzyme-linked immunosorbent assay
(ELISA) testing is sensitive for both stages
while stool exams for F. hepatica eggs are
positive only in the biliary stage. Radiographic
findings using computed tomography and
ultrasonography are not specific but support
the diagnosis. Endoscopic retrograde
cholangiopancreatography (ERCP) has been
increasingly used to diagnose F. hepatica and
After reading this article, readers should be able to discuss Fasciola
hepatica and its epidemiology, life cycle, clinical features, diagnosis, and
treatment.
to remove the adult fluke from the biliary tree.
Triclabendazole is currently the recommended
drug for treating F. hepatica infection. The
rarity of the disease in the United States can
result in a delayed diagnosis and sometimes in
mismanagement. Physicians should consider
this infection in patients with abnormal liver
function and peripheral eosinophilia, especially
in the immigrant population.
Microbiology 70802 questions and corresponding answer form are
located after this CE Update on page 429.
Epidemiology
Life Cycle
Fascioliasis is a worldwide disease caused by Fasciola
hepatica. The genus name is derived from the Latin word
fasciola, meaning fascia or band. Fasciola hepatica is a liver
fluke, a term that refers to the flat or rhomboid shape of the
adult form of the parasite. Fasciola hepatica infects herbivores
(such as sheep, goats, and cattle) as well as humans, who
become infected by ingesting contaminated water or plants,
including watercress, lettuce, and spinach.1 Up to 2.4 million
people are infected with F. hepatica worldwide.2 In 1998,
Esteban and colleagues compiled 7,071 human cases in 51
countries in 5 geographic regions during the preceding 25
years, distributed as follows: Africa (487), America (3,267),
Asia (354), Europe (2,951), and Oceania (12).2,3 Countries
with high and intermediate prevalence include Peru, Bolivia,
Egypt, Iran, Puerto Rico, and Portugal.2 Because fascioliasis
is a rare disease in the United States, there is no reported
prevalence of the disease in this country. Although most reported cases were related to travel outside the United States,
native cases have also been reported since the conditions
that allow completion of the life cycle, including snail host,
climate conditions (soil and sufficient moisture that is suitable for the snail population primarily in the Gulf Coast and
western states), and raising animals, are present in the United
States.2,4,5 Bovine fascioliasis is a significant problem in the
southern, central, and western regions of the United States.
For example, El Bahy and colleagues reported that approximately 5% of the cattle in the United States are infected4;
however, MacLean and Graeme-Cook reported that the
infection rate in beef cattle in California and Florida is 53%
and 68%, respectively.6
The eggs of F. hepatica are excreted in the feces of infected animals and hatch into ciliated miracidia in water after
9 to 15 days (Figure 1).7-9 The eggs measure 130 to 150 μm
by 63 to 90 μm and have an indistinct operculum (Figure
2). They are usually ellipsoidal and light yellow-brown in
color. The miracidia find the intermediate host (freshwater
Lymnaea snail) where they grow into the cercarial form. The
cercariae leave the snail, encyst on aquatic vegetation, and
develop into the metacercarial stage.10 When sheep, cattle, or
humans ingest metacercariae, these infective forms excyst in
the intestine, perforate the intestinal wall, and pass through
the peritoneum to the liver and biliary tree. The mature fluke
releases eggs into feces and ultimately to the environment,
where another life cycle begins.7 The adult form measures up
to 30 mm by 13 mm, has a cone-shaped anterior end, and the
internal organs are extensively branched (Figure 3).
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Clinical Features
Infection with F. hepatica has 2 clinical phases with different signs and symptoms.11 One to 3 months after ingestion of metacercariae, the hepatic (acute) phase occurs when
the worm enters the liver and begins to migrate through the
parenchyma.8,12 The clinical features and laboratory findings
of this stage include fever, right-upper-quadrant pain, nausea,
anorexia, vomiting, eosinophilia, urticaria, hepatomegaly,
jaundice, pruritis, weight loss, elevated liver enzymes, and
hypergammaglobulinemia.11 This stage can be complicated
by mild hepatitis, hepatic necrosis, and subcapsular hemorrhage. The biliary (chronic) stage can remain asymptomatic
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Fascioliasis is a worldwide infection caused
by the liver fluke, Fasciola hepatica. In the
United States, fascioliasis is an uncommon
infection and is mainly reported among the
immigrant population. Fasciola hepatica
infection comprises 2 distinct stages (hepatic
and biliary) and manifests mainly as abdominal
pain, elevated liver enzymes, and eosinophilia.
CE Update
Diagnosis and Treatment
Figure 2_Saline preparation of Fasciola hepatica egg in the stool
(40x). The arrow indicates the operculum of the egg.
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Figure 3_Gross appearance of the adult flukes of Fasciola hepatica. The
adult fluke is flat, brownish, and measures approximately 2.5 to 3 x 1 cm.
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Diagnosis of fascioliasis is difficult
without high clinical suspicion. Testing
the stool for the presence of F. hepatica
eggs is useful to establish the diagnosis;
however, these eggs are absent in the
stool in the acute stage of fascioliasis.
Antibody detection using the enzymelinked immunosorbent assay (ELISA)
has a high sensitivity (98%) in both
acute and chronic infections but lacks
optimal specificity due to cross reactivity
with other parasitic infections such as
echinococcosis and schistosomiasis.5,13
In animal models, antibodies are detected within 4 weeks of infection and
can persist for years. With effective treatment, titers return to baseline after 18
to 21 weeks.5 Imaging techniques, such
as computed tomography (CT) and ultrasonography (US), are not specific but
can support the diagnosis of fascioliasis
and assess the response to treatment.
Computed tomography may demonstrate different types of lesions, such as
single or multiple hypodense nodular
areas due to deposition of the parasite,
tunnel-like branching due to the migration of the parasite in the liver, frequent
subcapsular location of lesions, and dilatation of bile ducts.5,8,13 Ultrasonography
has variable sensitivities for detecting hepatic lesions and might be more useful in
biliary fascioliasis since it may show gallbladder wall thickening, duct dilatation,
and the adult fluke in the gallbladder
or bile duct.3,5,14 In biliary fascioliasis,
endoscopic retrograde cholangiopancreFigure 1_Life cycle of Fasciola hepatica. Reprinted from the Institute of Tropical Medicine
atography (ERCP) and sphincterotomy
(ITM), Antwerp, Belgium.
have been used for diagnosis and therapy
to extract the parasites from the biliary
tree by balloon or basket.1,8,10,15,16 In
for many years or present with intermittent right-upperfact, the infection is sometimes diagnosed unexpectedly by
quadrant pain, cholangitis, cholestasis, pancreatitis, bile duct
ERCP in patients suspected of having choledocholithiasis.
stones, and biliary obstruction due to duct-wall thickening or
Triclabendazole is currently the recommended treatment
mechanical obstruction.11
of choice. Bithionol may also be used but is less effective
CE Update
than triclabendazole. Mebendazole, albendazole, and praziquantel have been used with variable success.8
Fascioliasis in the United States
To examine the status of fascioliasis in the United States,
we searched the literature available on the Internet for cases
that have been reported in this country. We were able to find
9 cases reported in different states during the period from
1993 to 2006. We summarized the details of these cases for
the following: age and sex of the patient, state where the case
was reported, tests ordered to reach the final diagnosis, history of watercress ingestion and travel, time of presentation
after the patient returned to the United States in cases which
were associated with travel, and medication administered to
the patients for the suspected diagnosis. Table 1 shows that the
patients included 7 males and 2 females from different states
and with a mean age of 44.7 years. Some of these patients required multiple tests and a prolonged period (a few days to 4
months) to reach a final diagnosis of fascioliasis. Stool exams
for F. hepatica eggs was positive in only 2 of the 9 cases, possibly due to the absence of eggs in the stool in the acute phase
of the disease, sporadic release of eggs, and the wide variation
in the number of eggs excreted.5,11,17 Due to the presence of
eosinophilia in some of these patients, serology for other parasites including Entamoeba histolytica, Echinococcus granulosus,
and Toxocara canis were ordered and appeared to be negative.
Six cases were diagnosed by serology using ELISA, indirect
immunofluorescence (IIF), indirect hemagglutination, and
immunoelectrophoresis. In all of these cases, CT and US were
used to show the abnormalities in the liver and bile duct,
exclude other abnormalities, and support the final diagnosis.
Endoscopic retrograde cholangiopancreatography and sphincterotomy were necessary to diagnose and treat the infection in
2 cases. This scenario usually occurs in patients with extrahepatic bile dilatation, evidence of cholestasis, and a suspicion of
choledocholithiasis. Roig explored the importance of ERCP
and reported the increase in using ERCP in the diagnosis and
Conclusion
The long time required to reach a final diagnosis, extensive tests ordered for the patients, unexpected diagnosis
of fascioliasis by ERCP, and the inappropriate medication
administered to some patients reflect the rarity of the disease
and the low index of suspicion in the United States. Physicians should consider fascioliasis in the differential diagnosis
of abdominal pain, abnormal liver function, and eosinophilia,
especially in the immigrant population. LM
Table 1_Review of 9 Cases of Fascioliasis Reported in the United States
Age/Sex/
State
Tests Required for Final Dx
25/M/KY
O/P, US, CT, serology, ERCP
28/M/TX
O/P, CT, US, ERCP
26/F/NY
O/P, STOP, CT, RBC scan, MRI, serology (IIF, IEP)
51/M/FL
O/P, STOP, CT, liver bx, US, laparoscopy, ERCP, serology
(IIF, IH, IEP)
67/M/MA
US, CT, MRI, paracentesis, duodenal/liver bx, O/P, ELISA
65/M/NY
O/P, STOP, CT, liver bx,
MRI, serology (IIF, IEP)
56/M/WA
CT, liver bx, STOP, O/P
33/M/MA
O/P, US, ELISA
52/F/WA
O/P, CT, HIDA scan, STOP, ELISA
History of Watercress
Ingestion/Travel
Time of Presentation
After Return to USA
Medication
or Management
Reference
N/Y (Mexico)
Y/Y (Peru)
Y/Y (Dominican Republic)
2.5 yr
NA
1 mo
Antibiotics, mebendazole, cholecystectomy
Antibiotics, TCB, cholecystectomy
TCB
8
16
9
Y/N
NA
Antibiotics, albendazole, TCB
13
N/Y (Cape Verde)
3 wk *
TCB
5
Y/Y (Ireland)
1 mo
Prednisone, TCB
19
Praziquantel
TCB
Praziquantel, bithionol
20
5
20
N/Y (Puerto Rico, East Africa) 1 and 2 mo†
Y/Y (Cape Verde)
2 wk ‡
Y/Y (Cape Verde)
NA
Dx, diagnosis; NA, not available; O/P, stool for ova and parasite; STOP, serology to other parasites; IIF, indirect immunofluorescence; IH, indirect hemagglutination; IEP, immunoelectrophoresis;
CT, computed tomography; bx, biopsy; US, ultrasonography; ERCP, endoscopic retrograde cholangiopancreatography; TCB, triclabendazole; RBC, red blood cell; MRI, magnetic resonance imaging;
HIDA, hepatobiliary iminodiacetic acid; Y, present; N, not present. Bold words represent the test that revealed the presence of fascioliasis.
* Symptoms started 3 mo before returning to U.S.A.
† Symptoms started 1 and 2 mo after returning from Puerto Rico and East Africa respectively.
‡ Symptoms started 10 mo before returning to the U.S.A.
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treatment of fascioliasis during the period from 1980 to 2000
even in a hyperendemic area (Bolivia).18 Liver biopsy was used
in 4 cases and showed eosinophilic infiltration, loss of liver parenchyma, necrosis, and fibrosis. In 1 case, a red blood cell scan
was performed to rule out hepatic hemangioma or adenoma
suspected by magnetic resonance imaging (MRI).
The patients were treated with different regimens of medication that targeted the wrong diagnosis in 2 cases. The first
patient received steroids for the suspicion of drug reaction and
vasculitis, and the authors reported that steroids could have
allowed the flukes to develop more quickly and caused more
hepatic damage.19 The second patient received albendazole for
the suspicion of visceral larva migrans without improvement
of symptoms until the patient received triclabendazole.13 Two
patients underwent cholecystectomy to exclude the presence of
F. hepatica or stones in the gallbladder. Table 1 also shows that
8 of the 9 cases were associated with travel outside the United
States, and 6 of the 9 cases were associated with watercress
ingestion. The only native case that was reported in Florida
was associated with watercress ingestion. The patient stated
that he did so after watching a television news report about
the health benefits of watercress.13 The short time (up to 2
months) before presentation of these patients after their return
to the United States further supports that these infections
were acquired outside the United States. Only 1 patient had
symptoms after 2.5 years, probably due to an asymptomatic
infection.
CE Update
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