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Fasciolosis

Z Gastroenterol 2015; 53: 285–290

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Fasciolosis Fasziolose

Affiliations

b C. F. Dietrich1, A. Kabaalioglu2, E. Brunetti3, J. Richter4

1 2 3 4

Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim Akdeniz University Hospital, Department of Radiology, Antalya-Turkey Division of Infectious and Tropical Diseases, San Matteo Hospital Foundation, University of Pavia Tropenmedizinische Ambulanz, Klinik für Gastroenterologie, Hepatologie und Infektiologie, Heinrich-Heine Universität Düsseldorf

Schlüsselwörter

Zusammenfassung

Abstract

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Die Fasziolose ist eine Plattwurminfektion von Wiederkäuern, die durch Fasciola (F.) hepatica, und F. gigantica hervorgerufen wird. F. hepatica ist mitteleuropäischen Ursprungs und wurde in Steinzeitfunden nachgewiesen. Durch Viehexporte wurde diese Wurminfektion weltweit verbreitet. Diese Zoonose betrifft 2,4 bis 17 Millionen Menschen. Der klinische Verdacht beruht auf einer entsprechenden Reise- und Expositionsanamnese. Betroffen sind besonders Bewohner armer Regionen im Nildelta in Ägypten, im Iran, der Türkei, in Südostasien, Mexiko, der Karibik und in den Anden. In Europa tritt die Fasziolose besonders in Portugal, Spanien und Frankreich auf, Familien- und Cluster-Infektionen wurden aber auch in Deutschland beschrieben, nachdem durch Tierfaeces kontaminierte Wildkräuter oder Brunnenkresse konsumiert wurden. Auf den Pflanzen befinden sich infektiöse Wurmlarven (Metazerkarien), die nach Infektion zur Leber gelangen und dann durch die Leber wandern, wo sie eosinophile (Mikro-)Abszesse produzieren. Diese akute Phase kann je nach Wurmlast oligosymptomatisch oder hochakut febril mit einer hohen Eosinophilie verlaufen. Die Bildgebung kann eine unspezifische Hepatosplenomegalie und abdominelle Lymphadenopathie zeigen. Charakteristisch aber inkonstant sind hypodense abszedierende Areale, die im zeitlichen Verlauf die Leber durchwandern. Die Diagnose erfolgt serologisch, da in diesem Krankheitsstadium normalerweise noch keine Eier produziert werden. Im weiteren Verlauf wachsen im Gallensystem die unreifen Würmer zu Adultwürmern heran. Sie führen zu intermittierenden Gallenkoliken und können zu Cholezystitis, Cholangitis, Ulzerationen und Cholezystolithiasis führen. In der Bildgebung können mitunter spontan bewegliche 1,5 bis 3,5 cm lange Fasziolen im Gallensystem dargestellt werden. Hinweisend ist auch geformter Sludge, der nicht

Fasciolosis is a zoonosis affecting ruminants, caused by the liver flukes Fasciola (F.) hepatica, and F. gigantica, which infect at least 2.4 million people worldwide. This disease may occur in cluster or family infections or after travel in high-risk areas such as the Nile Delta in Egypt, Iran, Turkey, South-East Asia, Mexico, the Caribbean and the Andean Altiplano. In Europe, fasciolosis occurs more frequently in Portugal, Spain and France, although autochthonous infections have also been reported from Ireland and Germany. Infectious metacercariae are ingested with contaminated water or raw or undercooked vegetables. During their larval stage immature flukes migrate through the liver producing an acute febrile syndrome some weeks after infection, followed by a chronic-latent stage which may last for years or decades. Acute fasciolosis is characterized by fever, high eosinophilia and hepatosplenomegaly. At this stage ova are usually not yet produced. Diagnosis relies on the detection of specific antibodies and/or antigens in serum. Typical imaging features include multiple, ill-defined, fleeting hypodense or hypoechoic areas in the liver. Intraabdominal bleeding due to fluke’s penetration of the bowel wall or liver capsule, may occur. In chronic latent fasciolosis the diagnosis is achieved by specific serology tests, detection of eggs in bile and parasitological examinations of multiple enriched stools samples. Ultrasonography may sometimes reveal a dilated and thickened common bile duct or crescent-like parasites in the gallbladder or bile ducts. Some patients exhibit sludge which typically does not sediment. Triclabendazole at a single dose of 10 mg/kg body weight is the treatment of choice.

● Ultraschall ● Kontrastmittel-Ultraschall ● Fasciola spp. ● Fasciola hepatica ● Fasciola gigantica ● Plattwürmer ● Leber ● akute febrile Eosinophilie " " " " " " "

Key words

● ultrasound ● contrast ultrasound ● Fasciola spp. ● Faciola hepatica ● Fasciola gigantica ● flukes ● liver ● acute febrile eosinophilia " " " " " " " "

received accepted

7.8.2014 10.11.2014

Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1385728 Z Gastroenterol 2015; 53: 285–290 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0044-2771 Correspondence Prof. Christoph F. Dietrich Innere Medizin 2, Caritas Krankenhaus Bad Mergentheim Uhlandstr. 7 97980 Bad Mergentheim Germany Tel.: ++ 49/07 93/1 58 22 01 Fax: ++ 49/07 93/1 58 22 90 [email protected]

Dietrich CF et al. Fasciolosis … Z Gastroenterol 2015; 53: 285–290

Electronic reprint for personal use

Authors

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nach unten sedimentiert. Sonografische Kontrollen nach Therapie, insbesondere während Gallenkoliken, erhöhen die Sensitivität des Nachweises von Würmern. Die Diagnose beruht auf dem Nachweis der Wurmeier in wiederholten Stuhluntersuchungen, im Gallensaft und/oder serologisch. Die Therapie der Wahl ist Triclabendazol (Egaten®, Novartis), das aus der Schweiz importiert werden muss. Die Dosis beträgt 10 mg/kg einmalig zu einer fetthaltigen Mahlzeit und kann ggf. wiederholt werden.

Introduction


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Fasciolosis is due to foodborne trematodes such as the large liver flukes Fasciola (F.) hepatica, and F. gigantica. Whereas F. hepatica was endemic in Central Europe already in the Neolithic, F. gigantica is of tropical origin [1]. Subsequently, F. hepatica has been spread worldwide via exportation of infected domesticated ruminants. The group of foodborne trematodes comprises also the small liver flukes Opistorchis viverrini, Opistorchis felineus, Clonorchis sinensis, and Dicrocoelium dentriticum as well as lung and intestinal flukes. Fasciolosis is an infection of the liver and the bile ducts, and is estimated to infect between 2.4 and 17 million people worldwide [2]. Fasciolosis is a zoonosis affecting sheep, goats, donkeys, wild boars, dromedars and cattle. It may occur in cluster or family infections or be acquired after travel to high-risk areas such as the Nile Delta in Egypt, Iran, Turkey, South-East Asia, Mexico, the Caribbean and the Bolivian and Peruvian Altiplano [3]. In Europe, fasciolosis occurs more frequently in Portugal, Spain and France, although autochtonous infections have also been reported in Ireland and Germany [4, 5]. Infectious larvae (metacercariae) are ingested with contaminated water, with contaminated food such as raw or undercooked meat or " Fig. 1) [4]. Occasionally, inwild plants, water cress or salads (● fection is acquired from imported drugs kept moist such as khat " Table 1). The metacercariae excyst in the intestine and mi[6] (● grate within two to twenty-four hours into the peritoneal cavity. After forty-eight hours the larvae penetrate into the liver. For approximately seven weeks, the immature flukes migrate through the liver parenchyma and cause necrosis and eosinophilic absces-

Table 1

Spotlight on fasciolosis.

History, incubation and prepatency

Ingestion of water cress and other water-edge plants ingestion of contaminated water

Incubation of acute fasciolosis: 3 to 6 weeks Latency: years to decades Acute fasciolosis Clinical features

Laboratory findings

Imaging

Fever, internal bleeding

Increased inflammation parameters

Hepatosplenomegaly

malaise, abdominal pain

high eosinophilia

enlarged abdominal lymph nodes

cough, itching

high IgE, anemia

spontaneous intraabdominal bleeding

Increased antifasciola antibodies

fleeting hypoechogenic lesions in the liver

Non-specific

Specific

positive fasciola antigens in

specialized laboratories

Therapy

Triclabendazole, symptomatic antiallergic therapy, antibiotic coverage Chronic latent fasciolosis

Laboratory findings

Imaging

Malaise, biliary colics

Increased gammaGT, AP, lipase

Hepatosplenomegaly

abdominal pain

intermittent eosinophilia and intermittently increased IgE

enlarged CBD, thickened bile duct walls

Clinical features Non-specific

positive Murphy sign

increase of CBD during colics biliary sludge and concrements positive ultrasonographic Murphy sign periportal lymphadenopathy

Specific

increased antifasciola antibodies

Non sedimenting gallbladder sludge

fasciola ova detected in stools

crescents

positive fasciola antigens in feces (specialised laboratories)

moving flat worms especially after therapy

Therapy

Triclabendazole, symptomatic spasmolytic therapy, antibiotic coverage

Fig. 1

Life cycle of Fasciola hepatica and Fasciola gigantica (Quelle: CDC).


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Fig. 2 Acute fasciolosis: Hypoechoic liver lesions shown by B-mode imaging a and contrast enhanced ultrasound b. The central part of the lesions does not enhance, whereas hyperenhancement is shown in the surrounding area (mit freundlicher Genehmigung der European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB); www.efsumb.org).

ses. Subsequently, the flukes reach the biliary system, where they firmly attach using their ventral sucker and feed from blood oozing out of the ulcers in the hyperplastic mucosa. After 70 days, the hermaphrodite flukes start oviposition into the bile. During their larval stage, the immature flukes migrate through the liver, producing an acute febrile syndrome some weeks after infection, followed by a chronic latent stage, which may last years or decades [3].

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Ninety-one million people are estimated to be at risk for Fasciola spp. in Latina America, Middle East and Europe. Some authors believe that 2.6 million people are infected with Fasciola spp. in the world, but given the wide gaps in the epidemiology of this fluke infection and the dearth of population-based data on this helminthic disease, these figures are probably underestimates [7]. So far only only few case reports from Germany have been published [8 – 11]. Fasciolosis is a neglected disease, and convincing data are not available [12, 13]. Considering the high seroprevalences in some areas and the economic impact of fasciolosis, veterinarians should implement effective liver fluke control programmes [14]. A total of 20,749 bulk tank milk (BTM) samples were collected in November 2008 from all over Germany, corresponding to 20.9 % of all German dairy herds. The BTM samples were analysed for antibodies against Fasciola hepatica. The mean seroprevalence was 23.6 % and prevalences in different German federal states varied between 2.6 % and 38.4 %. Analysis revealed statistically significant positive associations between the proportion of grassed area and water bodies per postal code area and positive BTM ELISA results. This can be explained by the biology of the intermediate host, the amphibious snail Galba (Lymnea) truncatula and the pasture-borne nature of fasciolosis.

Fig. 3 Chronic fasciolosis: B-mode imaging shows a single spontaneously motile liver fluke a, b and three crescent-shaped flukes in the gallbladder c [27].

Fig. 4 Chronic fasciolosis: sensitivity of ultrasonography increases after treatment because the flukes detach from the walls of the biliary tract, fall into the lumen, and are expelled via the common bile duct causing biliary colics [27].

Fig. 5 Chronic fasciolosis: B-mode imaging shows non-sedimenting, sludge in the gallbladder [27].

Acute Fasciolosis !

The severity of acute fasciolosis depends on the parasite load. Severe cases present with fever, high eosinophilia and hepatosplenomegaly [15]. Since ova are not yet produced by the immature worms, diagnosis is achieved by detection of specific antibodies. Specialised laboratories offer tests for specific antigens in the blood [16]. At this stage ova cannot be detected in stools unless patients have been infected previously. Acute fasciolosis may exhibit a variety of ultrasound features. In most cases no specific signs are detectable. In more severe cases, hepatic necrosis and multiple abscess formation can be display-

ed. Contrast enhanced ultrasound is helpful in delineating the non-perfused and, therefore, necrotic eosinophilic abscess areas " Fig. 2). Particularly suspicious for a larval worm infection is (● the migration of abscesses through the liver over time. When ab-



Epidemiological Data

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Fig. 6 US image of a 73-year-old man shows a 7 cm hypoechoic liver mass. He was referred with suspicion of liver malignancy because of 10 kg weight loss and right upper quadrant pain. He had elevated liver function tests and hypereosinophilia a. On CT, the lesion does not show contrast enhancement. There is another subcapsular small hypodense lesion. The lesion was biopsied with the suspicion of malignancy, but the pathologist reported abundant eosinophilic infiltration, which made fasciolosis likely. Serology was positive for fasciolosis b.


scesses perforate the liver capsule, acute intra-abdominal or pleural effusions and bleeding may occur [3, 8, 15, 17 – 20]. Perihilar lymph nodes and spleen are frequently enlarged, but this is unspecific as it may occur in many other conditions, such as acute schistosomiasis, hepatitis, EBV and HIV infections [21, 22]. Differential diagnosis includes visceral larva migrans, acute lung fluke infection, amebic and bacterial liver abscesses. In both acute and chronic stages, ectopic localisations and atypical presentations due to erroneous worm migration may occur [22 – 24]. Since abnormalities detectable by imaging are inconstant, a normal abdominal imaging finding result does not rule out fasciolosis.

Chronic Latent Fasciolosis !

After some months, the larvae mature into adult worms. This stage is frequently a- or oligosymptomatic. Most symptoms are due to temporary obstruction of the common bile duct. In longlasting infections, dead worms may act as nuclei for the formation of gallstones. Diagnosis is achieved by specific serology tests and parasitological examination of multiple, specifically enriched stools samples [16, 25, 26]. Ultrasonography is not specific but may sometimes reveal crescent-like parasites in the gallbladder " Fig. 3, 4). The most frequent but unspeor common bile duct (● cific finding, is a dilated common bile duct. Some patients exhibit " Fig. 5) [27]. floating sludge that typically does not sediment (● Also during this stage acute intraabdominal bleeding may still occur [28]. Differential diagnosis includes cholestasis due to other parasites such as Echinococcus and Ascaris as well as cholelithiasis. Sometimes, findings may initially mimic malignancy, hepati" Fig. 6 ‑ 11). tis and cholangitis [22] (● Since the advent of triclabendazole, treatment of fasciolosis has become safe and efficacious. Triclabendazole given as a single dose of 10 mg/kg body weight together with a fatty meal cures infection in about 80 % of patients. The remaining 20 % may be cured by repeat of triclabendazole treatment with a double dose of 10 mg/kg each given 12−24 hours apart. Symptomatic acute patients should be hospitalised and monitored for adverse events, such as allergic reactions associated to the massive release of helminthic antigens due to parasite disintegration. Anthistaminics and antibiotics may be required. Asymptomatic latent and non-complicated chronic infections do not necessarily require hospitalisation, an important advantage in many endemic settings with limited health facilities. At this stage, the most frequent adverse event is biliary colics. In this case, spasmolytic drugs such as butylscopolamin should be given to treat or prevent biliary colics due to the expulsion of dying or dead parasites


Fig. 7 Wall-thickening of both CBD and GB, with flukes and sludge in a 28-year-old woman.

through the common bile duct which usually occurs two to three days after antiparasitic therapy [27, 29]. Exceptionally, papillotomy and endoscopic worm extraction and/or drainage (ERCP) might be required [30 – 32]. Patients sometimes suffer from cholangitis. In these cases, antibiotics such as ceftriaxone and metronidazole are required to prevent or treat bacterial superinfections. Triclabendazole is not licensed for use in humans in Germany (although it is in France and some other countries), but it can be provided through the producer from Switzerland (Egaten®, Novartis, Basle, Switzerland) [29]. If triclabendazole is not available, albendazole can be tried. In chronic infections also nitazoxanide has been shown to be effective (Alinia®, Romark, U. S. A.) [33]. Formerly, bithionol was the drug of choice but this drug is less effective and causes more adverse events [34, 35]. In animals, where triclabendazole resistance has been reported, clorsulon and closantel have been proved to be effective [36 – 38]. Praziquantel, the drug of choice in trematode infections, is of little use in fasciolosis.

Eosinophilia !

High eosinophil counts occur in acute symptomatic cases. Differential diagnosis includes other acute helminthic infections with a stage of systemic larval migration, including ascariasis, strongyloidiasis and toxocariasis (Larva migrans visceralis) which may also be found in Europe. In returnees and immigrants from tropical countries, acute schistosomiasis, filariasis, gnathostomiasis, and other tropical helminthic diseases have also to be considered. Eosinophilia, however is inconstant in pauciparasitic and chronic latent infections. The association of intermittent biliary colics and positive specific serology is diagnostic in these cases. Parasitological stool examinations are relatively insensitive since the worms produce a low number of ova. Since triclabendazole,

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Fig. 8 Multiple ill-defined hypoechoic lesions in a 39-year-old woman with fasciolosis a. Perihepatic lymphadenopathy (between calipers) in the same patient b.

Fig. 9 Typical hypodense, subcapsular, ill-defined liver lesions on computed tomography in a 57-year-old man with fasciolosis.

Fig. 10 ERCP image a of a 67-year-old female patient. The filling defects represent sludge along the flukes’ tracks (arrows). A similar ultrasound image is shown as well b. CBD: Common bile duct. Flukes and sludge seen as echogenic material within the dilated and edematous CBD.

Fig. 11 40-year-old woman operated on for suspicion of hepatoma. Surgical specimen of the liver a and microscopy of the same tissue b. The resected tissue has a tumour-like appearance a. In the histological specimens eggs are seen b.



the drug of choice, is safe, “ex juvantibus” diagnosis is justified in doubtful cases. The main adverse events described during drug therapy are not related to drug toxicity but to immunological or mechanical effects induced by dying worms with subsequent exposure of antigens to the immune system and biliary obstruction due to the expelled worms or worm fragments [29].

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