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Keywords:

  • Acute phase;
  • diagnosis;
  • Fasciola hepatica;
  • human fascioliasis;
  • portal vein thrombosis;
  • treatment

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Funding
  8. Transparency Declaration
  9. References

Clin Microbiol Infect 2012; 18: 91–96

Abstract

Because of its infrequent and protean presentation and the lack of clinical data, the management of acute infections with the foodborne trematode Fasciola hepatica is challenging. We report four serologically confirmed cases that illustrate our experience with this parasitic infection in Chile. All patients were adults presenting with upper abdominal pain. Other symptoms included fever, nausea/vomiting, and cutaneous manifestations. In all cases, marked eosinophilia was present. All patients lived in an urban environment, and three reported the consumption of raw watercress. Computed tomography (CT) scans showed hypodense hepatic lesions, whereas ultrasonography findings were unremarkable. One patient suffered portal vein thrombosis, which might be a rare complication of acute fascioliasis. All patients were successfully treated with triclabendazole. Our case series demonstrates that patients with acute fascioliasis typically present with a combination of upper abdominal pain, marked eosinophilia, and hypodense hepatic lesions on CT imaging. Diagnosis should be confirmed by serological investigation. A history of recent consumption of raw watercress is an important finding, but in some patients the source of infection remains obscure.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Funding
  8. Transparency Declaration
  9. References

Fascioliasis is a zoonotic disease caused by the foodborne trematodes Fasciola hepatica and Fasciola gigantica, which usually infect cattle, sheep, goats, and other domestic ruminants. Humans are infected after ingestion of larval stages, called metacercariae, which, after development in lymnaeid intermediate hosts, attach to aquatic and semi-aquatic plants. Interestingly, the role of humans as solely accidental hosts has recently been questioned, because, in some regions, human infection might play a significant role in the maintenance of the infectious cycle [1]. Originally a European disease, F. hepatica fascioliasis has spread to all continents, and is now the vector-borne disease with the widest geographical distribution. An estimated 2.4–19 million people are infected, and 180 million are at risk [2,3]. Hot spots are the South American highlands, the Nile delta, and the Caspian basin [1]. Owing to its emerging nature and high endemicity in some developing countries, the WHO classified the disease as a neglected parasitic infection that merits international attention. Furthermore, fascioliasis has been recognized as an emerging infection in international travellers and migrants, causing significant diagnostic and therapeutic problems [4–7].

Other than the larvae of minute liver flukes, which reach the biliary system ascending through the sphincter of Oddi, Fasciola larvae cross the intestinal wall, liver capsule and liver tissue on their way to the biliary tree. During this development, they cause significant tissue damage and, probably frequently, clinical symptoms [8]. However, the acute or hepatic phase of fascioliasis is difficult to diagnose, and it mostly occurs in areas with poor diagnostic possibilities, so it is not surprising that the clinical features of this infection are poorly defined. Furthermore, many reports mix acute and chronic cases of fascioliasis [4,8]. As a result, many physicians and even infectious diseases specialists outside countries of high endemicity are not familiar with the presentation and management of acute fascioliasis [9].

Our report aims to improve the comprehension of acute fascioliasis by presenting and analysing the clinical and diagnostic features of four Chilean patients.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Funding
  8. Transparency Declaration
  9. References

Between 2007 and June 2010, four patients with acute fascioliasis were diagnosed in the Hospital Militar in Santiago, Chile, a tertiary-care hospital that receives patients from Chile’s capital Santiago and also serves as a referral centre for military personnel and their families from all over Chile. Detailed patient data were obtained from clinical records, which were systematically analysed for demographic, epidemiological and clinical features, as well as laboratory values and imaging studies. Clinical laboratory values were all obtained from the hospital’s laboratory. All patients were examined by abdominal ultrasonography and computed tomography (CT) scan; the results were revised by an experienced radiologist using the digital database of the hospital.

Only confirmed cases of acute fascioliasis were included, defined as patients with the clinical diagnosis of acute fascioliasis and positive Fasciola serological findings. Serological assays were performed in the Instituto de Salud Pública (Chilean Institute of Public Health), a national reference centre for parasitological serology. The following assays were used: an in-house ELISA with commercial Fasciola antigen (LMD, Carlsbad, CA, USA); and a commercial immunoblot (LDBIO Diagnostics, Lyon, France). The former detects antibodies (IgG) against excretory–secretory antigen of F. hepatica; the latter uses whole cell extracts of adult F. hepatica and serves as a confirmatory assay detecting antibodies (IgG) against various Fasciola-specific antigens. Neither test is able to discriminate acute from chronic infections. All four patients were positive in both serological assays.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Funding
  8. Transparency Declaration
  9. References

Demographic, epidemiological and clinical variables

Three of our four cases occurred during the spring and summer months. All patients were residents of urban areas, two from Santiago de Chile and two from other Chilean cities. No patient reported rural activities or recent travel. Patients were middle-aged (mean 46.5 years), and one patient was female. Three patients reported a history of watercress consumption (Table 1).

Table 1.   Demographic, epidemiological, clinical and laboratory features in cases of acute fascioliasis (at admission)
 Case 1Case 2Case 3Case 4
  1. INR, international normalized ratio.

  2. aTime from hospital admission to initiation of Fasciola serological investigation.

  3. bTime from hospital admission to first dose of triclabendazole.

  4. cAs ratio to upper normal limit.

Demographic and epidemiological features
 Age (years)53562354
 SexMaleMaleMaleFemale
 Watercress consumption+++
 Patient background (urban/rural)UrbanUrbanUrbanUrban
 Season (year) of disease onsetSpring (2007)Summer (2010)Spring (2009)Winter (2007)
Clinical features
 Abdominal pain++++
 Localization of painEpigastricRight hypochondriumEpigastricRight hypochondrium
 Fever++
 Night sweats+
 Vomiting and nausea+
 Weight loss
 Cutaneous reactionsGeneralized pruritusFacial papular rash, head itch
Clinical timeline
 Duration of symptoms before admission (days)1014452
 Time until fascioliasis was suspected (days)a1303
 Time until treatment was started (days)b971112
 Duration of hospitalization (days)2171117
Laboratory features
 Haemoglobin (g/dL)1415.415.413.8
 Leukocyte count (cells/μL)34 20014 80014 70015 300
 Eosinophil count (cells/μL)15 100991049406130
 Relative eosinophil count (%)44673440
 Sedimentation rate (mm/h)30102513
 C-reactive proteinc7.341.54.020.42
 Glutamate aminotransferasec3.281.080.541.08
 Bilirubin (mg/dL)0.830.800.740.41
 Alkaline phosphatasesc2.351.652.620.84
 GGTc 1.471.872.17
 Prothrombin time (INR)1.781.201.561.07
 Serum albumin (g/dL)4.54.24.54.1

All patients presented with upper abdominal pain, one complained of nausea and vomiting, and two patients had fever. Two patients suffered from concomitant cutaneous manifestations (Table 1). Laboratory data demonstrated leukocytosis and severe eosinophilia (absolute eosinophil count ≥3000/μL). Other markers of inflammation, such as C-reactive protein and sedimentation rate, were only mildly affected; anaemia was absent. Liver parameters were mostly unremarkable. None of the patients had hyperbilirubinaemia, and the values for alkaline phosphatases, glutamate aminotransferases, γ-glutamyltransferase and prothrombin time were only slightly altered (Table 1).

Before the patients were admitted to our hospital, symptoms had been present for an average of 18 days (range 2–45 days). In all patients, shortly after hospitalization, Fasciola serological investigation was requested (0–3 days). Antiparasitic treatment was started after an average of 10 days (range 7–12 days). The average duration of hospitalization was 14 days (range 7–21 days) (Table 1).

Diagnostic studies

The results of imaging studies are summarized in Table 2. Ultrasound studies were unable to demonstrate focal hepatic lesions, and therefore did not contribute to the diagnosis of fascioliasis. In contrast, CT scan imaging demonstrated multiple hypodense hepatic lesions with irregular or diffuse borders (Figs 1 and 2); track-like or tunnel-like lesions were also visible. Furthermore, two patients had intra-abdominal lymph nodes, and one patient had a concomitant portal venous thrombosis (Fig. 1).

Table 2.   Abdominal ultrasonographic and computed tomography (CT) scan findings in cases of acute fascioliasis
 Case 1Case 2Case 3Case 4
UltrasoundPortal vein thrombosisNormalNormalHeterogeneously increased liver density. Minor dilatation of intrahepatic and extrahepatic biliary tree
CT scanSeveral hypodense lesions with irregular borders in posterior segment of right lobe, thrombosis of right portal vein branch, multiple lymph nodes up to 7 mm in celiac trunk and major omentumConfluent hypodense liver lesions in segments IV, V, and VIIIMild hepatomegalia, several hypodense lesions with irregular borders, tunnel-like irregular lesionsHypodense lesions with diffuse limits in segments VI and VII, dilated bile ducts, multiple para-aortic and interaorto-caval lymph nodes up to 1 cm
image

Figure 1.  Computed tomography scan of patient 1, showing several irregular hypodense focal lesions of the posterior segment of the right liver lobe (black arrow). The right branch of the portal vein is blocked by a thrombus (white arrow).

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image

Figure 2.  Computed tomography scan of patient 3, showing multiple hypodense areas with irregular borders and tunnel-like lesions (arrows) of the right liver lobe.

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As part of the inclusion criteria, all patients had positive results in Fasciola ELISA and immunoblot testing. One patient had an initial undetermined ELISA result, but tested positive with ELISA and immunoblot 1 month later.

Treatment and follow-up

Before the diagnosis of fascioliasis was made, three patients received empirical antibiotic treatment for pyogenic liver abscesses. All patients were treated with oral triclabendazole at a dose of 10 mg/kg/day for 1 day (three patients) or 2 days (one patient). No adverse reactions were recorded. Three patients were followed up on a monthly basis for 1–6 months. In all of these patients, eosinophil counts decreased and clinical symptoms disappeared. Recurrence was not reported. Controls for serological examinations or parasitological stool examinations were not performed.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Funding
  8. Transparency Declaration
  9. References

Acute fascioliasis refers to the initial, hepatic phase of the parasitic disease. It is characterized by tissue destruction caused by the migration of the immature parasites from the small intestine to the biliary system. Because of its invasive nature, the acute stage of fascioliasis causes far more morbidity than chronic infection when adult worms inhabit the biliary tree. However, as for other neglected diseases, comprehensive clinical studies are lacking, and the most convincing clinical data derive from small retrospective case series or single case reports [4,5,8,10]. The typical clinical spectrum of acute fascioliasis encompasses anorexia (sometimes associated with nausea and vomiting), which might lead to weight loss, abdominal pain, especially in the upper abdomen, tender hepatomegalia, night sweats, fever, and other immune-mediated manifestations, such as urticaria or arthralgias. Other, less frequently reported, findings include splenomegalia, ascites, subcapsular hepatic haematoma, intra-abdominal haemorrhage, pleural or pericardial effusion, and respiratory symptoms [2,8,11]. Ectopic larvae in other localizations, such as subcutaneous tissue, eyes, and the central nervous system, may cause a variety of other clinical manifestations [8]. The leading laboratory abnormality is hypereosinophilia; hypergammaglobulinaemia and anaemia might also be present [12]. The incubation period ranges from a few days to several weeks; the acute stage of fascioliasis usually lasts for 2–4 months [2].

The two hallmarks of acute fascioliasis, upper abdominal pain and marked eosinophilia, were present in all of our four patients. Other ‘typical’ symptoms, such as fever and cutaneous manifestations, were each present in two patients. It is noteworthy that the skin problems that we recognized were a papular facial rash with head itch and generalized pruritus, indicating that the spectrum of dermatological manifestations of acute fascioliasis might extend beyond the most commonly reported symptom, urticaria.

One patient (case 1) was diagnosed with thrombosis of the portal vein without having risk factors for thrombosis. To our knowledge, this is the second report of this complication in association with acute fascioliasis [13]. The thrombosis might result from local inflammation caused by the migration of the parasite, or from obstruction by reactive lymph nodes. Portal venous thrombosis has also been described in other parasitic infections affecting the liver, such as cystic and alveolar echinococcosis and chronic schistosomiasis [14,15].

In contrast to other highly endemic Andean countries such as Bolivia and Peru, Chile is a country of low endemicity [16]. In our hospital, only four patients with acute fascioliasis were diagnosed during 42 months of observation, with approximately 50 000 admissions. It is not only its rare occurrence that makes the diagnosis of this infection a diagnostic challenge. The main symptom, upper abdominal pain, is caused by variety of common diseases, such as gastritis or biliary diseases. This might be the one reason for the delayed diagnosis of acute fascioliasis that we and other authors have recognized [8]. In our patients, the time from symptom onset to suspicion of fascioliasis (and implementation of Fasciola serology) was 5–45 days (Table 1). Other important factors in the adequate management of this infection are the timely availability of serological results and antiparasitic treatment (triclabendazole). We recognized a time-lapse of 4–11 days between the initiation of serological investigation and treatment, which contributed to the prolonged hospital stays. During the time-span until the diagnosis of fascioliasis was made, most patients received unnecessary antibiotic treatment for possible pyogenic liver abscess.

Hepatic imaging is crucial in patients with possible acute fascioliasis. In concordance with other published data [4,8], abdominal ultrasound did not contribute to the diagnosis of acute fascioliasis in our four patients (Table 2). However, this technique is of value in chronic fascioliasis, when adult worms inhabit the biliary tract, causing inflammation and/or dilatation, and might be seen as mobile structures in the gall bladder or choledochus [17]. A useful imaging technique is CT, which reveals hypodense focal lesions that might be confused with metastasis or abscess; more typical for acute fascioliasis are hypodense tunnel-like lesions, which, over time, slowly change in a centripetal manner [10]. Magnetic resonance imaging, which offers no diagnostic advantage, is characterized by hypointense lesions in T1-weighted images, and hyperintense signals in T2 images [12]. Periportal lymph nodes are not infrequent but are non-specific. The combination of upper abdominal pain, marked eosinophilia and hypodense lesion in CT imaging is highly indicative of acute fascioliasis [12]. Other rare causes of this combination of findings include hepatic toxocariasis and hepatic capillariasis.

Possible or probable cases of acute fascioliasis should be confirmed by serological tests. As in one of our patients, serological findings might be negative or indeterminate in patients presenting during the early stages, and should be repeated after 2–3 weeks. Cross-reactions with other helminths, such as Schistosoma sp., small intestinal flukes, and Toxocara sp., have been described [18,19]. To increase specificity, a combination of two different immunoassays might be used. Serum antigen detection is another promising approach for the diagnosis of acute fascioliasis, including in the early stages [20]. Coprodiagnostic parasitological studies are worthless in acute fascioliasis, as this manifestation occurs during the prepatent period of the infection.

Commonly, fascioliasis is associated with rural environments and livestock breeding. In Chile and other regions of low endemicity, however, fascioliasis is not restricted to typical risk groups, such as children in rural areas [2]. In our case series, none of the patients lived in a rural setting, but most patients (three of four) reported recent consumption of raw watercress (‘berros’). Interestingly, reports from France indicate that commercially cultivated aquatic plants also pose a Fasciola risk [21]. In some endemic countries, seasonality of Fasciola infection has been observed [22,23]. Three of our four patients presented during the Chilean spring and summer months. Reasons for this probable seasonality might be climatic factors that influence the populations of intermediate snail hosts, and the higher availability and consumption of vegetables during these seasons.

Triclabendazole is the drug of choice for this parasitosis. It is active against mature and immature forms of the parasite. Treatment consists of a single oral dose of 10 mg/kg; in cases of failure, triclabendazole treatment is repeated at a higher dosage of 20 mg/kg (in two doses separated by 12–24 h) [2]. The drug is effective and has an excellent safety profile [24,25]. Adverse reactions are usually mild, and include abdominal pain and, less frequently, vomiting or nausea, cough, urticaria, and pruritus [2,25,26]. Criteria of cure of acute fascioliasis are alleviation of clinical symptoms (sometimes a temporary exacerbation might be observed), normalization of eosinophilia, and a decrease in Fasciola-specific antibodies or circulating antigen [2]. Stool examinations for ova and parasites might be applied several weeks after therapy to demonstrate eradication of the parasite. Nonetheless, neither for diagnosis nor follow-up is a standardized protocol available [2]. In all of our patients, triclabendazole was successfully administered, and no adverse effects or recurrence were reported.

Although limited by its low number and retrospective design, our case series demonstrates that, despite the non-specific and elusive nature of acute fascioliasis, patients typically present with a combination of abdominal pain, marked eosinophilia, and hypodense hepatic lesions on CT imaging. A history of recent consumption of raw watercress or other aquatic plants is normally but not always present. The diagnosis should be confirmed by serological investigation, although, in very early stages, repeated testing might be necessary. Unfamiliarity of physicians with the disease and delays in the availability of serological results and antiparasitic medication might contribute to prolonged hospitalization.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Funding
  8. Transparency Declaration
  9. References
  • 1
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