Abstract
Background
Human fascioliasis is an emerging zoonotic disease caused by the trematodes, or flatworms, Fasciola hepatica and Fasciola gigantica, also known as liver flukes. This retrospective study aimed to report the epidemiological findings in 95 cases of human fascioliasis in Dali, Yunnan Province, southwestern China, diagnosed between 2012 and 2021.
Material/Methods
The epidemiologic and clinical data of 95 patients diagnosed with human fascioliasis in Dali area from January 2012 to December 2021 were collected and retrospectively analyzed. The diagnosis of fascioliasis was based on the Chinese National Standard of Diagnosis of Fascioliasis (WS/T566-2017).
Results
The mean age of patients was 38.54±15.68 years, and there were more female patients than male (61.05% vs 38.95%). The high-incidence seasons were identified as summer and autumn. The patients with human fascioliasis lived in pastoral areas or were infected F. gigantica by consuming contaminated vegetables or water containing metacercaria. Meanwhile, human fascioliasis was diagnosed by positive serologic tests (1: 640), and Fasciola eggs (144–180×73–96 μm) were detected in stool samples of 6 patients. The most common clinical features were abdominal pain (70.53%), accompanied by elevated eosinophils in 89.5% of these patients. Antiparasitic treatment with triclabendazole at 10 mg/kg/day for 2 days led to symptom relief in all patients.
Conclusions
The findings from this observational epidemiological study have highlighted the importance of recognizing, diagnosing, and managing fascioliasis, which is an emerging zoonosis associated with increased human proximity to plant-eating domestic and farmed animals.
Keywords: Diagnosis, Epidemiology, Fascioliasis, Triclabendazole, Prognosis
Background
Fascioliasis is a zoonotic parasitic disease [1] caused mainly by the trematodes, or flatworms, Fasciola hepatica and Fasciola gigantica, which share similar morphology, clinical manifestations, and response to triclabendazole treatment [2]. Fasciola are primarily distributed in temperate and subtropical regions, and have the ability to infect a diverse range of mammals, including humans, ruminants, primates, and rodents. When the miracidia of the Fasciola invade the intermediate host (one of several species of amphibious snail) and undergo asexual reproduction, the mature metacercariae escape from the snail and adhere to the surface of aquatic plants or other objects in the water. The infection of humans or mammals, including cattle and sheep, can occur through the consumption of raw vegetables that have been contaminated with metacercaria or the ingestion of raw water [1]. Furthermore, in the Dali area, fascioliasis has been noted to be originally caused by F. gigantica, which is transmitted by the lymnaeid snail species Radix viridis (synonym, Galba previa) [3,4].
Current epidemiological data indicate that 180 million people worldwide are at risk of fascioliasis infection [5]; meanwhile, a meta-analysis showed a global prevalence of 4.5% for human fascioliasis [6]. Since the initial report of human fascioliasis in Fujian Province in 1921 [7], China experienced its first significant outbreak of 29 cases in Yunnan Province in 2012 [3]. Subsequently, the cumulative number of reported cases of human fascioliasis in China reached 306 as of 2019 [7].
Presently, the diagnosis of fascioliasis entails using enzyme-linked immunosorbent assay (ELISA) to identify antibodies against Fasciola [8], using the sedimentation technique to detect Fasciola eggs in fecal matter or duodenal drainage [3], or using pathological sectioning to identify adult Fasciola [9]. Notably, the diagnosis of fascioliasis should be established through the consideration of epidemiological history, clinical manifestations, and laboratory findings [9].
Triclabendazole is the drug of choice for treating fascioliasis. However, the exact mechanism of its action has not been fully elucidated. Results derived from in vitro studies and animal models suggest that triclabendazole and its active metabolites (sulfoxides and sulfones) can be absorbed by the cortex of immature and mature Fasciola, leading to a decrease in resting membrane potential, further inhibiting microtubule protein function and protein and enzyme synthesis [10].
To achieve effective management of fascioliasis, it is imperative to enhance health education, promote health awareness among individuals, and foster hygienic eating habits. Additionally, it is crucial to strengthen the management of animal husbandry by implementing regular preventive deworming of livestock using triclabendazole, taking into consideration the epidemiological characteristics of endemic areas. Lastly, enhancing the professional competence of healthcare personnel and minimizing misdiagnosis are essential steps toward realizing effective management of fascioliasis [7].
In recent years, a growing number of clinical studies on human fascioliasis have been reported [4,11,12], contributing to clinicians’ understanding of the disease. In addition, a previous study reported the clinical and epidemiological characteristics of human fascioliasis in Dali area [3]; however, people infected with fascioliasis are often subject to missed or misdiagnosis, resulting in a prolonged course and potentially life-threatening consequences. Therefore, this retrospective study aimed to report the epidemiological findings in 95 cases of human fascioliasis in Dali, China, diagnosed between 2012 and 2021, with the aim of providing diagnostic and treatment recommendations for human fascioliasis cases in China.
Material and Methods
Ethics Statement
This retrospective study was approved by the Institutional Review Board of the First Affiliated Hospital of Dali University (No. 20211020001), and informed consent was obtained from all participants or their family members.
Study Population
The study analyzed 95 cases of human fascioliasis treated between January 1, 2012, and December 31, 2021, at the First Affiliated Hospital of Dali University and People’s Hospital of Dali Bai Autonomous Prefecture. The diagnosis of fascioliasis was based on the National Standard of Diagnosis of Fascioliasis (WS/T566-2017) [9]. The diagnostic criteria for human fascioliasis include the following: (1) a documented history of residing, working, or traveling in an area where Fasciola is prevalent, along with a history of consuming aquatic plants or ingesting raw water; (2) the manifestation of symptoms such as fever, abdominal pain, malaise, anorexia, vomiting, abdominal distension, and diarrhea, as well as the identification of an enlarged liver and tenderness in the hepatic region; (3) an elevation in the percentage and/or absolute count of eosinophils in the peripheral blood; and (4) the diagnosis of fascioliasis involves the utilization of various testing techniques, such as ELISA, to detect antibodies against Fasciola, the sedimentation technique to detect Fasciola eggs in fecal matter or duodenal drainage, or pathological sectioning to identify adult Fasciola.
Data Collection
All patients’ data were collected from the hospital information system. The collected general information included demographics such as age, sex, and smoking and drinking history. Clinical manifestations included recorded vital signs, first symptoms, time from onset to admission, and length of hospital stay.
Auxiliary Examination
Routine blood tests assessed parameters such as white blood cells (WBC), percentage of neutrophils, percentage and absolute value of eosinophils, red blood cells, hemoglobin, and platelets. Liver and kidney function tests assessed total bilirubin, direct and indirect bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), globulin, albumin, blood urea nitrogen, serum creatinine, and uric acid levels. Tumor markers, including alpha-fetoprotein, carcinoembryonic antigen, carbohydrate antigen (CA)125, and CA199, were also analyzed.
For the fecal examination by sedimentation technique, 3 independent fecal samples per patient were analyzed using the sedimentation technique to detect the presence of Fasciola species egg [13].
For the abdominal imaging examination, color Doppler ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) scans were performed to assess the abdominal region.
For pathology, a liver biopsy, liver resection pathology, lower limb biopsy, and chest wall biopsy were conducted to examine the affected tissues.
Therapy and Prognosis
All patients diagnosed with human fascioliasis received triclabendazole therapy (10 mg/kg/day for 2 days). The triclabendazole used in the study was provided by the National Institute of Parasitic Disease, the Chinese Center for Disease Control and Prevention. The triclabendazole formulation included colloidal silicon dioxide, iron oxide red, lactose monohydrate, maize starch, magnesium stearate, and methyl-hydroxyethylcellulose. Patients were followed up via telephone during the first, third, and sixth months after treatment. The study reported that all patients had a good prognosis, with no deaths recorded.
Statistical Analysis
The variables were reported as mean±standard deviation for continuous variables and counts (proportions) for categorical variables. To assess the statistical significance of differences between groups, categorical variables were analyzed using the chi-square or Fisher’s exact test, while continuous variables were analyzed using the t test or Mann-Whitney U test. A P value <0.05 was considered statistically significant. All statistical analyses were performed using Microsoft Excel and SPSS, Version 26.0 (IBM Corp, Armonk, NY, USA).
Results
Baseline Characteristics of 95 Patients with Human Fascioliasis in Dali, Yunnan Province, Southwestern China
The cases of a total of 95 patients with human fascioliasis were analyzed, exhibiting female predominance (n=58, 61.05%) and a mean age of 38.54±15.68 years. Most of the patients were farmers from rural areas of Dali Bai Autonomous Prefecture and resided close to water resources. It was observed that all patients had a history of consuming raw food prior to the onset of the disease. The high-incidence seasons were identified as summer and autumn, specifically from August to November. The distribution of reported cases of human fascioliasis across the year is illustrated in Figure 1. Demographics and clinical features are shown in Tables 1 and 2.
Figure 1.
Distribution of 95 patients with human fascioliasis by hospital admission month. GraphPad Prism 9.0, GraphPad Software, Inc.
Table 1.
Clinical characteristics of 95 patients with human fascioliasis in Dali, Yunnan Province, southwestern China.
| Clinical characteristics | |
|---|---|
| Age (years) | 38.54±15.68 |
| male (n, %) | 37 (38.95%) |
| Smoking (n, %) | 17 (17.89%) |
| Alcohol (n, %) | 19 (20.00%) |
| Clinical features | |
| Abdominal pain (n, %) | 67 (70.53%) |
| Fever (n, %) | 37 (38.95%) |
| Lassitude (n, %) | 12 (12.63%) |
| Abdominal distension (n, %) | 10 (10.53%) |
| Loss of appetite (n, %) | 7 (7.37%) |
Table 2.
Laboratory characteristics of 95 patients with human fascioliasis in Dali, Yunnan Province, southwestern China.
| Laboratory characteristics | |
|---|---|
| WBC (×109/L) | 8.54 (6.14–12.14) |
| N (%) | 39.97±14.45 |
| E (%) | 30.70 (17.00–43.80) |
| E# (×109/L) | 2.36 (0.93–5.29) |
| HGB (g/L) | 126.01±20.41 |
| PLT (×109/L) | 259.96±86.56 |
| TBI (umol/L) | 9.60 (7.00–12.80) |
| ALT (U/L) | 24.00 (18.00–50.00) |
| AST (U/L) | 24.00 (18.00–35.00) |
| GLB (g/L) | 33.50 (28.60–40.70) |
| ALB (g/L) | 37.50 (33.00–41.40) |
| ALP (U/L) | 142.00 (98.00–201.00) |
| GGT (U/L) | 78.00 (44.00–131.00) |
| AFP (ng/mL) | 3.62 (2.27–5.65) |
| CEA (ng/mL) | 2.52 (1.23–5.16) |
| CA125 (U/mL) | 15.26 (9.92–18.90) |
| CA153 (U/mL) | 11.18±5.37 |
| CA199 (U/mL) | 15.82 (4.82–3.72) |
| CA724 (U/mL) | 2.03 (1.03–3.72) |
| CRP (mg/L) | 15.38 (4.46–42.82) |
| ESR (mm/h) | 32.00 (21.00–58.00) |
| Positive stool parasite (n,%) | 6 (6.31%) |
WBC – white blood cells; N% – the neutrophils percentage; E% – the eosinophils percentage; E – eosinophils; HGB – hemoglobin; PLT – platelets; TBI – total bilirubin; ALT – alanine transaminase; AST – aspartate transaminase; GLB – globulin; ALB – albumin; ALP – alkaline phosphatase; GGT – gamma-glutamyl transferase; AFP – alpha-fetoprotein; CEA – carcinoembryonic antigen; CRP – C-reactive protein; ESR – erythrocyte sedimentation rate.
Main Symptoms and Vital Signs
The most common symptoms were abdominal pain (70.53%); it is noteworthy that the abdominal pain was predominantly localized to the right upper quadrant areas, as reported by 52.63% of the patients. Other frequently reported symptoms included fever (38.95%) and fatigue (12.63%). The average duration from the onset of symptoms to hospitalization was 61.46±52.21 days. Physical examination findings revealed that tenderness in the epigastrium or right epigastrium was the most common symptom (66.31%), followed by splenomegaly (26.25%), pleural effusion (9.47%), and hepatomegaly (4.21%). Only 2 patients presented with yellowish discoloration of the skin, sclera, and mucous membranes. Five of the patients underwent surgery due to abdominal pain and abdominal imaging (CT/MRI), suggestive of biliary obstruction caused by bile duct stones. Adult Fasciola were isolated from the common bile duct in 2 patients. Additionally, 11 (11.58%) patients were initially misdiagnosed as having liver cancer or liver abscess, and 3 underwent partial hepatectomy due to liver cancer misdiagnosis.
Laboratory Test Results
Of the total, 89.5% of patients exhibited increased eosinophils in peripheral blood (ie, percentage of eosinophils in peripheral blood of more than 5%), with a mean absolute value of eosinophils of 11.54×109/L. The incidences of anemia and leukocytosis were 34.74% and 36.84%, respectively, with 1 patient who experienced a leukemoid reaction due to a secondary bacterial infection. It is worth noting that platelets were within the normal range in all patients. In terms of liver function, 44 (46.32%) patients and 65 (68.42%) patients had elevated ALP and GGT, respectively. Also, 23 (24.21%) patients and 13 (13.68%) patients had increased ALT and AST, respectively. One patient had a total bilirubin level exceeding 5 mg/dL (reference range: 0.28–1.06 mg/dL) due to bile duct obstruction caused by adult Fasciola. Furthermore, only 1 patient exhibited an elevated serum creatinine level, at 330 μmol/L. For serodiagnosis, ELISA using soluble crude antigen of adult Fasciola was conducted, and all results were positive (1: 640) for Fasciola-specific antibodies. Fasciola eggs (144–180×73–96 μm, ×400) were detected in stool samples of 6 patients (Figure 2A), and adult Fasciola were extracted from the common bile duct of 2 patients (Figure 2B, 2C).
Figure 2.
(A) Fasciola eggs (153×80 μm [× 400]) were detected in stool samples of patients with human fascioliasis; (B, C) Adult Fasciola were detected in bile ducts of patients with human fascioliasis (macroscopic view).
Imaging Results
Abdominal ultrasound, CT, or MRI were conducted for all patients. Ultrasonographic findings were nonspecific and included multiple heterogeneous, slightly hyperechoic, or cystic masses in the liver. The CT scan in Figure 3A shows gathered or scattered low-density shadows. The contrast-enhanced CT in Figure 3B shows clustered or tunnel-like lesions under the liver capsule, without significant enhancement (indicated by arrows). Figure 3C shows large cystic lesions with smooth edges in the liver parenchyma, measuring 5–6 cm in diameter, with scattered punctate calcifications around them. MRI results in Figure 3D (T2 axial) reveal the presence of adult Fasciola in the dilated common bile duct. Extrahepatic findings included intraperitoneal lymphadenopathy (40.6%), ascites (18.1%), bile duct dilatation (14.9%), liver enlargement (8.5%), and abdominal wall abscess (2.1%).
Figure 3.
(A) Abdominal computed tomography (CT) scan showing multiple low-density shadows under the liver capsule. (B) Abdominal CT and enhanced CT showing clustered and/or tunnel-like lesions under the liver capsule, without significant enhancement (arrowhead). (C) Upper-abdominal CT and enhanced CT showing large cystic lesions in the liver parenchyma with smooth edges, and multiple punctate calcifications scattered around. (D) Adult Fasciola in the dilated common bile duct in T2 axial of magnetic resonance imaging.
Pathological Results
A liver biopsy was performed on 15 patients to establish a histopathological diagnosis of fascioliasis. Also, 3 patients underwent partial hepatectomy due to misdiagnosis of liver cancer. Eosinophilic infiltration and abscesses characterized by irregular tunnel formation were observed in the aforementioned patient (Figure 4A, 4B), and Charcot-Leyden crystals were found in 17 patients; however, no parasites were detected in the liver specimens. A skin biopsy was conducted on 1 patient with a rash on the lower limbs. The results indicated intimal proliferation and thickening of local small vascular (Figure 4C) and eosinophil infiltration in the interlobular septum of subcutaneous fat (Figure 4D), which were considered as eosinophilic panniculitis secondary to fascioliasis. In addition, 1 patient developed pruritus, with nodules on the chest wall, and the biopsy showed significant eosinophil infiltrating with Charcot-Leyden crystals. Four patients underwent bone marrow biopsy, which indicated eosinophil infiltration. As displayed in Figure 5A–5D, the worm taken from the patient was diagnosed as Fasciola, according to its gross morphology and pathology.
Figure 4.
(A) Pathological results of liver biopsy results showing massive eosinophil infiltration and abscesses (hematoxylin and eosin [H&E] stain, ×100 magnification). (B) Pathological results of liver biopsy results showing eosinophilic infiltration and abscesses characterized by irregular tunnel formation (H&E stain, ×200 magnification). (C) Skin biopsy of lower limbs showing intimal proliferation and thickening of small vascular (H&E stain, ×200 magnification). (D) Skin biopsy of lower limbs showing eosinophil infiltration in the interlobular septum of subcutaneous fat (H&E stain, ×200 magnification).
Figure 5.
Pathology of adult Fasciola (hematoxylin and eosin stain, ×200 magnification). (A) is the head of the adult Fasciola; (B) is the body of the adult Fasciola; and (C, D) are tail of the adult Fasciola.
Therapy and Prognosis
In our study, triclabendazole was administered to 91 patients as the primary treatment for human fascioliasis. The oral daily dose of triclabendazole was 10 mg/kg, given in 3 doses for 2 days. Four patients initially received other medications, such as albendazole, mebendazole, or artemether, but later switched to triclabendazole due to the unsatisfactory effect of the previous treatment. Actually, the disappearance of clinical symptoms and images and the return to normal laboratory values in treated patients are strong evidence of the resolution of the infection. A total of 92 patients were successfully followed up for clinical symptoms, laboratory results, and imaging findings. The clinical symptoms of 90 patients almost disappeared 35 days after triclabendazole treatment. The eosinophil count and liver function parameters ALT, AST, ALP, and GGT returned to normal within 3 months. Imaging revealed that lesions completely disappeared in 60 patients (63.16%) after 6 months. No deaths were observed in our study.
Discussion
Human fascioliasis is a neglected disease prevalent in rural areas, particularly among schoolchildren. If left undiagnosed and untreated, the disease can persist for a long duration, causing severe damage to the health of the infected individuals. Over-reliance on imaging for diagnosis can lead to resource wastage and potentially unnecessary abdominal surgeries due to misdiagnosis, further burdening patients physically, mentally, and financially. In this study, the following findings were made by analyzing the epidemiological manifestations of 95 cases with human fascioliasis in the Dali area: (1) the prevalent species in the Dali area is mainly F. gigantica; (2) F. gigantica is endemic in summer and autumn; (3) females were more susceptible to F. gigantica infection than were males; (4) the primary clinical manifestations of human fascioliasis include fever, abdominal pain, elevated eosinophils, mildly abnormal liver function, and the presence of single or multiple hypodense shadows in liver imaging; (5) stool examination for Fasciola eggs has a low positivity rate; therefore, serological testing, specifically ELISA, is relied upon for diagnosis; and (6) triclabendazole is commonly used and is an effective anthelmintic drug against parasites at all stages of infection.
As already mentioned, the Dali area is known to be an endemic area for F. gigantica infections, given that Dali was an important stop in the past Tea Horse Road, a route connecting southwest and northwest China, Tibet, Nepal, Bhutan, Bangladesh, northeast India, and Myanmar for thousands of years [4]. The Tea Horse Road covered the western side of the Chinese provinces of Sichuan and Yunnan and the southeastern region of Tibet [4]. Current studies in these areas specifically indicate the prevalence of F. gigantica [4,14]. Mules were the animals primarily used for transporting cargo and people along the Tea Horse Road, facilitating the transmission of F. gigantica [4]. Moreover, according to a prior investigation, it has been determined that an occurrence of human fascioliasis outbreaks in the Dali region was attributed to F. gigantica [3].
In some areas of Dali, sheep and cattle are allowed to graze freely, and a study showed that 28.6% and 26% of cattle and sheep, respectively, in the region are infected with F. gigantica [3]. Epidemiological studies have revealed that all patients in these areas were infected by consuming contaminated vegetables (such as cordate houttuynia and wild coriander) or water containing metacercaria [15]. Meanwhile, the onset of the disease primarily occurs from August to November, corresponding to the temperature range of 22–28°C suitable for the growth of miracidia into cercariae. It is worth noting that August is the summer month in China, and Dali, located in the southwest, experiences favorable temperatures and abundant precipitation during the summer, which are conducive to the reproduction of fascioliasis. Furthermore, the number of tourists visiting Dali increases during the summer vacation period, and people tend to consume cold dishes (such as raw vegetables or raw pork), further contributing to the increase in infected individuals. The concentration of hospitalized patients in November is believed to be due to patients typically exhibiting clinical symptoms 2 to 12 weeks after infection. As a result, patients are often infected during the summer but experience a delay in hospitalization, leading to a peak in hospital admissions during the fall.
In the present study, it was observed that females exhibited a higher susceptibility to fascioliasis, which was consistent with the findings of Chen et al [3]. This observation can be attributed to the prevailing circumstances in rural areas, where the majority of men engage in occupational activities outside the household, leaving women with the responsibility of herding and farm work. Consequently, this sex-based division of labor exposes females to an elevated risk of contracting fascioliasis. It is noteworthy, however, that prior investigations have reported a higher likelihood of infection among males than females, which may be a result of discrepancies due to inconsistencies in the number of cases included [7].
It is now understood that fascioliasis is prone to sporadic or family aggregation and even outbreaks. Our study identified 2 cases of familial clustering, consistent with the study of Karahocagil et al [16].
Human fascioliasis can be classified into acute, chronic, and ectopic lesions based on clinical features, laboratory tests, and imaging results. Acute fascioliasis typically develops 2 to 12 weeks after ingestion of metacercariae, and the disease progression is relatively slow. In our study, most patients presented with symptoms such as abdominal pain, fever, fatigue, and splenomegaly. In addition, laboratory test results showed increased WBC, eosinophils, ALP, GGT, ALT, AST, and globulin, which were associated with the migration of Fasciola adolescaria in the abdominal cavity and liver parenchyma. Valero et al [17] conducted experiments with F. gigantica and found that during the acute phase, creatinine levels decreased, while GGT, AST, ALP, ALB, and C-reactive protein (CRP) levels increased. In the chronic phase, AST, GGT, total cholesterol, and CRP levels exhibited an increasing trend, while ALB, chlorine, and phosphorus levels decreased. Although we classified the patients in our study into acute (n=71) and chronic phases (n=24), the lack of dynamic monitoring of laboratory indicators prevented us from understanding the dynamic changes in liver and kidney function, which is a limitation of our study.
Moreover, we observed that some patients with fascioliasis exhibited symptoms of anemia, hepatomegaly, bile duct dilatation, and cholangitis/cholecystitis. Previous reports have also indicated that patients with fascioliasis often present with severe anemia and eosinophilia [18], which can be attributed to the mechanical injury caused by adult worms to the bile ducts and the stimulation of their metabolites during the chronic phase. The increased levels of CRP and erythrocyte sedimentation rate observed in most patients could be attributed to the host immune response mediated by cells and molecules of Fasciola.
Furthermore, 2 patients in our study exhibited ectopic lesions in the subcutaneous tissues of their lower limbs and muscles of the chest wall. These lesions likely resulted from the penetration of the worm body or its transportation to organs and tissues other than the liver through the bloodstream during the migration of the Fasciola adolescaria in the abdominal cavity. The main clinical manifestations in these 2 patients included redness, swelling, itching, and pain in the skin of the affected areas. Le et al [19] also reported cases of abnormal migration of F. gigantica in human skin. In our study, 2 cases of fascioliasis with ectopic cutaneous lesions were diagnosed, and the patients were promptly treated with triclabendazole at a dose of 10 mg/(kg/day), divided into 3 doses and administered for 2 consecutive days. After 3 months of treatment, the redness, swelling, itching, and pain in the lower extremities of both patients completely resolved.
In endemic areas such as Dali, it is important to be aware of the possibility of fascioliasis in patients presenting with abdominal pain, fever, and elevated eosinophils, as mentioned in previous studies [16,20]. Remarkably, we have presented a comprehensive analysis of the sizes and lengths of Fasciola eggs (144–180×73–96 μm, ×400) found in the stool samples of 6 patients, which fully fit within the range of F. gigantica eggs shed in human stools in areas where F. hepatica is absent [21]. This finding further substantiates the conclusion that the Dali region is an endemic area for F. gigantica infections. Fecal and serological examination are 2 mainstream diagnostic methods for fascioliasis [3], but the positive rate of Fasciola eggs in stool samples remains low (only 6.32% in this study), attributed to the following reasons: (1) Fasciola take about 10–14 weeks (chronic phase) to release eggs, and this study found that most patients sought medical attention during the acute phase, resulting in a low positivity rate for stool examination for parasite eggs [8]; (2) some Fasciola may be unable to lay eggs, which could be attributed to their lack of adaptation to the human host, consistent with previous research reports [22]; and (3) adult worms intermittently release eggs in the liver, or they may still be in the process of maturation. Considering the low positivity rate of stool examination for Fasciola eggs, the current diagnosis of fascioliasis mainly relies on serological testing techniques. ELISA is used to detect the presence of anti-Fasciola antibodies in the serum [8].
In fascioliasis, abdominal ultrasound findings are nonspecific and typically show liver hypoechoic or hyperechoic shadows. CT scans, on the other hand, often reveal multiple patchy or round low-density lesions with mild enhancement distributed in the liver parenchyma and capsule. In 3 patients who underwent surgery for suspected liver cancer, adult Fasciola were discovered and subsequently identified as F. gigantica [3]. Prior reports also confirmed that the adult Fasciola of human fascioliasis were all identified as F. gigantica [3,23,24]. Our results were similar to those of Apinya et al [23] in terms of a large number of lymphocytes and eosinophils infiltration, eosinophilic abscess formation, and Charcot-Leiden crystals among the 15 patients who underwent liver biopsy or hepatectomy.
Triclabendazole is an imidazole drug primarily used for treating fascioliasis in livestock, since 1983. Its use in human fascioliasis started in the 1990s, and in February 2019, triclabendazole (Egaten, Novartis, East Hanover, NJ, USA) received approval from the US Food and Drug Administration for the treatment of human fascioliasis. Triclabendazole is a broad-spectrum anthelmintic agent effective against all stages of Fasciola infection, and its mechanism of action may involve the inhibition of microtubule processes or adenylate cyclase activity [25]. In our study, triclabendazole was administered to 91 patients at a daily oral dose of 10 mg/kg, given in 3 doses over 2 days. Four patients initially received other drugs, such as albendazole, mebendazole, or artemether, but were switched to triclabendazole due to unsatisfactory effects from the previous treatment. No adverse reactions were observed following triclabendazole treatment, which was in line with results of Chen et al [3]. Fang et al [26] conducted an analysis of studies on albendazole and triclabendazole in the treatment of fascioliasis and found that triclabendazole is effective against both the adult worms and eggs of fascioliasis. It offers the advantages of a good cure rate, short treatment duration, and minimal adverse effects. While there have been reports of treatment failure and drug resistance with triclabendazole in treating fascioliasis [27], we did not encounter such issues in our study.
The clinical manifestations of human fascioliasis are nonspecific, highlighting the importance of healthcare professionals improving their diagnostic and treatment abilities based on clinical features, laboratory tests, imaging results, and epidemiology. Early diagnosis and treatment are crucial to reducing misdiagnosis and missed diagnoses, ultimately providing effective protection for at-risk populations.
Limitations
Although we made some important discoveries in this study, we need to point out some limitations. First, as a retrospective clinical study, it is important to acknowledge the potential presence of selection bias. Additionally, the limited sample size further emphasizes the necessity for a comprehensive prospective study involving multiple centers to validate our findings. Apart from the above, the adult Fasciola from patients included in Figure 2B and 2C do not show the typical form of F. gigantica, which suggests that they were probably immature young specimens, not appropriately fixed and mounted. Finally, owing to practical constraints, timely monitoring of dynamic changes in laboratory indicators was unfeasible, and the follow-up duration for patients with human fascioliasis was limited to 6 months, a relatively brief interval. Consequently, a longer follow-up period is warranted to enable a more comprehensive evaluation of the prognosis.
Conclusions
Human fascioliasis is a neglected parasitic disease caused by the parasites F. hepatica and F. gigantica. In summary, the findings from this observational epidemiological study have highlighted the importance of recognizing, diagnosing, and managing fascioliasis, which is an emerging zoonosis associated with increased human proximity to plant-eating domestic and farmed animals.
Acknowledgment
We thank all the patients who participated in this study.
Abbreviations
- CT
computed tomography
- F
hepatica, Fasciola hepatica
- F
gigantica, Fasciola gigantica
- WBC
white blood cells
- ALT
alanine transaminase
- AST
aspartate transaminase
- GGT
gamma-glutamyl transferase
- CA
carbohydrate antigen
- CRP
C-reactive protein
- MRI
magnetic resonance imaging
- SPSS
Statistical Product and Service Solutions
- ELISA
enzyme-linked immunosorbent assay
Footnotes
Conflict of interest: None declared
Declaration of Figures’ Authenticity
All figures submitted have been created by the authors, who confirm that the images are original with no duplication and have not been previously published in whole or in part.
Financial support: This investigation was funded by the Sub-Center Project of Infectious Diseases Clinical Medical Center of Yunnan Province and the Construction Project of Key Laboratory of Infectious Disease of Yunnan Provincial Education Department and the Foundation of Yunnan Provincial Department of Education (2021J0384; 2022J0694)
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