ABSTRACT
Fasciola spp., infections are distributed worldwide including the Andes region of Ecuador, affecting cattle, sheep, porcine, humans, and other herbivores. Triclabendazole (TCBZ) is commonly used to treat animal infections. However, prospective studies on TCBZ efficacy and fascioliosis prevalence have not been studied in the highlands of Ecuador. This study was performed in a rural community at central of the Ecuadorian Andes in freely roaming bovine and ovine aimed to 1) evaluate the efficacy of TCBZ by administering a single oral dose of 12 mg/kg body weight, 2) assess the prevalence of F. hepatica infection and 3) to monitor re-infections for a follow-up period of five months. In total, 122, 86, 111, 110, 89, and 90 and 49, 34, 47, 28, 27, and 31 stool samples were collected each month from bovines and ovine, respectively. Besides, 32 stool samples from porcine were also collected at the beginning of the study. Stools were microscopically analyzed by formalin-ether concentration method to detect F. hepatica ova. The prevalence of F. hepatica infections before treatment was 55,7% and 63,3% for bovine and ovine, respectively. The infection prevalence was of 22% in porcine. The efficacity of triclabendazole was 83% and 97% in bovines and ovine, respectively, at 30 days post-treatment. The re-infection reaches to 54,4% in bovines and 61,3% in ovine after five months. TCBZ had a high efficacy and could be used for bovines and ovine Fasciola infections in the study region; however, re-infections reach the initial prevalence after five months. Therefore, we recommend integrated control strategies, including chemotherapy with a single oral dose of TCBZ, vector control, and future drug resistance studies.
Subject(s)
Cattle Diseases , Fasciola hepatica , Moths , Sheep Diseases , Swine Diseases , Humans , Animals , Cattle , Sheep , Swine , Triclabendazole/therapeutic use , Ecuador/epidemiology , Reinfection/veterinary , Prevalence , Prospective Studies , Cattle Diseases/drug therapy , Cattle Diseases/epidemiology , Sheep Diseases/drug therapy , Sheep Diseases/epidemiologyABSTRACT
Fasciola hepatica infections lead to severe health problems and production losses in sheep farming, if not treated effectively. Triclabendazole has been used extensively over decades due to its unique efficacy range against all definitive hostfluke stages but published data about the susceptibility of F. hepatica to anthelmintics in Germany are lacking. This study aimed to identify current F. hepatica infections in German sheep flocks by coproscopic examinations and to evaluate the efficacy of anthelmintics with a focus on triclabendazole in a field study conducted from 2020 to 2022. Initial screening included 71 sheep farms, many of them with known history of fasciolosis. In this highly biased sample set, the frequency of F. hepatica infection at individual sheep and farm level were 12.8% and 35.2%, respectively. Additionally, eggs of Paramphistominae were found at frequencies of 4.8% and 15.5% at individual sheep and farm level, respectively. Due to low egg shedding intensity, faecal egg count reduction (FECR) tests could only be conducted on a few farms. The efficacy of triclabendazole was tested on 11 farms and albendazole on one farm, including 3-53 sheep/farm. Individual faecal samples were collected before and two weeks after treatment to evaluate the FECR using the sedimentation or FLUKEFINDER® or a modified FLUKEFINDER® method. On all farms a coproantigen reduction test was conducted in parallel. Lacking efficacy of triclabendazole even at double dosage was shown on one farm associated with a high number of animal losses due to acute fasciolosis. On this farm, the Fasciola miracidium development test was additionally performed, revealing a high in vitro ovicidal activity of albendazole while closantel was effective in vivo. On all other farms, sufficient efficacy of triclabendazole was observed. In conclusion, triclabendazole resistance appears not to be widespread on German sheep farms but, when present, can have serious effects on animal health.
Subject(s)
Anthelmintics , Fasciola hepatica , Fascioliasis , Sheep Diseases , Triclabendazole , Animals , Albendazole/therapeutic use , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Drug Resistance , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/veterinary , Farms , Fascioliasis/drug therapy , Fascioliasis/veterinary , Feces , Sheep , Sheep Diseases/drug therapy , Triclabendazole/therapeutic useABSTRACT
In the fall of 2022, decreased triclabendazole (TCBZ) efficacy against F. hepatica was suspected in a sheep farm located in the Santa Cruz province, Argentinian Patagonia. Since TCBZ-resistance in F. hepatica has never been reported in this province, this study aimed to confirm potential TCBZ-resistance in F. hepatica and to evaluate the efficacy of closantel (CLO) and nitroxinil (NTX), through faecal egg count reduction test (FECRT), and the efficacy of albendazole (ABZ) through the in vitro egg hatch test (EHT) in sheep. Sixty-eight (68) animals were selected from a herd of eighty (80) female Merino naturally infected with F. hepatica based on eggs per gram of F. hepatica (EPGFh) counts and assigned into four (4) groups (n = 17 per group): Group Control, animals did not receive anthelmintic treatment; Group TCBZ, animals were orally treated with TCBZ (12 mg/kg); Group CLO, animals were orally treated with CLO (10 mg/kg); and Group NTX, animals were subcutaneously treated with NTX (10 mg/kg). The fluke egg output was monitored on days 0 and 21 post-treatment. For the EHT, liver fluke eggs were isolated from faecal samples (approx. 50 g) collected from animals of the control group. TCBZ efficacy against liver fluke was 53.4%, confirming the presence of TCBZ-resistant isolates on the farm. CLO and NTX were highly effective (100%) for the treatment of F. hepatica on this farm. The EHT was carried out in two different laboratories, in which was observed an ABZ efficacy of 95.8 (Bariloche) and 96.5% (Tandil). These results indicate the ABZ susceptibility of this F. hepatica isolate and the inter-laboratory precision of the test.
Subject(s)
Fasciola hepatica , Fascioliasis , Sheep Diseases , Female , Sheep , Animals , Triclabendazole/therapeutic use , Fascioliasis/drug therapy , Fascioliasis/veterinary , Benzimidazoles/pharmacology , Benzimidazoles/therapeutic use , Drug Resistance , Sheep Diseases/drug therapy , Albendazole/pharmacology , Albendazole/therapeutic use , Nitroxinil , Sheep, DomesticABSTRACT
There is a lack of epidemiological data on fascioliasis in Egypt regarding disease characteristics and treatment outcomes across different governorates. We aimed to identify the demographic, epidemiologic, clinical, laboratory, and radiological characteristics and treatment outcomes of patients diagnosed with fascioliasis in Egypt. Data on human fascioliasis were collected retrospectively from patients' medical records in the period between January 2018 and January 2020. The study included 261 patients. More than 40% of enrolled patients were in the age group of 21-40 years old. Geographically, 247 (94.6%) were from Assiut Governorate with 69.3% were from rural areas. The most frequent symptoms were right upper quadrant pain (96.9%), and fever (80.1%). Eosinophilia was found in 250 cases (95.8%). Hepatic focal lesions were detected in 131 (50.2%); out of them 64/131 (48.9%) had a single lesion. All patients received a single dose of 10 mg/kg of triclabendazole, 79.7% responded well to a single dose, while in 20.3% a second ± a third dose of treatment was requested. After therapy, there was a reduction in leucocytes, Fasciola antibodies titer, eosinophilic count, bilirubin, and liver enzymes with an increase in hemoglobin level. According to our findings, a high index of suspicion should be raised in cases with fever, right upper abdominal pain, and peripheral eosinophilia, and further imaging workup is mandated to detect hepatic focal lesions. Prompt treatment by triclabendazole can serve as a standard-of-care regimen even for suspected cases.
Subject(s)
Eosinophilia , Fasciola hepatica , Fascioliasis , Animals , Humans , Young Adult , Adult , Fascioliasis/diagnostic imaging , Fascioliasis/drug therapy , Triclabendazole/therapeutic use , Retrospective Studies , Egypt/epidemiology , Abdominal PainABSTRACT
About a third of the world population is infected by helminth parasites implicated in foodborne trematodiasis. Fascioliasis is a worldwide disease caused by trematodes of the genus Fasciola spp. It generates huge economic losses to the agri-food industry and is currently considered an emerging zoonosis by the World Health Organization (WHO). The only available treatment relies on anthelmintic drugs, being triclabendazole (TCBZ) the drug of choice to control human infections. The emergence of TCBZ resistance in several countries and the lack of an effective vaccine to prevent infection highlights the need to develop new drugs to control this parasitosis. We have previously identified a group of benzochalcones as inhibitors of cathepsins, which have fasciolicidal activity in vitro and are potential new drugs for the control of fascioliasis. We selected the four most active compounds of this group to perform further preclinical studies. The compound's stability was determined against a liver microsomal enzyme fraction, obtaining half-lives of 34-169 min and low intrinsic clearance values (<13 µL/min/mg), as desirable for potential new drugs. None of the compounds were mutagenic or genotoxic and no in vitro cytotoxic effects were seen. Compounds C31 and C34 showed the highest selectivity index against liver fluke cathepsins when compared to human cathepsin L. They were selected for in vivo efficacy studies observing a protective effect, similar to TCBZ, in a mouse model of infection. Our findings strongly encourage us to continue the drug development pipeline for these molecules.
Subject(s)
Anthelmintics , Chalcones , Fasciola hepatica , Fascioliasis , Animals , Mice , Humans , Fascioliasis/drug therapy , Fascioliasis/parasitology , Chalcones/pharmacology , Chalcones/therapeutic use , Triclabendazole/pharmacology , Triclabendazole/therapeutic use , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , CathepsinsABSTRACT
PURPOSE: Fasciola hepatica is a globally distributed trematode that causes significant economic losses. Triclabendazole is the primary pharmacological treatment for this parasite. However, the increasing resistance to triclabendazole limits its efficacy. Previous pharmacodynamics studies suggested that triclabendazole acts by interacting mainly with the ß monomer of tubulin. METHODS: We used a high-quality method to model the six isotypes of F. hepatica ß-tubulin in the absence of three-dimensional structures. Molecular dockings were conducted to evaluate the destabilization regions in the molecule against the ligands triclabendazole, triclabendazole sulphoxide and triclabendazole sulphone. RESULTS: The nucleotide binding site demonstrates higher affinity than the binding sites of colchicine, albendazole, the T7 loop and pßVII (p < 0.05). We suggest that the binding of the ligands to the polymerization site of ß-tubulin can lead a microtubule disruption. Furthermore, we found that triclabendazole sulphone exhibited significantly higher binding affinity than other ligands (p < 0.05) across all isotypes of ß-tubulin. CONCLUSIONS: Our investigation has yielded new insight on the mechanism of action of triclabendazole and its sulphometabolites on F. hepatica ß-tubulin through computational tools. These findings have significant implications for ongoing scientific research ongoing towards the discovery of novel therapeutics to treat F. hepatica infections.
Subject(s)
Anthelmintics , Fasciola hepatica , Fascioliasis , Animals , Triclabendazole/pharmacology , Triclabendazole/metabolism , Triclabendazole/therapeutic use , Tubulin/genetics , Molecular Docking Simulation , Benzimidazoles/pharmacology , Benzimidazoles/chemistry , Benzimidazoles/metabolism , Ligands , Sulfones/metabolism , Sulfones/therapeutic use , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Fascioliasis/parasitologyABSTRACT
This is a case report of fascioliasis that progressed from the hepatic to the biliary phases over 2 years. A woman in her late 60s ate Zingiber mioga from the field, which was followed by abdominal pain that occurred 1 month later. Although CT and MRI studies revealed an increase in blood eosinophils as well as multiple hepatic nodules, they vanished quickly. After 2 years, an MRCP study revealed multiple flat lesions, which were diagnosed as adult fascioliasis. Definitive diagnosis was provided by enzyme-labeled antibody method using fasciola-specific antigen. Triclabendazole was administered once to complete the treatment.
Subject(s)
Anthelmintics , Fascioliasis , Female , Humans , Fascioliasis/diagnosis , Fascioliasis/drug therapy , Fascioliasis/pathology , Anthelmintics/therapeutic use , Benzimidazoles/therapeutic use , Triclabendazole/therapeutic useABSTRACT
The intensive use of anthelmintic drugs to control Fasciola hepatica infections in dairy cattle has resulted in the emergence of anthelmintic resistance. Cases of resistance to triclabendazole (TCBZ) have been reported worldwide. The main goal of this research was to evaluate the main five fasciolicides to control fasciolosis in dairy cattle in the Mantaro Valley, Peru. Two fecal egg count reduction tests were performed. In a first study, 24 naturally F. hepatica infected cattle were randomly grouped into three experimental groups (n = 8). Groups were treated with either TCBZ, nitroxynil (NTX) or closantel (CLOS). In a second experiment, 55 naturally infected cows were grouped into three experimental groups and treated with either TCBZ (n = 18), rafoxanide (RFX) + albendazole (ABZ) (n = 19) or clorsulon (CLN) + ivermectin (IVM) (n = 18). Therapeutic efficacy was determined following the WAAVP guidelines by measuring reduction in fluke egg output at days 15 and 30 post-treatment. Bootstrapping method was used to obtain the 95% confidence intervals. The efficacy of TCBZ was inadequate in both studies (≤80.8%). Closantel showed high efficacy (≥ 90%) at both days, while NTX showed 92.9% (83-100) and 82.1% (53.6-100), efficacy, at days 15 and 30, respectively. Efficacy for RFX were 92.1% (79.6-98.9) and 97.4% (94.1-99.4); and for CLN, 98.8% (97.6-100) and 80.1% (44.7-99.4), at days 15 and 30, respectively. The outcome of this study indicates reduced therapeutic efficacy of TCBZ against F. hepatica in an important dairy area of the Peruvian central highlands but also demonstrates the validity of four alternatives.
Subject(s)
Anthelmintics , Fasciola hepatica , Fascioliasis , Animals , Cattle , Female , Anthelmintics/therapeutic use , Fascioliasis/drug therapy , Fascioliasis/veterinary , Nitroxinil/therapeutic use , Peru , Rafoxanide/therapeutic use , Triclabendazole/therapeutic useABSTRACT
Fasciola hepatica infection is responsible for substantial economic losses in livestock worldwide and poses a threat to human health in endemic areas. The mainstay of control in livestock and the only drug licenced for use in humans is triclabendazole (TCBZ). TCBZ resistance has been reported on every continent and threatens effective control of fasciolosis in many parts of the world. To date, understanding the genetic mechanisms underlying TCBZ resistance has been limited to studies of candidate genes, based on assumptions of their role in drug action. Taking an alternative approach, we combined a genetic cross with whole-genome sequencing to localise a ~3.2Mbp locus within the 1.2Gbp F. hepatica genome that confers TCBZ resistance. We validated this locus independently using bulk segregant analysis of F. hepatica populations and showed that it is the target of drug selection in the field. We genotyped individual parasites and tracked segregation and reassortment of SNPs to show that TCBZ resistance exhibits Mendelian inheritance and is conferred by a dominant allele. We defined gene content within this locus to pinpoint genes involved in membrane transport, (e.g. ATP-binding cassette family B, ABCB1), transmembrane signalling and signal transduction (e.g. GTP-Ras-adenylyl cyclase and EGF-like protein), DNA/RNA binding and transcriptional regulation (e.g. SANT/Myb-like DNA-binding domain protein) and drug storage and sequestration (e.g. fatty acid binding protein, FABP) as prime candidates for conferring TCBZ resistance. This study constitutes the first experimental cross and genome-wide approach for any heritable trait in F. hepatica and is key to understanding the evolution of drug resistance in Fasciola spp. to inform deployment of efficacious anthelmintic treatments in the field.
Subject(s)
Anthelmintics , Fasciola hepatica , Fascioliasis , Animals , Humans , Triclabendazole/metabolism , Triclabendazole/pharmacology , Triclabendazole/therapeutic use , Benzimidazoles/pharmacology , Anthelmintics/pharmacology , Fascioliasis/drug therapy , Fascioliasis/parasitology , Drug ResistanceABSTRACT
Fascioliasis has been reported from many countries across the globe. Acute phase of liver fluke is characterised by fever, abdominal pain and peripheral blood eosinophilia while the chronic phase is marked by chronic inflammation involving biliary tract. It is commonly diagnosed by a radiologist due to characteristic branching abscesses seen on CT scan, highly suggestive of liver fluke. Diagnosis is made by demonstration of eggs on direct microscopic examination of duodenal aspirate or bile. Screening of family members is recommended once diagnosis is has been made. Triclabendazole is the drug of choice for treatment.
Subject(s)
Anthelmintics , Eosinophilia , Fasciola hepatica , Fascioliasis , Abdominal Pain/drug therapy , Abdominal Pain/etiology , Animals , Anthelmintics/therapeutic use , Eosinophilia/diagnosis , Eosinophilia/drug therapy , Fascioliasis/diagnosis , Fascioliasis/drug therapy , Female , Fever/drug therapy , Fever/etiology , Humans , Triclabendazole/therapeutic useABSTRACT
Fasciola hepatica, a worldwide-distributed liver fluke, is one of the causative agents of fasciolosis, a zoonotic disease that affects livestock and humans. In livestock, fasciolosis causes huge economic losses worldwide, reducing animal fertility, milk production, weight gain and condemnation of livers. In spite of the availability of drugs, such as triclabendazole (TCZ), for the treatment of fasciolosis, they do not necessarily prevent liver damage or parasite reinfection and can eventually increase parasite resistance. The aim of this research was to relate the hepatic function, haematological parameters, leukocyte counts in circulation and parasite egg shedding during F. hepatica acute and chronic phases of infection in cattle as well as to determine how these parameters change with TCZ-treatment of chronically infected cattle. Our results show that increased levels of serum aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT) were detected in early stages of the experimental infection. Moreover, high circulating eosinophil count and plateletcrit levels were correlated with fluke number in livers from infected cattle. On the other hand, although TCZ-treatment in the chronic phase of infection reduced parasite burden and damage in the liver, it was not able to completely avoid them. In conclusion, our work sheds light into the physiopathological mechanisms induced during fluke infection in cattle, revealing the complexity of the host response to the infection, together with the effects of TCZ-treatment in chronically infected animals.
Subject(s)
Cattle Diseases , Fasciola hepatica , Fascioliasis , Animals , Cattle , Cattle Diseases/drug therapy , Cattle Diseases/parasitology , Fascioliasis/drug therapy , Fascioliasis/parasitology , Fascioliasis/veterinary , Triclabendazole/therapeutic useABSTRACT
Fasciola gigantica, the causative agent of tropical fasciolosis, is a food-borne zoonotic trematode that affects around 80% livestock of Bangladesh. Triclabendazole (TCBZ), nitroxynil (NTON) and oxyclozanide (OCZN) are frequently used against fascioliasis; however, the current status of potency of these flukicides was unknown. In this study, in vitro efficacy of TCBZ, NTON and OCZN at various concentrations on F. gigantica has been evaluated by relative motility (RM), morphological distortions of apical cone through an inverted microscope, architectural and ultra-structural changes through histopathological and scanning electron microscopy (SEM). It is observed that TCBZ, NTON and OCZN at higher concentrations significantly (P < 0.05) reduced RM of the flukes compared to untreated control. NTON at 150 µg mL−1 was the most potent to reduce the motility within 4 h whereas TCBZ and OCZN were much delayed. Histopathological changes showed swollen, extensive cracking, numerous vacuoles and splitting of the tegument surrounding the spines; spine dislodged from its socket in treated flukes compared to untreated worms. Histopathological changes were more conspicuous at higher doses of TCBZ, NTON and OCZN. SEM has shown the disruption of the apical cone, apart from swelling of the tegument on the ventral surface corrugation and disruption of the ventral apical cone. All these changes indicate that NTON is the most potent in killing flukes in vitro among the tested flukicides and suggest the presence of TCBZ-resistant fluke populations in Bangladesh. It is imperative to explore the in vivo effects of these flukicides and subsequently their molecular mechanisms.
Subject(s)
Anthelmintics , Fasciola hepatica , Fasciola , Fascioliasis , Animals , Anthelmintics/therapeutic use , Bangladesh , Benzimidazoles/pharmacology , Benzimidazoles/therapeutic use , Fascioliasis/drug therapy , Fascioliasis/prevention & control , Fascioliasis/veterinary , Livestock , Triclabendazole/pharmacology , Triclabendazole/therapeutic useABSTRACT
A survey of livestock producers (graziers) located in north eastern NSW Australia, collected information on perceptions and management practices for liver fluke control in livestock. The total area farmed by the 161 respondents was 195,600 ha (ranging in size from 4 to 10,522 ha) with cattle and sheep being the dominant livestock enterprises. Overall, 80% of graziers relied exclusively on anthelmintics for liver fluke control and few of these graziers (9%) integrated parasite management (IPM) strategies to reduce disease prevalence. Of those relying on anthelmintic control, triclabendazole (TCBZ) was preferentially chosen by 75% of graziers. Fifty five percent of these graziers used TCBZ in combination with oxfendazole (46%), ivermectin (5%) or abamectin (4%) whilst 45% used TCBZ as a single active ingredient. Thirty eight percent of graziers drenched livestock one or more times per year for liver fluke despite claiming they had no liver fluke or confirmed knowledge of infection. Fifty one percent of graziers based anthelmintic dose on the known weight of the heaviest animal in the herd whilst 43% visually guessed livestock bodyweight to calculate anthelmintic dose. Choice of anthelmintic was predominately based on perceived efficacy (45%) despite very few graziers (2%) having conducted post-treatment fluke egg counts. The majority of graziers (76%) were unsure if they had anthelmintic resistance, 21% claimed they had no resistance whilst 3% of graziers had confirmed resistance. Most graziers (97%) also reported farms were cohabited by kangaroos highlighting additional grazing pressures on-farm. This current survey has revealed that graziers rely on anthelmintics as their primary choice for liver fluke control. Reluctance to adopt IPM strategies and a continued heavy reliance on TCBZ, whilst basing anthelmintic decisions on perception rather than measurement and testing, pose threats for the future control of liver fluke in livestock within this endemic area.
Subject(s)
Anthelmintics , Fasciola hepatica , Fascioliasis , Sheep Diseases , Animals , Anthelmintics/therapeutic use , Australia , Cattle , Fascioliasis/drug therapy , Fascioliasis/epidemiology , Fascioliasis/prevention & control , Fascioliasis/veterinary , Livestock , Sheep , Sheep Diseases/parasitology , Triclabendazole/therapeutic useABSTRACT
Introduction: Leishmaniasis is a neglected tropical disease, with approximately 1 million new cases and 30,000 deaths reported every year worldwide. Given the lack of adequate medication for treating leishmaniasis, drug repositioning is essential to save time and money when searching for new therapeutic approaches. This is particularly important given leishmaniasis's status as a neglected disease. Available treatments are still far from being fully effective for treating the different clinical forms of the disease. They are also administered parenterally, making it challenging to ensure complete treatment, and they are extremely toxic, in some cases, causing death. Triclabendazole (TCBZ) is a benzimidazole used to treat fasciolosis in adults and children. It presents a lower toxicity profile than amphotericin B (AmpB) and is administered orally, making it an attractive candidate for treating other parasitoses. The mechanism of action for TCBZ is not yet well understood, although microtubules or polyamines could potentially act as a pharmacological target. TCBZ has already shown antiproliferative activity against T. cruzi, T. brucei, and L. infantum. However, further investigations are still necessary to elucidate the mechanisms of action of TCBZ. Methods: Cytotoxicity assay was performed by MTT assay. Cell inhibition (CI) values were obtained according to the equation CI = (O.D treatment x 100/O.D. negative control). For Infection evaluation, fixated cells were stained with Hoechst and read at Operetta High Content Imaging System (Perkin Elmer). For growth curves, cell culture absorbance was measured daily at 600 nm. For the synergism effect, Fractional Inhibitory Concentrations (FICs) were calculated for the IC50 of the drugs alone or combined. Mitochondrial membrane potential (DYm), cell cycle, and cell death analysis were evaluated by flow cytometry. Reactive oxygen species (ROS) and lipid quantification were also determined by fluorimetry. Treated parasites morphology and ultrastructure were analyzed by electron microscopy. Results: The selectivity index (SI = CC50/IC50) of TCBZ was comparable with AmpB in promastigotes and amastigotes of Leishmania amazonensis. Evaluation of the cell cycle showed an increase of up to 13% of cells concentrated in S and G2, and morphological analysis with scanning electron microscopy showed a high frequency of dividing cells. The ultrastructural analysis demonstrated large cytoplasmic lipid accumulation, which could suggest alterations in lipid metabolism. Combined administration of TCBZ and AmpB demonstrated a synergistic effect in vitro against intracellular amastigote forms with cSFICs of 0.25. Conclusions: Considering that TCBZ has the advantage of being inexpensive and administrated orally, our results suggest that TCBZ, combined with AmpB, is a promising candidate for treating leishmaniasis with reduced toxicity.
Subject(s)
Antiprotozoal Agents , Leishmania , Leishmaniasis , Child , Humans , Amphotericin B , Triclabendazole/pharmacology , Triclabendazole/therapeutic use , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Leishmaniasis/parasitology , Lipids/pharmacologyABSTRACT
Fascioliasis is a foodborne zoonotic infection caused by the trematode liver flukes: Fasciola hepatica and Fasciola gigantica (F. gigantica). Infections may cause acute and chronic hepatobiliary tract diseases in herbivore animals and humans. Fascioliasis is present worldwide, particularly in regions where sheep and cattle are raised. The global burden of human fascioliasis is estimated to be 2.7 million. Human infections are rare in the United States, and most infections were acquired abroad. In the 1950s, several human cases of F. gigantica infection were reported from Hawai'i, but no subsequent cases have been reported until the case described here. This case report describes a man from Hawai'i Island who ate raw wild watercress, and 22 days later, developed acute phase fascioliasis with fever, acute hepatitis, peripheral eosinophilia, and hypodense lesions seen on liver diagnostic imaging. Immunodiagnostic tests were positive for Fasciola species. Based on earlier reports from Hawai'i, F. gigantica infection was likely. Clinical abnormalities resolved after treatment with triclabendazole. Physicians should consider fascioliasis in immigrants and travelers from endemic areas with acute hepatitis and eosinophilia after eating raw wild watercress or chronic hepatobiliary disease. Hepatobiliary imaging and serological testing are useful for diagnosis. Oral triclabendazole is the preferred treatment. Animal fascioliasis appears to be spreading in the United States, and the popularly perceived health benefits of eating raw wild watercress and other aquatic plants may lead to more human infections. The rarity of human infections in Hawai'i suggests that it is safe to eat commercially grown watercress cultivated in Hawai'i.
Subject(s)
Fasciola hepatica , Fasciola , Fascioliasis , Animals , Cattle , Fascioliasis/diagnosis , Fascioliasis/drug therapy , Fascioliasis/epidemiology , Hawaii/epidemiology , Humans , Sheep , Triclabendazole/therapeutic useABSTRACT
We report a case of human fascioliasis in the USA that encountered many diagnostic uncertainties. Numerous tests available for detection of fascioliasis were utilised but the diagnosis remained elusive. Confounders included three negative stool ova and parasite examinations, positive hepatitis A virus IgM antibody, cross-reactive false-positive Echinococcus IgG antibody, absence of characteristic image findings and unrevealing liver biopsy. Praziquantel was started as empiric treatment for helminth infections, but was ineffective. Due to the rarity of the disease in the USA, serologic testing and triclabendazole were only available from the Centers for Disease Control and Prevention, which led to a delay in diagnosis and treatment.
Subject(s)
Anthelmintics , Fascioliasis , Parasites , Animals , Anthelmintics/therapeutic use , Benzimidazoles/therapeutic use , Fascioliasis/diagnosis , Fascioliasis/drug therapy , Humans , Triclabendazole/therapeutic use , United StatesABSTRACT
Triclabendazole is the anthelminthic of choice for the treatment of fascioliasis, however, it is only registered in a few countries. We investigated the efficacy of a single-dose of triclabendazole (12 mg/kg) or albendazole (15 mg/kg) against Fasciola spp. infection in cattle on farms in the northern part of Côte d'Ivoire in a randomized clinical trial. Faecal samples were obtained from 196 cattle, of which 155 (79.1%) were found positive for Fasciola spp. by the sedimentation technique. Cattle infected with Fasciola spp. were randomly allocated (3:3:1) to receive triclabendazole (n = 66), albendazole (n = 67) or left untreated to serve as control (n = 22). Follow-up faecal samples were collected on days 21, 28, 90 and 188 post-treatment. No adverse events were observed as reported by farmers in any of the treatment groups. The proportion of non-egg shedding cattle, assessed at day 21 (primary outcome), was significantly higher in cattle treated with triclabendazole (95.4%) compared to those receiving albendazole (70.3%; odds ratio [OR] 8.73, 95% confidence interval [CI] 2.43-31.28, p <0.001). The egg reduction rate (ERR) expressed as number of eggs per gram of faeces, a secondary endpoint assessed at day 21 post-treatment, was significantly higher in the triclabendazole arm (arithmetic mean (AM) ERR = 99.8%) than in the albendazole arm (AM ERR = 92.2%), with a difference of 7.6%-points (95% CI: 0.9-14.5%-points, p=0.026). This is the first report of efficacy of triclabendazole against Fasciola spp. in naturally infected cattle in Côte d'Ivoire. Our results confirm that triclabendazole is the most effective treatment of fascioliasis and therefore, should be considered for the control of livestock fascioliasis; if resources allow in combination with intermediate host snail control and raising farmers awareness of pasture and livestock management to avoid reinfection.
Subject(s)
Albendazole , Anthelmintics , Cattle Diseases , Fascioliasis , Triclabendazole , Albendazole/therapeutic use , Animals , Anthelmintics/therapeutic use , Cattle , Cattle Diseases/drug therapy , Cote d'Ivoire , Fasciola , Fascioliasis/drug therapy , Fascioliasis/veterinary , Feces , Triclabendazole/therapeutic useABSTRACT
We conducted a retrospective cohort study of children who had chronic fascioliasis in the highlands of Peru to determine triclabendazole treatment efficacy. Children passing Fasciola eggs in stool were offered directly observed triclabendazole treatment (>1 doses of 10 mg/kg). Parasitologic cure was evaluated by using microscopy of stool 1-4 months after each treatment. A total of 146 children who had chronic fascioliasis participated in the study; 53% were female, and the mean ± SD age was 10.4 ± 3.1 years. After the first treatment, 55% of the children achieved parasitologic cure. Cure rates decreased after the second (38%), third (30%), and fourth (23%) treatments; 17 children (11.6%) did not achieve cure after 4 treatments. Higher baseline egg counts and lower socioeconomic status were associated with triclabendazole treatment failure. Decreased triclabendazole efficacy in disease-endemic communities threatens control efforts. Further research on triclabendazole resistance and new drugs to overcome it are urgently needed.
Subject(s)
Anthelmintics , Fasciola hepatica , Fascioliasis , Adolescent , Animals , Anthelmintics/therapeutic use , Child , Child, Preschool , Feces , Female , Humans , Peru , Retrospective Studies , Schools , Treatment Failure , Triclabendazole/therapeutic useABSTRACT
BACKGROUND: The popularity of new world camelids, particularly alpacas, is growing rapidly in Ireland, presenting a clinical challenge to veterinary practitioners who may not have worked with these species previously. To the authors' knowledge, the clinical course of a case of acute fasciolosis in an alpaca has not previously been reported, and fasciolosis has not been reported at all in alpacas in Ireland, making this case report a valuable addition to the current literature. CASE PRESENTATION: A three-year-old male castrated huacaya alpaca was admitted to UCD Veterinary Hospital with a two-day history of colic and tenesmus. He had been treated with albendazole, dexamethasone and potentiated amoxycillin by the referring veterinary practitioner with no response. On initial clinical exam, sensitivity to abdominal palpation was the only abnormality. However, the alpaca proceeded to show abnormal lying positions, tenesmus and reduced faecal output over the next 24 h. A general blood panel demonstrated moderate anaemia, marked hyperglobulinaemia and moderately increased hepatocellular and hepatobiliary enzyme activity. Abdominal radiography revealed enlargement of the first forestomach compartment without evidence of gastrointestinal obstruction or peritonitis. An abdominal ultrasound exam revealed an elongated, heterogenous mass in the caudoventral abdomen that appeared to be contiguous with the liver. FNA of this mass revealed that it was in fact a liver lobe with biliary stasis and inflammation. Faecal sedimentation demonstrated Fasciola hepatica eggs. In spite of treatment with triclabendazole and supportive treatment including blood transfusion, the alpaca's condition continued to deteriorate and he was euthanised. On post-mortem exam, acute fasciolosis was diagnosed. CONCLUSIONS: The clinical presentation and course of a case of acute fasciolosis in an individual alpaca is described, including the results of a range of diagnostic tests that were carried out. The final diagnosis is supported by a description of post-mortem findings. This information will serve as a resource for veterinary practitioners involved in the diagnosis and treatment of similar cases.
Subject(s)
Camelids, New World , Fascioliasis/veterinary , Acute Disease , Amoxicillin/therapeutic use , Animals , Anti-Bacterial Agents/therapeutic use , Antiplatyhelmintic Agents/therapeutic use , Colic/parasitology , Colic/veterinary , Fascioliasis/diagnosis , Fascioliasis/drug therapy , Ireland , Male , Treatment Outcome , Triclabendazole/therapeutic useABSTRACT
Fascioliasis is a zoonotic disease caused by Fasciola hepatica that infects mainly cattle, sheep, and goats. Humans can be infected by water or aquatic plants contaminated with metacercariae. The authors encountered two cases of F. hepatica infection. One patient reported abdominal discomfort with marked eosinophilia. The other patient had chest discomfort with marked eosinophilia. The abdominal CT images revealed hypodense lesions in the liver. The ultrasonography-guided liver biopsy findings in both patients were indicative of parasitic infections. Serological tests confirmed the definite diagnoses. Both patients were treated with a single dose of triclabendazole, which is the treatment of choice for fascioliasis. These findings suggest that a diagnosis of fascioliasis, particularly in the acute phase, should be considered in patients with abdominal pain, marked eosinophilia, and hypodense hepatic lesions on CT.