ABSTRACT
As an orally effective benzimidazole anthelmintic agent, fenbendazole was not only widely used in agriculture and animal husbandry to prevent and treat parasites, but also shows anti-cancer effects against several types of cancer, exhibits anti-cancer effects in paclitaxel and doxorubicin-resistant cancer cells. However, fenbendazole's poor in water solubility (0.3 µg/mL), limits its clinical applications. Even great efforts were made toward increasing its water solubility, the results were not significant to reach anti-cancer drug delivery requirement (5-10 mg/mL). Through single factor and orthogonal strategy, many complex conditions were designed and used to prepare the complexes, the inclusion complex with methyl-ß-cyclodextrin with 29.2 % of inclusion rate and 89.5% of inclusion yield can increase drug's water solubility to 20.21 mg/mL, which is the best result so far. Its structure was confirmed by differential scanning calorimetry, scanning electron microscopic image, 1D and 2D NMR spectra in D2O. In its in vitro pharmacokinetic study, fenbendazole was 75% released in 15 min., in its in vivo pharmacokinetic study, the bio-availabilities of fenbendazole, its major metabolic anthelmintic agent oxfendazole and its minor metabolic anthelmintic agent oxfendazole were increased to 138%, 149% and 169% respectively, which would allow for fewer drug doses to achieve the same therapeutic effect and suggest that the complex can be used as a potential anticancer agent.
Subject(s)
Fenbendazole , Solubility , beta-Cyclodextrins , Fenbendazole/pharmacokinetics , Fenbendazole/therapeutic use , Fenbendazole/chemistry , Animals , beta-Cyclodextrins/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Male , Anthelmintics/pharmacokinetics , Anthelmintics/chemistry , Anthelmintics/administration & dosageABSTRACT
Biomarkers are specific molecular, histological, or physiological characteristics of normal or pathogenic biological processes and are promising in the diagnosis of gastrointestinal nematodes (GINs). Although some biomarkers have been validated for infection by Ostertagia sp. in cattle raised in temperate regions, there is a lack of information for tropical regions. The aim of this project was to assess potential biomarkers and validate the most promising. In the first study, 36 bovines (Nelore breed) naturally infected by GINs were distributed into two groups: infected (not treated with anthelmintic) and treated (treated with fenbendazole on days 0, 7, 14, 21, 28, 42, and 56). The variables of interest were live weight, fecal egg count, hemogram, serum biochemical markers, phosphorus, gastrin, and pepsinogen. In the second step, pepsinogen was assessed in cattle of the Nelore breed distributed among three groups: infected (not treated with anthelmintic), MOX (treated with moxidectin), and IVM + BZD (treated with ivermectin + albendazole). In the first study, no difference between groups was found for weight, albumin, hematocrit (corpuscular volume [CV]), erythrocytes, or hemoglobin. Negative correlations were found between pepsinogen and both CV and albumin, and albumin was negatively correlated with the percentage of Haemonchus sp. in the fecal culture. Among the biomarkers, only pepsinogen differentiated treated and infected (beginning with the 28th day of the study). In the second study, a reduction in pepsinogen was found after anthelmintic treatment. Therefore, pepsinogen is a promising biomarker of worms in cattle naturally infected by the genera Haemonchus and Cooperia in tropical areas.
Subject(s)
Biomarkers , Cattle Diseases , Feces , Nematode Infections , Tropical Climate , Animals , Cattle , Cattle Diseases/parasitology , Cattle Diseases/drug therapy , Biomarkers/blood , Nematode Infections/veterinary , Nematode Infections/parasitology , Nematode Infections/drug therapy , Feces/parasitology , Parasite Egg Count , Anthelmintics/therapeutic use , Nematoda/isolation & purification , Nematoda/classification , Nematoda/drug effects , Gastrointestinal Diseases/parasitology , Gastrointestinal Diseases/veterinary , Intestinal Diseases, Parasitic/veterinary , Intestinal Diseases, Parasitic/parasitology , Fenbendazole/therapeutic useABSTRACT
Helminth infections pose a significant economic threat to livestock production, causing productivity declines and, in severe cases, mortality. Conventional anthelmintics, exemplified by fenbendazole, face challenges related to low solubility and the necessity for high doses. This study explores the potential of supramolecular complexes, created through mechanochemical modifications, to address these limitations. The study focuses on two key anthelmintics, praziquantel (PZQ) and fenbendazole (FBZ), employing mechanochemical techniques to enhance their solubility and efficacy. Solid dispersions (SD) of PZQ with polymers and dioctyl sulfosuccine sodium (DSS) and fenbendazole with licorice extract (ES) and DSS were prepared. The helminthicidal activity of these complexes was assessed through helminthological dissections of sheep infected with Schistosoma turkestanicum, moniesiasis, and parabronemosis. In the assessment of supramolecular complex of FBZ (SMCF) at doses ranging from 1.0 to 3.0 mg/kg for the active substance (AS), optimal efficacy was observed with the fenbendazole formulation containing arabinogalactan and polyvinylpyrrolidone at a 3.0 mg/kg dosage. At this concentration, the formulation demonstrated a remarkable 100% efficacy in treating spontaneous monieziosis in sheep, caused by Moniezia expansa (Rudolphi, 1810) and M. benedenii (Moniez, 1879). Furthermore, the SMCF, administered at doses of 1.0, 2.0, and 3.0 mg/kg, exhibited efficacy rates of 42.8%, 85.7%, and 100%, respectively, against the causative agent of parabronemosis (Parabronema skrjabini Rassowska, 1924). Mechanochemical modifications, yielding supramolecular complexes of PZQ and FBZ, present a breakthrough in anthelmintic development. These complexes address solubility issues and significantly reduce required doses, offering a practical solution for combating helminth infections in livestock. The study underscores the potential of supramolecular formulations for revolutionizing helminthiasis management, thereby enhancing the overall health and productivity of livestock.
Subject(s)
Anthelmintics , Cestode Infections , Schistosomiasis , Animals , Sheep , Fenbendazole/therapeutic use , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Praziquantel/therapeutic use , Cestode Infections/drug therapyABSTRACT
AIMS: To determine the concentration, in comparison with the maximum residue limit (MRL), of anthelmintic marker residues in the target tissues (liver and fat) of sheep treated concurrently with two oral drenches, one containing monepantel and abamectin and the other oxfendazole and levamisole. METHODS: On day 0 of the study, 12 sheep (six male and six female; 8-9-months old) were dosed according to individual body weight determined the day prior. Zolvix Plus (dual-active oral drench containing 25 g/L monepantel and 2 g/L abamectin) was administered to all animals prior to administration of Scanda (dual-active oral drench containing 80 g/L levamisole hydrochloride and 45.3 g/L oxfendazole). Six sheep (three male and three female) were slaughtered 21 and 28 days after treatment and renal fat and liver samples were collected.Using validated methods, analyses for monepantel sulfone, abamectin, levamisole and oxfendazole (expressed as total fenbendazole sulfone following conversion of the combined concentrations of oxfendazole, fenbendazole and fenbendazole sulfone) were performed on liver samples while renal fat specimens were analysed for monepantel sulfone and abamectin residues only. Detected concentrations were compared to the established MRL in sheep for each analyte determined by the Ministry for Primary Industries. RESULTS: All residues detected in samples of liver and fat collected 21 and 28 days after treatment were below the MRL for each analyte. All liver samples collected on day 21 had detectable monepantel sulfone (mean 232 (min 110, max 388) µg/kg) and oxfendazole (mean 98.7 (min 51.3, max 165) µg/kg) residues below the MRL (5,000 and 500 µg/kg, respectively). Monepantel sulfone (mean 644 (min 242, max 1,119) µg/kg; MRL 7,000 µg/kg) residues were detected in 6/6 renal fat samples. Levamisole residues were detected in 3/6 livers (mean 40.0 (min 14.3, max 78.3) µg/kg; MRL 100 µg/kg), and abamectin residues in 1/6 livers (0.795 µg/kg; MRL 25 µg/kg) and 2/6 fat samples, (mean 0.987 (min 0.514, max 1.46) µg/kg; MRL 50 µg/kg) 21 days after treatment. CONCLUSION AND CLINICAL RELEVANCE: These results suggest that concurrent administration of Zolvix Plus and Scanda to sheep is unlikely to result in an extended residue profile for any of the active ingredients, with all analytes measured being under the approved New Zealand MRL 21 days after treatment. This work was not completed in line with guidance for establishing official residue profiles, nor is it sufficient to propose a new withholding period.
Subject(s)
Aminoacetonitrile/analogs & derivatives , Anthelmintics , Benzimidazoles , Ivermectin/analogs & derivatives , Sheep Diseases , Animals , Male , Female , Sheep , Levamisole/therapeutic use , Fenbendazole/therapeutic use , Anthelmintics/therapeutic use , Sulfones/therapeutic use , Sheep Diseases/drug therapyABSTRACT
The present work evaluated the pharmacokinetics and efficacy of the association of 15cmg/kg toltrazuril +5cmg/kg fenbendazole against Eimeria spp. and gastrointestinal nematodes (GINs) in calves of different regions of Brazil (Center-West, Southeast, and South). A total of seven experiments were carried out, five of which determined formulation efficacy against Eimeria spp., considering the following aspects: therapeutic, preventive, metaphylactic, and residual efficacy. Therapeutic efficacy experiments for GINs were carried out by parasitological necropsy. The toltrazuril + fenbendazole association demonstrated ≥95% efficacy against Eimeria spp. for 21 days post-treatment (DPT). When used preventively and metaphylatically, the same association demonstrated ≥97% efficacy against E. zuernii, E. ellipsoidalis, E. cylindrica, E. bovis, E. wyomingensis and E. auburnensis. Toltrazuril + fenbendazole administered seven days before challenge was 100% effective against all these Eimeria species. Results of therapeutic, preventive, metaphylactic and residual efficacies can be related to the pharmacokinetic results, especially considering toltrazuril sulfone, which was detected in animal plasma for a longer period than the parent compound. Toltrazuril + fenbendazole achieved 100% anthelminthic efficacy against the GINs Haemonchus placei (L4), Cooperia pectinata and Oesophagostomum radiatum; 99.94% against adult H. placei; and 99.98% against C. puntacta. The association of toltrazuril + fenbendazole, associated with other measures, is an important and suitable tool for the control and treatment of Eimeria spp. and GINs in young cattle.
Subject(s)
Eimeria , Haemonchus , Animals , Cattle , Fenbendazole/therapeutic use , Triazines/therapeutic useABSTRACT
This study aimed to evaluate the efficacy of fenbendazole and ivermectin on strongyles and Parascaris sp. infecting adult riding horses in three regions with different climates. During 2021 and 2022 fecal specimens were randomly collected from 483 horses older than three years in 31 equestrian clubs in Hamedan (n = 217), Yazd (n = 146) and Tabriz cities (n = 120). Eggs were counted by McMaster technique, and the strongyle larvae were identified using coproculture, PCR and sequencing. Horses with strongyles and Parascaris egg counts ≥150 were enrolled in fecal egg count reduction (FECR) examination following treatment with ivermectin or fenbendazole. In total, 26.5% of examined horses were positive with at least one parasite. Infection rates varied in three cities i.e., 25.8% in Hamedan, 28.8% in Yazd, 25% in Tabriz. Fifty-seven horses had FECR measured. FECR below <90% was observed for IVM-strongyle in two horses in Tabriz, for FBZ-strongyle in two horses in Tabriz and two horses in Hamedan, for IVM-Parascaris in one horse in all three cities, and for FBZ-Parascaris in one horse in Yazd. Furthermore, FECR 90-100% was observed in IVM-Parascaris and FBZ -Parascaris groups in Tabriz. Data herein presented demonstrate different degrees of resistance of strongyles and Parascaris infecting horses in Iran against both ivermectin and fenbendazole. Since non-principled use of anthelminthics is common among horse owners, urgency of test-and-treatment strategy should be educated and implemented by policy-making organizations. Evaluating efficacy of different anthelminthics and choosing the most effective treatment in each region is suggested.
Subject(s)
Anthelmintics , Ascaridoidea , Horse Diseases , Horses , Animals , Ivermectin/therapeutic use , Fenbendazole/therapeutic use , Iran , Horse Diseases/drug therapy , Horse Diseases/epidemiology , Horse Diseases/parasitology , Drug Resistance , Ovum , Anthelmintics/therapeutic use , Anthelmintics/pharmacology , Strongyloides , Feces/parasitology , Parasite Egg Count/veterinaryABSTRACT
Strongyloides stercoralis, the causative agent of strongyloidiasis, is a potentially zoonotic intestinal nematode endemic to northern Australia. Strongyloidiasis is typically observed in immunocompromised hosts and is characterised by gastrointestinal signs, respiratory symptoms and a failure to thrive. In immunocompromised hosts, hyperinfection syndrome and disseminated infections can prove life-threatening. A 24-month-old Boston Terrier dog was referred for investigation of chronic small and large intestinal watery hematochezic diarrhoea, emaciation and hematemesis. Small intestinal histology identified a nematode despite consecutive negative faecal flotations. A real-time polymerase chain reaction and Baermann test subsequently confirmed infection with S. stercoralis. The dog had received an oral parasiticide comprising milbemycin oxime and afoxolaner every month for the 11 months prior to this diagnosis. Despite fenbendazole being reported as successful in the treatment of canine strongyloidiasis, a course of fenbendazole failed to clear the infection. Eradication of S. stercoralis infection was confirmed after the administration of off-label ivermectin fortnightly for 12 doses. Attention should be paid to this nematode as the failure of routine copromicroscopic methods to diagnose S. stercoralis infections can result in misdiagnosis, mistreatment and progression of the disease. Off-label ivermectin may be an alternative to fenbendazole for the treatment of Strongyloides spp. infection in dogs.
Subject(s)
Dog Diseases , Strongyloides stercoralis , Strongyloidiasis , Dogs , Animals , Strongyloidiasis/diagnosis , Strongyloidiasis/drug therapy , Strongyloidiasis/veterinary , Ivermectin/therapeutic use , Fenbendazole/therapeutic use , Feces , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Dog Diseases/epidemiologyABSTRACT
Fasciolosis is an important zoonotic disease caused by the trematode Fasciola hepatica, and it causes great losses in bovine production. The anthelmintic resistance is a major problem in the control of fasciolosis. In this study, the F. hepatica egg development and hatching test (EDHT) was used for the evaluation of the ovicidal activity of commercial drugs, commonly used for treating infected cattle, which reflects F. hepatica anthelminthic resistance in infected bovines, according to recent literature. Bile samples from F. hepatica naturally parasitized cattle were obtained from slaughterhouses in the cities of Lages and Otacílio Costa, Santa Catarina State, Brazil. The bile was washed, the eggs were recovered, quantified, and distributed in universal collectors, with a minimum of 1,000 eggs per vial. Four commercial drugs were used in this study, containing albendazole sulfoxide (ABDZ), closantel (CSTL), nitroxynil (NTXL), and triclabendazole with fenbendazole (TBZF). The drugs were diluted according to the manufacturer instructions. All drugs, and the respective control, were tested in triplicates, with the quantity of recovered eggs determining the number of drugs to be tested. The vials were incubated for 28 days at 27 °C, and the eggs were classified according to their degree of development under a stereomicroscope. In total, 121 egg samples were analyzed. Two samples were identified as resistant to TBZF. Undetermined resistance/susceptibility has been found in two isolates treated with ABDZ, one treated with NTXL and six treated with TBZF. CSTL did not present ovicidal activity and cannot be used in EDHT. This is the first time that commercial drugs were used in F. hepatica EDHT.
Subject(s)
Anthelmintics , Cattle Diseases , Fasciola hepatica , Fascioliasis , Cattle , Animals , Drug Resistance , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Triclabendazole , Fascioliasis/drug therapy , Fascioliasis/veterinary , Nitroxinil/therapeutic use , Fenbendazole/therapeutic use , Cattle Diseases/drug therapy , FecesABSTRACT
Many generic anthelmintics are commercially available; however, little information exists regarding product effectiveness compared to pioneer brands. The objective of this study was to compare the effectiveness of a generic eprinomectin to the pioneer eprinomectin, as well as to fenbendazole and fenbendazole in combination with the pioneer eprinomectin in grazing beef steers via a fecal egg count reduction test. Forty naturally infected steers were allocated into five treatment groups based on ranked fecal egg counts: 1. pioneer eprinomectin (Eprinex®, topical), 2. generic eprinomectin (Eprizero®, topical), 3. fenbendazole (Safeguard® 0.5% oral suspension), 4. combination of pioneer eprinomectin topical and fenbendazole oral suspension, 5. negative control. Fecal samples were collected on days -14, 0, 14, and 29. Data were analyzed using the MIXED procedure of SAS 9.4. Neither the pioneer nor the generic eprinomectin groups reached a 90% fecal egg count reduction (FECR) throughout the study with reductions of 50% and 11% for pioneer eprinomectin and 79% and - 5% for generic eprinomectin at days 14 and 29 post-treatment, respectively. Both the fenbendazole and combination groups showed 98% and 99% FECR, respectively, at 14 days post-treatment; these reductions dropped slightly at day 29 post-treatment to 94% and 89%, respectively. Primarily Cooperia punctata, Cooperia oncophora and Ostertagia ostertagi larvae were recovered from the coprocultures across all treatment groups. Interestingly, the proportions of C. punctata and C. oncophora essentially demonstrated a post-treatment reversal in the both the fenbendazole and combination treatment groups when comparing days 0 and 29, demonstrating prepatency period differences or a fenbendazole treatment effect.
Subject(s)
Anthelmintics , Trichostrongyloidea , Cattle , Animals , Fenbendazole/therapeutic use , Ivermectin/therapeutic use , Anthelmintics/therapeutic useABSTRACT
A 16-month-old Sarplaninac Shepherd cross dog presented for a 1-month history of a productive cough that was unresponsive to an empirical 10-day course of cephalexin. Thoracic computed tomography (CT) showed multifocal, well-defined, smoothly marginated, soft tissue attenuating, minimally contrast enhancing nodular airway mural thickenings protruding into the airway lumen in the caudal trachea and principal bronchi. These nodules were also visualized on bronchoscopy, and cytology revealed parasitic larvae consistent with Oslerus osleri. The dog was treated with oral fenbendazole for 26 days. Clinical signs resolved within 3 weeks of treatment initiation and had not relapsed at 7-month follow-up.
Subject(s)
Dog Diseases , Metastrongyloidea , Animals , Dogs , Dog Diseases/diagnostic imaging , Dog Diseases/drug therapy , Trachea , Fenbendazole/therapeutic use , Bronchi , Bronchoscopy/veterinaryABSTRACT
An outbreak of the nematode Strongyloides sp. occurred in a population of 18 male and 29 female panther chameleons (Furcifer pardalis) at the Singapore Zoo. The parasite was first detected in one individual during routine microscopic examination of feces using the direct examination and magnesium sulfate flotation methods. The parasite was later found to have a closest match (98.96%) with Strongyloides sp. Okayama by DNA sequencing. Over a period of 6 mon, 97.9% (46/47) of the panther chameleons tested positive for the parasite, and 25.5% (12/47) of the animals died due to the disease. All the animals that died were female. Of the positive tests, magnesium sulfate flotation identified the parasite 98.1% (105/107) of the time, compared to direct fecal microscopy, which identified the parasite only 43.9% (47/107) of the time. Parasite eggs were detected in 100% (105/105) of the positive magnesium sulfate flotation tests but only 66.0% (31/47) of the positive direct fecal microscopy tests. Parasite larvae were detected in 61.7% (29/47) of the positive direct fecal microscopy tests but only 9.5% (10/105) of the magnesium sulfate flotation tests. Treatments with fenbendazole and pyrantel pamoate at published doses were ineffective at eliminating the parasite. Ivermectin (0.2 mg/kg PO q2wk for two doses) was successful at treating the parasite, with all animals testing negative for the parasite at the end of the treatment course without any observed adverse reactions. However, complete eradication of the parasite could not be achieved, as Strongyloides sp. could still be detected in the population on routine coproscopy intermittently over 3 yr. There were no further mortalities due to the disease with prompt treatment with ivermectin. Strongyloidiasis may cause high morbidity in panther chameleons, but severe disease leading to mortality can be prevented with the use of ivermectin.
Subject(s)
Lizards , Strongyloidiasis , Male , Female , Animals , Ivermectin/therapeutic use , Strongyloidiasis/drug therapy , Strongyloidiasis/epidemiology , Strongyloidiasis/veterinary , Magnesium Sulfate , Pyrantel Pamoate/therapeutic use , Fenbendazole/therapeutic use , Feces/parasitologyABSTRACT
Fenbendazole (FBZ) is a common antiparasitic treatment used in research rodent colonies for biosecurity purposes. The effect of this compound has been studied in C57 mice, but never before in a strain of mice that has co-morbidities, such as the blood pressure high (BPH)/5. The BPH/5 mouse is an inbred genetic model of hypertension. While both male and female BPH/5 have high blood pressure, there is a metabolic sexual dimorphism with females displaying key features of obesity. The obese gut microbiome has been linked to hypertension. Therefore, we hypothesized that fenbendazole treatment will alter the gut microbiome in hypertensive mice in a sex dependent manner. To test the influence of FBZ on the BPH/5 gut microbiota, fecal samples were collected pre- and post-treatment from adult BPH/5 mice (males and non-pregnant females). The mice were treated with fenbendazole impregnated feed for five weeks. Post-treatment feces were collected at the end of the treatment period and DNA was extracted, and the V4 region of 16S rRNA was amplified and sequenced using the Illumina MiSeq system. The purpose was to analyze the fecal microbiome before and after FBZ treatment, the results demonstrate changes with treatment in a sex dependent manner. More specifically, differences in community composition were detected in BPH/5 non-pregnant female and males using Bray-Curtis dissimilarity as a measure of beta-diversity (treatment p = 0.002). The ratio of Firmicutes to Bacteroidetes, which has been identified in cases of obesity, was not altered. Yet, Verrucomicrobia was increased in BPH/5 males and females post-treatment and was significantly different by sex (treatment p = 5.85e-05, sex p = 0.0151, and interaction p = 0.045), while Actinobacteria was decreased in the post-treatment mice (treatment p = 0.00017, sex p = 0.5, interaction p = 0.2). These results are indicative of gut dysbiosis compared to pre-treatment controls. Lactobacillus was decreased with FBZ treatment in BPH/5 females only. In conclusion, fenbendazole does alter the gut microbial communities, most notable in the male rather than female BPH/5 mouse. This provides evidence that caution should be taken when providing any gut altering treatments before or during mouse experiments.
Subject(s)
Hypertension , Microbiota , Animals , Female , Male , Mice , Blood Pressure , Feces/microbiology , Fenbendazole/pharmacology , Fenbendazole/therapeutic use , Hypertension/drug therapy , Obesity/drug therapy , Obesity/microbiology , RNA, Ribosomal, 16S/geneticsABSTRACT
OBJECTIVE: Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models. METHODS: EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC. RESULTS: FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well. CONCLUSION: FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials.
Subject(s)
Nanoparticles , Ovarian Neoplasms , Humans , Animals , Mice , Female , Fenbendazole/therapeutic use , Ovarian Neoplasms/pathology , Carcinoma, Ovarian Epithelial/drug therapy , Cell Line, Tumor , WaterABSTRACT
Dentostomella translucida is an oxyurid nematode that was first discovered in the Mongolian gerbil but has also been detected in other wild and housed rodents. In conventional laboratory animals, oxyurid nematode parasites are widespread infections. A proven treatment strategy for pinworm eradication is the oral application of benzimidazoles, such as fenbendazole. In general, this drug is regarded as safe with minimal side effects. Nevertheless, in Sprague Dawley rats, a significantly reduced litter size could be seen after longer treatment with fenbendazole. Even though Dentostomella translucida was already described in Syrian golden hamsters (Mesocricetus auratus), data on treatment with fenbendazole and its effects on reproduction is lacking. Therefore, the main purposes of the study were (1) the verification of the effectiveness of fenbendazole as medicated feed (150 ppm) against this parasite in naturally infected Syrian golden hamsters in conventional husbandry and (2) monitoring of possible effects on reproduction during the treatment. Results show that fenbendazole treatment was highly effective against Dentostomella translucida, as numbers of pinworm eggs in the faeces were significantly reduced already after the first week of treatment in all animals. After four weeks of treatment, eggs were eradicated entirely. Interestingly, the average weaning weight was significantly reduced during treatment, but the litters were in good health.
Subject(s)
Fenbendazole , Nematoda , Animals , Rats , Cricetinae , Mesocricetus , Fenbendazole/therapeutic use , Rats, Sprague-Dawley , Gerbillinae/parasitologyABSTRACT
The pharmacokinetics and bioavailability of fenbendazole and levamisole were determined in Caspian turtles after a single intravenous (i.v.) and subcutaneous (s.c.) administration. Thirty turtles diagnosed as naturally infected with Serpinema microcephalus and Falcaustra armenica nematodes received fenbendazole (50 mg/kg) or levamisole (10 mg/kg) by i.v. and s.c. administrations. Blood samples were collected at time 0, 0.125, 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 48 h after drug administration. Plasma drug concentrations were determined by a validated high-performance liquid chromatography method. Data were analyzed by noncompartmental methods. The mean elimination half-life of levamisole was 5.16 h and 12.03 h for i.v. and s.c. routes, respectively, and for fenbendazole, the mean elimination half-life was 25.38 h (i.v.) and 29.77 h (s.c.). The total clearance and volume of distribution at steady-state for levamisole and fenbendazole following i.v. administration were 0.22, 0.44 ml/g/h, and 1.06 and 7.35 ml/g, respectively. For the s.c. route, the peak plasma concentration of levamisole and fenbendazole was 10.53 and 5.24 µg/mL, respectively. The s.c. bioavailability of levamisole and fenbendazole was complete. Considering high anthelmintic efficacy and bioavailability after s.c. administration of levamisole and fenbendazole, and the absence of adverse effects, this route of administration is an easy and efficacious way of treating nematodes in Caspian turtles.
Subject(s)
Anthelmintics , Helminths , Turtles , Animals , Fenbendazole/therapeutic use , Levamisole/therapeutic use , Anthelmintics/therapeutic useABSTRACT
Parasites are highly prevalent in poultry; thus, the management of parasites is a key component in the profitable production of poultry. The most common nematode parasite of poultry, Heterakis gallinarum, typically causes no direct pathology but is the vector of Histomonas meleagridis, a highly pathogenic protozoan parasite that causes blackhead disease. There are no approved treatments for H. meleagridis, making control reliant on controlling the helminth vector. In the United States, the benzimidazole anthelmintic fenbendazole (FBZ) is the only approved treatment for H. gallinarum. We were contacted by an industry veterinarian regarding clinical problems with histomoniasis despite frequent anthelmintic treatments. Given that we had recently diagnosed FBZ resistance in the closely related parasite Ascaridia dissimilis, we were interested to determine if H. gallinarum had also evolved resistance. An initial on-farm pilot study using 20 birds suggested that FBZ was poorly effective, therefore a larger controlled study was initiated. Heterakis gallinarum eggs were isolated from litter at the farm and used to infect 118 chicks. Treatment groups included a non-treated control, a label-, and a 2×-label dose of FBZ, with 36 birds per group divided into two replicates of 18 birds. Three weeks post-hatch, birds were infected with 150 embryonated eggs. Two weeks post-infection treated birds were administered either a label- or 2× label-dose of FBZ in water for five days (SafeGuard® Aquasol, 1 mg/kg BW). To increase the likelihood that all birds consumed the full intended dose, the dosage was calculated using 1.25 times the average body weight. One-week post-treatment, birds were euthanized, and parasites enumerated. There were no significant differences in worm numbers recovered from any of the three groups (p-value = 0.3426), indicating that both dosages of FBZ failed to provide the expected levels of efficacy. These data provide strong evidence that H. gallinarum has developed resistance to FBZ on this farm. Consequently, on this farm, or any farm with FBZ-resistant H. gallinarum, H. meleagridis will continue to cycle in an unrestricted manner despite administration of anthelmintic treatments. Given recent evidence of increasing problems with histomoniasis, and the fact that resistance was documented on the first farm we investigated, further investigations are needed to determine the prevalence of resistance in H. gallinarum on poultry farms. These data, when viewed together with our recent findings of FBZ resistance in A. dissimilis on multiple farms, suggest that drug resistance in ascarid nematodes may be an emerging problem in the US poultry industry.
Subject(s)
Ascaridida , Nematoda , Poultry Diseases , Protozoan Infections , Animals , Fenbendazole/therapeutic use , Farms , Chickens , South Carolina , Pilot Projects , Poultry Diseases/drug therapy , Poultry Diseases/epidemiology , Poultry Diseases/parasitology , Protozoan Infections/drug therapy , Protozoan Infections/epidemiologyABSTRACT
The intensive use of anthelmintics has resulted in resistant parasite populations in horses. The objective of this trial was to evaluate the anthelmintic efficacies of the anthelmintics fenbendazole, ivermectin and abamectin in 24 horse farms in Northern Minas Gerais. Egg counts per gram of faeces (EPG) were performed individually in 619 animals. Animals presenting EPG counts greater than or equal to 150 were used in the tests on faecal egg count reduction (FECR), totalling 436 equines. These animals received the anthelmintics, fenbendazole, ivermectin, and abamectin. Faeces were collected 14 days after the administration of anthelmintics to perform the EPG. Pre- and post-treatment EPG counts were used to calculate the FECR for each anthelmintic group, and faecal culture was used to identificy of the strongyles. The resistance status was evaluated based on the FECR and LCL95%. Fenbendazole was effective in 11 (45.8%) of the horse farms. Ivermectin was effective in 17 (77.3%) and abamectin in 17 (74%) of the farms; side-resistance was detected in 3 (12.5%) of the farms. Intestinal strongyle resistance to anthelmintics was observed in 14 (58.3%) of the farms. Cyathostomin larvae were found in 100% of the farms, Strongylus vulgaris in 13 (54.2%), and S. equinus in 3 (12.5%). Only cyathostomins larvae were detected post-treatment with ivermectin and abamectin.
Subject(s)
Anthelmintics , Fenbendazole , Horses , Animals , Fenbendazole/therapeutic use , Ivermectin/therapeutic use , Parasite Egg Count/veterinary , Brazil , Drug Resistance , Anthelmintics/therapeutic use , Anthelmintics/pharmacologyABSTRACT
Canine schistosomiasis is a well-established cause of a granulomatous enteropathy and hepatopathy in dogs. In a small subset of patients, infection triggers significant hypercalcemia. Clinical signs and clinicopathologic findings are fairly nonspecific but ultrasonographic evidence of heterogenous small intestinal wall layering and pin-point hyperechoic foci in bowel, nodes, and liver is highly suggestive of infection. A sensitive, commercially available, fecal polymerase chain reaction test can be used to establish the diagnosis. Treatment protocols rely on praziquantel with fenbendazole. Most dogs will recover, although retreatment may be necessary in a substantial proportion. Housemates should be screened as infection can be asymptomatic.
Subject(s)
Dog Diseases , Hypercalcemia , Schistosomiasis , Dogs , Animals , United States/epidemiology , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Dog Diseases/pathology , Schistosomiasis/complications , Schistosomiasis/diagnosis , Schistosomiasis/veterinary , Fenbendazole/therapeutic use , Hypercalcemia/veterinary , LiverABSTRACT
Giardiosis is a worldwide intestinal parasitosis, affecting both humans and animals. Treatment in dogs remains limited and the lack of efficacy of the few approved medications is a rising concern. In this study, 23 dogs raised by veterinary students and naturally infected with Giardia duodenalis were treated in home conditions with fenbendazole (50 mg/kg orally for 5 consecutive days). Fecal samples were collected immediately before treatment (FS1), 2-4 days after treatment (FS2) and 8-10 days after treatment (FS3). Giardia duodenalis cyst excretion was measured quantitatively by direct immunofluorescence assay (DFA) at FS1, FS2 and FS3. Molecular typing with a nested PCR targeting the SSU rDNA locus was also performed at FS1 and FS2. Fecal consistency improved in 16/21 dogs (76%) and mean cyst shedding was reduced by 84% after treatment. However, only 8/23 dogs (35%) achieved therapeutic success (≥90% reduction of cysts) and only 4/23 dogs (17%) had complete elimination of G. duodenalis. Molecular typing showed that dogs harbored only canine-specific assemblages, with a high prevalence of assemblage C in analyzed samples (30/39). We also detected different assemblages after treatment and nucleotide substitutions in assemblage C sequences that have not been described previously. Eight to ten days after treatment, high Giardia cyst excretion was measured, suggesting possible reinfection despite hygiene measures and/or multiplication. These data suggest that fenbendazole treatment may improve fecal consistency but has limited therapeutic efficacy against giardiosis in this population of dogs. Further research is still needed to assess the efficacy of fenbendazole against canine giardiosis.
Title: Absence d'efficacité du fenbendazole contre Giardia duodenalis dans une population de chiens naturellement infectés en France. Abstract: La giardiose est une parasitose intestinale mondiale, touchant à la fois l'homme et les animaux. Chez le chien, le traitement reste limité et le manque d'efficacité des quelques médicaments autorisés inquiète de plus en plus. Dans cette étude, 23 chiens d'étudiants vétérinaires et infectés naturellement par Giardia duodenalis ont été traités en conditions réelles avec du fenbendazole (50 mg/kg par voie orale pendant 5 jours consécutifs). Des échantillons de selles ont été collectés juste avant le traitement (FS1), 24 jours après traitement (FS2) et 810 jours après traitement (FS3). L'excrétion de kystes de G. duodenalis a été mesurée quantitativement par immunofluorescence directe (IFD) à FS1, FS2 et FS3. Un génotypage par PCR nichée ciblant le locus SSU ADNr a également été réalisé à FS1 et FS2. La consistance des selles a été améliorée chez 16/21 (76 %) chiens et la moyenne d'excrétion des kystes a été réduite de 84 % juste après le traitement. Seulement 8/23 (35 %) chiens ont atteint un succès thérapeutique (≥ 90 % de réduction d'excrétion de kystes) et 4/23 (17 %) chiens ont eu une élimination complète de G. duodenalis. L'analyse des séquences a montré que les chiens présentaient seulement des assemblages génotypiques spécifiques de l'espèce canine, avec une forte prévalence de l'assemblage C dans les échantillons analysés (30/39). Des changements d'assemblage après traitement et des substitutions nucléotidiques jamais décrites au sein de l'assemblage C ont également été observés. Huit à dix jours après traitement, une forte excrétion de kystes de G. duodenalis a été mesurée : malgré les mesures hygiéniques, une réinfection et/ou une multiplication semblent probables. Ces données suggèrent que le traitement au fenbendazole peut améliorer la consistance des selles mais a une efficacité thérapeutique limitée contre la giardiose dans cette population de chiens. Des recherches supplémentaires sont encore nécessaires pour évaluer l'efficacité du fenbendazole contre la giardiose canine.
Subject(s)
Cryptosporidium , Cysts , Dog Diseases , Giardia lamblia , Giardiasis , Humans , Dogs , Animals , Giardia lamblia/genetics , Fenbendazole/therapeutic use , Giardia/genetics , Dog Diseases/drug therapy , Dog Diseases/epidemiology , Oocysts , Giardiasis/drug therapy , Giardiasis/veterinary , Giardiasis/epidemiology , Feces , Cysts/drug therapy , GenotypeABSTRACT
BACKGROUND: Control of strongyle infections presents a global challenge for horse practitioners due to the development of anthelmintic resistance (AR), however comprehensive information on AR in Lithuania is still lacking. The aim of this study was to assess the current situation of fenbendazole (FBZ) AR in horses at stable level in Lithuania. RESULTS: Faecal samples from 121 horses from six stables were examined using the Mini-FLOTAC method. Of these, 89 horses met the inclusion criteria that included strongyle faecal egg counts (FEC) exceeding 200 eggs per gram (EPG). Faecal egg count reduction tests (FECRTs) were performed in these. AR was evaluated at horse stable level based on faecal egg count reduction (FECR) and the lower limit of the 95% credible interval (LLCI) using the Bayesian hierarchical model. This study confirmed that strongylids (Cyathostominae (CYA)) resistant to FBZ are pervasive in Lithuania. FBZ was ineffective in three of the six stables (FECR 77.1-79.0%; 49.8-99.8 LLCI), was suspected to be ineffective in one stable (FECR 93.6%; 85.4-100 LLCI) and was effective (FECR 99.8-100%; 99.8-100 LLCI) in two stables. FEC showed a significant (P < 0.01) difference between the treatment and control groups. Only CYA larvae were detected in larval cultures derived from strongyle-positive faecal samples collected 14 days after treatment of a test group with FBZ. CONCLUSION: This in vivo study showed that resistance to FBZ in the treatment of strongyle nematodes is prevalent in horse stables in Lithuania. These findings should guide the implementation of more sustainable management of strongyle infections in horses in Lithuania.