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The contamination of the environment by some veterinary medicines and their impact on wild animals is of increasing concern. However, there is a lack of information about their residues in wildlife. The sentinel animals most commonly used for monitoring the level of environmental contamination are birds of prey, and information on other carnivores and scavengers scarce. This study examined the livers from 118 foxes for residues of a range of 18 veterinary medicines (16 anthelmintic agents and 2 metabolites) used on farm livestock. The samples were collected from foxes, primarily in Scotland, shot during legal pest control activities conducted between 2014 and 2019. Closantel residues were detected in 18 samples, and the concentrations found ranged from 6.5 µgkg−1 to 1383 µgkg−1. No other compounds were found in significant quantities. The results show a surprising frequency and level of closantel contamination, raising concerns about both the route of contamination and the potential impacts on wild animals and the environment, such as the potential for significant wildlife contamination to contribute to the development of closantel-resistant parasites. The results also suggest that red fox (Vulpes vulpes) could be a useful sentinel species for detecting and monitoring some veterinary medicine residues in the environment. • The livers from 118 foxes were examined. • Tissues were screened for residues of 16 anthelmintic veterinary medicines and 2 metabolites. • Closantel was detected in 18 (>15%) of the samples. • The concentrations found ranged from 6.5 ugkg−1 to 1383 ugkg−1. • Red fox may be a useful sentinel to detect environmental residues of veterinary medicines. [ABSTRACT FROM AUTHOR]

Background: Closantel is a halogenated salicylanilide with a potent anti parasitic activity. It is widely used in management of parasitic infestation in animals, but is contraindicated in humans. Case presentation: A 34-year-old man with depression was referred to our center with progressive loss of vision in both eyes 10 days after unintentional ingestion of three 500 mg tablets of Closantel. On fundus examination, left optic disc margin was blurred. His bilateral visual acuity was no light perception (NLP) despite prescribed IV erythropoietin injections 20,000 units daily for 3 days and 1gr intravenous methylprednisolone acetate for 3 days followed by 1 mg/kg oral prednisolone. On macular optical coherence tomography (OCT), a disruption in outer retina was observed. Electroretinogram and visual evoked potential tests showed visual pathway involvement. Conclusions: Destruction of neurosensory retina and visual pathways after accidental Closantel use is related to severe visual loss. This case alerts us about the destructive effect of this drug on humans even in low dosage which necessitates preventive efforts to reduce the chance of this morbid side effect. [ABSTRACT FROM AUTHOR]

Copyright of Revista Acadêmica: Ciência Animal is the property of Revista Academica: Ciencia Animal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Descrevem-se dois surtos de intoxicação por clo-santel, um em ovinos e outro em caprinos, no Estado de San-ta Catarina. No primeiro surto, de 12 ovinos que adoeceram 5 apresentaram cegueira, desses três morreram (Ovinos 1-3) e dois (Ovinos 4 e 5) foram eutanasiados, 6 meses após ficarem cegos. No segundo surto, de 26 caprinos que adoeceram, seis animais sobreviveram, porém ficaram cegos, e um deles foi eutanasiado. Clinicamente os animais apresentavam depressão, ataxia, incoordenação motora e reflexo pupilar diminuído a ausente. Em alguns animais esse quadro evoluiu para cegueira bilateral com ausência de reflexo de ameaça e midríase bilateral irresponsiva. Ao exame oftálmico verificou-se atrofia dos vasos da retina e hiperreflexia. Pelo exame histológico observou-se edema mielínico levando a status spongiosus no sistema nervoso central e neuropatia compressiva no nervo óptico, acompanhada de degeneração e/ou atrofia da retina. O objetivo deste trabalho é descrever os aspectos epidemiológicos, clínicos e patológicos da intoxicação por closantel em ovinos e caprinos.Two outbreaks of closantel overdosage in sheep and goat flocks are described. In the first outbreak 12 sheep were affected, 5 of them showed blindness, three sheep died (Sheep 1-3) and two were euthanized 6 months after the onset of clinical manifestation (Sheep 4 and 5). In the second outbreak 26 goats were affected, from which six survived despite blindness and one was euthanized. Clinically the animals showed depression, ataxia, motor incoordination, decreased or absent pupil reflexes. In some animals this clinical picture developed to bilateral blindness, with no reaction to threat and bilateral irresponsive midriasis. In the ophthalmic examination retinal vessel atrophy and hyperreflexia were observed. The histological examination showed myelin edema leading to status spongiosus in the central nervous system and compressive neuropathy of the optic nerve, associated with retinal degeneration and/or atrophy. This report aims to describe the epidemiologic, clinic and pathologic aspects of closantel overdosage in sheep and goats.

Alterações oftálmicas foram experimentalmente induzidas em caprinos após superdosagem com o anti-helmíntico closantel. Foram usados cinco caprinos com sete a oito meses de idade, produtos do cruzamento da raça Saanen com a Pardo Alpino. Os animais mostraram sinais de intoxicação entre quatro e cinco dias após a administração do closantel. Os sinais clínicos caracterizaram-se principalmente por distúrbios neurológicos centrais e cegueira. Ao exame clínico, observaram-se midríase bilateral, perda do reflexo pupilar à luz e cegueira bilateral. À oftalmoscopia indireta, foram observadas degeneração aguda de retina e papiledema. As alterações crônicas mostravam disco óptico acinzentado, atrofia de vasos e da retina. Nos fundos tapetal e não-tapetal notavam-se áreas de despigmentação e lesões irregulares castanho-amareladas. As alterações histológicas consistiam em perda dos neurônios da camada ganglionar e das células da camada nuclear interna e externa da retina. As alterações agudas no nervo óptico e na substância branca do encéfalo foram de degeneração espongiforme. As alterações crônicas do nervo óptico caracterizavam-se por extensa necrose e infiltração de células Gitter.Ophthalmic alterations were experimentally induced after overdose with the anthelmintic closantel. Five seven to eight- months-old, Saanen x Alpine caprine were used. The animals showed clinical signs of toxicosis four to five days after the administration of closantel. Clinical signs were primarily characterized by central nervous disturbances and blindness. Clinically, bilateral mydriasis, loss of pupillary light reflex, and blindness were observed. At indirect ophthalmoscopic examination, there was acute retinal degeneration and papilledema. Chronic ocular changes consisted of paleness of the optic disc, vascular atrophy, and retinal atrophy. Areas of pigment loss and irregular yellowish-brown foci were present in the tapetal and non-tapetal fundus. Histological alterations consisted of neuronal loss in the ganglion cell layer and depletion of cells in both the outer and inner nuclear layers of the retina. Acute changes of spongy degeneration were noted in the optic nerve and in the cerebral white matter. Chronic lesions in the optic nerve were characterized by extensive necrosis and infiltration by Gitter cells.

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., Competing Interests: Declaration of Competing Interest Daniel Zarate Rendon reports article publishing charges, equipment, drugs, or supplies, and travel were provided by Flemish Interuniversity Council and the Universidad Nacional Agraria La Molina, Perú., (Copyright © 2022 Elsevier B.V. All rights reserved.)

• Establish a reliable HPLC method for determining closantel enantiomers. • Investigate the enantioselective pharmacokinetics of closantel in black goats. • Closantel is highly enantioselective in the plasma of black goats. Closantel is a broad-spectrum antiparasitic drug widely used in livestock. It is a chiral drug consisting of a pair of enantiomers. An accurate, selective, and validated method was established for separating and detecting closantel enantiomers in black goat plasma. Separation of enantiomers was achieved in Chiralpak AD-3 based on amylose tris (3,5-dimethyl phenyl carbamates) under a gradient mobile phase composed of n -hexane-TFA (100:0.1, v / v) and IPA-MeOH-TFA (99:1:0.1, v / v / v). Mean recoveries of the two enantiomers at three spiking levels ranged from 97.4 % to 102.0 % with a relative standard deviation ≤ 4.5 %. The limit of quantification was 1.35 µg/mL for each enantiomer in plasma. The proposed method was successfully applied to investigate the enantioselective pharmacokinetics of closantel enantiomers (E1 and E2) in black goats following an intramuscular closantel sodium at 5 mg/kg b.w. The results revealed that peak plasma concentration and area under the curve were significantly different between the two enantiomers (p < 0.05). C max and AUC 0-∞ for closantel E1 were approximately 3 times greater than closantel E2. These findings would help in further evaluation of pharmacokinetic, pharmacodynamic, and toxicity of the individual enantiomers of closantel in food animals. [ABSTRACT FROM AUTHOR]

Sheep production requires the constant assessment of parasitic burden and the efficacy of existing treatments for proper management. In this study, the administration of five different treatments was evaluated for the reduction of the percentage of eggs per gram of feces (EPG) shed by gastrointestinal nematodes (GIN) from sheep on three different sheep-breeding farms in Mexico (Texcoco, Estado de Mexico; Hueytamalco, Puebla; and Tlaltizapán de Zapata, Morelos). In these farms, ivermectin and benzimidazole derivatives had been routinely administered for two consecutive years. To determine whether drugs with different pharmacological properties decreased GIN fecal egg excretion, the treatments closantel (CLOS), albendazole (ABZ) and fenbendazole (FBZ) were administered alone and in combinations of CLOS + ABZ and CLOS + FBZ, to five groups of sheep, with an additional untreated control group on each farm (n = 28 per flock). Anthelmintic resistance was determined using Fecal Egg Count Reduction Tests (FECRT) as recommended in the guidelines of the World Association for the Advancement of Veterinary Parasitology. Fecal samples were collected 14 and 21 days after treatment. The anthelmintic resistance status was determined based on the reduction in the fecal egg count arithmetic mean and 95 % confidence limits. According to the FECRT, resistance developed to CLOS, ABZ, FBZ and CLOS + FBZ because the mean percentage of EPG reduction was ≤ 95 % with a lower confidence limit of ≤ 90 %. By contrast, nematode susceptibility was confirmed for the CLOS + ABZ combination, as it reduced the percentage of GIN fecal egg output by 96.46 ± 3.04 % (day 14) and 96.88 ± 3.04 % (day 21). Based on the morphometric identification of larvae, Haemonchus spp., Cooperia spp. and Teladorsagia spp. were the most abundant genera on all farms before the administration of these five treatments. In conclusion, the use of the anthelmintic combination of closantel plus albendazole may reduce the development of anthelmintic resistance in gastrointestinal nematodes. [ABSTRACT FROM AUTHOR]

In Ontario, Canada, widespread resistance to ivermectin and fenbendazole, the only readily available ovine anthelmintics, has been documented, primarily in Haemonchus sp. In other parts of the world, closantel has been used to control such infections; however, the drug was not currently licensed for use in Canada and the USA. A randomized controlled trial was conducted on six client-owned farms in Ontario in 2013 and 2014 to determine the efficacy of closantel (Flukiver ® 5% Oral Suspension, Elanco Animal Health, 10 mg/kg bodyweight) against ivermectin- and fenbendazole-resistant Haemonchus sp. infections in periparturient ewes and grazing lambs. Three farms were randomly assigned to treat all ewes, and three farms were randomly assigned to selectively treat individual ewes at lambing, using predetermined criteria. Fecal samples were collected from a minimum of 15 randomly selected ewes and 13 lambs per group on each farm at the time of treatment and approximately 14 days later. Trichostrongyle-type fecal egg counts (FEC) were performed using a modified McMaster technique with a lower detection limit of 8.3 eggs per gram of feces (epg). Haemonchus -specific FECs were determined by multiplying FECs by the proportion of Haemonchus sp. identified from coproculture for each farm; Haemonchus- specific FEC reductions were calculated for each farm. Twenty grazing lambs had FECs conducted monthly, and when mean monthly FECs surpassed 200 epg, all lambs were randomly allocated to either closantel, positive control (ivermectin, fenbendazole, or levamisole) or negative control groups. Pre-treatment Haemonchus- specific mean FECs ranged from 27 to 3359 epg in ewes and 0–5698 epg in lambs. Efficacy of closantel against Haemonchus sp. ranged from 99% (95% CI: 97%–99%) to 100% in recently lambed ewes on all farms in both years (total n = 274 ewes), and from 99% (95% CI: 98%–99%) to 100% in grazing lambs in both years on all but one farm (total n = 171 lambs). On the latter farm, a whole flock treated farm, closantel efficacy in grazing lambs was 84% (95%CI: 81%–88%) in the first year, but 100% in the second year. Levamisole was effective against overall GIN in lambs on only two farms. Ivermectin and fenbendazole resistance continued to be present, particularly in Haemonchus sp. Closantel had excellent efficacy against Haemonchus sp. over the two year study period, regardless of treatment group, and therefore should be considered one viable component of sustainable integrated parasite control programs for farms with documented anthelmintic resistance and problems with haemonchosis. [ABSTRACT FROM AUTHOR]

The influence of closantel on the rheological and physicochemical properties (particle size and by UV–Vis absorption spectroscopy) of PVA aqueous solutions is studied here. About 1% PVA aqueous solutions were prepared by varying the closantel content. The increase of closantel content led to a reduction in the particle size of final solutions. All the solutions were buffered at pH 7.4 and exhibited shear-thinning behavior. Furthermore, in oscillatory flow, a “solid-like” type behavior was observed for the sample containing 30 μg/mL closantel. Indicating a strong interaction between the dispersed and continuous phases and evidencing an interconnected network between the nanoparticle and PVA, this sample also showed the highest shear viscosity and higher shear thinning slope, indicating a more intrincate structure disrupted by shear. In conclusion, PVA interacts with closantel in aqueous solution and the critical concentration for closantel encapsulation by PVA was about 30 μg/mL; above this concentration, the average particle size decreased notoriously which was associated to closantel interacting with the surface of the PVA aggregates and thus avoiding to some extent direct polymer–polymer interaction. [ABSTRACT FROM AUTHOR]

Anthelmintic resistance in livestock parasites is currently a worldwide problem. Fasciola hepatica is a cosmopolitan parasite which causes considerable loss in sheep and cattle production systems all over the world. Chemotherapy is currently the main tool available for its control. The intensive use of triclabendazole, the drug of choice for more than 20 years, has resulted in the development of resistant strains. The therapeutic options are adulticides such as closantel (salicylanilide anthelmintic that binds extensively to plasma albumin) to treat chronic fascioliasis in sheep, and cattle. In the present work, an Egg Hatch Assay (EHA) and morphometric studies were used to evaluate in vivo the ovicidal activity and morphology F. hepatica eggs, recovered from closantel treated sheep collected at different time intervals post treatment. Statistically significant differences (p < 0.0001) were observed in egg morphometry between the control and the treated groups in all the parameters studied. Eggs recovered from treated animals tend to be narrower and longer. Significant differences were found in the embryonation and hatching of eggs between 36 h post treatment (32, 5%) vs. approximately 85% in control, 12 h and 24 h post treatment. Our results confirm that closantel affects in vivo the normal development of the eggs. As one of the first effects, this drug affects the performance of the trematode's reproductive physiology. Even though closantel treated animals may still eliminate eggs in the first days post treatment, these are not viable. [ABSTRACT FROM AUTHOR]

Control of Fasciola hepatica infection in livestock is based on annual treatment using flukicides such as triclabendazole, albendazole and closantel. However, triclabendazole resistant F. hepatica populations are emerging worldwide and resistance is emerging to albendazole, whereas it has until now never been described for closantel. In Sweden, a topical formulation containing a combination of closantel and ivermectin (Closamectin Pour On) has been registered for use in cattle only since 2011. This study evaluated the efficacy of closantel against F. hepatica in naturally infected beef cattle using both coproantigen and faecal egg count reduction tests. Faecal egg counts (FEC) and coproantigen ELISA examinations were conducted in February 2014 in three beef cattle herds (A, B, C) in south-western Sweden. On each farm, 10 F. hepatica coproantigen-positive and F. hepatica egg-positive animals were allocated after 12–16 weeks of housing into groups and treated topically with a minimum of 20 mg closantel per kg body weight. Faecal samples were collected from selected animals on 0, 7 and 21 day post-treatment (PT). Based on FEC, closantel efficacy 21 days PT was 72% (95% CI: 65–77%) and 97% (95% CI: 95–98%) on farms A and B, respectively. No FEC reduction at all was observed on farm C. In total, 4, 1 and 6 animals remained coproantigen-positive at 21 days PT on farms A, B and C, respectively. Closantel treatment failure was confirmed on two of the farms. As the animals were housed 12–16 weeks before treatment and thereafter during the entire study, failure due to the presence of juvenile flukes was excluded. Although the cause of closantel failure currently remains unclear, development of resistance or/and absorption failure of topical administration should be considered. To our knowledge, this is the first report of closantel treatment failure against F. hepatica in cattle. [ABSTRACT FROM AUTHOR]

A total of 1,724 beef and 2,941 dairy cattle older than one year from 66 beef and 67 dairy farms in the Czech Republic were examined for the presence of rumen and liver fluke eggs in 2019-2022. Out of 227 positive animals, all were positive for paramphistome and five for fasciolid eggs. Molecular analysis of the ITS2 rDNA revealed the presence of Calicophoron daubneyi (Dinnik, 1962) and Fasciola hepatica Linnaeus, 1758. Faecal egg count (FEC) showed low infection intensity (12 EPG) in animals infected with F. hepatica and high variability in C. daubneyi infections (2-589 EPG). Efficacy of oxyclozanide, albendazole, ivermectin, and closantel against C. daubneyi infection was evaluated at eight beef cattle herds. Faecal samples were collected from all positive animals at 0 and 21days post-treatment. Based on FEC, albendazole, ivermectin and closantel reduced the number of C. daubneyi eggs shed by 0-9.9%, with no effect on the number of infected animals. The use of oxyclozanide on two beef farms showed 100% efficacy against C. daubneyi and F. hepatica. Follow-up examination 5-6 months after drug application showed reinfection of most animals with C. daubneyi, but the FEC was significantly lower. The finding of four dairy cows infected with C. daubneyi housed in a stable without pasture suggests the possibility of the infection being introduced through roughage.

Copyright of Pesquisa Veterinaria Brasileira is the property of Colegio Brasileiro de Patologia Animal - CBPA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recently, sharp increases in the prevalence of rumen fluke infections have been recorded throughout Western Europe. However, scarce information is available on the diagnosis, pathogenic importance and control of this parasite. We undertook 3 pilot studies to gain more insights into these aspects of rumen fluke biology in cattle. First, we evaluated the diagnostic performance of mini-FLOTAC to detect adult rumen fluke infections based on faecal egg count in an abattoir survey and found high sensitivity (0.94) and specificity (0.98). Moreover, there was an association between ruminal fluke burden (assessed by visual scoring) and faecal egg count and a cut-off of 200 eggs per gram is proposed to detect highly infected animals (>200 flukes present in the rumen and/or reticulum). There was also a significant association between ruminal fluke burden and faecal consistency. However, in a second study, we performed a case-control field survey to investigate the association between rumen fluke infection and herd-level problems with diarrhoea and no association was found. Finally, we evaluated the use of closantel (Flukiver ® , Elanco Animal Health, subcutaneous administration at 10 mg/kg) to treat rumen fluke infection on 3 herds, but no significant reduction in egg output post-treatment was found. Because this result is in contrast with a previous study using an oral dose of closantel, more research is required into the effect of administration route on the efficacy of closantel on rumen fluke. [ABSTRACT FROM AUTHOR]

The present work was undertaken to evaluate the therapeutic efficacy of ivermectin, closantel and fenbendazole under field conditions against Gastrointestinal Nematodes (GIN) of cross bred merino sheep in Budgam area of Kashmir Valley. A total of 115 sheep having Egg per gram of faeces (EPG) greater than or equal to 150 (mean EPG 258.89) were selected. The animals were randomly divided into four groups comprising of 30 animals each in three treatment groups (ivermectin, closantel and fenbendazole) and twenty-five in fourth untreated infected control group. Faecal samples from the selected animals were collected on day '0' pre treatment and on days 8th and 14th post treatment. Based on Faecal Egg Count Reduction Test (FECRT), ivermectin was found to be 98.80 % effective against strongyles on 8th day post treatment, however an efficacy of 100 % was seen against strongyle worms on 14th day post treatment. 98.80 and 100 % efficacy was observed on day 8th post treatment against strongyles in case of closantel and fenbendazole respectively, however efficacy decreased to 97.60 and 98.8 % respectively on 14th day post treatment. There was no evidence of development of resistance by GIN of cross bred merino sheep in District Budgam of Kashmir Valley to ivermectin, closantel and fenbendazole. [ABSTRACT FROM AUTHOR]

Highlights: [•] LC–MS/MS method for quantitative determination of closantel in bovine and ovine milk. [•] Optimized extraction and clean-up using Oasis® MAX® SPE columns. [•] Method validation of bovine milk according to EU Volume 8 (2005). [•] Method validation of ovine milk according to EU Volume 8 (2005) and VICH GL49 (2012). [•] Although both guidelines cover similar parameters, significant differences exist. [ABSTRACT FROM AUTHOR]

Combination therapy of many anthelmintic drugs has been used to achieve fast animal curing. Q-DRENCH is an oral suspension, containing four different active drugs against GIT worms in sheep, commonly used in Australia and New Zeeland. The anti-parasitic drugs are Albendazole (ALB), Levamisole HCl (LEV), Abamectin (ABA), and Closantel (CLO). The main purpose of this study is to present a new simultaneous stability-indicting HPLC-DAD method for the analysis of the four drugs. The recommended liquid system was 1 mL of Triethylamine/L water, adjusting the pH to 3.5 by glacial acetic acid: acetonitrile solvent (20:80, v/v). Isocratic elusion achieved the desired results of separation at a 2 mL/min flow rate using Zorbax C-18 as a stationary phase. Detection was performed at 210 nm. The linearity ranges were 15.15 to 93.75 μg/mL for ALB, 25 to 150 μg/mL for LEV, 30 to 150 μg/mL for ABA, and 11.7 to 140.63 μg/mL for CLO. Moreover, the final greenness score was 0.62 using the AGREE tool, which reflects the eco-friendly nature. Moreover, the four drugs were determined successfully in the presence of their stressful degradation products. This work presents the first chromatographic method for simultaneous analysis for Q-DRENCH oral suspension drugs in the presence of their stressful degradation products. [ABSTRACT FROM AUTHOR]

Abstract: The paramphistomicidal activity of four anthelmintics in dairy cattle naturally infected by Calicophoron (Paramphistomum) daubneyi was evaluated. Seventy Friesian adult cows were treated at drying-off (19 albendazole; 23 netobimin; 13 closantel and 15 oxyclozanide), and 21 remained untreated as controls. The anthelmintic efficacy was determined by estimating the faecal egg count reduction (FECR) values for each of the anthelmintics. The reduction in the number of cows shedding eggs in the faeces was also estimated. The C. daubneyi egg-output was not fully suppressed following the administration of any of the parasiticides. The FECR values ranged from 0% to 26% in the cows receiving albendazole or netobimin, with 11–39% of cattle becoming negative after therapy. Better results were achieved with closantel and oxyclozanide, with FECR values of 97–99% and CPCR (cattle positive by coprology reduction) percentages of 85–93%. The observation of a similar efficacy with closantel and oxyclozanide against C. daubneyi led us to recommend the administration of closantel in those countries where oxyclozanide is not available. [Copyright &y& Elsevier]

Abstract: The objective of this study was to evaluate the efficacy of a pour-on solution containing moxidectin plus triclabendazole (MOX plus TCBZ) against immature and adult stages of the liver fluke in cattle and compare the efficacy with other commercially available preparations. To this end, 104 male Holstein-Friesian calves aged between 3 and 4 months, were randomly allocated to 13 groups of eight animals each, and infected with approximately 500 Fasciola hepatica metacercariae. One group remained untreated, four groups were treated with MOX plus TCBZ at a dose rate of 0.1mL/kg, four other groups were treated with ivermectin (IVM) plus clorsulon injectable at a dose rate of 0.02mL/kg, and the remaining four groups were treated with IVM plus closantel pour-on at a dose rate of 0.1mL/kg. Each treatment was applied to one of the groups at 4 weeks, 6 weeks, 8 weeks and 12 weeks after the experimental infection. At necropsy (99–102 days after infection), all untreated animals were infected with a minimum of 30 flukes. The MOX plus TCBZ treated animals had significantly (P <0.0001) lower fluke counts compared to the untreated control animals at all time points after treatment. Efficacy against 8-week old and adult flukes was >99.5%. For 6-week old immature fluke, the efficacy was 98.0% and for 4-week old immature fluke the efficacy was 90.9%. The IVM plus closantel pour-on treated animals had significantly lower fluke counts compared to the untreated control animals for adult and 8-week old flukes (P <0.0001), and for 6-week old flukes (P =0.002). The efficacy was 26.8%, 68.2%, 90.6% and 99.3% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. The IVM plus clorsulon treated animals had significantly lower fluke counts compared to the untreated control animals for adult (P <0.0001) and 8-week old (P <0.05) flukes. The efficacy was 29.7%, 43.4%, 53.2% and 99.2% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. For treatments at 4, 6 and 8 weeks after infection, the fluke counts were significantly (P <0.0001) lower for the MOX plus TCBZ treatment than for IVM plus closantel or IVM plus clorsulon. The results confirm the high efficacy (>90%) of the MOX plus TCBZ pour-on combination against 4-week old to adult liver fluke in cattle. The IVM plus closantel pour-on combination was effective (>90%) against 8-week old and adult flukes, but had low efficacy against 4- and 6-week old fluke. The IVM plus clorsulon injectable combination was effective (>90%) against adult fluke only. [Copyright &y& Elsevier]

The aim of this study was to compare the efficacy of ivermectin and closantel for controlling larvae Oestrus ovis in naturally infested adult sheeps. To carry out this experiment, 27 Pelibuey animals, from a farm of Guantánamo province, were selected based on clinical signs, suspicious of an infestation by the agent. Those sheeps were random allotted into four groups of six animals each. At the beginning of the experiment (day 0), each group received a different treatment: group (G1), treated with 1% ivermectin injection at doses of 200 mcg / kg (1 mL/50 kg) subcutaneously (SC); group (G2), treated with a dose of 2 mL per 10 kg weight of oral closantel 5%; group (G3) untreated control, injected with saline (1 mL/50 kg) and group (G4) sentinel. This latter group was sacrificed on day 0 to estimate the parasite load. All animals from the other groups (G1, G2 and G3) were sacrificed on day 28 post-treatment. The efficacy of drugs used, based on the percentage reduction of live larvae with respect to the infested control animals, was 100% in both cases (G1 & G2). It is conclude that both drugs tested were highly effective for controlling the different larval stages of O. ovis. [ABSTRACT FROM AUTHOR]

Abstract: AtoSC two-component system participates in many indispensable processes of Escherichia coli. We report here that the AtoSC signal transduction is inhibited by established histidine kinase inhibitors. Closantel, RWJ-49815 and TNP-ATP belonging to different chemical classes of inhibitors, abrogated the in vitro AtoS kinase autophosphorylation. However, when AtoS was embedded in the membrane fractions, higher inhibitor concentrations were required for total inhibition. When AtoS interacted with AtoC forming complex, the intrinsic histidine kinase was protected by the response regulator, requiring increased inhibitors concentrations for partially AtoS autophosphorylation reduction. The inhibitors exerted an additional function on AtoSC, blocking the phosphotransfer from AtoS to AtoC, without however, affecting AtoC~P dephosphorylation. Their in vivo consequences through the AtoSC inhibition were elucidated on atoDAEB operon expression, which was inhibited only in AtoSC-expressing bacteria where AtoSC was induced by acetoacetate or spermidine. The inhibitor effects were extended on the AtoSC regulatory role on cPHB [complexed poly-(R)-3-hydroxybutyrate] biosynthesis. cPHB was decreased upon the blockers only in acetoacetate-induced AtoSC-expressing cells. Increased ATP amounts during bacterial growth reversed the inhibitory TNP-ATP-mediated effect on cPHB. The alteration of pivotal E. coli processes as an outcome of AtoSC inhibition, establish this system as a target of two-component systems inhibitors. [Copyright &y& Elsevier]

Abstract: The objective of this study was to determine the level of resistance of Haemonchus contortus and Trichostrongylus colubriformis in sheep to levamisole, albendazole, ivermectin, moxidectin, closantel and trichlorfon. The parasites were isolated from sheep naturally infected by gastrointestinal nematodes and were then kept in monospecifically-infected lambs for production of infective larvae (L3) of both species. Forty-two lambs, at three months of age, were simultaneously artificially infected with 4000 L3 of H. contortus and 4000 L3 of T. colubriformis. The animals were allocated into seven groups with six animals each that received one of the following treatments: Group 1—control, no treatment; Group 2—moxidectin (0.2mg/kg body weight (BW)); Group 3—closantel (10mg/kg BW); Group 4—trichlorfon (100mg/kg BW); Group 5—levamisole phosphate (4.7mg/kg BW); Group 6—albendazole (5.0mg/kg BW); and Group 7—ivermectin (0.2mg/kg BW). Nematode fecal egg counts (FEC) were carried out on the day of treatment and again at 3, 7, 10 and 14days post-treatment. On the same occasions, composite fecal cultures were prepared for each group for production of L3, which were identified into genus. The animals were sacrificed for worm counts at 14days after treatment. The efficacy of each treatment was calculated from the arithmetic mean of the FEC or worm burden of the treated group, compared with the values of the control group. Only trichlorfon and moxidectin treatments resulted in a significant reduction of H. contortus recorded at necropsy (73% and 45% respectively). Moxidectin reduced T. colubriformis worm burdens by 82% and albendazole by 19%. All other anthelmintics resulted in no significant reduction in the numbers of worms found at necropsy. In conclusion, the isolates of H. contortus and T. colubriformis showed multiple resistance to all groups of anthelmintics tested. This is the first report, based on the controlled efficacy test, to show resistance of T. colubriformis to macrocyclic lactones in Brazil. [Copyright &y& Elsevier]

Onchocerciasis, or river blindness, is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus that affects more than 37 million people, mainly in third world countries. Currently, the only approved drug available for mass treatment is ivermectin, however, drug resistance is beginning to emerge, thus, new therapeutic targets and agents are desperately needed to treat and cure this devastating disease. Chitin metabolism plays a central role in invertebrate biology due to the critical structural function of chitin for the organism. Taken together with its absence in mammals, targeting chitin is an appealing therapeutic avenue. Importantly, the chitinase OvCHT1 from O. volvulus was recently discovered, however, its exact role in the worm's metabolism remains unknown. A screening effort against OvCHT1 was conducted using the Johns Hopkins Clinical Compound Library that contains over 1,500 existing drugs. Closantel, a veterinary anthelmintic with known proton ionophore activities, was identified as a potent and specific inhibitor of filarial chitinases, an activity not previously reported for this compound. Notably, closantel was found also to completely inhibit molting of O. volvulus infective L3 stage larvae. Closantel appears to target two important biochemical processes essential to filarial parasites. To begin to unravel closantel's effects, a retro-fragment-based study was used to define structural elements critical for closantel's chitinase inhibitor function. As resources towards the development of new agents that target neglected tropical diseases are scant, the finding of an existing drug with impact against O. volvulus provides promise in the hunt for new therapies against river blindness. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes an analytical method for four phenolic and salicylanilide anthelmintics authorised for use within the EU (nitroxinil, oxyclozanide, rafoxanide and closantel) in bovine kidney, and the extension of this procedure to include a number of related compounds; ioxynil, niclosamide, salicylanide and 3-trifluoromethyl-4-nitrophenol (TFM). The method comprises a solvent extraction with 1% acetic acid in acetone and clean-up using a mixed-mode anion-exchange solid phase extraction column. Determination is by reversed phase LC–MS/MS. The method was validated to the latest EU requirements (Commission Decision 2002/657/EC) using both spiked and incurred tissues and was subject to second laboratory evaluation. [Copyright &y& Elsevier]

Closantel is an antiparasitic drug marketed in a racemic form with one chiral center. It is meaningful to develop a method for separating and analyzing the closantel enantiomers. In this work, two enantiomeric separation methods of closantel were explored by normal-phase high-performance liquid chromatography. The influences of the chiral stationary phase (CSP) structure, the mobile phase composition, the nature and proportion of different mobile phase modifiers (alcohols and acids), and the column temperature on the enantiomeric separation of closantel were investigated in detail. The two enantiomers were successfully separated on the novel CSP of isopropyl derivatives of cyclofructan 6 and n-hexane-isopropanol-trifluoroacetic acid (97:3:0.1, v/v/v) as a mobile phase with a resolution (Rs) of about 2.48. The enantiomers were also well separated on the CSP of tris-carbamates of amylose with a higher Rs (about 3.79) when a mixture of n-hexane-isopropanol-trifluoroacetic acid (55:45:0.1, v/v/v) was used as mobile phase. Thus, the proposed separation methods can facilitate molecular pharmacological and biological research on closantel and its enantiomers. [ABSTRACT FROM AUTHOR]

Abstract: Three studies were performed to test the efficacy of an ivermectin/closantel injection (200μg/kg−1 ivermectin and 5mg/kg−1 closantel) in cattle. Two were experimentally induced infections of Ostertagia ostertagi, Cooperia oncophora and Fasciola hepatica in calves, and the third had natural field infections in cattle with several species of gastrointestinal nematodes and F. hepatica. In the two studies with artificial infections, four groups of 8 calves were used. All calves were infected with metacercariae on Day 0. Infection with the nematodes took place on Day 33 in groups 1 and 2 and on Day 54 in groups 3 and 4. Treatment was given to calves of group 1 on Day 63 and to calves of group 3 on Day 84. Calves of groups 2 and 4 served as untreated control groups. Calves of groups 1 and 2 were sacrificed on Day 84, calves of groups 3 and 4 on Day 105. The field study was carried out on a commercial farm in the Netherlands. Six groups of cattle were used. Groups A and B consisted of 10 parasite free calves, introduced to the farm and grazed for four weeks on pastures naturally infected with gastrointestinal nematode larvae and liver fluke metacercariae. Group C were the farmers own calves (15), group D heifers (10), group E dry cows (6) and group F milking cows (20). Treatment was given to animals of group A, C, D and E 10 weeks after housing of group A and B. Animals of groups B and F served as untreated controls. Calves of groups A and B were sacrificed 14 days after treatment. The efficacy of the treatment was calculated on basis of the post-mortem fluke and nematode worm counts in the first two studies and on a combination of post-mortem fluke and nematode worm counts and faecal egg output in the field study. In the two experimental studies, the efficacy of the treatment against F. hepatica was 99.2% and 94.5% for 9-week-old flukes and 98.4% and 99.5% for 12-week-old flukes. For O. ostertagi in both studies efficacy was 100% and against C. oncophora in both Groups 1 efficacy was 84.9% and 99.0% and in Groups 3 85.0% and 99.4%. In the field study, based on the post mortem fluke and nematode worm counts in groups A and B, efficacy against F. hepatica was 98.4%, O. ostertagi 100%, C. oncophora 99.4%, C. punctata 100%, Nematodirus helvetianus 60.8%, Trichuris spp. 100% and against larval intestinal nematodes 100%. The results of the faecal examinations 14 days after treatment confirmed the post-mortem results with 100% reduction of egg output for O. ostertagi, C. punctata, Trichostrongylus spp. and Trichuris spp. and low egg output of C. oncophora and N. helvetianus. [Copyright &y& Elsevier]

Summary: Toxicity of closantel, a halogenated salicylanilide anthelmintic, is described in 11 sheep and a goat, humanely killed 4–70 days after accidental overdosage. Status spongiosis of the cerebrum and cerebellum was present, its severity decreasing with time after treatment. Ultrastructurally, vacuoles in the cerebral white matter were seen to be intramyelinic due to splitting of myelin lamellae at the intraperiod lines, indicating myelin oedema. In the optic nerves, Wallerian degeneration and eventual fibrosis and atrophy of the nerves followed myelin vacuolation. Lesions in the optic nerves were particularly advanced in the intracanalicular portion, indicating a compressive neuropathy within the optic canal. Acute retinal lesions consisted of papilloedema, necrosis of the outer retinal layers (especially the photoreceptor layer), and retinal separation in tapetal and non-tapetal areas. In more chronic cases, the outer nuclear layer was diffusely attenuated and generally reduced to a single row of cells. [Copyright &y& Elsevier]

Abstract: Sixteen calves approximately 6 months old were each infected with 500 metacercariae of Fasciola hepatica. Thirty-two days later they were weighed and divided into two groups, and on day 35 all calves in one of the groups were injected subcutaneously with an ivermectin/closantel combination. Both groups were sacrificed between days 70 and 72 to enable counting and examination of the flukes recovered from the bile ducts. Eggs released by the flukes were collected for incubation, hatching and estimation of egg viability. Flukes were counted, flat-fixed in 70% ethanol, stained with catechol and carmine and measured. The reproductive organs, namely testis, vitelline glands, ovary and uterus, were examined and scored on a 0–3 scale according to their state of development. This was visually assessed on the basis of size, distribution and staining density of their constituent tissues and the abundance of eggs in the uterus. A representative sample of flukes from each animal was fixed in formalin for histological sectioning to enable more detailed examination of the reproductive structures. Treatment of the immature flukes reduced the population in cattle by 42.6% as compared with the controls and as a result of the stunting effect due to the presence of closantel during early development the size of treated flukes was reduced by 43.9%. A bimodal pattern of size and reproductive score was also observed in flukes from treated cattle, suggesting that the stunting effect on individual flukes differed depending on whether or not they had gained access to the bile ducts or were still migrating in the hepatic parenchymal tissue at the time of drug exposure with the effect being greater once the fluke had gained access to the bile ducts. The mean reproductive score for untreated flukes was 8.76 and for treated flukes 5.64, a 35.6% reduction. This difference was highly significant (p <0.001). Egg shedding from treated flukes was significantly less than that from controls (p <0.05), but there were no differences in hatchability, suggesting that whilst drug treatment reduced the energy supply available for gametogenesis/oogenesis, it did not induce functional defects in the gonads or accessory reproductive organs. Histological examination confirmed that there was a reduction in development of testes, ovaries and vitellaria in treated flukes, with a consequent reduction in egg production. In the treated flukes, early spermatogonia and oogonia were the predominant cell types in the testes and ovary, whilst undifferentiated stem cells were abundant in the vitelline follicles. In untreated flukes, cells representing more advanced stages in gametogenesis and vitellogenesis predominated in the respective organs. It is likely that this inhibition of gametogenesis and vitellogenesis was caused by the effects of closantel treatment on intermediary metabolism in the flukes. Clearly these effects were evident even at a relatively early stage of fluke growth, and because of the impact on egg output may have epidemiological importance in addition to the reduction in fluke numbers. [Copyright &y& Elsevier]

According to the SANCO/1805/2000 document and the EMEA/CVMP/573/00 guideline, one of the performance characteristics to be determined for an analytical method is the analyte stability. A practical approach is presented for the stability testing of veterinary drugs in solvents and in biological matrices during storage. These drugs comprise analytes belonging to the classes of antibiotics, sulfonamide chemotherapeutics, anthelminthics and non-steroidal anti-inflammatory drugs. Examples of the stability in solution are given for clindamycin, ketoprofen, oxytetracycline, 4-epioxytetracycline, sulfadiazine, trimethoprim, tylosin A and their respective internal standards. For the stability in matrix during storage, plasma or tissues are fortified with the analyte. Results of the recovery after storage are shown for amoxycillin in pig tissue, doxycyclin, sulfachloropyridazin and trimethoprim in broiler tissue and clindamycin, closantel, doxycyclin and ketoprofen in animal plasma. The analysis of incurred plasma samples containing closantel revealed that the temperature at which the samples are processed is critical. Compounds are analyzed by liquid chromatography with UV or tandem mass spectrometric detection. [Copyright &y& Elsevier]

The strategic use of moxidectin or closantel in combination with levamisole (LEV) to control gastrointestinal nematodes of sheep in the highlands of central Kenya was examined. Thirty Corriedale female lambs aged between 6 and 8 months were assigned to three treatment groups of ten lambs each. The three groups of lambs were set stocked on separate paddocks for the entire study period of 12 months. Lambs in Group 1 were dewormed strategically with moxidectin at 0.2 mg/kg body weight and those in Group 2 with closantel at 10 mg/kg body weight together with LEV at 7.5 mg/kg body weight. These strategic treatments were given 3 weeks after the onset of both the short and long rains and at the end of the long rainy season. The third group of lambs remained untreated (control group). Nematode infections in the treated groups of lambs and larval infectivity for the pastures on which the lambs were grazing were well controlled compared with the untreated control group. This resulted in higher weight gains and packed cell volume (PCV) in the treated lambs compared with the untreated lambs. These parameters were comparable between the lambs treated with moxidectin and those treated with closantel plus LEV. The estimated monitory benefit per animal from the control of gastrointestinal nematodes using moxidectin or closantel in combination with LEV when compared with animals in the control group were US $26 and 25, respectively. It was concluded that worm control strategies for sheep in the study area, which are based on anthelmintic treatments during the rainy seasons, are effective. Due to the extended period during which pastures remain infective in the high rainfall central highlands of Kenya, anthelmintics with sustained action such as moxidectin or closantel may be most effective. On farms where resistance to the commonly used benzimidazoles or LEV groups of anthelmintics has developed, moxidectin or closantel may be used in helminth control programs for sheep. [Copyright &y& Elsevier]

Simple Summary: Parasitism with gastrointestinal nematodes represents a significant risk to the health of livestock populations. Besides the local oxidative damage caused by the parasite, the host reacts by increasing the production of oxidants. The study of thiol-disulphide homeostasis can be of help in the evaluation of the oxidative status of sheep during this type of parasitism. In this study, the thiol-disulphide homeostasis, together with other biomarkers of oxidative stress and inflammation, were assessed in the serum of lambs infected with gastrointestinal nematodes and were evaluated after 70 days of integrated crop-livestock system and anthelmintic treatment. This study showed that the thiol-disulphide balance was impaired in the infected lambs and the changes were correlated with the parasite load, which therefore could indicate their potential use as a tool to evaluate and monitor the disease in sheep. This work aimed to evaluate the thiol-disulphide homeostasis in serum of lambs naturally infected by gastrointestinal nematodes presenting different levels of parasite load indirectly indicated by faecal worm egg counts (EPG). Furthermore, the possible changes in the thiol-disulphide dynamic after different procedures to reduce the parasitic charge, such as the integrated crop-livestock system or anthelmintic treatment, were assessed. The results were compared with a panel of various oxidative stress and inflammatory biomarkers. The lambs were divided into three groups: animals highly infected (EPG higher than 5000) and packed cell volume (PCV) lower than 24% (G1); animals highly infected (EPG higher than 5000) and normal PCV (>24%) (G2); and animals presenting EPG lower than 5000 and normal PCV (>24%) (G3). The highly infected lambs (G1 and G2) showed lower total thiol (TT) and native thiol (SH) (p ≤ 0.01) than those from G3. After treatment, TT and SH increased significantly in all groups (p ≤ 0.01), and the disulphide (SS)/TT and SS/SH ratios decreased significantly (p < 0.01) in G1 and G2. These results show that the thiol-disulphide balance was impaired in lambs infected by gastrointestinal nematodes and that it could be potentially used as a biomarker to monitor this disease. [ABSTRACT FROM AUTHOR]

• Fosfatriclaben is an experimental fascioliscide solubilized as a prodrug for intramuscular administration in sheep. • It shows high fasciolicidal efficacy similar to its predecessor (Triclabendazole). • The clinical dose to achieve 100% efficacy, is only 6mg/kg/IM in comparison to its predecessor which requires 10 mg/kg/PO. • The dose used, leads to lower residues excreted in feces. Therefore, it generates less contamination in the environment. • Fosfatriclaben prodrug, could be an alternative to control fasciolosis in sheep. In this work, we present an evaluation of the fasciolicidal efficacy of a new injectable formulation of fosfatriclaben in comparison with the subcutaneous closantel and oral triclabendazole formulations currently used in veterinary practice as fasciolicides. The study was carried out in vivo on Fasciola hepatica at 2, 4, 6 and 8 weeks of age in experimentally infected sheep. To evaluate the formulation, the percent reduction of the parasite load was measured and the number of fluke eggs. Fosfatriclaben was used at 6 mg/kg/IM (dose equivalent to triclabendazole content), closantel at 5% at 10 mg/kg/SC, and triclabendazole at 10 mg/kg/PO; the control group received no treatment. Fosfatriclaben showed fasciolicidal efficacies of 95.5 %, 100 %, 100 % and 100 %, and triclabendazole showed similar efficacies of 97.4 %, 100 %, 100 % and 100 %, at the different treatment weeks (P > 0.05). Closantel showed limited efficacy against 2-, 4- and 6-week-old flukes but 100 % efficacy in adult flukes. All three evaluated formulations eliminated all 8-week-old F. hepatica trematode eggs. Although fosfatriclaben and triclabendazole showed similar fasciolicidal efficacy, the intramuscular administration of fosfatriclaben has several advantages over the oral administration of triclabendazole, such as ease of administration for veterinary use and a reduced risk of accidents for both the operator and the animals. In addition, the dose used in this injectable formulation is only 60 % of the oral dose, which reduces environmental contamination. [ABSTRACT FROM AUTHOR]

Background: Closantel is a veterinary drug used as anthelmintic for ruminants while it is contraindicated for humans. This report describes a rare case of blindness, increased liver enzymes and coagulopathy following closantel poisoning. Case report: A 5-year-old girl was presented with acute blindness following closantel poisoning. She was given mistakenly a dose of 500 mg/day (25mg/kg/day) for 8 days. Clinical examination revealed a well-appearing child with bilateral mydriasis, loss of pupillary light reflex and absence of blinking to threat. Fundoscopic exam revealed bilateral pre-atrophic papilledema. Electroretinogram showed a highly significant decrease in retinal activity. Laboratory examinations revealed 52% increase in prothrombin time, prolongation of activated partial thromboplastin time to 1.3 times the normal and rise of aspartate aminotransferase to 120 IU/L. In addition, creatine kinase peaked at 904 IU/L. Moreover, normocytic normochromic anemia with hemoglobin at 10.7 mg/L and leukocytosis with lymphocytic predominance was noted. The patient received glucocorticoids, vitamin B12 and vitamin K and was discharged after correction of blood and coagulation parameters and normalization of liver enzymes. Partial recovery in visual acuity was found two months after ingestion of the last dose. Discussion: Closantel can cause significant spongiform change (intra-myelin vacuolation) in the white matter of the cerebrum and the cerebellum. It can also induce optic nerve damage as a result of Wallerian degeneration, fibrosis and atrophy. On the retina, closantel leads to papilledema, necrosis of the outer layers, and retinal detachment. It can also cause fatty change and hydropic degeneration in the liver and hepatocellular degeneration. Conclusion: Closantel is a toxic drug for humans causing blindness, hematologic and hepatic disorders. Public awareness should be raised regarding the risks of use of unapproved drugs for human. [ABSTRACT FROM AUTHOR]

The strategic use of single therapeutic doses of closantel, tetramisole or sustained low-level administration of albendazole in feed pellets in controlling naturally acquired parasitic gastroenteritis in sheep was investigated on a farm in semi-arid Rajasthan, India. A total of 303 5- to 6-month-old sheep were divided into three groups. Two groups were dosed with single therapeutic doses of closantel and tetramisole and the third group was given a low-level medication with albendazole through feed pellets for 30 days. Faecal egg counts revealed significantly lower counts (p<0.001) in the group treated with closantel compared to the other two groups. The faecal egg counts in the group receiving sustained low-level albendazole rose after withdrawal of the medication but remained significantly lower than those in the group treated with tetramisole up to 7 weeks after treatment (p<0.05). On the other hand, in the group treated with tetramisole, the mean faecal egg count rose from 3 weeks after treatment and remained continuously higher than those in any other group up to 12 weeks after treatment. The closantel-treated group gained more body weight but the first six-monthly greasy fleece yield was greater in the group treated with medicated pellets. During the first 3 months of the experiment, three animals in the group treated with tetramisole died of parasitic gastroenteritis. Following sustained low-level administration of albendazole in feed pellets, the plasma disposition curve of both the sulphoxide and sulphone metabolites reached its plateau level by day 5 and remained almost constant thereafter. The comparative cost-effectiveness of the three treatment regimes during the first 3 months of treatment was best for the group treated with closantel followed by the group treated with medicated feed pellets. [ABSTRACT FROM AUTHOR]

The strategic use of closantel, a narrow-spectrum salicylanilide anthelmintic against bloodsucking helminths, and of albendazole, a broad-spectrum benzimidazole anthelmintic, in the control of gastrointestinal nematodes of sheep was investigated on a farm in Nyandarua District in the highlands of Kenya. Thirty Corriedale female lambs aged between 9 and 12 months were assigned to three treatment groups of 10 lambs each. The three groups were set stocked on separate paddocks for 12 months. Lambs in group 1 (strategic treatment group) were treated with closantel and albendazole at the beginning and towards the end of the long rains (April and June, respectively) and towards the end of the short rains (December). During the intervening dry season, the lambs were treated with albendazole. Lambs in group 2 (suppressive treatment group) were kept ‘worm free’ by regular deworming with albendazole at 3-weekly intervals for 12 months. The third group of lambs remained untreat ed (control group). Gastrointestinal nematode infections and pasture infectivity were well controlled in the case of the strategic treatment group. This resulted in higher weight gains, wool production, packed cell volume, and serum albumin and protein concentrations compared with the untreated control lambs. These parameters were comparable between the strategic treatment and the suppressive treatment groups of lambs. It was concluded that worm control strategies based on the epidemiology of the parasites and the sustained anthelmintic action of closantel in combination with broad-spectrum anthelmintics can provide effective control of gastrointestinal nematodes of sheep in the study area. [ABSTRACT FROM AUTHOR]

Multiple resistance to albendazole, thiophanate, levamisole and orally administered ivermectin was detected in an isolate of Haemonchus contortus in sheep on a farm where benzimidazole resistance had already been identified. Following a faecal egg count reduction test, this was confirmed by both critical and controlled anthelmintic tests. Different groups of sheep infected naturally or given an experimental infection with the benzimidazole-resistant isolate were treated with the recommended doses of various anthelmintics. Compared to the control group, the percentage reductions in the faecal egg counts of sheep treated with albendazole, thiophanate, levamisole and ivermectin varied between 38.2% and 79.1% and the residual worm counts between 27.3% and 57.5%. The results indicate the presence of multiple anthelmintic resistance in this isolate of H. contortus. Sheep treated with closantel showed 100% reductions in faecal egg and worm counts, indicating that this drug was very effective against the population of H. contortus on the farm. [ABSTRACT FROM AUTHOR]

A molecularly imprinted polymer (MIP) for the selective solid-phase extraction (SPE) was prepared applying polymerization of pyrrole monomer in the presence of closantel (CLS) as a template molecule. The quantitative measurements were carried out using UV–Vis spectrophotometry. Several important parameters control the performance of polypyrrole sorbent. The influence of seven factors including loading time, polymerization time, amount of sorbent, stirring rate, desorption time, initiator concentration and monomer to template ratio were investigated. The optimization of parameters was performed using Plackett–Burman design (PBD), central composite design (CCD), artificial neural network (ANN) and genetic algorithm (GA). The Pareto plot showed that the effects of loading time, reaction time and amount of sorbent are most important to the process. These significant factors were investigated using CCD and the obtained data were used to train the ANN. The predicted model obtained from the trained ANN was introduced to GA as the fitness function to be optimized. The calibration curve demonstrated linearity over a concentration range of 0.010–10 mM with a correlation coefficient (R 2) of 0.9833 under optimal condition. The synthesized MIP sorbent showed a good selectivity and sensitivity toward CLS. The limit of detection (LOD) for CLS was obtained 1.0 μM. The real sample analysis was performed to determine CLS in pharmaceutical and human serum samples. Unlabelled Image • A molecularly imprinted polymer for closantel was prepared. • The optimization was performed using PBD, CCD, ANN and GA. • Closantel in pharmaceutical and biological samples was determined. [ABSTRACT FROM AUTHOR]