fenbendazole

芬苯达唑
  • 文章类型: Journal Article
    根据CPGSec615.115,在美国,用于野鸡的处方芬苯达唑含药饲料被认为是标签外药物使用,并且必须在对该次要食品施用后使用安全的估计戒断间隔(WDI)生产物种。这项研究旨在确定芬苯达唑及其主要代谢产物的药代动力学和残留消耗曲线,以估计芬苯达唑作为口服药物饲料给药后野鸡的WDI。
    野鸡(n=32)作为口服药物饲料(100ppm)给药7天。芬苯达唑,芬苯达唑亚砜,使用HPLC-UV分析肝脏和肌肉样品中的芬苯达唑砜(FBZ-SO2)。使用FDA估计组织WDI,欧洲药品管理局(EMA)和美国家禽耐受性的半衰期倍增方法,EMA最大残留限值,和分析检测限(LOD;0.004ppm)。终末组织消除半衰期(T1/2)通过非房室分析使用初始汇集数据方法来估计。
    肝脏组织T1/2为14.4h,大腿肌肉13.2h,胸肌为14.1小时。使用FDA耐受方法,胸肌FBZ-SO2的最大估计戒断间隔为153小时(7天)(第99百分位数的95%置信区间),和LOD作为残留限制。
    本研究的结果支持使用FBZ-SO2作为鸡肝脏中的标记物残留物,并在标签外施用芬苯达唑含药饲料(100ppm)7天后提供基于证据的WDI。
    UNASSIGNED: Prescribing fenbendazole medicated feed for pheasants in the USA is considered extra-label drug use under CPG Sec 615.115, and a safe estimated withdrawal interval (WDI) must be applied following administration to this minor food-producing species. This study sought to determine the pharmacokinetic and residue depletion profile for fenbendazole and its major metabolites to estimate a WDI for pheasants following fenbendazole administration as an oral medicated feed.
    UNASSIGNED: Pheasants (n = 32) were administered fenbendazole as an oral medicated feed (100 ppm) for 7 days. Fenbendazole, fenbendazole sulfoxide, and fenbendazole sulfone (FBZ-SO2) in liver and muscle samples were analyzed using HPLC-UV. Tissue WDIs were estimated using FDA, European Medicines Agency (EMA), and half-life multiplication methods for US poultry tolerances, EMA maximum residue limits, and the analytical limit of detection (LOD; 0.004 ppm). Terminal tissue elimination half-lives (T1/2) were estimated by non-compartmental analysis using a naïve pooled data approach.
    UNASSIGNED: The tissue T1/2 was 14.4 h for liver, 13.2 h for thigh muscle, and 14.1 h for pectoral muscle. The maximum estimated withdrawal interval was 153 h (7 days) for FBZ-SO2 in pectoral muscle using the FDA tolerance method (95% confidence interval for the 99th percentile of the population), and the LOD as the residue limit.
    UNASSIGNED: The results from this study support the use of FBZ-SO2 as the marker residue in the liver of pheasants and the provision of evidence based WDIs following the extra-label administration of fenbendazole medicated feed (100 ppm) for 7 days.
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  • 文章类型: Journal Article
    背景:虚假的健康相关新闻通过互联网迅速传播,对个人和社会造成伤害。尽管采取了干预措施,芬苯达唑丑闻最近在韩国肺癌患者中传播。适当干预以防止假新闻的传播至关重要。
    目的:本研究调查了干预措施的适当时机,以最大程度地减少假新闻的副作用。
    方法:使用易感感染恢复(SIR)模型进行了模拟,这是典型的病毒传播机制。我们将该模型应用于假新闻传播机制。参数设置类似于数字环境中的参数,芬苯达唑丑闻发生的地方。NetLogo,基于代理的模型,被用作分析工具。
    结果:假新闻在没有干预的情况下持续了278天。由于调整和分析了因芬苯达唑丑闻的干预时间,我们发现,更快的干预导致假新闻持续时间更短(54天的干预=持续210天的假新闻;16天的干预=持续187天的假新闻;10天的干预=持续157天的假新闻)。然而,在10天内进行干预时,没有观察到显著差异.
    结论:在10天内实施的干预措施有效地减少了假新闻传播的持续时间。我们的研究结果表明,及时的干预对于防止假新闻在数字环境中的传播至关重要。此外,应该开发一个可以检测假新闻的监控系统,以便做出快速反应。
    BACKGROUND: Fake health-related news has spread rapidly through the internet, causing harm to individuals and society. Despite interventions, a fenbendazole scandal recently spread among patients with lung cancer in South Korea. It is crucial to intervene appropriately to prevent the spread of fake news.
    OBJECTIVE: This study investigated the appropriate timing of interventions to minimize the side effects of fake news.
    METHODS: A simulation was conducted using the susceptible-infected-recovered (SIR) model, which is a representative model of the virus spread mechanism. We applied this model to the fake news spread mechanism. The parameters were set similarly to those in the digital environment, where the fenbendazole scandal occurred. NetLogo, an agent-based model, was used as the analytical tool.
    RESULTS: Fake news lasted 278 days in the absence of interventions. As a result of adjusting and analyzing the timing of the intervention in response to the fenbendazole scandal, we found that faster intervention leads to a shorter duration of fake news (intervention at 54 days = fake news that lasted for 210 days; intervention at 16 days = fake news that lasted for 187 days; and intervention at 10 days = fake news that lasted for 157 days). However, no significant differences were observed when the intervention was performed within 10 days.
    CONCLUSIONS: Interventions implemented within 10 days were effective in reducing the duration of the spread of fake news. Our findings suggest that timely intervention is critical for preventing the spread of fake news in the digital environment. Additionally, a monitoring system that can detect fake news should be developed for a rapid response.
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  • 文章类型: Journal Article
    Oxyspirurapetrowi是一种异氧线虫,可感染鸟类的Harderian腺和其他眼部组织。高强度感染通常会对感染组织造成损害。由于感染部位的性质,在这些宿主中治疗O.petrowi可能很困难。芬苯达唑(FBZ)是一种常见的驱虫药,用于治疗鸟类的蠕虫感染;但是,关于该药物对O.petrowi感染的疗效的信息很少。本研究旨在估计FBZ对O.petrowi的致死浓度。将成年O.petrowi维持在体外,并暴露于5、50、100和200μM浓度的FBZ剂量,并包括阴性和媒介物对照。暴露持续7.5天,并确定每种治疗的致死率。阴性和车辆控制没有差异,在治疗期结束时,两者均有75%的生存率。按浓度升序排列的存活率百分比,针对控件进行了更正,为66.67%,44.44%,33.33%,和0%。LC10、LC50和LC90估计值分别为7.5±0.26、49.1±1.69和163.2±5.63µM,分别。在已知的FBZ在鸟类中的药代动力学的背景下,单次口服FBZ可以达到对O.petrowi致命的暴露水平,但是药物在系统中停留的时间不够长。因此,治疗O.petrowi感染需要在几天内多次口服剂量。
    Oxyspirura petrowi is a heteroxenous nematode that infects the harderian gland and other ocular tissues in birds. High-intensity infections often cause damage to the infected tissues. Due to the nature of the infection sites, treatment of O. petrowi in these hosts can be difficult. Fenbendazole (FBZ) is a common anthelmintic used to treat birds for helminth infections; however, little information exists as to the efficacy of the drug on O. petrowi infections. The present study aims to estimate lethal concentrations of FBZ to O. petrowi. Adult O. petrowi were maintained in vitro and exposed to doses of 5, 50, 100, and 200 µM concentrations of FBZ and included both negative and vehicle controls. Exposure lasted 7.5 days and lethality was determined for each treatment. Negative and vehicle controls did not differ, and both had 75% survival at the end of the treatment period. The percentage survivorship in ascending order of concentration, corrected for the controls, was 66.67%, 44.44%, 33.33%, and 0%. LC10, LC50, and LC90 estimates were 7.5 ± 0.26, 49.1 ± 1.69, and 163.2 ± 5.63 µM, respectively. In the context of known pharmacokinetics of FBZ in birds, a single oral dose of FBZ can achieve exposure levels that are lethal to O. petrowi, but the drug does not stay in the system long enough. Thus, treatment of O. petrowi infections will require multiple oral doses over several days.
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  • 文章类型: Journal Article
    该研究旨在评估五种不同抗寄生虫药物的治疗浴的效果,在不同的浴和持续时间:芬苯达唑(25mgl-1、12h和2×12h),甲醛(0.17mll-1,15分钟),伊维菌素(0.031mgl-1,1小时),甲苯咪唑(1mgl-1,12h)和左旋咪唑(50mgl-1,2h和3×1h)降低了幼鱼单基因感染(Dactylogyrusanchoratus)的强度和患病率。用甲醛浴(0.17mll-1,15分钟)和芬苯达唑(25mgl-1,2×12小时,24小时中断)达到了降低寄生虫数量的最佳效果,感染减少了90%以上。具有芬苯达唑活性物质的注册兽药(VMPs)可以成功替代未注册的甲醛用于治疗单基因感染。
    The study aimed to assess the effects of a therapeutic bath of five different antiparasitic drugs, in different baths and durations: fenbendazole (25 mg l-1, 12 h and 2 × 12 h), formaldehyde (0.17 ml l-1, 15 min), ivermectin (0.031 mg l-1, 1 h), mebendazole (1 mg l-1, 12 h) and levamisole (50 mg l-1, 2 h and 3 × 1 h) on the reduction on the intensity and prevalence of a monogenean infection (Dactylogyrus anchoratus) in juvenile carp. The best effect on reducing the parasite number was achieved with the bath in formaldehyde (0.17 ml l-1, 15 min) and fenbendazole (25 mg l-1, 2 × 12 h with 24 h break), where the infection was reduced by more than 90%. Registered veterinary medicinal products (VMPs) with the active substance of fenbendazole can successfully replace the use of unregistered formaldehyde in the treatment of monogenean infections.
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  • 文章类型: Journal Article
    作为口服有效的苯并咪唑驱虫药,芬苯达唑不仅在农业和畜牧业中广泛用于预防和治疗寄生虫,而且还显示了对几种癌症的抗癌作用,在紫杉醇和多柔比星耐药的癌细胞中表现出抗癌作用。然而,芬苯达唑水溶性差(0.3µg/mL),限制了其临床应用。甚至为提高其水溶性做出了巨大的努力,结果对于达到抗癌药物递送要求(5-10mg/mL)并不显著.通过单因素和正交策略,许多复杂的条件被设计和使用来制备复合物,包合物与甲基-β-环糊精的包合率为29.2%,包合收率为89.5%,可将药物的水溶性提高到20.21mg/mL,这是迄今为止最好的结果。通过差示扫描量热法证实了其结构,扫描电子显微镜图像,在D2O中的1D和2DNMR光谱。在其体外药代动力学研究中,芬苯达唑在15分钟内释放75%。,在体内药代动力学研究中,芬苯达唑的生物利用率,其主要代谢驱虫药奥芬达唑和次要代谢驱虫药奥芬达唑增加到138%,分别为149%和169%,这将允许更少的药物剂量来实现相同的治疗效果,并表明该复合物可以用作潜在的抗癌剂。
    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-β-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.
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  • 文章类型: Journal Article
    绵羊寄生胃肠线虫的抗蠕虫性普遍存在,是一个严重的健康和经济问题,但德国的耐药性和相关寄生虫种类尚不清楚。这里,使用芬苯达唑对八个农场进行了粪便卵数减少试验(FECRT),伊维菌素和莫西丁,四个农场只使用莫西丁。使用问卷调查来获取有关管理实践的数据,以潜在识别存在耐药性的风险因素。应用了最近修订的WAAVP指南中使用FECRT诊断驱虫药耐药性的所有要求。用线虫组方法分析了处理前和后处理样品中的线虫物种组成。使用eggCounts统计包,对芬苯达唑的耐药性,伊维菌素和莫西丁在7/8、8/8和8/12农场发现,分别。没有进行正式的风险因素分析,因为大多数农场都存在耐药性。与贝叶斯计数R包结果的比较表明,方法之间有很大的一致性(科恩κ=0.774)。相比之下,对修订后的WAAVP指南和原始指南进行比较的数据解释得出了中等一致性(科恩κ=0.444)。莫昔克丁的FECR明显高于伊维菌素和芬苯达唑。Nemabiome数据确定了预处理样品中的4至12个物种,并且处理导致了物种多样性的小幅但显着下降(辛普森指数倒数)。使用非度量多维缩放和k均值聚类来识别治疗前和治疗后样品中的常见模式。然而,处理后样品分散在处理前样品中。农场之间的抗性寄生虫种类不同。总之,修订后的FECRT指南允许可靠地检测驱虫药耐药性.抗药性广泛存在,涉及多种寄生虫。在同一农场对两种药物的耐药性很普遍。进一步的研究,包括额外的药物(左旋咪唑,monepantel,closantel)应将敏感的FECRT与线虫组数据结合起来,以全面表征德国绵羊线虫的驱虫敏感性状况。
    Anthelmintic resistance in sheep parasitic gastrointestinal nematodes is widespread and a severe health and economic issue but prevalence of resistance and involved parasite species are unknown in Germany. Here, the faecal egg count reduction test (FECRT) was performed on eight farms using fenbendazole, ivermectin and moxidectin and on four farms using only moxidectin. A questionnaire was used to obtain data on management practices to potentially identify risk factors for presence of resistance. All requirements of the recently revised WAAVP guideline for diagnosing anthelmintic resistance using the FECRT were applied. Nematode species composition in pre- and post-treatment samples was analysed with the nemabiome approach. Using the eggCounts statistic package, resistance against fenbendazole, ivermectin and moxidectin was found on 7/8, 8/8 and 8/12 farms, respectively. No formal risk factor analysis was conducted since resistance was present on most farms. Comparison with the bayescount R package results revealed substantial agreement between methods (Cohen\'s κ = 0.774). In contrast, interpretation of data comparing revised and original WAAVP guidelines resulted in moderate agreement (Cohen\'s κ = 0.444). The FECR for moxidectin was significantly higher than for ivermectin and fenbendazole. Nemabiome data identified 4 to 12 species in pre-treatment samples and treatments caused a small but significant decrease in species diversity (inverse Simpson index). Non-metric multidimensional scaling and k-means clustering were used to identify common patterns in pre- and post-treatment samples. However, post-treatment samples were scattered among the pre-treatment samples. Resistant parasite species differed between farms. In conclusion, the revised FECRT guideline allows robust detection of anthelmintic resistance. Resistance was widespread and involved multiple parasite species. Resistance against both drug classes on the same farm was common. Further studies including additional drugs (levamisole, monepantel, closantel) should combine sensitive FECRTs with nemabiome data to comprehensively characterise the anthelmintic susceptibility status of sheep nematodes in Germany.
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  • 文章类型: Journal Article
    生物标志物是特定的分子,组织学,或正常或致病性生物过程的生理特征,并且在胃肠道线虫(GINs)的诊断中很有前途。尽管一些生物标志物已被Ostertagiasp。在温带地区饲养的牛中,热带地区缺乏信息。该项目的目的是评估潜在的生物标志物并验证最有希望的生物标志物。在第一项研究中,自然感染GINs的36头牛(Nelore品种)分为两组:感染(未用驱虫药治疗)和治疗(在第0、7、14、21、28、42和56天用芬苯达唑治疗)。感兴趣的变量是活体重,粪便卵数,血象,血清生化标志物,磷,胃泌素,和胃蛋白酶原。第二步,在Nelore品种的牛中评估了胃蛋白酶原,分布在三组中:感染(未用驱虫药治疗),MOX(用莫西丁治疗),和IVM+BZD(用伊维菌素+阿苯达唑处理)。在第一项研究中,两组之间的体重没有差异,白蛋白,血细胞比容(红细胞体积[CV]),红细胞,或血红蛋白。发现胃蛋白酶原与CV和白蛋白之间呈负相关,白蛋白与Haemonchussp的百分比呈负相关。在粪便培养中。在生物标志物中,只有胃蛋白酶原分化治疗和感染(从研究的第28天开始)。在第二项研究中,驱虫治疗后发现胃蛋白酶原减少。因此,胃蛋白酶原是热带地区自然感染Haemonchus和Cooperia的牛中蠕虫的有希望的生物标志物。
    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.
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  • 文章类型: Case Reports
    芬苯达唑是一种批准用于兽医应用的驱虫药。即使它没有被美国食品和药物管理局批准用于人类使用,由于芬苯达唑的潜在抗癌作用在社交媒体上的普及,这种用途似乎正在增加。我们描述了第一例组织学证实的严重药物性肝损伤,肝细胞模式,与一名出现2周黄疸的67岁女性的芬苯达唑自我给药有关。停止芬苯达唑后3个月肝功能检查恢复正常。
    Fenbendazole is an anthelmintic agent approved for veterinary applications. Even though it is not approved by the US Food and Drug Administration for human use, such use appears to be increasing due to the popularization of fenbendazole\'s potential anticancer effects by social media. We describe the first case of histologically confirmed severe drug-induced liver injury, hepatocellular pattern, associated with the self-administration of fenbendazole in a 67-year-old woman who presented with 2 weeks of jaundice. Liver function tests normalized in 3 months after the cessation of fenbendazole.
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  • 文章类型: Journal Article
    新生隐球菌每年造成超过10万人死亡,这种真菌病的治疗是昂贵的,并不总是有效的。揭开新的治疗途径至关重要。以前的研究表明,驱虫药芬苯达唑是一种负担得起的无毒候选药物,可以对抗隐球菌病。然而,它的抗癌作用机制仅得到了肤浅的研究。在这项研究中,我们使用蛋白质组学方法(数据可通过具有标识符PXD047041的ProteomeXchange获得)检查了新生梭菌对芬苯达唑的总体细胞反应。芬苯达唑治疗主要影响与代谢途径相关的蛋白质的丰度,RNA加工,和细胞内交通。蛋白激酶,特别是,均受到芬苯达唑治疗的显著影响。使用一组新生梭菌突变体对蛋白质组学数据进行实验验证,从而鉴定了五种蛋白激酶在芬苯达唑抗真菌活性中的关键作用。事实上,与野生型细胞相比,缺乏编码Chk1,Tco2,Tco3,Bub1和Sch9激酶的基因表达的突变体对芬苯达唑具有更大的抗性。与标准抗真菌药物两性霉素B联合使用,芬苯达唑降低了小鼠的隐球菌负担。这些发现不仅有助于阐明芬苯达唑的作用方式,而且支持其与两性霉素B联合治疗的应用。我们的数据表明,芬苯达唑有望进一步发展为一种抗肿瘤药。
    Cryptococcus neoformans is responsible for over 100 000 deaths annually, and the treatment of this fungal disease is expensive and not consistently effective. Unveiling new therapeutic avenues is crucial. Previous studies have suggested that the anthelmintic drug fenbendazole is an affordable and nontoxic candidate to combat cryptococcosis. However, its mechanism of anticryptococcal activity has been only superficially investigated. In this study, we examined the global cellular response of C. neoformans to fenbendazole using a proteomic approach (data are available via ProteomeXchange with identifier PXD047041). Fenbendazole treatment mostly impacted the abundance of proteins related to metabolic pathways, RNA processing, and intracellular traffic. Protein kinases, in particular, were significantly affected by fenbendazole treatment. Experimental validation of the proteomics data using a collection of C. neoformans mutants led to the identification of critical roles of five protein kinases in fenbendazole\'s antifungal activity. In fact, mutants lacking the expression of genes encoding Chk1, Tco2, Tco3, Bub1, and Sch9 kinases demonstrated greater resistance to fenbendazole compared to wild-type cells. In combination with the standard antifungal drug amphotericin B, fenbendazole reduced the cryptococcal burden in mice. These findings not only contribute to the elucidation of fenbendazole\'s mode of action but also support its use in combination therapy with amphotericin B. In conclusion, our data suggest that fenbendazole holds promise for further development as an anticryptococcal agent.
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  • 文章类型: Case Reports
    这项研究评估了2023年3月至12月在法国疾驰的赛马种马农场中,强线虫对常用驱虫(AH)药物的驱虫抗性。在三组不同的纯种一岁鸟(一组6只雄性,一组13名女性和一组8名女性和3名男性)遵循新的世界兽医寄生虫学促进协会(WAAVP)指南。监测期间(3月)对两组患者进行一次芬苯达唑的疗效检测,伊维菌素3组2次(3-4月和11-12月),吡喃酮1组1次(5-6月)。对于每个FECRT,使用混合Frequentist/Bayesian分析方法计算粪便卵数减少百分比的90%置信区间。观察到强叶黄素对芬苯达唑的抗性,吡喃酮和伊维菌素在所有这些药物的测试组中。每组中的动物数量足以达到抗性测试的≥80%功率。结果突出了法国强黄体中三重AH抗性的首例。需要进行涉及更多农场和马匹的进一步研究,以评估法国AH抗性的流行程度,并为业主提出建议。
    This study assessed the anthelmintic resistance in strongylid nematodes against commonly used anthelmintic (AH) drugs in a French galloping racehorse stud farm from March to December 2023. Faecal egg count reduction tests (FECRTs) were conducted in three different groups of Thoroughbred yearlings (a group of 6 males, a group of 13 females and a group of 8 females and 3 males) following the new World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines. The efficacy of fenbendazole was tested in two groups once during the monitoring period (in March), the efficacy of ivermectin in 3 groups twice (in March-April and in November-December) and the efficacy of pyrantel in one group once (in May-June). For each FECRT, the 90% confidence interval of the percentage faecal egg count reduction was calculated using the hybrid Frequentist/Bayesian analysis method. The resistance in strongylids was observed to fenbendazole, pyrantel and ivermectin in all the groups in which these drugs were tested. The number of animals in each group was sufficient to reach ≥80% power for the resistance test. The results highlight the first case of triple AH resistance in strongylids in France. Further studies involving more farms and equids are required to assess the prevalence of AH resistance in France and refine recommendations for owners.
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