Reduction of egg reappearance period of cyathostomins in naturally infected horses after increasing doses of ivermectin in Brazil: a grim picture for sustainable parasite control.

Cyathostomins are the largest group of parasites in horses that can be controlled by ivermectin (IVM). This study aimed to run a four-dose titration trial of IVM in 28 naturally infected Thoroughbred yearlings. The local Strongyle population had been recorded to be resistant to IVM (200 µg/kg). The parasite fecal egg count (FEC) was performed to investigate the egg reappearance period (ERP) of two and five weeks (w2pt and w5pt) after IVM treatment. FEC was > 1000 on day zero for all groups. Although 100% FEC reduction was reported at w2pt for all concentrations, the FEC at w5pt revealed < 83% efficacy. This study reports the reduction of ERP using the label dose as well as 300, and 400 µg/kg (double dose) of IVM. The protocol allowed IVM to significantly suppress FEC w2pt although not eliminating adult worms, failing to guarantee an extension of its protection period over 8 weeks. Moreover, the FEC at w5pt possibly means the infection was not cleared, and worms reestablished egg laying. We raised the possibility of withdrawing IVM of control programs when the drug has less than 80% FEC reduction at w5pt.

First report of ivermectin resistance in cyathostomins (small strongyles) of horses in Argentina.

In Argentina, as in the rest of the world, cyathostomins are the most common nematodes parasitizing horses. Control is based almost exclusively on the administration of benzimidazoles, pyrimidines, and macrocyclic lactones. However, intensive use of these drugs is resulting in the development of anthelmintic resistance (AR). For example, AR to benzimidazoles is currently distributed throughout Argentina, while incipient AR to pyrimidines (pyrantel embonate) is appearing in areas where this drug is used. Macrocyclic lactones and especially ivermectin, are by far the most used drugs by the vast majority of equine premises in the country. Although ivermectin has been used since 1982, its efficacy against equine strongylid parasites has remained very high until the present. In this study we report for the first time, the presence of a cyathostomin population with resistance to ivermectin in adult horses belonging to an equine premise located in central Argentina. Fecal egg count reduction tests (FECRT) were performed following the most recent guidelines of the World Association for the Advancement of Veterinary Parasitology (WAAVP) for the diagnosis of anthelmintic resistance (research protocol) and resistance was considered when the Upper 90% Credible Interval fell below the expected efficacy threshold of 99.9%. Calculations were carried out using two different online calculation interfaces suggested by WAAVP. For the 14-day post-treatment interval, ivermectin efficacy was 79.5% (90% Credible Interval: 68.1-88.8) and 79.3% (74.2-83.6.3%) with the two methods, respectively. At 19 days post treatment, fecal egg count reductions were 68.6% (50.5-83.1) and 68.4% (61.9-74.1), respectively. At both intervals, this cyathostomin population fullfilled the criteria for AR. These findings suggest dispersion of ivermectin resistant cyathostomins in Argentina. Given the widespread use of macrocyclic lactones, it is important that veterinarians and the equine industry promote a more selective and evidence-based use of these drugs and establish routine monitoring to determine anthelmintic field efficacy to detect treatment failures as early as possible and avoid potential health problems as well as further spread of resistant genes.

Feasibility of selective anthelmintic therapy to horses in tropical conditions: the Cuban scenario.

For the past several decades, selective anthelmintic therapy (SAT) has been recommended in temperate climate countries for controlling gastrointestinal parasites in horses. However, the feasibility of this approach in tropical climates remains unknown, given the very different parasite transmission patterns and a larger representation of working equids. The aim of this study was to evaluate the bio-economic feasibility of SAT in horses kept under tropical conditions of Camagüey, Cuba. Fecal egg counts were determined from 794 adult horses and used for evaluating three different putative treatment thresholds; > 500 strongylid eggs per gram of feces (EPG); > 1000 EPG; and treatments yielding > 80% of the total herd egg output. These scenarios were evaluated under three treatment frequencies (every 2, 6, and 12 months). The bio-economic feasibility of these nine possible selective anthelmintic therapy scenarios was evaluated taking into account the cost of parasitological tests, and the mean cost of anthelmintic treatment in Camagüey. The majority (96.7%) of the samples tested were positive for strongyle eggs, with a mean of 1549 EPG. The percentage of horses exceeding the cut-off points at the nine scenarios varied between 40.1 and 93.8%. All owners surveyed used extra-label anthelmintic product in their horses on a routine basis. The economic analysis demonstrated that selective therapy generally was much more costly than deworming the entire herd without determining egg counts. However, we consider that the deworming every 6 months of the horses that expel 80% of the eggs in the herd allows a reduction of the treatment intensity without increasing costs, and it can be considered as a viable selective deworming scheme under similar conditions.

Multiple resistance in equine cyathostomins: a case study from military establishments in Rio Grande do Sul, Brazil.

Semi-intensive equine breeding system favors gastrointestinal nematode infections. The treatment of these infections is based on the use of anthelmintics. However, the inappropriate use of these drugs has led to parasitic resistance to the available active principles. The objective of this study was to evaluate the efficacy of the main classes of antiparasitic (ATP) used in control in adult and young animals, including: benzimidazoles (fenbendazole), pyrimidines (pyrantel pamoate), macrocyclic lactones (ivermectin and moxidectin), as well as the combination of active ingredients (ivermectin + pyrantel pamoate). The study was carried out in two military establishments, located in Rio Grande do Sul (RS), from January to December, 2018. The intervals between the treatments of the animals were performed from 30 to 90 days. Coproparasitological evaluations were determined by the egg count reduction in the faeces. Cyatostomine larvae were identified in pre and post-treatment cultures. The results demonstrated the multiple parasitic resistance of cyathostomins to fenbendazole, moxidectin in young animals, and to fenbendazole, pyrantel pamoate in adult animals. Thus, it is necessary to define or diagnose parasitic resistance to assist in the creation of prophylactic parasitic control, using suppressive treatment with ATP associated with integrated alternatives. The progress of parasitic resistance can be slowed.

Eficacy of ivermectin, moxidectin and febendazole in equine in Brazil.

The objectives of the present study were to evaluate the efficacy of three anthelmintic drugs, i.e. fenbendazole, ivermectin and moxidectin; to determine the genera and species of the most abundant strongyles; and to investigate parasite control measures used in herds of horses in the western region of the state of São Paulo, Brazil. This study was onducted between February and December 2013 on 10 farms in this region. Coprological evaluations were conducted for counting the numbers of eggs per gram of feces (EPG) and coprocultures were made in order to identify third-stage larvae (L3) of strongyles. Parasite control measures were investigated by surveying each farm's management and characteristics. A fecal egg count reduction test (FECRT) was used to determine the anthelmintic efficacy based on EPG count results before and after treatment. The FECRT showed that anthelmintic resistance to fenbendazole was present and that ivermectin and moxidectin had high effectiveness in the western region of the state of São Paulo. Identification of L3 revealed that there was high prevalence of cyathostomins among strongyle larvae. The highest prevalence of Strongylus vulgaris occurred on farms where the intervals between deworming were long. The questionnaire applied showed that ivermectin was the drug most used among these farmers.

Multiple resistance in equine cyathostomins: a case study from military establishments in Rio Grande do Sul, Brazil / Múltipla resistência de ciatostomíneos de equinos: um estudo de caso em estabelecimentos militares no Rio Grande do Sul, Brasil

Abstract Semi-intensive equine breeding system favors gastrointestinal nematode infections. The treatment of these infections is based on the use of anthelmintics. However, the inappropriate use of these drugs has led to parasitic resistance to the available active principles. The objective of this study was to evaluate the efficacy of the main classes of antiparasitic (ATP) used in control in adult and young animals, including: benzimidazoles (fenbendazole), pyrimidines (pyrantel pamoate), macrocyclic lactones (ivermectin and moxidectin), as well as the combination of active ingredients (ivermectin + pyrantel pamoate). The study was carried out in two military establishments, located in Rio Grande do Sul (RS), from January to December, 2018. The intervals between the treatments of the animals were performed from 30 to 90 days. Coproparasitological evaluations were determined by the egg count reduction in the faeces. Cyatostomine larvae were identified in pre and post-treatment cultures. The results demonstrated the multiple parasitic resistance of cyathostomins to fenbendazole, moxidectin in young animals, and to fenbendazole, pyrantel pamoate in adult animals. Thus, it is necessary to define or diagnose parasitic resistance to assist in the creation of prophylactic parasitic control, using suppressive treatment with ATP associated with integrated alternatives. The progress of parasitic resistance can be slowed.

Resumo O sistema semi-intensivo de criação de equinos favorece infecções por nematoides gastrointestinais. O tratamento dessas infecções é baseado no uso de anti-helmínticos. No entanto, o uso inadequado desses medicamentos levou à resistência parasitária aos princípios ativos disponíveis. O objetivo deste estudo foi avaliar a eficácia das principais classes de antiparasitários (ATP), utilizados no controle em animais adultos e jovens, incluindo: benzimidazois (fenbendazol), pirimidinas (pamoato de pirantel), lactonas macrocíclicas (ivermectina e moxidectina), bem como a combinação de ingredientes ativos (ivermectina + pamoato de pirantel). O estudo foi realizado em dois estabelecimentos militares, localizados no Rio Grande do Sul (RS), de janeiro a dezembro de 2018. Os intervalos entre os tratamentos foram realizados de 30 a 90 dias. As avaliações coproparasitológicas foram determinadas pela redução da contagem de ovos nas fezes. Foram identificadas larvas de ciatostomíneos nas coproculturas pré e pós tratamentos. Os resultados demonstraram a resistência parasitária múltipla dos ciatostomíneos ao fenbendazol, moxidectina em animais jovens, febendazole e pamoato de pirantel em animais adultos. Estabelecer o diagnóstico da resistência parasitária auxiliará na elaboração de um controle parasitário profilático, reduzindo o tratamento supressivo com ATP juntamente com alternativas de controle integrado. Dessa forma, o avanço da resistência parasitária poderá ser retardado.

First report of anthelmintic resistance of equine cyathostomins in Cuba.

Anthelmintic resistance in equine cyathostomins has been described worldwide, with resistance to the benzimidazole class being particularly widespread. The status of anthelmintic efficacy in Cuba has been virtually unknown due to the lack of equine labelled products. One recent report documented suboptimal efficacy levels of extra-label albendazole products against cyathostomins, but it remains unknown to which extent benzimidazole resistance exists in the population. The aim of the present study was to evaluate the anthelmintic efficacy of two benzimidazole products labelled for equines, fenbendazole and oxibendazole. A fecal egg count reduction test (FECRT) was carried out on 132 horses aged 4 months to 18 years in 14 herds, belonging to six provinces. Ten herds exhibited signs of resistance to at least one of the benzimidazoles (mean FECRT<90%). Overall, oxibendazole exhibited higher efficacy than fenbendazole (p = 0.0062), and higher efficacy levels were found in horses never dewormed before compared to those treated within 3-12 months prior to the study (p = 0.0015). Pre-treatment larval cultures revealed the presence of large strongyles and cyathostomin larvae in all herds, while only cyathostomin larvae were detected post treatment. The present work is the first report of anthelmintic resistance in equine cyathostomins in Cuba, and suggests pre-selection for resistant strains by extra-label use of albendazole on the studied farms.

The route of administration drastically affects ivermectin activity against small strongyles in horses.

The goal of the current study was to evaluate the comparative efficacy of ivermectin (IVM) against small strongyles (cyathostomins) following its oral and intramuscular (IM) administration, in naturally parasitized horses. The parasitological data were complemented with the assessment of the plasma disposition kinetics of IVM. The trial included two different experiments. In experiment I, 40 horses naturally infected with small strongyles were randomly allocated into four experimental groups (n=10) and treated with IVM (0.2mg/kg) as follows: IVM oral paste, animals were orally treated with Eqvalan® (IVM 1.87% paste, as the reference formulation) by the oral route; IVM oral solution, animals were orally treated with Remonta® (IVM 2% solution, as a test formulation); IVM IM solution, animals were IM treated with the test product (Remonta® IVM 2% solution); and control, animals were kept without treatment as untreated controls. In experiment II, 24 horses naturally parasitized with small strongyles were randomly allocated into the same four experimental groups (n=6) described for experiment I. Faecal samples were individually collected directly from the rectum of each horse prior (day -1) and at 7 and 15 (Experiment I) or 7, 15 and 21 (Experiment II) days after-treatment, to assess the eggs per gram (epg) counts and estimate the efficacy of the treatments. Additionally, the comparative plasma disposition kinetics of IVM in treated animals was assessed in experiment II. In both experiments, an excellent (100%) IVM efficacy was observed after its oral administration (test and reference formulations). However, the IM administration of IVM resulted in a low efficacy (36-64%). Similar IVM plasma concentration was observed after its oral administration as a paste or as a solution. The higher IVM plasma profiles observed after the IM administration accounted for an enhanced systemic availability. The improved IVM efficacy observed against adult cyathostomins after its oral administration can be explained by an enhanced drug exposure of the worms located at the lumen of the large intestine. These findings may have a direct impact on the practical use of macrocyclic lactones in horses.

Lack of Cyathostomin sp. reduction after anthelmintic treatment in horses in Brazil.

The increase of anthelmintic resistance in the last years in the nematode population of veterinary importance has become a major concern. The objective of the present study was to evaluate the efficacy of the main anthelmintic drugs available in the market against small strongyles of horses in Brazil. A total of 498 horses from 11 horse farms, located in the states of Paraná, São Paulo, Rio de Janeiro and Minas Gerais, in Brazil, were treated with ivermectin, moxidectin, pyrantel and fenbendazole, orally at their recommended doses. The fecal egg count reduction test (FECRT) was used to determine the product's efficacy and fecal culture was used to determine the parasite genus. Reduction on anthelmintic efficacy was found for fenbendazole in all horse farms (11/11), pyrantel in five yards (5/11) and ivermectin had low efficacy in one of the yards studied (1/11). Multidrug resistance of up to 3 drugs classes was found in one of the tested farms (1/11). Cyathostomin were the most prevalent parasite. The results showed that resistance to fenbendazole is widespread; the efficacy of pyrantel is in a critical situation. Although the macrocyclic lactones compounds still showed high efficacy on most farms, suspected resistance to macrocyclic lactones is of great concern.

Comparative performance of macrocyclic lactones against large strongyles in horses.

Several formulations of macrocyclic lactones (abamectin, ivermectin, moxidectin), including ivermectin combined with pyrantel (tetrahydropyrimidine) and ivermectin combined with praziquantel (pyrazinoisoquinolin derivative), were tested regarding their efficacy to control gastrointestinal nematodes of horses on a stud farm in southern Brazil. In addition, we tested a pharmaceutically produced generic paste containing ivermectin 4%. Similar formulations of avermectins had different efficacies measured by reduction of EPG. Levels of efficacy of the tested drugs varied against Strongylus edentatus, S. equinus and S. vulgaris. The generic paste (ivermectin 4%) was less effective than the conventional drugs.

Prevalence of strongyles and efficacy of fenbendazole and ivermectin in working horses in El Sauce, Nicaragua.

Horses, mules and donkeys are indispensable farming and working animals in many developing countries, and their health status is important to the farmers. Strongyle parasites are ubiquitous in grazing horses world-wide and are known to constitute a threat to equine health. This study determined the prevalence of strongyle infection, the efficacy of ivermectin and fenbendazole treatment, and strongyle re-infection rates of working horses during the dry months in Nicaragua. One hundred and five horses used by farmers for transport of people and goods were randomly allocated into three treatment groups, i.e., the IVM group treated with ivermectin, the FBZ group treated with fenbendazole and the control group treated with placebo. Determined by pre-treatment faecal egg counts (FECs), horses showed a high prevalence (94%) of strongyle parasites with high intensities of infection (mean FEC of 1117 eggs per gram (EPG) with an SD of 860 EPG, n=102). Body condition scores of all horses ranged from 1.5 to 3.5 with a mean of 2.4 (scales 1-5). Fourteen days after treatment faecal egg count reductions (FECRs) were 100% and 94% in the IVM and the FBZ groups, respectively. The egg reappearance period (ERP) defined as the time until the mean FEC reached 20% of the pre-treatment level, was estimated as 42 days for the FBZ group and 60 days for the IVM group. Individual faecal cultures were set up and the larval differentiation revealed a 36% prevalence of Strongylus vulgaris before treatment (n=45). In the FBZ group, 25% of the horses were S. vulgaris-positive 70 days post treatment compared to 11% in the IVM group. Our results indicate that strongyle infection intensities in Nicaragua are high and that S. vulgaris is endemic in the area. Furthermore, efficacies and ERPs of IVM and FBZ were within the expected range with no signs of anthelmintic resistance.