First report of in vitro resistance of Psoroptes ovis to ivermectin in Argentina.

Sheep scab, or psoroptic mange, a disease caused by the mite Psoroptes ovis, is commonly treated with ivermectin (IVM) and other macrocyclic lactones. In Argentina, in vivo trials have shown a decrease in IVM effectiveness to treat both sheep and bovine scab. In this work, we used an in vitro technique to establish the efficacy of IVM and two other macrocyclic lactones, doramectin (DRM) and moxidectin (MXD), against P. ovis in sheep. Mites were exposed to plates with culture medium and either ethanol or each of the acaricides, and mite mortality at a diagnostic concentration of IVM was assessed. Total survival in one of the strains studied demonstrated the presence of resistance, associated with control failures previously described by the authors. These resistant mites also presented larger LC50 values for both DRM and MXD than expected. Since, in in vivo trials, we had also previously observed a decrease in DRM effectiveness, cross-resistance may exist between DRM and IVM. We propose the use of in vitro tests to evaluate the efficacy of acaricides, considering their practicality, low cost and proven usefulness in detecting resistance in cases of low effectiveness against sheep scab.

Doramectin efficacy against Psoroptes ovis in sheep: Evaluation of pharmacological strategies.

The aims of this study were to evaluate the efficacy of two injectable formulations of doramectin (DRM) against Psoroptes ovis in sheep infested under controlled experimental conditions and to characterize the DRM plasma disposition kinetics in the infested animals. To this end, sheep were experimentally infested with a P. ovis strain from a farm with a history of treatment failure, and then treated either with DRM 1% (traditional preparation) on days 0 and 7 or with DRM 3.15% (long-acting formulation) on day 0. The efficacy of each treatment was calculated by counting live mites in skin scrapings. Plasma samples were obtained from each animal and DRM concentrations were measured by HPLC. After the two doses of DRM 1%, the maximum efficacy (98.8%) was reached on day 28, whereas after the single dose of DRM 3.15%, the maximum efficacy (100%) was reached on day 35 and ratified on day 42. The long-acting formulation allowed obtaining higher exposure and more sustained concentrations of DRM than the traditional preparation. Although both DRM formulations studied were effective according to international protocols, they did not reach 100% effectiveness in the time required for approved pharmaceutical products against sheep scab, according to Argentine regulations.

Evaluación de la efectividad del Triclabendazol como fasciolicida en caprinos de la provincia de Neuquén, Argentina / Evaluation of the efficacy of Triclabendazol to treat liver worm in goats in Nequen province, Argentina

Resumen Debido al uso frecuente del triclabendazol (TCBZ) por parte de los productores, sumado al reporte reciente de resistencia de Fasciolahepatica al fármaco detectada en rodeos y majadas de Neuquén, se llevó a cabo el presente trabajo con el objetivo de evaluar la eficacia del TCBZ como fasciolicida en caprinos bajo un sistema de producción trashumante del norte de la provincia de Neuquén, Argentina. La eficacia se evaluó mediante un test de reducción de conteo de huevos de F. hepatica en caprinos Criollo Neuquino parasitados naturalmente. Se utilizaron dos grupos de animales: un Grupo Control (n: 10) que no recibió tratamiento y un Grupo Tratado (n: 10) al que se le administró TCBZ al 10% (Biofasiolex T10-Biogénesis Bagó ®) vía oral a dosis de 10 mg/kg PV. Al día 0 y 21 post tratamiento, se tomaron muestras de materia fecal para análisis coproparasitológicos. Se evidenció una reducción del conteo de huevos de F. hepatica del 100%, indicando el mantenimiento de la eficacia del fasciolicida en los caprinos evaluados. Se discuten los alcances del uso del test de reducción de conteo de huevos en zonas con producción trashumante del ganado.

Abstract Because of the frequent use of triclabendazole TCBZ by farmers and the recent reports of Fasciola hepatica resistance to this drug in herds and flocks from Neuquén, we carried out this study with the aim to evaluate the efficacy of TCBZ as fasciolicide in goats under a transhumance system from northern of Neuquén, Argentina. A fecal egg count reduction test (FECRT) was performed on Creale Neuquino goats naturally parasitized with F. hepatica. Twenty goats were divided into two groups: A control group (n: 10) which was left untreated, and a treatment group (n: 10) that was dosed orally with TCBZ 10% (Biofasiolex T10-Biogénesis Bagó ®). On Day 0 and Day 21 post-treatment, fecal samples were taken and analyzed by coproscopical examination. According to the FECRT, drug efficacy was 100 % and confirms that TCBZ maintains its efficacy against F. hepatica on goats. The usefulness of the FECRT in these zones under transhumance livestock production is discussed.

Falla en la eficacia de dos formulaciones de ivermectina contra Psoroptes ovis (Hering, 1838) en ovinos / Failure of efficacy of two ivermectin formulations against Psoroptes ovis (Hering, 1838) in sheep

Resumen El presente trabajo evaluó la relación entre la eficacia y la farmacocinética de dos formulaciones comerciales inyectables de ivermectina (IVM) en ovinos merino adultos artificialmente infestados con Psoroptes ovis. Los animales fueron tratados por vía subcutánea con IVM 1 % en dos dosis con un intervalo de aplicación de 7 días, (0.2 mg/kg) o con una única dosis de IVM 3.15%, (1.05 mg/kg). Se realizaron conteos semanales de ácaros vivos mediante raspajes de piel entre el día 0 y 28 post-tratamiento para determinar la eficacia de los tratamientos, y se tomaron muestras de sangre para medir las concentraciones de IVM en plasma. Se observó una disminución significativa en los conteos de ácaros a partir del día 14 post-tratamiento, sin embargo, se encontraron ácaros vivos en todos los muestreos para ambos grupos. En el Grupo IVM 1%, la máxima eficacia se observó el día 28 post tratamiento (93.3%), mientras que en el Grupo IVM 3,15% este registro se obtuvo el día 21 (95.9%). Mayores concentraciones de IVM fueron observadas en los animales tratados con la formulación 3.15 %. La falla para obtener una cura parasitológica tras el tratamiento con ambas formulaciones de IVM puede ser indicativo de la presencia de ácaros resistentes a este principio activo.

Abstract The current work evaluated the relationship between efficacy and pharmacokinetics of two commercial injectable formulations of ivermectin (IVM) in adult merino sheep artificially infested with Psoroptes ovis. Animals were treated subcutaneously with IVM 1% formulation (two doses on days 0 and 7) at 0.2 mg / kg or with a single dose of IVM 3.15% preparation at 1.05 mg / kg. Live mites were counted weekly by performing skin scrapings between days 0 and 28 post-treatment to determine the efficacy of each IVM formulation. Blood samples were taken up to 35 days post-treatment to measure IVM plasma concentrations. A significant decrease in mite counts was observed from day 14 post-treatment. However, live mites were found in all samples for both groups throughout the entire trial. After IVM 1% administration, the highest effcacy was observed on day 28 (93.3% whereas in the IVM 3,15% group was obtained on day 21 post treatment (95.9%). Higher IVM plasma concentrations were observed in animals treated with the IVM 3.15% formulation. Failure to obtain a parasitological cure after treatment with both IVM formulations may reflect the presence of resistant mites to this drug.

Resistance of Fasciola hepatica against triclabendazole in cattle in Patagonia (Argentina).

In the winter of 2008, cattle on a farm in the province of Neuquen, Argentina died from subacute and chronic liver fluke disease despite four previous treatments with Triclabendazole (TCBZ). In the spring of 2009, a preliminary efficacy test revealed good performance using nitroxynil, whereas TCBZ efficacy was only 18% by egg counts of Fasciola eggs in the faeces. Resistance to Fasciola hepatica to TCBZ has never been reported in South America, so in January of 2010 a controlled trial was conducted to confirm and to define the degree of resistance in this herd. In a clinical trial, the fluke egg output was monitored on Days 14 and 21 and serum enzymes gamma-glutamyl transpeptidase (GGT) and glutamic-oxaloacetic transaminase (GOT) on Days 0 and 21 in 36 calves treated with TCBZ or with closantel. The results showed a reduction of 100% in fluke egg output at Days 14 and 21 for closantel. The mean epg in the TCBZ-treated groups did not decrease. Because of the fact that in this study TCBZ treatment in cattle had no effect, even at double the recommended dose, it is highly indicative that resistance of F. hepatica against TCBZ is present on this farm. The GGT and GOT levels decreased in the closantel-treated group as a result of the treatment at 21 days after dosing. To evaluate the importance of TCBZ resistance in F. hepatica in Argentina, a study on more farms from endemic areas is needed.