Fosfatriclaben, a prodrug of triclabendazole: Preparation, stability, and fasciolicidal activity of three new intramuscular formulations.

In this study, we present the preparation, stability, and in vivo fasciolicidal activity of three new intramuscular formulations in sheep of a prodrug based on triclabendazole, named fosfatriclaben. The new formulations were ready-to-use aqueous solutions with volumes recommended for intramuscular administration in sheep. The use of poloxamers (P-407 and P-188) and polysorbates (PS-20 and PS-80) in the new formulations improved the aqueous solubility of fosfatriclaben by 8-fold at pH 7.4. High-performance liquid chromatography with UV detection was used to evaluate the stability of fosfatriclaben in the three formulations. High recovery (> 90%) of fosfatriclaben was found for all formulations after exposure at 57 ± 2 °C for 50 h. The three intramuscular formulations showed high fasciolicidal activity at a dose of 6 mg/kg, which was equivalent to the triclabendazole content. The fasciolicidal activity of fosfatriclaben was similar to commercial oral (Fasimec®) and intramuscular (Endovet®) triclabendazole formulations at a dose of 12 mg/kg. In the in vivo experiments, all formulations administered intramuscularly reduced egg excretion by 100%, and formulations F1, F2, and F3 presented fasciolicidal activities of 100%, 100%, and 99.6%, respectively.

Effectiveness of an experimental injectable prodrug formulation against Fasciola hepatica of different ages in experimentally infected 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.

First report of Libyostrongylus douglassii (Strongylida: Trichostrongylidae) in ostriches (Struthio camelus) from Mexico.

Nematodes of the Libyostrongylus genus are hematophagous parasites found under the ostrich's proventriculus membrane: they are frequent and can cause 50% of mortality in chicks and occasionally death in adults. With the aim of determining the presence of the Libyostrongylus genus in two private collections, one located in Ayapango, State of Mexico and the other in Amacuzac, Morelos, a total of 27 fecal samples were collected between August and December of 2016. Samples were analyzed using the flotation technique. The eggs were quantified using the McMaster technique. Positive samples were cultured to obtain infective larvae and to be identified by their morphometric characteristics. Only 18 samples collected in Ayapango were positive to Libyostrongylus douglassii. This is the first time that L. douglassii is reported in Mexico.

Transmission dynamics of Fasciola hepatica in the Plateau Region of Mexico. Effect of weather and treatment of mammals under current farm management.

The aim of the present work was to study the dynamics of Fasciola hepatica natural infection in ovines, caprines, bovines and two mollusc species, Lymnaea (Fossaria) humilis and Lymnaea (F.) bulimoides, from 2004 to mid 2007 under normal farm management conditions, and the relation to climate changes. The study was performed in a research centre in the plateau of Mexico. Temperature and rainfall were registered every month, as well as the number and intensity of infection in livestock and molluscs, as determined by coprology and direct observation/cercariae release, respectively. The first two years mammals were treated with clorsulon/ivermectin because the animals were harbouring concomitant intestinal nematode infections and this was the available drug combination. During the second period treatment was with triclabendazole. The temperature ranged from around cero to 30 °C, except during September 2005 to January 2006, when a cold climate prevailed. The rainfall augmented every year in July-August, and slightly in April, 2006. Lymneid snails appeared during or immediately after the rainfall peaks of 2004 and 2006, while few L. humilis and no L. bulimoides were present during the same period of 2005, probably because it was cold. A total of 15564 cercariae were released from molluscs during the wet time of 2004, 76 during 2005 and 368 in 2006. Several peaks of infection in mammals were observed, most occurring up to 4 months after the snails had disappeared. As expected, the weather had strong impact on snails and then on livestock infection. Also, treatment given to livestock was related to reduced cercarieae release five months later. Therefore, the combination of treatment and inspection of snails in the biotopes where the livestock graze may facilitate control of fasciolosis under current farm management.

Efecto de una nueva formulación de ivermectina + abamectina de larga duración contra nematodos gastrointestinales y la diferencia en ganancia de peso en bovinos / Effect of a new long life formulation of ivermectin + abamectin against gastrointestinal nematodes and the difference in weight gain in bovines

With the aim to evaluate the effect of ivermectin 2.25% + abamectin 1.25% in the reduction of gastrointestinal nematodes eggs per gram (epg) and the weight gain in bovines in 90 days, twenty four Santa Gertrudis breed, weaned calves localized in a ranch in Malpaso, Tecpatan municipality, Chiapas, Mexico, with a warm humid climate, were used. The calves were in extensive grazing on African Star and native grasslands. They were naturally infected with gastrointestinal nematodes (GIN), and were weighed on day -3. According to the individual weight and the egg count, two groups of 12 animals each, were integrated, without statistical difference in the weight and the average of epg, above of 700 eggs (P < 0.05). Group 1 was treated with one formulation of ivermectin at 2.25% + abamectina at 1.25%, in doses of 700 mcg/kg corresponding to 1 mL per 50 kg, by subcutaneous via. Group 2 was the control without anthelminthic treatment. Coprological examination was done at -3, 10, 45 and 90 days, moreover, coprocultures from each group were prepared with homogenized feces, in order to obtain larvae (L3). Weights were recorded on-3, and 45, 90 days after treatment. It was found that weight gain between Group 1, treated with 2.25% ivermectin + 1.25% abamectin, was 30.7 kg, equivalent to 350 g per day in average, with significant statistical difference (P < 0.05), in relation to the control group. The reduction percentage of epg showed difference at 10 and 45 days (P < 0.05), between the control and treated group; however, at 90 days they were not different. The genuses of GIN identified by frecuency order were: Haemonchus, Cooperia, Trichostrongylus, Oesophagostomum and Ostertagia.

Con el objetivo de evaluar el efecto de ivermectina 2.25% + abamectina 1.25% en la reducción de huevos de nematodos gastrointestinales por g de heces (hpgh) y la diferencia en la ganancia de peso en bovinos, se emplearon 24 becerros de la raza Santa Gertrudis, destetados, localizados en un rancho en Malpaso, municipio de Tecpatán, Chiapas, México, con clima cálido-húmedo. Los becerros estaban en pastoreo extensivo en potreros con pasto Estrella de África y gramas nativas. Dichos becerro, infectados con nematodos gastrointestinales (NGI) de manera natural, se pesaron el día -3 de acuerdo con los pesos individuales y las cuentas de hpgh, se conformaron dos grupos de 12 animales cada uno, sin que hubiera diferencia estadística en el peso ni en la media de hpgh, superior a 700 (P < 0.05). El Grupo1 fue tratado con una formulación de ivermectina a 2.25% + abamectina a 1.25%, en dosis de 700 mcg/kg equivalente a 1 mL por 50 kg, por vía subcutánea. El Grupo 2 fue el testigo, sin tratamiento antihelmíntico. Se realizaron exámenes coprológicos los días -3, 10, 45 y 90, además con homogeneizados de heces de cada grupo se prepararon coprocultivos para la cría de larvas (L3), el peso se registró el día -3, 45 y 90 después del tratamiento. Se encontró que la diferencia en la ganancia de peso en el G1 tratado con ivermectina 2.25% + abamectina 1.25%, fue de 30.7 kg, equivalente a 350 g por día en promedio, con diferencia estadísticamente significativa (P < 0.05) con el grupo testigo. En el porcentaje de reducción de hpgh hubo diferencia a los 10 y 45 días (P < 0.05) entre el testigo y el tratado; sin embargo, a los 90 días no la hubo. Los géneros de NGI identificados por orden de frecuencia fueron: Haemonchus, Cooperia, Trichostrongylus, Oesophagostomum, y Ostertagia.

Dynamics of Fasciola hepatica infection in two species of snails in a rural locality of Mexico.

The aim of the present study was to identify the species that are natural intermediate hosts of Fasciola hepatica in a Research Centre in Chapa de Mota, State of Mexico, Mexico, where temperate and humid conditions prevail. Also, the magnitude and dynamics of the natural infection in four biotopes were analysed. The study was performed between October 2000 and November 2001. The molluscs were collected, identified and studied for trematode infection. Soil humidity and temperature were determined monthly. A total of 4042 snails were collected 3372 (83%) were Fossaria humilis and 670 (17%) F. bulimoides. F. hepatica was present in 2537 (75.2%) and 515 (76.9%) of the two snail species, respectively. Temperature, soil humidity and microenvironment affected the dynamics of the host population and the parasite infestation, with a significant increase from August to November 2001. The highest prevalence was observed in the warmer and more humid biotopes.