Toltrazuril + fenbendazole for cattle: Pharmacokinetics and efficacy against Eimeria spp. and gastrointestinal nematodes.

The present work evaluated the pharmacokinetics and efficacy of the association of 15cmg/kg toltrazuril +5cmg/kg fenbendazole against Eimeria spp. and gastrointestinal nematodes (GINs) in calves of different regions of Brazil (Center-West, Southeast, and South). A total of seven experiments were carried out, five of which determined formulation efficacy against Eimeria spp., considering the following aspects: therapeutic, preventive, metaphylactic, and residual efficacy. Therapeutic efficacy experiments for GINs were carried out by parasitological necropsy. The toltrazuril + fenbendazole association demonstrated ≥95% efficacy against Eimeria spp. for 21 days post-treatment (DPT). When used preventively and metaphylatically, the same association demonstrated ≥97% efficacy against E. zuernii, E. ellipsoidalis, E. cylindrica, E. bovis, E. wyomingensis and E. auburnensis. Toltrazuril + fenbendazole administered seven days before challenge was 100% effective against all these Eimeria species. Results of therapeutic, preventive, metaphylactic and residual efficacies can be related to the pharmacokinetic results, especially considering toltrazuril sulfone, which was detected in animal plasma for a longer period than the parent compound. Toltrazuril + fenbendazole achieved 100% anthelminthic efficacy against the GINs Haemonchus placei (L4), Cooperia pectinata and Oesophagostomum radiatum; 99.94% against adult H. placei; and 99.98% against C. puntacta. The association of toltrazuril + fenbendazole, associated with other measures, is an important and suitable tool for the control and treatment of Eimeria spp. and GINs in young cattle.

Efficacy of leptospiral commercial vaccines on the protection against an autochtonous strain recovered in Brazil

Abstract In swine and bovines, leptospirosis prevention and control is carried out via vaccination of susceptible animals using bacterins. However, the efficiency of leptospirosis vaccines has been questioned. This work aimed to investigate the potency of five leptospirosis vaccines sold commercially in Brazil, challenging the animals with one autochthonous strain of Leptospira, Canicola serovar, denoted LO4, isolated from swine. The standard protocol was followed, and renal carriers of Leptospira were identified among the surviving animals by culture and PCR. Of the five vaccines tested, only two proved effective. None of the surviving animals was positive by culture; however, one animal was positive by PCR. Three of the five vaccines sold commercially in Brazil for the immunization of swine or bovines failed the test of the efficacy to protect the vaccinated animals following challenge with an autochthonous Leptospira strain, Canicola serovar. The two vaccines provided protection against the renal carrier state in the surviving animals. The criteria used to produce leptospirosis bacterins sold commercially in Brazil must be reviewed. The industry should support researches on leptospiral vaccinology to improve the quality of the present vaccines and discover new immunogenic strains, because it is known that vaccination is one of the most important tools to increase the reproduction rates in livestock.

Efficacy of leptospiral commercial vaccines on the protection against an autochtonous strain recovered in Brazil.

In swine and bovines, leptospirosis prevention and control is carried out via vaccination of susceptible animals using bacterins. However, the efficiency of leptospirosis vaccines has been questioned. This work aimed to investigate the potency of five leptospirosis vaccines sold commercially in Brazil, challenging the animals with one autochthonous strain of Leptospira, Canicola serovar, denoted LO4, isolated from swine. The standard protocol was followed, and renal carriers of Leptospira were identified among the surviving animals by culture and PCR. Of the five vaccines tested, only two proved effective. None of the surviving animals was positive by culture; however, one animal was positive by PCR. Three of the five vaccines sold commercially in Brazil for the immunization of swine or bovines failed the test of the efficacy to protect the vaccinated animals following challenge with an autochthonous Leptospira strain, Canicola serovar. The two vaccines provided protection against the renal carrier state in the surviving animals. The criteria used to produce leptospirosis bacterins sold commercially in Brazil must be reviewed. The industry should support researches on leptospiral vaccinology to improve the quality of the present vaccines and discover new immunogenic strains, because it is known that vaccination is one of the most important tools to increase the reproduction rates in livestock.

The effectiveness of a fixed-dose combination pour-on formulation of 1.25% fipronil and 2.5% fluazuron against economically important ectoparasites and associated pharmacokinetics in cattle.

The present work consisted of eight studies to evaluate the ectoparasiticidal spectrum and determine the pharmacokinetic parameters of a pour-on combination of fipronil 1.25mg/kg+fluazuron 2.5mg/kg for cattle against Rhipicephalus microplus, Haematobia irritans and the larvae of Dermatobia hominis and Cochliomyia hominivorax. The analysis fipronil and fluazuron were performed by liquid chromatography using a mass detector for the detection and quantification of analytes (LC-MS/MS). Additionally, in two of these studies, the animals were artificially infested with R. microplus ticks (stall tests), and the efficacy of this formulation was compared with that of two other standalone pour-on formulations of fipronil 1.0mg/kg and fluazuron 2.5mg/kg. In the two stall studies, 28 calves were artificially infested with 5000 R. microplus (different strains), and daily collections of all of the engorged female ticks that detached from each calf were performed until 60 and 100days post-treatment (dpt). For the R. microplus field trials, 20 bovines were selected by counting the semi-engorged females, and the therapeutic and residual efficacy was evaluated by taking tick counts at 3, 7, 14, 21, 28, 35, 42, 49 and 56dpt. Forty bovines that were naturally infested with Dermatobia hominis larvae were selected, and the numbers of larvae were counted by visual and tactile inspection on 3, 7, 14, 28, 35, 42 and 49dpt. To address the efficacy on C. hominivorax larvae, two circular skin incisions (one on each side of the body) measuring approximately 4cm in diameter each were made in 12 crossbred calves, and the natural exposure of the lesions to C. hominivorax infestations was then allowed. The incisions from the 12 animals were carefully examined daily from 1 to 10dpt. Based on the PK results obtained for this pour-on combination containing fipronil 1.25mg/kg+fluazuron 2.5mg/kg, the maximum concentrations (Cmax) and the half-lives (T1/2) of these two active ingredients were detected on days 2, 5/6 and 19 (±2)/24, 4 (±3.5) days for fipronil and fluazuron, respectively. Furthermore, the combination showed higher therapeutic and residual efficacy against R. microplus (P≤0.05) when compared with commercial standalone formulations that were administered separately. A high efficacy for this new combination was also found against C. hominivorax and D. hominis larvae (efficacy≥99%). This study's results show that the combination of these two active ingredients, as opposed to their separate use, could represent a tool for extending the life cycle of these two molecules against cattle ectoparasites, especially R. microplus. Further studies would be desirable to further confirm this.