Relationship between pharmacokinetics of fluazuron and its efficacy for controlling Rhipicephalus microplus: A comprehensive evaluation of tick drug uptake.

Relationship between fluazuron (FZN) concentrations in cattle plasma and ticks and its therapeutic efficacy percentage (EP) against Rhipicephalus microplus was analyzed. The extent of FZN uptake by ticks after its topical administration was also evaluated. Heifers, naturally infested with R. microplus, were divided in treated and no treated groups. Blood and tick samples were taken to measure FZN concentrations and female ticks were counted to evaluate the EP of the treatment from day 0 to 45 post-treatment (PT). Ticks exposed (TE) and not exposed (TNE) to topical contact with the drug were collected at 12 and 24 h PT. Artificial feeding (AF) of ticks was also performed with blood from a treated heifer. The EP on days 21, 28, 35, 42 and 45 PT was 99.1, 92.3, 81.2, 74.7 and 76.5 %, respectively. Fluazuron disposition within ticks during the first 2 days post-treatment did not mirror the corresponding FZN levels in the bovine plasma, but a statistically significant positive correlation was evident from day 3. Mean FZN concentrations in TE at 12 h and 24 h PT were significantly higher than in TNE. The FZN concentrations in AF ticks were significantly lower than those in TE but comparable to the levels in TNE. The efficacy and pharmacokinetics analysis suggest that maintaining a threshold FZN plasma concentration above 20-25 ng/mL is crucial to prevent the development of larvae into engorged females. The results also indicate that direct absorption of FZN through the tick's integument occurs in the initial days after treatment.

Successive treatments with ivermectin (3.15%) to control the tick Rhipicephalus (Boophilus) microplus in cattle: Pharmacokinetic and efficacy assessment.

This study aimed to evaluate the pharmacokinetics, the potential accumulation in the body of treated animals and the efficacy of ivermectin long-acting formulation (3.15%) against the cattle tick Rhipicephalus (Boophilus) microplus in a scheme of three successive treatments. Fifteen 12-month-old heifers, naturally infested with R. microplus, were divided into two groups (G). Cattle from GI (n = 10) were subjected to three treatments with ivermectin 3.15% (IVOMEC GOLD®, Merial Argentina S.A.) at a rate of 1 mL/50 kg on days 0, 35, and 70. Cattle from GII (n = 5) were not treated. From day 1 to 202 post-treatment blood samples were taken to measure ivermectin concentrations by HPLC and female ticks (4.5-8 mm) were counted to evaluate the efficacy of the treatment. The level of tick resistance to ivermectin was evaluated before and after finishing the scheme of successive treatments by larval immersion test (LIT) bioassay from engorged females collected from GI. The area under the concentration vs. time curves (AUC0-35d) obtained post-second treatment was 1.51 ± 0.39-fold higher than those observed post-first treatment (P<0.05). The mean plasma concentrations of ivermectin 3.15% at 20 days after the first, second and third treatment were 17.0, 27.5 and 37.8 ng/mL, respectively (P<0.01). The elimination half-life of ivermectin post-third treatment was significantly longer than that was previously reported after a single dose (P<0.01). Values of therapeutic efficacy percentage reached 75.6% post-first treatment and between 95.9 and 100% after the second treatment. Ticks evaluated by LIT showed a significant increase in lethal concentrations after treatments. Although the efficacy level was high, the successive treatments with long-acting ivermectin formulation generate a significant accumulation of drug in plasma and could increase the levels of resistance to this drug in the tick population.

Evaluación de un esquema de control integrado de Rhipicephalus (Boophilus) microplus en vacas preñadas y con cría en el noreste argentino / Evaluation of an integrated control scheme against Rhipicephalus (Boophilus) microplus in pregnant cows and in cows with calf in northeastern Argentina

Resumen El objetivo fue evaluar un esquema de control integrado para Rhipicephalus (Boophilus) microplus en vacas preñadas y con cría combinando dos tratamientos con acaricidas químicos y el descanso de potreros en una localidad representativa del noreste argentino. Este esquema fue diseñado para combinar el efecto terapéutico del control estratégico (dos tratamientos aplicados entre fines del invierno y la primavera) con el que tiene el descanso de las pasturas (en el presente trabajo de tres meses) sobre la cantidad de larvas presentes en un potrero. Veintidós vacas y vaquillas de biotipo Braford fueron distribuidas en dos grupos en potreros infestados naturalmente con garrapatas, con un descanso de tres meses previo al ingreso de los animales. El grupo I recibió dos tratamientos acaricidas con fluazurón y flumetrina y el grupo II permaneció sin tratamientos como grupo control. Se estimó mensualmente la infestación con garrapatas y se calculó la eficacia terapéutica. La infestación con Rhipicephalus (Boophilus) microplus en el grupo I fue significativamente menor que la del grupo control y los niveles de eficacia fueron siempre superiores al 93%, con la excepción del conteo de febrero dónde el porcentaje de eficacia fue del 89,1%. La integración complementaria de la descontaminación parcial ejercida mediante un descanso de pasturas de tres meses con un esquema de tratamientos estratégicos (dos en un período de 10 meses) permitió alcanzar niveles significativos de eficacia en el control de Rhipicephalus (Boophilus) microplus manteniendo bajos niveles de infestación con mínimos movimientos a corral, y brindando sustentabilidad al uso de los acaricidas.

Abstract The aim was to evaluate an integrated control scheme for Rhipicephalus (Boophilus) microplus in pregnant and calving cows combining two treatments with chemical acaricides and paddock rest in a representative locality of northeastern Argentina. This scheme was designed to combine the therapeutic effect of strategic control (two treatments applied between late winter and spring) with the rest of pastures (in the present work of three months) on the amount of larvae present in a paddock. Twenty-two Braford-type heifers and cows were divided into two groups in paddocks naturally infested with ticks, with a rest of three months before the animals were admitted. Group I received two acaricidal treatments with fluazuron and flumethrin and group II remained without treatment as a control group. Tick ​​infestation was monitored monthly and therapeutic efficacy was calculated. The infestation with Rhipicephalus (Boophilus) microplus in group I was significantly lower than that of the control group and the efficacy levels were always higher than 93%, with the exception of the February count, where the efficacy was 89.1%. The complementary integration of the partial decontamination applied through a three-month pasture rest with a strategic treatment scheme (two in a 10-month period) allowed reaching significant levels of efficacy in the control of Rhipicephalus (Boophilus) microplus while maintaining low levels of infestation with minimal movements to management pens, and providing sustainability to the use of acaricides.