Pour-on Formulation Research Articles

Development of a Physiologically Based Pharmacokinetic Model for Flunixin in Cattle and Swine Following Dermal Exposure.

Flunixin meglumine is a nonsteroidal anti-inflammatory drug (NSAID). Banamine® Transdermal is a pour-on formulation of flunixin approved for pain control in beef and dairy cattle, but not for calves and some classes of dairy cattle or swine. Violative flunixin residues in edible tissues in cattle and swine have been reported and are usually attributed to non-compliant drug use or failure to observe an appropriate withdrawal time. This project aimed to develop a physiologically based pharmacokinetic (PBPK) model for flunixin in cattle and swine to predict withdrawal intervals (WDI) after exposures to different therapeutic regimens of Banamine® Transdermal. Due to the lack of comprehensive skin physiological data in cattle, the model was initially developed for swine and then adapted for cattle. Monte Carlo simulation was employed for population variability analysis. The model predicted WDIs were rounded to 1 and 2 days for liver and muscle in cattle, respectively, under FDA tolerance levels, while under EU maximum residue limits (MRLs), the WDIs were rounded to 1, 3, 2, and 2 days for liver, kidney, muscle, and fat, respectively, following a labeled single transdermal 3.3 mg/kg dose in cattle. The model was converted into a user-friendly interactive PBPK (iPBPK) interface. This study reports the first transdermal absorption model for drugs in cattle. This iPBPK model provides a scientifically based tool for the prediction of WDIs in cattle and swine administered with flunixin in an extra-label manner, especially by the transdermal route.

The efficacy of essential oil components with ivermectin against Rhipicephalus annulatus: An in-vitro study

Ivermectin (Iv) is widely used to control Rhipicephalus annulatus infestations in cattle in Egypt. However, increasing resistance to ivermectin necessitates alternative approaches. This study aimed to address this resistance by investigating the interactions between ivermectin and essential oil components (EOCs)—carvacrol, cinnamaldehyde, D-limonene, trans-anethole, and thymol—against four R. annulatus tick isolates collected from Beni-Suef, El-Minia, and El-Fayoum. The larval immersion test was conducted using various ivermectin concentrations (3, 1.5, 0.75, 0.38, 0.19, 0.09, 0.045, 0.025, and 0.0125 mg/mL) prepared in EthTX1 %. Additionally, EOCs were tested at different concentrations (20, 10, 5, and 2.5 mg/mL) prepared by dilution in 5 % ethyl alcohol and EthTX 1 %. Ivermectin and each EOC were tested individually against the isolates. Subsequently, the LC50 of ivermectin was combined with the LC50 of each EOC in a 1:1 ratio to evaluate potential synergistic effects. All EOCs demonstrated significant toxicity against the isolates. The combination of carvacrol and thymol with ivermectin increased mortality, but the combination index (CI) exceeded one for all isolates, indicating no synergism. Similarly, while D-limonene, cinnamaldehyde, and trans-anethole also resulted in high mortality rates, including up to 100 %, no synergism was observed (CI > 1). However, these three EOCs exhibited CIs close to 1, suggesting an additive effect when combined with ivermectin. In conclusion, combining ivermectin with certain EOCs, particularly D-limonene, cinnamaldehyde, and trans-anethole, may offer an effective tool for controlling cattle ticks. Developing topical or pour-on formulations of ivermectin-EOC combinations could be an integral part of integrated management strategies to combat resistance to macrocyclic lactones like ivermectin. Further studies, including tests on adult ticks and field trials, are needed to evaluate the efficacy of these combinations.

Impact of fluazuron on oocyte maturation: May the antiparasitic affect bovine reproduction?

Fluazuron is a novel veterinary pour-on antitick formulation which can be applied simultaneously with bovine reproduction management strategies. Considering the economic importance of the livestock industry in many countries, it is important to know whether antiparasitics such as fluazuron may cause embryonic loss. The aim of this study was to evaluate the toxicological effect of fluazuron on bovine oocytes during in vitro maturation. The best fluazuron concentrations were determined in a preliminary experiment on Chinese hamster ovary (CHO)-K1 cells and further used to compare fluazuron toxicity in both study models. Results of the annexin V and alkaline single cell gel electrophoresis assays demonstrated that fluazuron caused cytotoxicity and genotoxicity in bovine cumulus cells at all the concentrations tested (50, 75 and 100 μg fluazuron/mL). The evaluation of cortical granules and mitochondria distribution showed that cytoplasmic maturation was not affected by fluazuron treatment. However, a decrease in metaphase II + polar body, degenerate oocytes as well as disorganized chromatin in polar body were observed at all concentrations tested. Whereas the fertilization process was not altered by 50 μg/mL fluazuron, the embryo development rate decreased significantly. No significant differences were observed in any of the oxidative stress parameters assessed. This study contributes to a better understanding of fluazuron in bovines, suggesting that the antiparasitic may affect bovine reproduction and might cause embryo loss.

Acaricide resistance status of livestock ticks from East and West Africa and in vivo efficacy of acaricides to control them

Through a collaborative effort across six Sub-Saharan African countries, using recognized international assessment techniques, 23 stocks of three tick species (Rhipicephalus microplus, Rhipicephalus appendiculatus and Amblyomma variegatum) of economic importance for rural small holder farming communities from East and West Africa were collected from cattle, and evaluated in in vitro larval packet tests (LPT). The results demonstrated medium to high resistance to chlorfenvinphos and amitraz across species. Rhipicephalus microplus demonstrated high level alpha-cypermethrin and cypermethrin resistance. Stocks of A. variegatum (West Africa) and R. appendiculatus (Uganda) demonstrated medium level ivermectin resistance.The four least susceptible stocks (East and West African R. microplus, A. variegatum and R. appendiculatus) were taken into in vivo controlled cattle studies where fipronil was found effective against West and East African R. microplus isolates although persistent efficacy failed to reach 90%. Cymiazole and cypermethrin, and ivermectin based acaricides were partially effective against R. microplus without persistent efficacy. Flumethrin spray-on killed A. variegatum within 72 h for up to 10 days posttreatment, however product application was directly to tick attachment sites, which may be impractical under field conditions. A flumethrin pour-on formulation on goats provided persistent efficacy against A. variegatum for up to one-month. Therapeutic control was achieved against R. appendiculatus through weekly spraying cattle with flumethrin, amitraz or combined cymiazole and cypermethrin. A fipronil pour-on product offered four-week residual control against R. appendiculatus (with slow onset of action).Few studies have assessed and directly compared acaricidal activity in vitro and in vivo. There was some discordance between efficacy indicated by LPT and in vivo results. This observation calls for more research into accurate and affordable assessment methods for acaricide resistance.No single active or product was effective against all three tick species, emphasising the need for the development of alternative integrated tick management solutions.

Enzootic stability of tick fever in Holstein calves grazing in a tropical region, subjected to strategic cattle tick control with fluralaner

BackgroundIn 2022, fluralaner was launched on the market for use in the control of the cattle tick Rhipicephalus microplus after showing 100% efficacy in registration trials against the causative agents of cattle tick fever (TFAs). The aim of the present study was to determine whether a strategic control regimen against R. microplus using fluralaner (FLU) in Holstein calves grazing in a tropical region would alter the enzootic stability status of cattle tick fever, triggering outbreaks in these animals up to 22 months age.MethodsIn this study, a group of calves treated with FLU was compared with a control group treated with the regimen currently being used on the farm, which consisted of the fipronil + fluazuron formulation (FIFLUA). In the first experiment, the efficacy of the FIFLUA pour-on formulation was evaluated in a field study. In the second experiment, which lasted 550 days, two experimental groups (n = 30/group) of Holstein calves naturally infested with R. microplus were analyzed. Calves aged 4 to 10 months received either a specific treatment regimen with FLU (experimental group) or FIFLUA (control group). During this period, tick counts, animal weight measurement, feces collection (to determine eggs and oocysts per gram of feces), tick fever monitoring, blood smears (to ascertain enzootic stability of the herd), PCR testing for TFAs and serology (indirect enzyme-linked immunosorbent assay [iELISA]) were performed. All calves were evaluated for signs of tick fever between ages 11 and 22 months.ResultsFIFLUA showed an acaricidal efficacy of > 90% from post-treatment days 14 to 35. Regarding treatments against the TFAs, the average number of treatments was similar between groups, but animals treated with FLU had a smaller reduction in packed cell volume on some of the evaluation dates of the second and third treatment against TFAs. In calves aged 10 months in the FLU group, B. bovis was not detected by PCR (0/15 samples), 40% of the samples had antibody titers and 33% (10/30) of the samples had positive blood smears. Regarding B. bigemina, > 86% of the samples in both groups tested positive for B. bigemina DNA and antibodies; there was no difference in the antibody titers between the groups. There were no clinical cases of cattle tick fever in calves aged 11 to 22 months.ConclusionsIn comparison with the control treatment, the strategic control regimen against R. microplus with FLU that was implemented in the present study did not negatively affect the enzootic stability status of A. marginale and B. bigemina in the herd up to 22 months of age. The enzootic stability status of B. bovis was not reached by either group. These results likely represent a characteristic of the local tick population, so further studies should be performed.Graphical

Comparative Pharmacokinetics and Bioequivalence of Pour-On Ivermectin Formulations in Korean Hanwoo Cattle.

This study aimed to conduct a bioequivalence study of applying three pour-on ivermectin formulations at a dose of 1 mg/kg on the back of Korean native beef cattle (Hanwoo). To conduct bioequivalence testing, the pharmacokinetics of three groups (control Innovator, test Generic A, and test Generic B) of five clinically healthy Korean Hanwoo cattle (average weight 500 kg) were studied. After topical application to the skin, blood samples were drawn at the indicated times. These blood samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The time required to reach the maximum concentration (Tmax), the maximum concentration (Cmax), and the area under the curve (AUClast) of each pharmacokinetic parameter were compared for bioequivalence. The results showed that the control had a Tmax of 41 ± 1.24 h, a Cmax of 0.11 ± 0.01 μg/mL, and an AUClast of 9.33 ± 0 h*μg/mL). The comparator Generic A had a Tmax of 40 ± 1.14 h, a Cmax of 0.10 ± 0.01 (μg/mL, and an AUClast of 9.41 ± 0.57 h*μg/mL, while Generic B had a Tmax of 40 ± 2.21 h, a Cmax of 0.10 ± 0.01 μg/mL, and an AUClast of 9 h*μg/mL. The values of the bioequivalence indicators Cmax, Tmax, and AUC were all within the range of 80% to 120%, confirming that all three tested formulations were bioequivalent. In conclusion, the study showed that the two generic products were bioequivalent to the original product in Hanwoo cattle.

Alleviating lesions of chronic progressive lymphedema in Belgian draft horses by successfully treating Chorioptes bovis infestation with moxidectin 0.5% pour-on

The aim of this prospective, randomized, single-blinded, and placebo-controlled clinical trial was to investigate the efficacy of a moxidectin pour-on solution for the treatment of Chorioptes bovis infestation in Belgian draft horses, and in addition, to evaluate the effect of this treatment on the clinical signs and lesions associated with chronic progressive lymphedema (CPL). Nineteen privately owned Belgian draft horses were randomly assigned to either a treatment group (moxidectin pour-on formulation, n = 10) or a placebo group (phosphate-buffered saline (PBS), n = 9). On Day 0, all 19 horses tested positive for the presence of C. bovis in superficial skin scrapings. Prior to treatment, all feathering on the distal limbs of the horses was clipped. Treatment was applied twice (Day 0 and 7). Pour-on moxidectin (Cydectin 0.5% Pour-On; Zoetis) was evenly distributed over the distal legs of the horses at a dose of 1.5 mg moxidectin/kg body weight. Animals in the placebo group were treated with PBS. Pretreatment and follow-up examinations consisted of counting living mites in superficial skin scrapings, scoring pruritus, and scoring mange-associated and CPL-associated lesions (skinfold score and skin lesion score). Horses in the placebo group and moxidectin group were followed up to 8 weeks and 24 weeks after the first treatment, respectively. On Day 14, no living mites were found in any of the horses in the moxidectin group (p = 0.013). These horses continued to remain free of mites, until the final sampling conducted at 24 weeks following the initial application of moxidectin, when three horses again showed living mites in skin scrapings. Treatment with moxidectin resulted in a significant reduction of both CPL-associated skin lesion scores (p = 0.003) and pruritus scores (p = 0.001) after only seven days. By Day 56, still no signs of pruritus (p < 0.0001) were detected, with significant improvement of mange-associated lesions (p < 0.0001). Although the skinfold score did not show a significant reduction by Day 56, the score for skin lesions associated with CPL had significantly improved (p < 0.0001). In conclusion, the results of this study demonstrate that pour-on moxidectin, at a high dose and applied directly to the mite predilection site, was an effective treatment for C. bovis infestation in feathered draft horses, providing positive effects on CPL lesions, pruritus and mange-associated lesions. Furthermore, these findings emphasize the therapeutic significance of addressing mange in the management of CPL-affected draft horses.

First report of the efficacy of a fluralaner-based pour-on product (Exzolt® 5%) against ectoparasites infesting cattle in Brazil

BackgroundThis study describes the effectiveness of a novel active pharmaceutical ingredient, fluralaner (isoxazoline class), against important ectoparasites infesting cattle in Brazil.MethodsA total of 13 studies involving a 5% fluralaner-based pour-on formulation (Exzolt 5%; further referred to as Exzolt) were conducted. Specifically, the effectiveness of this formulation was studied against Rhipicephalus microplus (6 studies), Cochliomyia hominivorax larvae (4 studies), Dermatobia hominis larvae (1 study) and Haematobia irritans flies (2 studies).ResultsThe therapeutic efficacy of Exzolt was found to exceed 98% at 4 days post treatment (DPT), while persistent efficacy (> 90% efficacy) against repeated infestations of R. microplus was observed for up to 79 DPT. In field studies, ≥ 98% therapeutic efficacy was demonstrated at all study sites by 7 DPT, and a persistent efficacy (> 90% efficacy) was observed for 42, 49 or 56 DPT. Exzolt prevented C. hominivorax eggs from developing to the larval stage, thus mitigating the development of myiasis in cattle naturally and artificially infested with this screworm. The efficacy of Exzolt against D. hominis larvae was 98% at 3 DPT, while persistent efficacy (> 90% effectiveness) was found to last for up to 70 DPT. Against H. irritans, Exzolt showed therapeutic efficacy (≥ 90%) within the first day of treatment at both study sites, while persistent efficacy (≥ 90%) was observed for 7 DPT at one site and for 21 DPT at the other site.ConclusionsOverall, the results from these studies confirm that Exzolt is therapeutically efficacious against the most important ectoparasites infesting cattle in Brazil. The novel active pharmaceutical ingredient, fluralaner, provides a new treatment option for farmers to control cattle ectoparasites, especially where there is resistance to other chemical classes. In addition, an effective control of ectoparasites will improve overall cattle health and well-being as well as production.Graphical

Gastrointestinal parasites in captive olive baboons in a UK safari park.

From the safety inside vehicles, Knowsley Safari offers visitors a close-up encounter with captive olive baboons. As exiting vehicles may be contaminated with baboon stool, a comprehensive coprological inspection was conducted to address public health concerns. Baboon stools were obtained from vehicles, and sleeping areas, inclusive of video analysis of baboon–vehicle interactions. A purposely selected 4-day sampling period enabled comparative inspections of 2662 vehicles, with a total of 669 baboon stools examined (371 from vehicles and 298 from sleeping areas). As informed by our pilot study, front-line diagnostic methods were: QUIK-CHEK rapid diagnostic test (RDT) (Giardia and Cryptosporidium), Kato–Katz coproscopy (Trichuris) and charcoal culture (Strongyloides). Some 13.9% of vehicles were contaminated with baboon stool. Prevalence of giardiasis was 37.4% while cryptosporidiosis was <0.01%, however, an absence of faecal cysts by quality control coproscopy, alongside lower than the expected levels of Giardia-specific DNA, judged RDT results as misleading, grossly overestimating prevalence. Prevalence of trichuriasis was 48.0% and strongyloidiasis was 13.7%, a first report of Strongyloides fuelleborni in UK. We advise regular blanket administration(s) of anthelminthics to the colony, exploring pour-on formulations, thereafter, smaller-scale indicator surveys would be adequate.

Experimental oral delivery of the systemic acaricide moxidectin to free-ranging white-tailed deer (Artiodactyla: Cervidae) parasitized by Amblyomma americanum (Ixodida: Ixodidae).

Orally delivered, host-targeted, systemic acaricide treatment has potential to be an effective areawide tick abatement strategy. Past efforts using ivermectin for livestock were reported effective at controlling both Amblyomma americanum (L.) and Ixodes scapularis Say on Odocoileus virginianus (Zimmermann). However, the labeled 48-day withdrawal period for human consumption largely prevented utilization of this strategy targeting I. scapularis in autumn, when peak adult host-seeking activity coincides with regulated white-tailed deer hunting seasons. The modern-day compound moxidectin is the active ingredient in the pour-on formulation Cydectin (5 mg moxidectin/ml; Bayer Healthcare LLC), with a labeled 0-day withdrawal period for human consumption of treated cattle. We sought to re-examine the systemic acaricide approach for tick management by determining if we could successfully deliver Cydectin to free-ranging white-tailed deer. Over 2 yr in late spring/early summer, coinciding with adult and nymphal A. americanum activity, we fed Cydectin-coated corn to free-ranging white-tailed deer in coastal Connecticut. Through serum analysis, we documented moxidectin levels at or above those previously reported effective for control of ectoparasites (5-8 ppb for moxidectin and ivermectin) in 24 of 29 white-tailed deer captured (83%) while exposed to treated corn. While we did not document differences in burdens of parasitizing A. americanum based on moxidectin sera levels, we did document fewer engorged specimens on deer with increased sera levels. The systemic use of moxidectin for tick management in critical reproductive hosts has the potential to be effective in an areawide capacity while also permitting human consumption of treated venison.

PS-4 Evaluating the Effects of Artificial Rainfall and Permethrin Resistance Status on the Efficacy of Common Pour-On Formulation Delivered to Beef Heifers in a Controlled Environment

Abstract The objective of this study is to determine the impact of rainfall on the duration of efficacy of a commercial pour-on against susceptible (SS) and permethrin resistant (PR) horn flies. Eighteen Angus-Hereford crossbred heifers (BW) were used in a completely randomized design with repeated measures to determine the efficacy and longevity of a permethrin-based pour-on. Animals were randomly assigned to one of two fly infestations (SS or PR) and within infestation to one of three rainfall regimens [no rain (NR), no rain with a pour-on (NP) treatment, and rain with a pour-on (RP) treatment]. All heifers were housed in outdoor roofed pens within the corresponding treatment group and animals with NP and RP groups were treated once on day 0 at the label rate. Once a week for four weeks all animals were placed into individual indoor screened rooms where the fly infestations were administered. Live fly counts were acquired 24 h following each infestation. Animal with RP received approximately 2.54 cm of artificially provided rainfall within 2 hours following each weakly horn fly count. A treatment × day x fly interaction (P &amp;lt; 0.01) was observed. In general, NR groups maintained higher (P &amp;lt; 0.05) populations of SS and PR for 22 and 8 days post-treatment, respectively. Regardless, of fly species, rainfall had no (P &amp;gt; 0.05) influence on product efficacy. In conclusion, insecticide resistance status appears to be more influential than heavy rainfall in the longevity of permethrin-based pour-on products.

Is the suckling period and application pattern relevant for fluazuron against tick infestation in cows and their suckling calves?

BackgroundFluazuron is a chitin synthesis inhibitor administered as a pour-on formulation in cattle for tick control. This study analyzes under endemic tick infestation, the incidence of the pour-on application pattern on the plasma levels of fluazuron in calves and cows in the lactation period of the beef cow. Two hundred and ninety-two beef cows around parturition were treated with a commercial pour-on formulation of fluazuron at a rate of 2.5 mg/kg of body weight. A total of 4 treatments were carried out on days 0, 32, 77, and 117. At each administration time, the cows were grouped according to the pour-on administration pattern: long (~ 60 cm pour-on application surface) and short (~ 30 cm pour-on application surface). Fluazuron levels in cows and calves plasma were determined before the third and fourth application for each subgroup (n = 10) by HPLC-MS/MS. During the entire study, cow-calf pairs were maintained under field conditions and qualitatively examined for tick infestation on the day of each treatment. Both treatments (long and short) schemes were designed to prevent the annual persistence of ticks.ResultsNo animals with presence of ticks were identified during the first 117 days of the study, except for three cows and one calf at the time of the third application (day 77). There were no differences after 40 days (day 77) post-treatment of the second application (30 ± 5 ppb vs. 28.5 ± 12 ppb, p > 0.05) and 45 days (day 117) after the third application (147 ± 55 ppb vs 140 ± 46 ppb, p > 0.05) between groups of cows treated with the long or short pour-on application, respectively. Plasma concentration of fluazuron at second and third application was increased (3.3 and 2.9 times, respectively) in calves under free suckling compared to cows. Nevertheless, both groups of cows and calves showed a significant increase in plasma concentration of fluazuron between times (4.9 times, p < 0.0001 and 2.8 times, p < 0.0001, respectively). In both groups, tick prevalence was 0% throughout the trial, except for day 77, which reached 1%.ConclusionsThe main conclusions of this study were the following: 1) Different administration patterns (long vs. short) did not differ in plasma levels of fluazuron.; 2) Given that only the cows were treated and lactating calves presented higher plasma levels of fluazuron than cows, passage through milk appears to be relevant and possibly due to a cumulative effect and continuous drug intake.

Poisoning of calves reared with cows treated with abamectin

The aim of the present study was to describe an outbreak of poisoning by abamectin in calves less than four months of age whose mothers were treated with a pour-on product containing this ingredient. The diagnosis was based on the history, clinical signs, absence of macroscopic and histopathological findings (characteristic of this type of poisoning) and the detection of abamectin in tissues of the animals submitted to necropsy. Based on this report, the recommendation is the use with caution of pour-on formulations containing abamectin on cows having given birth less than four months earlier.

Optimizing long-acting acaricide use for integrated tick management of Rhipicephalus australis-infesting cattle in New Caledonia.

The tick Rhipicephalus australis, formerly known as Rhipicephalus microplus, is the most economically important ectoparasite of livestock in New Caledonia, affecting cattle health and production. Decades of control attempts based on the application of chemical acaricides have exerted a strong selective pressure on R. australis populations, some of which have evolved resistance to these treatments. Research to develop integrated tick control programs is now focused on decreasing applications of chemicals. This study reports the implementation of a method of pasture and herd management involving minimal strategic use of long-acting acaricides, here defined as those having substantial efficacy against larvae for several weeks. Diverse parameters concerning the utilization of long-acting acaricides in association with pasture and herd management on 21 New Caledonian farms over a 5-year period were analyzed to optimize their strategic use. Longer larval acaricidal effect was achieved with a commercial pour-on formulation of fluazuron than with a commercial injectable (subcutaneous) formulation containing 3.15% ivermectin. Pasture and herd management allowed an increase in the delay between a long-lasting acaricide application and the subsequent acaricide treatment from 11.0weeks to 17.7weeks. However, if ticks were detected and reported by producers on the day of a long-acting acaricide application, the delay to the following treatment was reduced from 18.5weeks to 11.2weeks. The impact of a long-acting acaricide treatment on larval populations in pastures was greatest with a stocking rate of 5 animals per hectare grazing during 1week. These results provide science-based evidence to cattle producers for adaptive integrated tick management in order to delay the development of acaricide resistance.

Tickicidal Efficacy of a Pour-on Formulation of Flumethrin against Ticks on Dogs

Tickicidal Efficacy of a Pour-on Formulation of Flumethrin against Ticks on Dogs

Do rainfall and tick burden affect the efficacy of pour-on formulations against Rhipicephalus (Boophilus) microplus?

Rhipicephalus (Boophilus) microplus is the most important livestock tick, causing economical losses especially in tropical and subtropical regions. Pour-on formulations using synthetic chemicals, remain the most farmer friendly conventional form of tick control method. Misuse of acaricides can lead to the emergence of resistance, residual chemicals in animal products, the poisoning of vertebrates and environment contamination. Despite the increase in the use of pour-on formulations, little is known regarding the therapeutic and residual efficacy of these products after the treated animals are exposed to rainfall. Moreover, information is scanty on whether efficacy is modulated by different levels of tick burden. Three studies were conducted. In the two first experiments, we evaluated the therapeutic and residual efficacies of commercial pour-on products (fluazuron 2.5 mg/kg and fipronil 1.0 mg/kg, respectively) on cattle naturally infested with R. (B.) microplus under the condition of simulated rainfall. In the third study, we investigated whether tick burden affects the efficacy of the drugs used a chemical control method involving three different formulations (Day 0: cypermethrin 5.0 mg/kg + chlorpyrifos 7.0 mg/kg + citronellal 0.5 mg/kg; Day 7: fluazuron 3.0 mg/kg + abamectin 0.5 mg/kg and Day 56: fipronil 1.0 mg/kg + fluazuron 3.0 mg/kg). Tick counts were performed on different days to assess efficacy. It was observed that the residual efficacy of the commercial formulations was lower on animals that received simulated rain. In addition, therapeutic and residual efficacies of the products were reduced in the group of animals with a high tick burden of R. (B.) microplus. In conclusion, rainfall decreases the efficacy of acaricides. Also, the tick burden must be considered when selecting a pour-on formulation.

Assessing anthelmintic resistance risk in the post-genomic era: a proof-of-concept study assessing the potential for widespread benzimidazole-resistant gastrointestinal nematodes in North American cattle and bison.

As genomic research continues to improve our understanding of the genetics of anthelmintic drug resistance, the revolution in DNA sequencing technologies will provide increasing opportunities for large-scale surveillance for the emergence of drug resistance. In most countries, parasite control in cattle and bison has mainly depended on pour-on macrocyclic lactone formulations resulting in widespread ivermectin resistance. Consequently, there is an increased interest in using benzimidazole drugs which have been used comparatively little in cattle and bison in recent years. This situation, together with our understanding of benzimidazole resistance genetics, provides a practical opportunity to use deep-amplicon sequencing to assess the risk of drug resistance emergence. In this paper, we use deep-amplicon sequencing to scan for those mutations in the isotype-1 β-tubulin gene previously associated with benzimidazole resistance in many trichostrongylid nematode species. We found that several of these mutations occur at low frequency in many cattle and bison parasite populations in North America, suggesting increased use of benzimidazole drugs in cattle has the potential to result in widespread emergence of resistance in multiple parasite species. This work illustrates a post-genomic approach to large-scale surveillance of early emergence of anthelmintic resistance in the field.

Comparison of parasite load and average daily weight gain in suckling beef calves treated with macrocyclic lactones in either an extended-release injectable or a pouron formulation

The objective of the study was to compare the effect of macrocyclic lactones anthelmintic in either an extended-release injectable (ERI) or a pour-on (PO) formulation on parasite load and average daily weight gain in suckling beef calves. Spring born Angus cross beef calves (n=1228) grazing on 17 pastures from 4 cow-calf operations in Washington State during 2017 were included. Calves in each pasture were randomly assigned to ERI (n=611; Long Range®, 50 mg of eprinomectin/ml, Merial Inc., Duluth, GA, USA; @ 50 mg or 1ml/50 kg BW) or PO (n=671; Ivomec®, 5 mg ivermectin/ml; Merial Inc., Duluth, GA; @ 500 mcg or 1 ml/10 kg BW) treatment 105 days prior to weaning (approximately at 8 months of age) at the time of pasture turn-out in mid-May. Calves were weighed initially, at mid-trail (approximately 55 days after start) and at weaning. Faecal samples were taken from a subset of calves (n=30/pasture; 15 in each treatment group, a total of 510 calves) for faecal egg counts (FEC) at the start of the study and again at 15, 30, 60 and 90 d later. The data were analyzed using a mixed model. The FEC did not vary between calves in treatment and control groups on day 0 (P>0.1). However, accounting for temperament by treatment interaction, ERI treated calves had lower FEC compared with PO treated calves on day 90 (P<0.01). Accounting for gender (P<0.05), temperament (P<0.05) and treatment by age (P<0.01), ERI treated calves gained more weight compared with PO treated calves (P<0.01). In conclusion, treatment of nursing calves at late-spring with ERI experienced a reduction in GI (gastrointestinal) parasite load and a measurable but modest increase in weight gain compared with calves treated with PO.

Fipronil and ivermectin treatment of cattle reduced the survival and ovarian development of field-collected Anopheles albimanus in a pilot trial conducted in northern Belize

BackgroundMost malaria vector control programmes rely on indoor residual spraying of insecticides and insecticide-treated bed nets. This is effective against vector species that feed indoors at night and rest inside the house afterwards. In Central America, malaria vectors have different behaviours and are typically exophagic (i.e., bite outdoors), exophilic (i.e., remain outdoors after feeding), and zoophagic (i.e., as likely to feed on non-humans as humans). Thus, malaria elimination in Central America may require additional tactics. This pilot study investigated whether commercially-available products used to treat livestock for ticks could also be used to kill and/or sterilize zoophagic malaria vectors that feed on treated cattle in Belize.MethodsCattle were treated with either a pour-on formulation of 1% fipronil (3 heifers) or injection of 1% ivemectin (1 heifer). Control heifers (n = 2) were left untreated. Field-collected Anopheles albimanus contained in screen-top cages were strapped onto cattle at 2, 5, 7, and 14 days after treatment. Mosquito mortality was monitored once a day for 4 successive days. Surviving mosquitoes were dissected to assess blood meal digestion and ovarian development.ResultsA total of 1078 female An. albimanus mosquitoes were fed and monitored for mortality. Both fipronil and ivermectin significantly reduced survivorship of An. albimanus for up to 7 days after treatment. By 14 days, efficacy had declined. The ivermectin treatment completely lost its effectiveness and even though the fipronil-treated heifers were still killing significantly more mosquitoes than the untreated heifers, the amount of mosquito killing had diminished greatly. Both treatments significantly reduced ovary development in mosquitoes fed on treated cattle for the duration of the 2-week trial.ConclusionsTreatment of cattle in northern Belize with topical fipronil and injectable ivermectin had significant lethal and sublethal effects on wild An. albimanus females. These results suggest that efforts towards eliminating residual transmission of malaria by zoophagic vectors in Central America may benefit by the judicious, targeted treatment of livestock with mosquitocidal compounds, such as fipronil or ivermectin.

Repellency effect of flumethrin pour-on formulation against vectors of Crimean-Congo haemorrhagic fever.

Ticks are able to transmit important diseases to humans, including Rocky Mountain spotted fever, Q fever, Crimean-Congo haemorrhagic fever, summer Russian encephalitis, and relapsing fever. To determine the repellency effect of 1% flumethrin pour-on formulation against hard ticks. The concentration of flumethrin pour-on formulation was 1 mg/10 kg body weight and was administered on the dorsal midline from the head to the base of the tail. The livestock included cows, goats, oxen and sheep in 2 villages in Ardabil Province, Islamic Republic of Iran. We studied 200 livestock comprising 5 age groups (< 2, 3-4, 5-6, 7-8 and >8 years). The main hard ticks identified were Hyalomma species (62.5%) and Rhipicephalus bursa (37.5%). In the treatment village, the maximum number of ticks per animal was 11.6 in oxen, 9.5 in sheep, 8.9 in goats and 8.6 in cattle. The repellency effect of flumethrin remained for 2 months. Flumethrin provided 2 months protection against hard ticks. Therefore, it could be used in the livestock industry. Control of ticks is important for prevention of disease transmission.