The combined effect of bromadiolone and ivermectin (iBr) in controlling both rodents and their fleas.

Rodent pests not only cause severe agricultural loss but also spread zoonotic pathogens to human beings. Anticoagulant rodenticides are widely used to decrease the population densities of rodents but often lead to the spillover of ectoparasites because fleas and ticks may gather on surviving rodents. Therefore, it is necessary to kill fleas and ticks before culling rodents to minimize the risk of pathogen transmission. In this study, we used a mixture of ivermectin (an antiparasitic drug) and bromadiolone (an anticoagulant rodenticide) to control both rodent and flea/tick abundances. We found that in a laboratory test, 0.01% ivermectin bait was not lethal for greater long-tailed hamsters after 7 days of treatment, while 0.1% ivermectin bait was lethal for approximately 33% of treated rodents. In a field test, bait containing 0.001%, 0.005%, 0.01%, and 0.05% ivermectin decreased the number of fleas per vole of Brandt's voles to 0.42, 0.22, 0.12, and 0.2, respectively, compared with 0.77 in the control group, indicating that 0.01% ivermectin bait performed best in removing fleas. In another laboratory test, bait containing a 0.01% ivermectin and 0.005% bromadiolone mixture caused the death of all voles within 6-14 days after the intake of the bait. In the field test, the bait containing 0.01% ivermectin and 0.005% bromadiolone reduced the average number of fleas per vole to 0.35, which was significantly lower than the 0.77 of the control group. Our results indicate that a 0.01% ivermectin and 0.005% bromadiolone mixture could be used to control both rodents and fleas to minimize the spillover risk of disease transmission when using traditional rodenticides.

Efficacy of an oral formulation of afoxolaner and milbemycin oxime against Tunga penetrans in naturally infected dogs.

BACKGROUND: The sand flea Tunga penetrans is one of the agents of tungiasis, an important parasitic skin disease affecting humans and several mammalian species. Tungiasis is mainly observed in disadvantaged rural and peripheral urban communities in Latin America and sub-Saharan Africa. The dog is a major reservoir of Tunga fleas. Hematophagous adult female Tunga spp. embed and grow in their host's epidermis and cause cutaneous inflammatory disorders. NexGard Spectra® is an orally administered endectocide for dogs, a co-formulation of the isoxazoline afoxolaner and the macrocyclic lactone milbemycin oxime. The objective of this study was to assess the efficacy of this product against canine tungiasis. METHODS: A blinded, negative-controlled field trial was conducted in a Brazilian community known to be highly endemic for tungiasis. Sixty-six dogs naturally infected with live T. penetrans were randomly allocated to a treated group (44 dogs) and an untreated control group (22 dogs). In a first phase, dogs from the treated group were treated on days 0, 30, and 60. Efficacy was evaluated on the basis of the macroscopic parasitic skin lesions (Fortaleza classification) on days 7, 14, 21, 30, 45, 60, 75, and 90. In a second phase, to evaluate natural reinfections, all dogs were treated on day 90 and evaluated every 2 weeks thereafter until at least 30% of dogs were infected with live sand fleas. RESULTS: During the first phase, efficacy (reduction in live sand fleas) of 92.4% was demonstrated on day 7. From day 14 until day 90, the efficacy of NexGard Spectra® was 100%. In the second phase, all dogs were free of live T. penetrans from 15 until 45 days after the day 90 treatment; 60 days post-treatment, 11% of dogs were reinfected, and 75 days post-treatment, 40% of dogs were reinfected. CONCLUSIONS: NexGard Spectra® was demonstrated to be highly effective against canine tungiasis. In addition to an obvious beneficial effect on the health and welfare of the treated dog, the use of this product may have a one-health benefit on human cases by controlling the main reservoir of sand fleas.

Year-round efficacy of a single treatment of fluralaner injectable suspension (Bravecto Quantum™) against repeated infestations with Rhipicephalus sanguineus (sensu lato) and Ctenocephalides felis in dogs.

BACKGROUND: Poor owner compliance with monthly control measures means that dogs in Australia can remain susceptible to infestations with fleas, present throughout the whole year, and brown dog ticks, which thrive in tropical and subtropical areas. A 150 mg/ml injectable fluralaner suspension (Bravecto Quantum™) was developed to help ensure year-round protection against these parasites. A study investigated the persistent efficacy of this formulation against repeated challenges with Rhipicephalus sanguineus (sensu lato) and Ctenocephalides felis throughout 12 months following a single subcutaneous treatment. METHODS: Twenty dogs were blocked by pre-treatment R. sanguineus s.l. counts and randomized to an untreated control group or to a group treated once, on day 0, with the fluralaner injection (15 mg/kg). Infestations of 50 mixed-sex, unfed adult R. sanguineus s.l. and up to 100 C. felis were done on days 7, 14, 35, 63, 91, 126, 154, 182, 210, 245, 273, 301, 336 and 365. Live flea and tick counts were completed 48 h post-infestation. Flea infestations were also done on day -1, with counts on day 2. Infestations were considered adequate if at each evaluation, at least six dogs in the control group retained at least 20% of tick challenges and 25% of flea challenges. RESULTS: The fluralaner injectable suspension was well tolerated. Efficacy against existing flea infestations was > 99% (arithmetic and geometric means) at 48 h post-treatment. At all subsequent assessments throughout the year following treatment, efficacy against fleas remained at 100%. Arithmetic mean tick count reductions relative to the control group ranged from 97.6% to 100% from day 7 through 11 months and was 92.6% at 12 months (geometric means 95.2% to 100% through 12 months). CONCLUSION: The injectable fluralaner suspension was effective against fleas and brown dog ticks for 12 months following a single treatment. Compared with more frequently administered products where compliance may be suboptimal, the year-round efficacy of this veterinarian-administered fluralaner formulation has the potential to improve owner compliance for control of fleas and ticks. In turn, by reducing the detrimental effects of flea and tick infestations and risk of transmission of flea- and tick-borne pathogens, canine health can be enhanced.

EVALUATING BAITS WITH LUFENURON AND NITENPYRAM FOR FLEA CONTROL ON PRAIRIE DOGS (CYNOMYS SPP.) TO MITIGATE PLAGUE.

Plague, caused by Yersinia pestis, is a widespread threat to endangered black-footed ferrets (Mustela nigripes) and their primary prey, prairie dogs (Cynomys spp.). Wildlife biologists most commonly manage plague using insecticides to control fleas, the primary vectors of Y. pestis. We tested edible baits containing the insecticides lufenuron and/or nitenpyram in prairie dogs. During a laboratory study, we treated 26 white-tailed prairie dogs (Cynomys leucurus) with lufenuron at 300 mg/kg body mass. All animals remained clinically healthy over the 9 wk monitoring period. Although serum lufenuron concentrations were >130 ppb in two treatment groups at week 1, concentrations declined to ≤60 ppb after 3 wk in non-torpid prairie dogs and after 7 wk in torpid prairie dogs. In a field experiment, we tested baits containing a combination of 75 mg lufenuron and 6 mg nitenpyram, respectively, in black-tailed prairie dogs (Cynomys ludovicianus). We uniformly distributed baits at 125 baits/ha on two plots (treated once) and 250 baits/ha on two plots (each treated twice 4.4 wk apart). Following treatments, flea abundance increased on prairie dogs and remained stable in burrows. Our findings indicate that baits containing lufenuron and nitenpyram, at the reported treatment rates, are ineffective tools for flea control on prairie dogs. Future experiments might evaluate efficacy of higher doses of lufenuron and nitenpyram, and repetitive treatments at differing intervals over time to evaluate potentially therapeutic treatments.

Ocimum gratissimum essential oil and eugenol against Ctenocephalides felis felis and Rhipicephalus sanguineus: In vitro activity and residual efficacy of a eugenol-based spray formulation.

Fleas and ticks are among the main ectoparasites that affect pets. The indiscriminate and incorrect use of chemical antiparasitics may be related to increased insect resistance and environmental contamination, requiring prospection for active ingredients that are less harmful to animals, humans and the environment. The use of essential oils and their isolated compounds has been reported as a potential alternative to synthetic antiparasitics, but there is a lack of studies involving the design and development of stable and safe natural products-based formulations. Therefore, the aim of this study was to establish LC50 and LC90 of Ocimum gratissimum essential oil and eugenol on immature stages and adults of Ctenocephalides felis felis and Rhipicephalus sanguineus; and to design and to determine the in vitro efficacy and residual effect of a natural product-based spray formulation for flea and tick control in pets. Bioassays were carried out according to the filter paper impregnation technique for fleas and through the larval packet test for ticks. O. gratissimum essential oil and eugenol presented pulicidal and acaricidal activity in vitro against immature stages and adults of C. felis felis and immature stages of R. sanguineus. The greater potency of eugenol against fleas and ticks led to the choice of eugenol as the active ingredient in the pharmaceutical form developed. The developed eugenol-based sprays presented adequate physical and chemical characteristics and stability, had pulicidal and acaricidal efficacy after 24 h and residual effect against fleas for up to 48 days.

Assembling a safe and effective toolbox for integrated flea control and plague mitigation: Fipronil experiments with prairie dogs.

BACKGROUND: Plague, a widely distributed zoonotic disease of mammalian hosts and flea vectors, poses a significant risk to ecosystems throughout much of Earth. Conservation biologists use insecticides for flea control and plague mitigation. Here, we evaluate the use of an insecticide grain bait, laced with 0.005% fipronil (FIP) by weight, with black-tailed prairie dogs (BTPDs, Cynomys ludovicianus). We consider safety measures, flea control, BTPD body condition, BTPD survival, efficacy of plague mitigation, and the speed of FIP grain application vs. infusing BTPD burrows with insecticide dusts. We also explore conservation implications for endangered black-footed ferrets (Mustela nigripes), which are specialized predators of Cynomys. PRINCIPAL FINDINGS: During 5- and 10-day laboratory trials in Colorado, USA, 2016-2017, FIP grain had no detectable acute toxic effect on 20 BTPDs that readily consumed the grain. During field experiments in South Dakota, USA, 2016-2020, FIP grain suppressed fleas on BTPDs for at least 12 months and up to 24 months in many cases; short-term flea control on a few sites was poor for unknown reasons. In an area of South Dakota where plague circulation appeared low or absent, FIP grain had no detectable effect, positive or negative, on BTPD survival. Experimental results suggest FIP grain may have improved BTPD body condition (mass:foot) and reproduction (juveniles:adults). During a 2019 plague epizootic in Colorado, BTPDs on 238 ha habitat were protected by FIP grain, whereas BTPDs were nearly eliminated on non-treated habitat. Applications of FIP grain were 2-4 times faster than dusting BTPD burrows. SIGNIFICANCE: Deltamethrin dust is the most commonly used insecticide for plague mitigation on Cynomys colonies. Fleas on BTPD colonies exhibit the ability to evolve resistance to deltamethrin after repeated annual treatments. Thus, more tools are needed. Accumulating data show orally-delivered FIP is safe and usually effective for flea control with BTPDs, though potential acute toxic effects cannot be ruled out. With continued study and refinement, FIP might be used in rotation with, or even replace deltamethrin, and serve an important role in Cynomys and black-footed ferret conservation. More broadly, our stepwise approach to research on FIP may function as a template or guide for evaluations of insecticides in the context of wildlife conservation.

Efficacy of two endectoparasiticide products combining fipronil and (S)-methoprene or esafoxolaner with eprinomectin and praziquantel against fleas and intestinal helminths in cats naturally infested in Brazil.

Eprinomectin and praziquantel, nematodicide and cestodicide compounds, are both combined with the insecticide and acaricide compounds fipronil and (S)-methoprene in Frontline® Protect/Broadline®, or esafoxolaner in NexGard® Combo. These topical feline endectoparasiticide products were tested for efficacy against fleas and intestinal helminths in a field trial in Brazil. Flea- and/or helminth-infested domestic cats were treated twice at a monthly interval following label instructions: 160 cats with Frontline® Protect/Broadline® and 165 cats with NexGard® Combo. The flea and intestinal helminth infestations were evaluated using comb counts and copromicroscopy, respectively before first treatment for baseline value, then 9 and 30 days after each treatment for fleas, and 9 days after each treatment for helminths. Multiparasitism was very frequent at baseline, as amongst the 325 included cats, 295, 280, 86 and 93 cats were at least infested with Ctenocephalides fleas, Ancylostoma, Toxocara and Dipylidium caninum, respectively. Efficacies were calculated by comparing the geometric means at baseline and at post-treatment timepoints for each parasite genus/species. Inclusive of both products and of all evaluation timepoints, the Ctenocephalides, Ancylostoma, Toxocara and D. caninum efficacies were at least 98.3%, 99.8%, 99.8% and 96.3%, respectively. No adverse reactions were observed, except for a few instances of mild, transient, and self-resolving hypersalivation occurring on the day of treatment in both groups. This field trial demonstrated high-level efficacy of Frontline® Protect/Broadline® and NexGard® Combo against major parasites of cats in Brazil.

TITLE: Efficacité de deux produits endectoparasiticides associant fipronil et (S)-méthoprène ou esafoxolaner à l'éprinomectine et au praziquantel contre les puces et les helminthes intestinaux chez les chats naturellement infestés au Brésil. ABSTRACT: L'éprinomectine et le praziquantel, composés nématodicides et cestodicides, sont tous les deux associés aux composés insecticides et acaricides fipronil et (S)-méthoprène dans Frontline® Protect/Broadline®, ou esafoxolaner dans NexGard® Combo. Ces produits endectoparasiticides félins topiques ont été testés pour leur efficacité contre les puces et les helminthes intestinaux lors d'un essai sur le terrain au Brésil. Des chats domestiques infestés de puces et/ou d'helminthes ont été traités deux fois à intervalle d'un mois en suivant les instructions d'utilisation, 160 chats avec Frontline® Protect/Broadline® et 165 chats avec NexGard® Combo. Les infestations par les puces et les helminthes intestinaux ont été évaluées en utilisant respectivement par comptage au peigne et par copromicroscopie, avant le premier traitement pour la valeur de base, puis 9 et 30 jours après chaque traitement pour les puces, et 9 jours après chaque traitement pour les helminthes. Le multiparasitisme était très fréquent à l'inclusion puisque parmi les 325 chats inclus, 295, 280, 86 et 93 chats étaient au moins infestés respectivement par les puces Ctenocephalides, ou Ancylostoma, Toxocara et Dipylidium caninum. Les efficacités ont été calculées en comparant les moyennes géométriques au départ et aux points d'évaluation post-traitement pour chaque genre/espèce de parasite. En incluant les deux produits et tous les points temporels d'évaluation, les efficacités contre Ctenocephalides, Ancylostoma, Toxocara et D. caninum étaient respectivement d'au moins 98,3 %, 99,8 %, 99,8 % et 96,3 %. Aucun effet indésirable n'a été observé à l'exception de quelques cas d'hypersalivation légère, transitoire et auto-résolvante survenant le jour d'un traitement dans les deux groupes. Cet essai sur le terrain a démontré une efficacité de haut niveau de Frontline® Protect / Broadline® et NexGard® Combo contre les principaux parasites des chats au Brésil.

Oral pharmacokinetic profile of fipronil and efficacy against flea and tick in dogs.

Fipronil (FIP) is an ectoparasiticide of the phenylpyrazole class, used in veterinary medicine in topical form. Supported by evidence of uncontrolled human exposure to FIP and environmental damage caused by commercially available formulations, its use by oral administration has become promising. The effectiveness of FIP against the flea Ctenocephalides felis felis and the tick Rhipicephalus sanguineus and its pharmacokinetics and main active metabolite, fipronil sulfone (SULF) were evaluated after single oral administration of tablets in three different doses (2, 4, and 6 mg/kg) in dogs. Through the plasma concentration curves, it was possible to observe that the FIP showed rapid absorption and metabolization and slow elimination. The values of Cmax (ß = 0.7653) and AUC0- t (ß = 0.3209) did not increase proportionally with increasing dose. At 48 h after treatment, doses of 4 mg/kg (AUC0- t  = 442.39 ± 137.35 µg/ml*h) and 6 mg/kg (AUC0- t  = 421.32 ± 102.84 µg/ml*h) provided 100% and 99% efficacy against fleas, and 95% and 98% against ticks, respectively. The estimated EC90 of FIP +SULF was 1.30 µg/ml against C. felis felis and 2.16 µg/ml against R. sanguineus. The correlation between the FIP pharmacokinetic and efficacy data demonstrated its potential for oral administration in the form of tablets for the control of ectoparasites in dogs, as a safer alternative for animals, humans, and the environment, aligned with the One Health concept.

Therapeutic Potential of Tea Tree Oil for Tungiasis.

Tungiasis (sand flea disease) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, into a person's skin usually in their feet. The disease inflicts immense pain and suffering on millions of people, particularly children. The condition is most prevalent in Latin America, the Caribbean, and sub-Saharan Africa. Currently, there is no standard drug treatment for tungiasis. The available treatment options are fairly limited and unrealistic to use in endemic areas; as a result, in desperation, the affected people do more harm to themselves by extracting the fleas with non-sterile instruments, further exposing themselves to secondary bacterial infections and/or transmission of diseases such as hepatitis B virus, hepatitis C virus, or HIV. This highlights the urgent need for simpler, safer, and effective treatment options for tungiasis. Tea tree oil (TTO) has long been used as an antiseptic with extensive safety and efficacy data. The evidence on parasiticidal properties of TTO against ectoparasites such as head lice, mites, and fleas is also compelling. The purpose of this review is to discuss the current tungiasis treatment challenges in endemic settings and highlight the potential role of TTO in the treatment of tungiasis.

Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) against natural flea and tick infestations on dogs presented as veterinary patients in Europe.

BACKGROUND: A pivotal randomised, blinded, positive-controlled, multicentre, European field study was conducted to evaluate the effectiveness and safety of a novel combination tablet of lotilaner and milbemycin oxime (Credelio® Plus) administered orally to client-owned dogs naturally infested with fleas and/or ticks. METHODS: In this field study, households with flea- or tick-infested dog(s) were enrolled on Day 0 into the study to provide data for either the tick or flea infestation cohorts. Households were randomised in a 2:1 ratio to receive either the combination investigational product (IP, Credelio Plus® tablets) or the control product (CP: Nexgard Spectra® tablets). Dogs were administered IP (flea cohort n = 135; tick cohort: n = 147) or CP (flea cohort: n = 67; tick cohort: n = 74) once every 4 weeks for a total of three times at a dose rate of 20.0-41.5 mg/kg bodyweight lotilaner and 0.75-1.53 mg/kg bodyweight milbemycin oxime (IP) or as recommended (CP). Percentage reduction was calculated by comparing individual dog flea and tick counts at each assessed post-treatment time point to their respective baseline (pre-treatment) infestation. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea-allergic dogs on the days that flea counts were performed. RESULTS: Flea effectiveness of Credelio Plus® after 3 consecutive monthly treatments was 100% against Ctenocephalides felis, C. canis and Pulex irritans. Tick effectiveness of Credelio Plus® over the same time frame was 99.3% for Ixodes ricinus and 100% against Rhipicephalus sanguineus (s.l.). Flea effectiveness of the CP after three consecutive monthly treatments was 100% against C. felis, C. canis and P. irritans. Tick effectiveness of the CP over the same time frame was 99.8% for I. ricinus and 100% against R. sanguineus. Credelio Plus® was well tolerated based on the safety assessments in all treated dogs in this field study. Within both treatment groups there was a reduction in total FAD scores from baseline. CONCLUSIONS: This pivotal European field study demonstrated the excellent effectiveness and safety of a combination of lotilaner and milbemycin oxime (Credelio Plus®) administered orally to dogs naturally infested with fleas and/or ticks.

Analysis of gaps in feline ectoparasiticide purchases from veterinary clinics in the United States.

BACKGROUND: The study objective was to examine cat owner ectoparasiticide purchases in the United States and estimate the impact of purchase gaps on timely ectoparasite protection administration. These purchase gaps lead to periods of time when cats are unprotected from ectoparasites. METHODS: Ectoparasiticide purchase transactions for individual cats from 671 U.S. veterinary clinics from January 1, 2017 through June 30, 2019 were evaluated to determine time "gaps" between doses of ectoparasiticides purchased in a defined 12-month period. Ectoparasiticides examined were topically applied products that contained fluralaner, fipronil/(S)-methoprene/pyriproxyfen, imidacloprid/pyriproxyfen or selamectin as active ingredients. The duration of protection following administration of one dose was 8-12 weeks for the fluralaner-containing product and one month for the other products. RESULTS: Ectoparasiticide purchase records were obtained from 114,853 cat owners and analysis found that most owners bought ≤ 6 months of protection during the year, with 61-75% (depending on the product) purchasing just 1-3 months of protection. The size of the average purchase gap was determined for all dose combinations out to 12 months of protection (5-7 doses for fluralaner and 12 doses for the other three products dosed monthly. The largest gaps occurred between the first and second doses and the second and third doses. Average purchase gaps for the four different products between doses 1 and 2 ranged from 11.2 to 13.9 weeks and between doses 2 and 3 ranged from 7.7 to 12.2 weeks. The fraction of purchases separated by gaps and the average length of the gap tended to decrease with increasing number of doses purchased. Owners purchasing the 8 to 12-week duration product containing fluralaner provided ectoparasite protection ("doses plus gap period") for a larger proportion of each 2-dose period compared with owners purchasing products administered monthly. CONCLUSIONS: When cat owners purchase flea and tick medication, gaps between subsequent purchases reduces the proportion of time ectoparasite protection can be provided. The duration of the gap between doses has an impact on the effectiveness of flea/tick medication because it inserts a period without flea and tick protection between doses of flea and tick medication. The gaps between purchases were shorter and the period of ectoparasite protection was larger for owners purchasing a 12-week product than for owners purchasing a monthly product.

Flea and tick treatment satisfaction, preference, and adherence of US cat owners prescribed topical fluralaner (Bravecto® Topical Solution for Cats).

Background: Fluralaner is a novel isoxazoline compound and the only systemically distributed ectoparasiticide approved in the United States for redosing at up to 12-week intervals for flea and tick control in cats. Other feline ectoparasiticides, including other systemic isoxazolines, are approved for redosing at monthly intervals. A survey developed in 2016 to assess the satisfaction, preference, and adherence of dog owners prescribed fluralaner as an ectoparasiticide with the treatment and veterinary flea and tick protection recommendations was adapted for completion by cat owners in the USA. Aim: The study objective was to use cat-owner survey data obtained at US veterinary practices to assess client satisfaction and utilization practices for fluralaner, and to evaluate owner adherence to current flea and tick control recommendations. Methods: US veterinary practices (n = 26) were asked to obtain completed surveys for up to 25 active clients who were currently treating their cats with a topical preparation of fluralaner for flea and tick control. Clients who had previously used flea and tick products for cats other than fluralaner were enrolled in the study. Participating cat owners completed an 11-question survey on their satisfaction with, preference for, and adherence to treatment recommendations for topically applied fluralaner as a feline flea and tick control medication. Results: The average cat in this study had a mean (± SD) body weight of 5.1 (± 0.9) kg and was 7.1 (±1.4) years old. Most cats lived in a home versus an apartment and more than half spent some time outside. Satisfaction was assessed with a 5-point Likert scale, with nearly all cat owners (97%) indicating that they were satisfied or very satisfied with fluralaner. Most of them (66%) had previously used other monthly flea and tick products for cats. Owners were not excluded if they had previously used a canine flea and tick product. The extended dosing interval up to 12 weeks was the most frequently selected benefit of fluralaner. Nearly 9 out of 10 respondents indicated they readministered fluralaner mostly on time or delayed by a few days, and most said they were more likely to give a repeat dose of fluralaner at the recommended redosing interval compared to monthly products. 87% of the responding cat owners preferred topical fluralaner over the monthly flea and tick products they had used. Conclusion: The extended dosing interval of up to 12 weeks was the leading preference factor and the key driver of user satisfaction with fluralaner leading to improved adherence to redosing recommendations. Cat owners said they were more likely to administer fluralaner at the recommended redosing interval compared to monthly products, indicating that less frequent redosing contributes to improved adherence.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against adult cat flea Ctenocephalides felis and flea egg production in cats.

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard® Combo, a novel topical endectoparasiticide formulation for cats. The efficacy of this novel formulation against adult and immature stages of Ctenocephalides felis fleas was tested in four experimental studies. Two studies were designed to test adulticide efficacy, one to test inhibition of immature stages, and one to test both adulticide efficacy and inhibition of immature stages. In each study, cats were randomly allocated to a placebo control group or to a novel formulation group treated once at the minimum recommended dose. Cats were experimentally infested weekly for one to two months with unfed C. felis originating from North America or Europe. For adulticide efficacy evaluations, live fleas were counted 24 h after treatment and after subsequent weekly infestations. For immature stages, flea eggs were collected and counted weekly for evaluation of egg production inhibition and incubated for larval hatching evaluation. In the three studies testing adult fleas, curative efficacies, 24 h after treatment, were 92.1%, 98.3% and 99.7%; preventive weekly efficacies, 24 h after weekly infestations, remained higher than 95.5% for at least one month. In the two studies testing immature stages, egg production and larval hatching was significantly reduced for at least one month. These studies provide robust evidence of efficacy of the novel formulation against experimental adult flea infestations and for the prevention of environmental contamination by immature flea stages, for at least one month.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre la puce du chat adulte Ctenocephalides felis et la production d'œufs de puce chez le chat. ABSTRACT: L'esafoxolaner, un énantiomère purifié de l'afoxolaner aux propriétés insecticides et acaricides, est associé à l'éprinomectine et au praziquantel dans NexGard® Combo, une nouvelle formulation endectoparasiticide topique pour chats. L'efficacité de cette nouvelle formulation contre les stades adultes et immatures des puces Ctenocephalides felis a été testée dans quatre études expérimentales. Deux études ont été conçues pour tester l'efficacité des adulticides, une pour tester l'inhibition des stades immatures et une pour tester à la fois l'efficacité des adulticides et l'inhibition des stades immatures. Dans chaque étude, les chats ont été répartis au hasard dans un groupe témoin placebo ou dans un groupe de formulation traité une fois par la nouvelle formulation à la dose minimale recommandée. Des chats ont été expérimentalement infestés chaque semaine pendant un à deux mois par des C. felis non nourris provenant d'Amérique du Nord ou d'Europe. Pour les évaluations de l'efficacité des adulticides, les puces vivantes ont été comptées 24 heures après le traitement et après les infestations hebdomadaires suivantes. Pour les stades immatures, les œufs de puces ont été collectés et comptés chaque semaine pour l'évaluation de l'inhibition de la production d'œufs, et incubés pour l'évaluation de l'éclosion des larves. Dans les trois études testant les puces adultes, les efficacités curatives, 24 heures après le traitement, étaient de 92,1 %, 98,3 % et 99,7 %, et les efficacités hebdomadaires préventives, 24 heures après les infestations hebdomadaires, sont restées supérieures à 95,5 % pendant au moins un mois. Dans les deux études testant les stades immatures, la production d'œufs et l'éclosion des larves ont été considérablement réduites pendant au moins un mois. Ces études fournissent des preuves solides de l'efficacité de la nouvelle formulation contre les infestations expérimentales de puces adultes et pour la prévention de la contamination environnementale par les stades de puces immatures, pendant au moins un mois.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against fleas in cats, under field conditions.

Esafoxolaner is a purified afoxolaner enantiomer with insecticidal and acaricidal properties. It is combined with eprinomectin and praziquantel, nematodicidal and cestodicidal compounds, in a novel topical endectoparasiticide formulation for cats. This novel formulation was tested in four field studies, in the United States, Europe, Japan and Australia. In all studies, naturally flea-infested domestic cats were treated with the novel formulation at the label dose and conditions of use. The main objective, identical in the four studies, was to assess efficacy on fleas, based on comparison of mean number of fleas found on infested cats before and one month after treatment. Tolerance to the product was also evaluated in the four studies. Otherwise, the studies had some differences in their design and secondary objectives, for example testing for a reduction in flea infestation-related cutaneous signs, testing of one treatment or of three monthly treatments, and use of a positive control group. In the four studies, a total of 307 cats were treated with the novel formulation. The reduction of fleas one month after treatment was 97.7%, 98.8%, 100% and 99.7% in the United States, Europe, Japan and Australia, respectively. There were no significant health abnormalities attributed to treatment in any of the studies.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre les puces chez les chats, dans des conditions de terrain. ABSTRACT: L'esafoxolaner est un énantiomère d'afoxolaner purifié aux propriétés insecticides et acaricides, et il est associé à l'éprinomectine et au praziquantel, des composés nématodicides et cestodicides, dans une nouvelle formulation d'endectoparasiticide topique pour chats. Cette nouvelle formulation a été testée dans quatre études sur le terrain, aux États-Unis, en Europe, au Japon et en Australie. Dans toutes les études, des chats domestiques naturellement infestés de puces ont été traités avec la nouvelle formulation à la dose et aux conditions d'utilisation indiquées sur l'étiquette. L'objectif principal, identique dans les quatre études, était d'évaluer l'efficacité contre les puces, sur la base de la comparaison du nombre moyen de puces trouvées sur des chats infestés avant et un mois après le traitement. La tolérance à l'application du produit a également été évaluée dans les quatre études. Sinon, les études présentaient des différences dans leur conception et leurs objectifs secondaires, par exemple test de réduction des signes cutanés liés à l'infestation par les puces, test d'un traitement ou de trois traitements mensuels, utilisation d'un groupe témoin positif. Dans les quatre études, un total de 307 chats ont été traités avec la nouvelle formulation. La réduction du nombre de puces un mois après le traitement était de 97,7 %, 98,8 %, 100 % et 99,7 % aux États-Unis, en Europe, au Japon et en Australie, respectivement. Aucune anomalie de santé significative n'a été attribuée au traitement dans aucune des études.

Efficacy of lotilaner (Credelio™) against experimentally induced infestations of the adult cat flea, Ctenocephalides felis, and flea eggs following oral administration to cats.

BACKGROUND: Credelio™ (lotilaner; Elanco) is indicated for the treatment of flea and tick infestations on cats at a recommended lotilaner dose rate of 6-24 mg/kg. This study evaluated the efficacy and safety of lotilaner following a single oral administration to cats for the treatment and prevention of adult Ctenocephalides felis fleas and flea egg production under laboratory conditions. METHODS: Two treatment groups of ten cats each were used in this study. One group was treated with lotilaner at a dose rate of 6-9 mg/kg on Day 0 and the other group served as the control group. Each cat was infested with 100 unfed adult fleas on days -1, 6, 13, 20 and 29. At 24 h post-treatment or post-infestation, each cat was combed to remove and count adult live fleas. At each time point, flea eggs were also collected and counted from under each cat cage. RESULTS: Following a single oral administration of lotilaner at a minimum dose rate of 6 mg/kg (range 6.00-8.57 mg/kg), the lotilaner group displayed 100%, 100%, 99.9%, 99.9% and 99.8% efficacy against adult live flea counts as compared to the control group on Days 1, 7, 14, 21 and 30, respectively. At each time point, adult flea counts from the lotilaner-treated cats were significantly lower (P < 0.0001) than from the control group. A mean flea egg count of 22.6 in the lotilaner-treated cats (compared to 441.7 in the control animals) was observed 24 h post-treatment. No eggs were present from any of the treated cats on Days 7, 14 and 30 and a single egg was detected on a single treated cat on Day 21. One adverse event (regurgitated food) was observed during the study in one treated cat approximately 1 h after dosing. CONCLUSIONS: Lotilaner was well tolerated; only one adverse event was observed in the treated group. Virtually all adult fleas were killed within 24 h post-treatment or post-infestation in cats treated with a single dose of lotilaner as compared to the control group, thus significantly reducing the number of flea eggs being produced for 30 days after treatment.

A randomized, controlled field study to assess the efficacy and safety of lotilaner flavored chewable tablets (Credelio™ CAT) in eliminating fleas in client-owned cats in the USA.

BACKGROUND: Studies show that the novel isoxazoline, lotilaner (Credelio™ CAT; Elanco Animal Health), which is administered orally to cats, provides rapid and sustained flea kill for least 1 month following administration with a wide safety margin. A clinical trial was undertaken to confirm its efficacy, impact on flea allergy dermatitis (FAD) and safety under field conditions. METHODS: A total of 343 cats were enrolled in the study at 11 veterinary clinics in the USA. Upon inclusion, cat households were randomized at a ratio of 2:1 to receive lotilaner tablets at the recommended dose (minimum 6 mg/kg) or a topical formulation containing fipronil + S-methoprene (Frontline® Plus for cats; Boehringer Ingelheim), administered per label. Owners were dispensed treatments for administration on days 0, 30 and 60; all household cats were administered the same treatment. Flea counts were made on primary cats (1 cat per household) on days 0 (pre-treatment), 30, 60 and 90. Flea allergy dermatitis was assessed on days 30, 60 and 90 for all cats with signs of FAD on day 0. Lotilaner-treated cats were also assessed for their acceptance of oral tablet administration by the pet owner, and safety was assessed for all cats in both groups. RESULTS: Lotilaner efficacy was 98.3, 99.9 and 99.9% on days 30, 60 and 90, respectively, while the efficacy of fipronil + S-methoprene was 61.6, 75.4 and 84.7%, respectively (P < 0.0001, within both groups and all days). Flea counts were significantly lower in the lotilaner group than in the fipronil + S-methoprene group (P < 0.0001) on each assessment day. On day 90, 98.3% of lotilaner-treated cats and 28.8% of fipronil + S-methoprene-treated cats were free of fleas. Owners successfully administered 99.5% of tablets to their cats. Total FAD score was reduced significantly following treatment in both groups by day 30 (lotilaner: P < 0.0001; fipronil + S-methoprene: P = 0.0041) and continued to decrease following multiple treatments. Total FAD scores were also significantly lower in the lotilaner group than in the fipronil + S-methoprene group on day 90 (P = 0.0006 for FAD total score). Pruritus scores were significantly lower in the lotilaner group on all assessment days. CONCLUSION: A single lotilaner treatment, administered by the pet owner, was > 98% efficacious in reducing flea counts within 30 days. Three consecutive monthly lotilaner treatments resulted in nearly 100% reduction in flea infestation. In the evaluations of flea counts, number of cats free from fleas and pruritus FAD score, lotilaner was shown to be superior to fipronil + S-methoprene at all time points. Lotilaner was more efficacious than fipronil + S-methoprene and was associated with greater reduction in FAD signs. Lotilaner flavored tablets were well accepted by cats. Adverse reactions were mild and infrequent, confirming the safety of lotilaner tablets in client-owned cats.

Ecology and Management of Plague in Diverse Communities of Rodents and Fleas.

Plague originated in Asia as a flea-borne zoonosis of mammalian hosts. Today, the disease is distributed nearly worldwide. In western United States of America, plague is maintained, transmitted, and amplified in diverse communities of rodents and fleas. We examined flea diversity on three species of prairie dogs (Cynomys spp., PDs) and six species of sympatric small rodents in Montana and Utah, United States of America. Among 2896 fleas, 19 species were identified; 13 were found on PDs and 9 were found on small rodents. In Montana, three flea species were found on PDs; the three species parasitize PDs and mice. In Utah, 12 flea species were found on PDs; the 12 species parasitize PDs, mice, voles, chipmunks, ground squirrels, rock squirrels, and marmots. Diverse flea communities and their willingness to parasitize many types of hosts, across multiple seasons and habitats, may favor plague maintenance and transmission. Flea parasitism on Peromyscus deer mice varied directly with elevation. Fleas are prone to desiccation, and might prosper at higher, mesic elevations; in addition, Peromyscus nest characteristics may vary with elevation. Effective management of plague is critical. Plague management is probably most effective when encompassing communities of rodents and fleas. Treatment of PD burrows with 0.05% deltamethrin dust, which suppressed fleas on PDs for >365 days, suppressed fleas on small rodents for at least 58 days. At one site, deltamethrin suppressed fleas on small rodents for at least 383 days. By simultaneously suppressing fleas on PDs and small rodents, deltamethrin should promote ecosystem resilience and One Health objectives.

Fleas infesting cats and dogs in Great Britain: spatial distribution of infestation risk and its relation to treatment.

The spatial pattern of flea (Siphonaptera: Pulicidae) infestation risk in cats and dogs across Great Britain is quantified, using data collected from a national survey undertaken in 2018, with particular attention given to the association between insecticidal treatment and infestation risk. Flea infestation risk declined significantly from south to north. None of the factors: pet breed, sex, neutered status or whether the pet had been abroad, showed any relationship with the underlying geographic distribution, which is most likely to be associated with climatic factors. However, overall, only 23.6% of the cats and 35% of the dogs inspected had been treated with identifiable flea products that were still 'in date' at the point of inspection. The percentage of owners treating their pet broadly followed infestation risk. The insecticide fipronil is a common active in a wide range of flea treatments and was the most frequently applied insecticide class, particularly in cats. However, 62% of cats and 45% of dogs that had been treated with a fipronil-based product that was 'in date' at the point of inspection still had fleas. Persistent flea infestation is likely to be due to a range of factors, including compliance and application failure, but the data provide strong inferential evidence for a lack of efficacy of fipronil-based products. Given the ubiquity of flea infestation, this finding and the relatively low-level of treatment compliance, highlight a clear need for greater owner education about the importance of flea management and a better understanding of the efficacy of different products.