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Fluralaner is a recent external parasiticide, first of a new class of drugs (isoxazoline parasiticides). It is widely used in companion animals both for its wide spectrum (fleas, ticks and other mites) but also for its ease of use (oral tablets given once for 1 to three months). It is known to be eliminated primarily via the feces (>90%) as the unchanged compound. In zoo carnivores, controlling external parasites is also important and there are no specific products with a marketing authorization to control them. The first objective of this study was to evaluate the pharmacokinetic profile of fluralaner in zoo carnivores. The second objective was to demonstrate that fluralaner can be eliminated over a prolonged period of time, thereby raising questions about its potential impact on non-target species such as arthropods. After adjusting the oral dose using allometric equations, animals were dosed and fecal samples were collected on a regular basis for up to three months to determine the fecal elimination curve of fluralaner as a surrogate of plasma kinetics (for ethical and safety reasons, plasma samples were not considered). All samples were analyzed with a validated LC-MSMS technique. Our results show that, despite limitations and a limited number of animals included, most carnivores eliminate fluralaner in their feces for several weeks to months (in Lions, fluralaner was still detectable after 89 days). To our knowledge, this is the first study demonstrating such a long elimination period in animals. Further studies would be required to investigate the risk associated with the presence of active residues in other carnivore feces for the environment, especially in dogs and cats, considering the large use of this class of compounds.

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Among approaches aimed at reducing Lyme disease risk in the environment, those targeting reservoirs of Borrelia burgdorferi Johnson are promising because they have the potential to reduce both the density of questing Ixodes scapularis Say (Acari: Ixodidea) ticks and the prevalence of B. burgdorferi in the tick population. In this 4-yr field study, we treated a population of wild small mammals with 2 densities of fluralaner baits and investigated the effect of the treatment on 3 parameters of the endemic cycle of B. burgdorferi: (i) the prevalence of infected Peromyscus mice (PIM), (ii) the density of questing nymphs (DON), and (iii) the prevalence of infected questing nymphs (NIP). We demonstrated that fluralaner baiting is effective at reducing tick infestation of Peromyscus mice, the main reservoir of B. burgdorferi in central and northeastern North America, in the laboratory and the field. Results from this study showed a significant decrease in B. burgdorferi infection in mice (odds ratio: 0.37 [CI95: 0.17 to 0.83]). A reduction in the DON between 45.4% [CI95: 22.4 to 61.6] and 62.7% [CI95: 45.9 to 74.2] occurred in treated area when compared with control areas. No significant effect was reported on the NIP. These results confirm the hypothesis that fluralaner baits have an effect on B. burgdorferi endemic cycle, with the potential to reduce the density of B. burgdorferi-infected ticks in the environment. Further studies performed in various habitats and public health intervention contexts are needed to refine and operationalize this approach for reducing Lyme disease risk in the environment.

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There is a critical need for advancements in disease management strategies for wildlife, but free-living animals pose numerous challenges that can hinder progress. Most disease management attempts involve fixed interventions accompanied by post hoc outcome assessments focused on success or failure. Though these approaches have led to valuable management advances, there are limitations to both the rate of advancement and amount of information that can be gained. As such, strategies that support more rapid progress are required. Sarcoptic mange, caused by epidermal infection with Sarcoptes scabiei mites, is a globally emerging and re-emerging panzootic that exemplifies this problem. The bare-nosed wombat (Vombatus ursinus), a marsupial endemic to southeastern Australia, is impacted by sarcoptic mange throughout its geographic range and enhanced disease management capabilities are needed to improve upon existing in situ methods. We sought to advance in situ wildlife disease management for sarcoptic mange in free-living bare-nosed wombats, implementing an adaptive approach using fluralaner (Bravecto, MSD Animal Health) and a structured process of learning and method-optimisation. By using surveillance of treated wombats to inform real-time management changes, we have demonstrated the efficacy of topically administered fluralaner at 45 and 85 mg/kg against sarcoptic mange. Importantly, we observed variation in the effects of 45 mg/kg doses, but through our adaptive approach found that 85 mg/kg doses consistently reduced mange severity. Through modifying our surveillance program, we also identified individual-level variation in wombat observability and used this to quantify the level of surveillance needed to assess long-term management success. Our adaptive intervention represents the first report of sarcoptic mange management with fluralaner in free-living wildlife and evaluation of its efficacy in situ. This study illustrates how adapting interventions in real time can advance wildlife disease management and may be applicable to accelerating in situ improvements for other host-pathogen systems.

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The development of interventions targeting reservoirs of Borrelia burgdorferi sensu stricto with acaricide to reduce the density of infected ticks faces numerous challenges imposed by ecological and operational limits. In this study, the pharmacokinetics, efficacy and toxicology of fluralaner were investigated in Mus musculus and Peromyscus leucopus mice, the main reservoir of B. burgdorferi in North America. Fluralaner showed rapid distribution and elimination, leading to fast plasma concentration (Cp) depletion in the first hours after administration followed by a slow elimination rate for several weeks, resulting in a long terminal half-life. Efficacy fell below 100% while Cp (± standard deviation) decreased from 196 ± 54 to 119 ± 62 ng/mL. These experimental results were then used in simulations of fluralaner treatment for a duration equivalent to the active period of Ixodes scapularis larvae and nymphs. Simulations showed that doses as low as 10 mg/kg have the potential to protect P. leucopus against infestation for a full I. scapularis active season if administered at least once every 7 days. This study shows that investigating the pharmacology of candidate acaricides in combination with pharmacokinetic simulations can provide important information to support the development of effective interventions targeting ecological reservoirs of Lyme disease. It therefore represents a critical step that may help surpass limits inherent to the development of these interventions.

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The demand for the use of fluralaner in an extra label manner is increasing due to lack of efficacious treatment to combat mites and bed bugs in the poultry industry in the United States. Fluralaner residue data in eggs is lacking and residues might cause risks to human health. The present study aimed to determine the depletion profiles of fluralaner in eggs and estimate the drug withdrawal interval in whole eggs by adopting the US Food and Drug administration tolerance limit method with single intravenous (0.5 mg/kg) or transdermal administration (average 58.7 mg/kg) in healthy shaver hens. Hens were treated intravenously or trans-dermally with fluralaner. The eggs were collected daily for 28 d for intravenous treated and for 40 d from the transdermal route group. Fluralaner concentrations in yolk and albumen were determined by mass spectrometry. The greater percentage of fluralaner was observed in yolk when compared to the albumen for both administration routes. Noncompartmental analysis was used to calculate the pharmacokinetic parameters in yolk, albumen and whole egg. The longest apparent half-life confirmed in yolk was 3.7 d for intravenous and 14.3 d for the transdermal route. The withdrawal intervals in whole egg for fluralaner following the intravenous and transdermal administration were 7 d and 81 d, respectively, with maximum residue limits (1.3 µg/g) at 13 d and 171 d, respectively, based on the limit of quantification (0.4 µg/g) from the analytical assay reported by EMA and APVMA.

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Case summary: A 1-year-old female intact Scottish Fold cat was presented with a 1-month history of excessive hair shedding with white scales on the coat without pruritus. The cat lived mostly indoors and had no history of any systemic disease. Dermatological examinations were performed step by step. Several Demodex gatoi were identified from cellophane tape impressions from the scales and examined under a low-power objective (10×) microscope. Skin cytology showed keratinocytes without any microorganisms. Based on the findings, fluralaner (Bravecto for cats; MSD) spot-on was used once every 12 weeks for ectoparasiticidal control. An essential fatty acid supplement was recommended to repair and restore the coat and skin barrier. After 4 weeks of treatment, the cat showed substantial improvement, with a normal coat and no scales. Re-examination using a cellophane tape impression for mites was negative. Ectoparasitic control is highly recommended regularly for the treatment and prevention of ectoparasites. Relevance and novel information: Feline demodicosis is an uncommon parasitic dermatosis with primary clinical signs that may cause generalised or localised dermatitis with frequent pruritus, erythema and alopecia. The aims of this study were to report on dermatological lesions with excessive hair shedding and scales in a cat that were caused by demodicosis, without presenting the main clinical sign of pruritus or overgrooming. In addition, to the authors' knowledge, this is the first report of the successful treatment of demodicosis due to D gatoi infestation with fluralaner single spot-on in an off-label use that was safe and easy to apply clinically.

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BACKGROUND: Triatoma infestans, Triatoma brasiliensis, Triatoma pseudomaculata and Rhodnius prolixus are vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Chickens serve as an important blood food source for triatomines. This study aimed to assess the insecticidal activity of fluralaner (Exzolt®) administered to chickens against triatomines (R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata). METHODS: Twelve non-breed chickens (Gallus gallus domesticus) were randomized based on weight into three groups: negative control (n = 4); a single dose of 0.5 mg/kg fluralaner (Exzolt®) (n = 4); two doses of 0.5 mg/kg fluralaner (Exzolt®) (n = 4). Nymphs of 3rd, 4th and 5th instars of R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata (all n = 10) were allowed to feed on chickens before treatment, and at intervals of 1, 7, 14, 21, 28, 35 and 56 days after treatment, with insect mortality determined. RESULTS: Treatment with two doses of fluralaner showed higher insecticidal efficacy against R. prolixus, T. infestans and T. brasiliensis compared to the single-dose treatment. Similar insecticidal efficacy was observed for T. pseudomaculata for one and two doses of fluralaner. Insecticidal activity of fluralaner (Exzolt®) against triatomine bugs was noted up to 21 and 28 days after treatment with one and two doses of fluralaner, respectively. CONCLUSIONS: The results demonstrate that treatment of chickens with fluralaner (Exzolt®) induces insecticidal activity against triatomines for up to 28 days post-treatment, suggesting its potential use as a control strategy for Chagas disease in endemic areas.

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BACKGROUND: Sarcoptic mange is a serious animal welfare concern in bare-nosed wombats (Vombatus ursinus). Fluralaner (Bravecto®) is a novel acaricide that has recently been utilised for treating mange in wombats. The topical 'spot-on' formulation of fluralaner can limit treatment delivery options in situ, but dilution to a volume for 'pour-on' delivery is one practicable solution. This study investigated the in vitro acaricidal activity of Bravecto, a proposed essential oil-based diluent (Orange Power®), and two of its active constituents, limonene and citral, against Sarcoptes scabiei. METHODS: Sarcoptes scabiei were sourced from experimentally infested pigs. In vitro assays were performed to determine the lethal concentration (LC50) and survival time of the mites when exposed to varying concentrations of the test solutions. RESULTS: All compounds were highly effective at killing mites in vitro. The LC50 values of Bravecto, Orange Power, limonene and citral at 1 h were 14.61 mg/ml, 4.50%, 26.53% and 0.76%, respectively. The median survival times of mites exposed to undiluted Bravecto, Orange Power and their combination were 15, 5 and 10 min, respectively. A pilot survival assay of mites collected from a mange-affected wombat showed survival times of < 10 min when exposed to Bravecto and Orange Power and 20 min when exposed to moxidectin. CONCLUSIONS: These results confirm the acaricidal properties of Bravecto, demonstrate acaricidal properties of Orange Power and support the potential suitability of Orange Power and its active constituents as a diluent for Bravecto. As well as killing mites via direct exposure, Orange Power could potentially enhance the topical delivery of Bravecto to wombats by increasing drug penetration in hyperkeratotic crusts. Further research evaluating the physiochemical properties and modes of action of Orange Power and its constituents as a formulation vehicle would be of value.

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Two captive-bred golden-handed tamarins, Saguinus midas L., 1758 (Primates: Cebidae), kept in households in Japan, presented with psoriasis-like plaques on their faces, along with scale, alopecia, and itching. Histopathological examination revealed numerous Demodex mites in the hair follicles, and the clinical symptoms in both cases improved after treatment with fluralaner. Based on the morphological and genetic characteristics of the mites collected from tamarins, we describe a new species of Demodex. This new species is the fifth valid Demodex species recorded from primates.

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Vector control is a key intervention against mosquito borne diseases. However, conventional methods have several limitations and alternate strategies are in urgent need. Vector control with endectocides such as ivermectin is emerging as a novel strategy. The short half-life of ivermectin is a limiting factor for its application as a mass therapy tool for vector control. Isoxazoline compounds like fluralaner, a class of veterinary acaricides with long half-life hold promise as an alternative. However, information about their mosquitocidal effect is limited. We explored the efficacy of fluralaner against laboratory reared vector mosquitoes-Aedes aegypti, Anopheles stephensi, and, Culex quinquefasciatus. 24 h post-blood feeding, fluralaner showed a significant mosquitocidal effect with LC50 values in the range of 24.04-49.82 ng/mL for the three different mosquito species tested. Effects on life history characteristics (fecundity, egg hatch success, etc.) were also observed and significant effects were noted at drug concentrations of 20, 25 and 45 ng/mL for Ae. aegypti, An. stephensi, and, Cx. quinquefasciatus respectively. At higher drug concentration of 250 ng/mL, significant mortality was observed within 1-2 h of post blood feeding. Potent mosquitocidal effect coupled with its long half-life makes fluralaner an excellent candidate for drug based vector control strategies.

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BACKGROUND: The citrus red mite, Panonychus citri (McGregor) is a globally distributed agricultural pest. Of late, resistance to common acaricides has raised concerns that chemical control of P. citri is an inefficient means of control. Fluralaner, a highly toxic isoxazoline insecticide used to treat various ectoparasites, presents one potential alternative. However, little information has been reported about the effect of fluralaner on the citrus red mite. This study aims to evaluate the toxicity, sublethal and transgenerational effects of fluralaner on P. citri. RESULTS: In both laboratory and field populations of P. citri, we found fluralaner to be more toxic than conventional alternatives, including fenpropathrin, bifenazate, azocyclotin and chlorpyrifos. Interestingly, fluralaner proved more toxic to female adults than to the eggs of P. citri, with median lethal concentrations (LC50) of 2.446 and 122.7 mg L-1, respectively. Exposure to sublethal concentrations of fluralaner (LC10, LC20 and LC30) significantly reduced the fecundity and longevity of female adults P. citri individuals. Although concentrations of fluralaner applied to the parental female adults (F0) led to some changes in the developmental parameters, there were no significant changes in most of the life table parameters or population growth of the F1 generation. CONCLUSION: Our results indicate that fluralaner is highly toxic to P. citri, and a significant sublethal effect on F0 could suppress the population growth of P. citri, but not for F1. Fluralaner may be considered as a pesticide for the future management of the citrus red mite. © 2024 Society of Chemical Industry.

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A 9-month-old mixed-breed dog developed generalised pustular dermatitis, accompanied by lethargy and hyperthermia, 7 days after oral fluralaner administration. Dermatopathological and microbiological evaluations were consistent with a pustular acantholytic dermatitis. A 4-month course of immunosuppressive therapy resulted in complete remission of lesions, which did not recur after therapy was withdrawn.

Un chien croisé âgé de 9 mois a développé une dermatite pustuleuse généralisée, accompagnée de léthargie et d'hyperthermie, 7 jours après l'administration orale de fluralaner. Les évaluations dermatopathologiques et microbiologiques sont compatibles avec une dermatite acantholytique pustuleuse. Un traitement immunosuppresseur de 4 mois induit une rémission complète des lésions, qui n'ont pas récidivé après l'arrêt du traitement.

Um cão mestiço de nove meses de idade desenvolveu uma dermatite pustular generalizada, acompanhada de letargia e hipertermia, 7 dias após administração de fluralaner. As avaliações dermatohistopatológicas e microbiológicas foram consistentes com uma dermatite pustular acantolítica. Um curso de quatro meses com terapia imunossupressiva resultou em remissão completa das lesões, que não recidivaram após o fim do tratamento.

Un perro mestizo de 9 meses desarrolló dermatitis pustulosa generalizada, acompañada de letargo e hipertermia, 7 días después de la administración oral de fluralaner. Las evaluaciones dermatopatológicas y microbiológicas fueron compatibles con una dermatitis pustulosa acantolítica. Un tratamiento inmunosupresor de 4 meses dio como resultado la remisión completa de las lesiones, que no reaparecieron después de retirar el tratamiento.

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Ectoparasite infestations negatively affect both backyard and commercial chicken flocks in the United States. Fluralaner is an isoxazoline shown to be efficacious in treating mite and bed bug infestations in poultry. Fluralaner is approved to treat fleas and ticks in dogs and cats in the United States and to treat mite infestations of chickens in Europe and Australia; however, the use of fluralaner in poultry is not yet approved in the United States. This study aimed to investigate the plasma fluralaner pharmacokinetic profile of intravenous and transdermal routes and apparent bioavailability of fluralaner administered trans-dermally in healthy shaver hens. A total of 12 individually housed healthy shaver hens received a single dose of either intravenous technical grade fluralaner at 0.5 mg/kg, or transdermal fluralaner (Bravecto (fluralaner transdermal solution) for dogs, 280 mg/mL, Merck Animal Health) at mean 58.7 mg/kg. Plasma from each hen was collected from the jugular, ulnar, or medial metatarsal vein at multiple intervals. Fluralaner concentrations in plasma were determined using Ultra Performance Liquid Chromatography with Mass Spectrometry (UPLC/MS). Noncompartmental analysis revealed that the geometric mean elimination half-life for intravenous and transdermal routes were 80.5 and 179.6 h, respectively. The geometric mean apparent bioavailability of transdermal routes was estimated as 3.4%. Prolonged fluralaner concentration in plasma above minimum inhibitory concentration of bed bugs following the single dose was observed in healthy shaver hens for both routes. It is important to understand the pharmacokinetic profile could be useful in determining the appropriate treatment strategy.

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South American Camelids, including alpacas, have gained popularity in Europe as pets and prized wool sources. Skin health concerns, particularly mite infestations, have emerged as a notable problem in these animals. Sarcoptic mange can lead to severe itching, papules, and chronic symptoms such as alopecia, crusts, and emaciation if left untreated. This case report documents a 2-year-old female alpaca suffering from sarcoptic mange. Despite initial treatment with ivermectin, its condition worsened, leading to severe weight loss, abortion, and a continued presence of mites. Considering the lack of effective treatments for sarcoptic mange in alpacas and the unavailability of registered drugs for this species in Italy, fluralaner, a drug previously used in other animal species, has been administered orally at a dosage of 5 mg/kg. Within a week after the treatment with fluralaner, the patient exhibited significant improvement, including the resolution of itching, healing of skin lesions, and an increase in appetite. Follow-up skin scrapings confirmed the absence of mites, and the patient's condition continued to improve. Fluralaner demonstrated to be a highly effective and fast-acting treatment for sarcoptic mange in alpacas, offering potential economic benefits attributed to its single-dose administration.

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A brood of laying hens infested with the lice Menacanthus cornutus (Phthiraptera: Menoponidae) evidenced itching, irritation, and damage to their zootechnical performance. A study was conducted to evaluate the zootechnical performance and infestation control using a 1% solution of fluralaner in a brood of white laying hens infested naturally with lice. The experiment was carried out using 10,560 naturally infested chickens divided into 2 groups: a treatment group of animals that received a 1% solution of fluralaner in drinking water, at a dose of 0.05 mL/kg of body weight, in 2 administrations, 7 d apart; and a control group of infested and untreated chickens. The groups of chickens were followed for 120 d to evaluate the score of infestation and zootechnical performance. It was observed that birds in the treatment group became free of lice infestation 7 d after the administration of the first dose of a 1% solution of fluralaner. For up to 120 d after the experiment was initiated, there was no evidence of subsequent lice infestation, while continued infestation with all life stages of lice (adults, young, or eggs) was evident in the untreated control group, remaining stable during all evaluations performed. The birds in the treatment group showed improved zootechnical performance when compared to a 9.94% egg production decrease in the control group. The feed conversion and egg mass data showed statistically significant differences between the 2 groups. This study allows us to conclude that treatment with a 1% solution of fluralaner effectively controlled Menacanthus cornutus lice infestation and promoted recovery of egg production in a brood of laying hens treated with the test formulation.

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BACKGROUND: Reducing mosquito abundance or interfering with its ability to support the parasite cycle can help to interrupt malaria in areas of significant risk of malaria transmission. Fluralaner is a safe and effective drug for veterinary use indicated for the treatment against fleas and ticks which acts as an antagonist of chloride ion channels mediated by γ-aminobutyric acid (GABA), preventing the entry of these ions into the postsynaptic neuron, leading to hyperexcitability of the postsynaptic neuron of the central nervous system of arthropods. Fluralaner demonstrated insecticidal activity against different insect species. METHODS: The study aimed to evaluate the effects of fluralaner on the biology, survival, and reproductive fitness of Anopheles aquasalis. The following lethal concentrations (LC) were determined for An. aquasalis: LC5 = 0.511 µM; LC25 = 1.625 µM; LC50 = 3.237 µM. RESULTS: A significant decrease (P < 0.001) was evident in the number of eggs, larvae, and pupae in the group exposed to a sublethal dose of fluralaner when compared to a control group (without the drug). Using blood from dogs after administration of fluralaner, it was observed that the drug causes 100% mortality in An. aquasalis in less than 24 h after feeding; this effect remains even after 90 days in all samples. DISCUSSION: Fluralaner showed the same result for up to 60 days, and after that, there was a slight reduction in its effect, evidenced by a decrease in the percentage of dead females; however, still significant when compared to the control group. CONCLUSION: Fluralaner affects the biology and reduction of survival in An. aquasalis in a lasting and prolonged period, and its fecundity with lower dosages, is a strong candidate for controlling disease vectors.

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BACKGROUND: Around 200-300 million people are estimated to be affected by scabies annually worldwide. However, the mechanisms by which this disease may affect the general condition of the host are not entirely clear. The aim of the present study was to evaluate the systemic changes that may accompany crusted scabies in both treated and non-treated experimental animals. METHODS: Male New Zealand rabbits were infected with Sarcoptes scabiei var. cuniculi and divided into the following three groups: control, ivermectin-treated, and fluralaner-treated. Several methods were used to evaluate the systemic changes, including histopathological examination of the liver, kidney, heart, and spleen, as well as the measurement of serum biochemical parameters and immunological parameters. RESULTS: Several definite structural and functional changes at the systemic level were revealed, as evidenced by the observed histopathological changes in the tissue sections of internal organs and the highly significant increases in markers of systemic inflammation, serum procalcitonin, and oxidative stress markers. Abnormalities in the liver and renal function results, as well as in the serum lipid profile, were also noted. Additionally, a disorganized immune response was noted, evidenced by a mixed type 1 and type 2 helper T cell response. Although there was notable clinical and parasitological cure in the ivermectin-treated group, the histopathological, biochemical, and immunological markers indicated incomplete resolution. In contrast, the fluralaner-treated group exhibited a nearly complete resolution of changes in these parameters. CONCLUSIONS: We conclude that crusted scabies is a systemic syndrome that can affect several organs besides the skin. Inflammation, oxidative stress, and possibly bacterial infections, are all implicated as underlying mechanisms of tissue damage due to the disease. We recommend that fluralaner, a promising scabicidal agent, should be studied for possible human use, and especially for control programs.

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BACKGROUND: Adult, nymph, and larval Rhipicephalus sanguineus sensu lato infest dogs and thrive in premises including homes and kennels. Ticks emerge from hiding to seek and attach to dogs, engorge, then leave their hosts to hide then molt or oviposit. This study evaluated the effect of either external or systemic canine treatment on R. sanguineus s.l. populations in premises. METHODS: Thirty-two dogs in eight kennels were divided into three groups; one group (eight dogs in two kennels) served as untreated controls; one group (12 dogs in three kennels) received oral fluralaner (25-56 mg/kg); and one group (12 dogs in three kennels) received topical flumethrin/imidacloprid impregnated collars. Treatments were administered once on day 0. Prior to treatment, R. sanguineus s.l. infestations were established in kennels holding dogs, by placing ticks every 2 weeks from day -84 through day -14. Kennel surfaces (walls and floors) were smooth except for uniform "hideouts" to permit precise off-host tick counting. RESULTS: Control dog kennel mean tick counts (all life stages) increased from 737 ticks/kennel at day -7 to 2213 at day 63 when all control kennel dogs were acaricide-treated as a humane endpoint. Kennels housing dogs subsequently treated with systemic fluralaner had a mean of 637 counted ticks/kennel on study day -7 (7 days before treatment). One fluralaner treatment eliminated all premises ticks (100% reduction) by day 70, and these kennels remained tick-free through study completion (day 84). Kennels housing dogs subsequently treated with an external imidacloprid/flumethrin collar had a mean of 614 counted ticks/kennel at study day -7. Collar treatment reduced counts by 90% on day 63, with kennel tick counts climbing after this and ending the study with a 75% reduction. Systemic fluralaner treatment was significantly (P = 0.003) more effective at reducing engorged adult female tick counts than external imidacloprid/flumethrin treatment. CONCLUSIONS: Fluralaner treatment eliminated off-host R. sanguineus life stages in infested kennels by day 70 following treatment and was significantly more effective than imidacloprid/flumethrin collar treatment in reducing the premises population of engorged female ticks. Imidacloprid/flumethrin treatment did not eliminate premises tick populations, with populations increasing before the study end.

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The red imported fire ant (RIFA), Solenopsis invicta, is an invasive pest that causes damage to agricultural and ecological environments worldwide. Fluralaner is a new isoxazoline pesticide with the potential to become a control agent against RIFA. However, it is not clear whether S. invicta responds the same way to fluralaner at different reproductive stages. The present study firstly evaluated the toxicity of fluralaner to S. invicta at different developmental stages, finding that fourth instar larvae (LD50, 1744.23 mg/kg) and worker ants (LD50, 8.62 mg/kg) were differently susceptible to fluralaner, while the mortality rate of fourth instar larvae was significantly lower at the same concentration of 10 mg/L (5.56 ± 3.14%) than that of worker ants (62.22 ± 3.14%), demonstrating a greater tolerance to fluralaner. Subsequently, the metabolic responses of worker and larval ants to fluralaner stress (10 mg/L) were investigated using non-targeted metabolomics, which indicated that the amount of differential metabolites and the KEGG metabolic pathways enriched were different between workers and larvae when exposed to the same dose (10 mg/L) of fluralaner. Differential metabolites of larvae and worker ants under fluralaner stress were mainly concentrated in organic acids and their derivatives, lipids and lipid-like molecules, nucleosides, nucleotides, and analogues, combined with the enriched metabolic pathways, revealed that the differential metabolic responses of larvae and worker ants were mainly in energy metabolism, detoxification metabolism, and neurotransmitter ligands. Workers consumed more substrates in the arginine synthesis pathway (l-glutamic acid, l-aspartic acid, and fumaric acid) to provide energy for the detoxification (glutathione) of pesticides when exposed to fluralaner stress, and the high accumulation of l-aspartic acid induced excitotoxicity in the worker ants. Larval ants consumed more arachidonic acid to synthesize PG D2, and changes in the metabolism of antioxidants such as catechins, hesperidin, and l-ascorbic acid suggested that larvae were more capable of scavenging the ROS response than worker ants. The results of non-targeted metabolomics successfully revealed differences in the sensitivity of larvae and workers to fluralaner agents, providing insights into the fluralaner control of Solenopsis invicta.

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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.

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