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Oclacitinib is a novel Janus kinase (JAK) inhibitor that potently inhibits JAK1-dependent cytokines involved in allergy, inflammation, and pruritus (IL-2, IL-4, IL-6, IL-13, and IL-31). Oclacitinib (Apoquel®, Zoetis Inc, Parsippany, NJ) is approved for the treatment/control of pruritus associated with allergic dermatitis and treatment/control of clinical manifestations of atopic dermatitis in dogs at least 12 months of age. To evaluate the effectiveness of oclacitinib in dogs with flea allergy dermatitis, the JAK1 selective inhibitor was tested in a placebo-controlled, masked, single-dose (0.4 mg/kg) or repeat-dose (0.4 mg/kg, twice daily for 2 weeks) study. Pruritic behaviors were quantitated by video recording, and erythema and skin lesions were assessed using a 10-cm visual analog scale (VAS). Results showed that oclacitinib reduced pruritus by 61% as early as 1.5 h after a single oral dose compared to placebo, with an average reduction (compared to placebo) of 85% 1-5 h after dosing (0.4 mg/kg; p < .0001). Oclacitinib also significantly reduced erythema (p < .0001) and skin lesion (p < .0005) VAS scores on Day 14 compared to placebo in a repeat dose study. No adverse events were noted during the conduct of these studies. IL-31 concentrations were elevated in the majority of dogs after flea infestation, suggesting JAK1-dependent cytokines may drive clinical signs of flea allergy dermatitis. These findings show that oclacitinib, an inhibitor of JAK1-dependent cytokines involved in allergy and inflammation can rapidly reduce clinical signs associated with flea allergic dermatitis in dogs., (© 2024 John Wiley & Sons Ltd.)

Irgarol 1051 is an herbicide extensively utilized in antifouling paint due to its ability to inhibit photosynthesis. Irgarol and its photodegradation products are highly persistent in waters and sediments, although they are present in low concentrations. However, our understanding of the harmful effects of Irgarol on non-target organisms remains limited. In this study, we assessed the effects of acute (24 h) and chronic (14 days across three generations) exposure to different concentrations (including the 1/10 NOEC, NOEC, and 1/10 LC50 calculated from the 24-h acute toxicity test) of Irgarol using the water flea Moina macrocopa. Acute exposure to 1/10 LC50 significantly decreased survival, feeding rate, thoracic limb activity, heart rate, and acetylcholinesterase activity. Elevated levels of intracellular reactive oxygen species and malondialdehyde, along with a significant increase in catalase and superoxide dismutase activity, suggested the induction of oxidative stress in response to 1/10 LC50. An initial boost in glutathione level and the enzymatic activities of glutathione peroxidase and glutathione reductase, followed by a plunge, implies some compromise in the antioxidant defense system. Upon chronic exposure to the NOEC value, both generations F1 and F2 displayed a significant decrease in survival rate, body length, number of neonates per brood, and delayed sexual maturation, suggesting maternal transfer of potential damage through generations. Taken together, Irgarol induced acute toxicity through physiological and cholinergic damage, accompanied by the induction of oxidative stress, in the water flea. Even its sub-lethal concentrations can induce detrimental effects across generations when consistently exposed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), a primary approach for evaluating gene expression, requires an appropriate normalization strategy to confirm relative gene expression levels by comparison, and rule out variations that might occur in analytical procedures. The best option is to use a reference gene whose expression level is stable across various experimental conditions to compare the mRNA levels of a target gene. However, there is limited information on how the reference gene is differentially expressed at different ages (growth) in small invertebrates with notable changes such as molting. In this study, expression profiles of nine candidate reference genes from the brackish water flea, Diaphanosoma celebensis, were evaluated under diverse exposure to toxicants and according to growth. As a result, four different algorithms showed similar stabilities of genes for chemical exposures in the case of limited conditions using the same developmental stage (H2A was stable, whereas Act was fairly unstable in adults), while the results according to age showed a significantly different pattern in suite of candidate reference genes. This affected the results of genes EcRA and GST, which are involved in development and detoxification mechanisms, respectively. Our finding is the first step towards establishing a standardized real-time qRT-PCR analysis of this environmentally important invertebrate that has potential for aquatic ecotoxicology, particularly in estuarine environments., (© 2021. The Author(s).)

In western North America, sylvatic plague (a flea-borne disease) poses a significant risk to endangered black-footed ferrets (Mustela nigripes) and their primary prey, prairie dogs (Cynomys spp.). Pulicides (flea-killing agents) can be used to suppress fleas and thereby manage plague. In South Dakota, US, we tested edible "FipBit" pellets, each containing 0.84 mg fipronil, on free-living black-tailed prairie dogs (Cynomys ludivicianus). FipBits were applied along transects at 125 per ha and nearly eliminated fleas for 2 mo. From 9-14 mo post-treatment, we found only 10 fleas on FipBit sites versus 1,266 fleas on nontreated sites. This degree and duration of flea control should suppress plague transmission. FipBits are effective, inexpensive, and easily distributed but require federal approval for operational use., (© Wildlife Disease Association 2021.)

The cytochrome P450 (CYP) enzyme family is extensive; these enzymes participate in phase I enzyme metabolism and are involved in xenobiotic detoxification in all living organisms. Despite their significance in xenobiotic detoxification, little is known about the species-specific comparison of CYPs and their molecular responses in aquatic invertebrates. We identified 31 CYPs in the brackish water flea Diaphanosoma celebensis via thorough exploration of transcriptomic databases and measured the transcript profiles of 9 CYPs (within full sequences) in response to benzo[α]pyrene (B[α]P) and two heavy metals (cadmium [Cd] and copper [Cu]). Through phylogenetic analysis, the CYPs were separated and clustered into four clans: mitochondrial, CYP2, CYP3, and CYP4. The expression of 9 CYPs were differentially modulated (up- and/or downregulated) in response to B[α]P, Cd, and Cu. In particular, CYP370A15 was significantly upregulated in response to B[α]P, Cd, and Cu, suggesting that the identified CYPs are involved in xenobiotic detoxification and are useful as biomarkers in response to B[α]P, Cd, and Cu. This study aimed to comprehensively annotate cladoceran CYPs; our results will add to the existing knowledge on the potential roles of CYPs in xenobiotic detoxification in cladocerans.

Background: Safe and effective flea and tick treatment options for cats are important in companion animal practice because of feline ectoparasite infestation prevalence and the potential for parasitic disease transmission. Retrospective cat owner purchasing transactions at United States of America (USA) veterinary clinics were obtained for three topical feline flea and tick ectoparasiticides. One medication, fluralaner, had a 12-week redosing interval, while two other medications (fipronil/s-methoprene/pyriproxyfen; imidacloprid/pyriproxyfen) were approved for monthly redosing. The annual number of doses purchased by cat owners was determined for each of the three medications and then compared between medications. The objective was to evaluate whether 12-week retreatment intervals resulted in a different duration of coverage compared to monthly treatments for ectoparasiticide products., Methods: Study results were obtained by analyzing the transactional records from a commercial database derived from veterinary practice management software. The study database consisted of cat owner purchasing records from January 2017 through June 2019 from 671 veterinary practices representing 41,630 cats., Results: Cat owners purchased an average of 1.5 doses of fluralaner per year which, based on a 12-week redosing interval, provides 4.2 months of treatment coverage. Cat owners who used monthly flea and tick medications respectively purchased 3.6 months (fipronil/s-methoprene/pyriproxyfen combination) and 2.8 months (imidacloprid/pyriproxyfen) annually of each of the two medications. Average yearly cat owner purchases of fluralaner provide a significantly longer duration of coverage than for cat owners purchasing fipronil/s-methoprene/pyriproxyfen (17% more) or imidacloprid/pyriproxyfen (50% more)., Conclusions: Cat owners who obtained a flea and tick treatment with a 12-week redosing interval (fluralaner) protected their cats for up to 17% or 50% longer duration each year, respectively, compared to the duration of protection obtained by cat owners who used a medication re-dosed monthly. Cat owners should increase their duration of flea and tick coverage to come closer to achieving veterinary recommendations.

Background: The safety and efficacy of a new spot-on formulation of selamectin plus sarolaner were evaluated for the treatment and control of natural flea infestations on cats in two non-randomised, multi-centre clinical trials conducted in 8 different locations in Queensland, Australia., Methods: One hundred and four cats from 65 different households were enrolled across the two studies. Demographic characteristics of cats in the two studies were similar. The new spot-on formulation of selamectin and sarolaner was administered topically once a month for 3 consecutive months at a minimum dosage of 6 mg/kg selamectin (dose range 6-12 mg/kg) plus 1 mg/kg sarolaner (dose range 1-2 mg/kg). Cats were dosed on Days 0 (pre-treatment), 30 and 60 and physical examinations and flea counts were conducted on Days 0, 30, 60 and 90. Efficacy assessments were based on the percentage reduction in live flea counts post-treatment compared to Day 0., Results: In Study A, at enrolment, primary cats had flea counts ranging from 6 to 107 (arithmetic mean 21.0). The selamectin and sarolaner spot-on formulation resulted in arithmetic mean efficacy of 98.0%, 100% and 100% on Days 30, 60 and 90, respectively. In Study B, at enrolment, primary cats had flea counts ranging from 6 to 22 (arithmetic mean 10.0). The selamectin and sarolaner spot-on formulation resulted in arithmetic mean efficacy of 99.7%, 100% and 100% on Days 30, 60 and 90, respectively., Conclusions: The new spot-on formulation of selamectin plus sarolaner topically administered at monthly intervals at the minimum dosage of 6.0 mg/kg selamectin and 1.0 mg/kg sarolaner was safe and highly effective against natural infestations of fleas under a range of geographical conditions, representative of both tropical and subtropical regions of Australia.

Bubonic is the most prevalent plague form in Madagascar. Indoor ground application of insecticide dust is the conventional method used to control potentially infected rodent fleas that transmit the plague bacterium from rodents to humans. The use of bait stations is an alternative approach for vector control during plague epidemics, as well as a preventive control method during non-epidemic seasons. Bait stations have many advantages, principally by reducing the amount of insecticide used, lowering the cost of the treatment and minimizing insecticide exposure in the environment. A previous study reported promising results on controlling simultaneously the reservoir and vectors, when slow-acting rodenticide was incorporated in bait stations called "Boîtes de Kartman". However, little evidence of an effective control of the fleas prior to the elimination of rodents was found. In this study, we evaluated bait stations containing insecticide powder and non-toxic attractive rodent bait for their potential to control rat fleas. Its efficacy was compared to the standard method. The impact of both methods on indoor and outdoor rodent fleas, as well as the human household flea Pulex irritans were analyzed at different time points after treatments. Bait stations did not cause any significant immediate or delayed reduction of rat fleas and increasing the number of operational bait stations per household did not significantly improve their efficacy. Insecticide ground dusting appeared to be the most efficient method to control indoor rat fleas. Both methods appeared to have little impact on the density of outdoor rat fleas and human fleas. These results demonstrate limited effectiveness for bait stations and encourage the maintenance of insecticide dusting as a first-line control strategy in case of epidemic emergence of plague, when immediate effect on rodent fleas is needed. Recommendations are given to improve the efficacy of the bait station method., Competing Interests: The authors have declared that no competing interests exist.

Plague, a flea-borne disease, hampers efforts to restore populations of black-footed ferrets ( Mustela nigripes ), which occupy colonies of prairie dogs ( Cynomys spp.) in North America. Plague is managed by infusing prairie dog burrows with DeltaDust ® 0.05% deltamethrin, a pulicide that kills fleas. Experiments are needed to identify pulicides that can be used in rotation with DeltaDust for integrated plague management. In South Dakota, USA, we tested the efficacy of four pulicide dusts when applied at a rate of 8 g per burrow on colonies of black-tailed prairie dogs ( Cynomys ludovicianus ): Sevin ® 5% carbaryl; Dusta-cide ® 6% malathion; Alpine ® 0.25% dinotefuran with 95% diatomaceous earth; and Tri-Die ® 1% pyrethrum with 40% amorphous silica and 10% piperonyl butoxide. We also tested systemic 0.005% fipronil, which was distributed as ½ cup of laced grain per burrow. We sampled prairie dogs on 3294 occasions and detected 10,041 fleas. Sevin and Dusta-cide suppressed fleas but only for 1 month. Neither Alpine nor Tri-Die had any noticeable, consistent effect on fleas. Fipronil suppressed fleas by 97-100% for 3 months. The residual effect of fipronil persisted for ∼12 months. Efficacy of fipronil seems comparable with DeltaDust, which exhibited a residual effect for ∼10 months in prior studies. Continued research is needed to optimize fipronil treatments for plague management on prairie dog colonies.

The efficacy of a single application of a new topical formulation containing selamectin plus sarolaner (Revolution ® Plus / Stronghold ® Plus, Zoetis) was evaluated against fleas and ticks infesting cats enrolled as veterinary patients in two field studies conducted in Japan and against Haemaphysalis longicornis ticks on cats in a laboratory study. In the laboratory study, sixteen cats were ranked based on pre-treatment tick counts and allocated randomly to treatment on Day 0 with either selamectin plus sarolaner or placebo. Cats were infested with adult H. longicornis on Days -2, 5, 12, 19, 26 and 33. Efficacy relative to placebo was based on live attached tick counts conducted 48 h after treatment and subsequent re-infestations. Selamectin plus sarolaner reduced live, attached H. longicornis counts by 96.4% within 48 h of treatment, and by ≥91.7% within 48 h of weekly re-infestation for 35 days, based on arithmetic means. In the field studies, 67 client-owned cats harboring six or more live fleas and 63 cats harboring four or more live attached ticks were enrolled to evaluate selamectin plus sarolaner for efficacy and safety compared with a registered product. Cats were allocated randomly to treatment with selamectin plus sarolaner or fipronil plus (S)-methoprene based on order of presentation. Treatment was administered once on Day 0 and efficacy was assessed by parasite counts conducted on Days 14 and 30 compared to the pre-treatment count. In the flea field study, live flea counts on Days 14 and 30 were reduced by 99.5% and 99.9% in the selamectin plus sarolaner group, and by 97.6% and 98.6% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Clinical signs typically associated with flea allergy dermatitis improved following treatment. In the tick field study, live tick counts on Days 14 and 30 were reduced by 97.5% and 97.7% in the selamectin plus sarolaner group, and by 91.5% and 93.4% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Selamectin plus sarolaner was determined to be non-inferior to fipronil plus (S)-methoprene in both field studies. There were no treatment-related adverse events in any study. A single topical dose of Revolution ® Plus / Stronghold ® Plus providing a minimum dosage of 6.0 mg/kg selamectin and 1.0 mg/kg sarolaner was confirmed to be effective against H. longicornis ticks on cats for one month and safe and effective in the treatment of fleas and ticks on cats enrolled as veterinary patients in Japan., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

Two randomised, single-masked, multi-center field studies were conducted in the United States in cats presented as veterinary patients. The first study evaluated the efficacy and safety of a topically applied formulation of selamectin plus sarolaner (Revolution ® Plus/Stronghold ® Plus, Zoetis) against natural flea infestations; the second study evaluated its efficacy against natural ear mite infestations. The product was administered topically by the cats' owners at the dose range provided in the market product of 6.0-12.0 mg selamectin and 1.0-2.0 mg sarolaner per kg bodyweight. Imidacloprid plus moxidectin (Advantage ® Multi for Cats, Bayer) was used as a positive control in both studies at the label dosage. In the flea study, treatments were administered on Days 0, 30, and 60. Efficacy was calculated based on the mean percent reduction of live flea counts on Days 30, 60, and 90 relative to the pre-treatment count. In the ear mite study, a single treatment was applied on Day 0 and efficacy was determined on Days 14 and 30 based on the presence or absence of ear mites. In both studies, patients were randomly allocated to treatments in the ratio of 2:1, selamectin plus sarolaner: imidacloprid plus moxidectin. In the two studies, 405 cats received treatment with selamectin plus sarolaner; of these, 256 cats received three monthly treatments in the flea study. There were no serious adverse reactions to treatment with selamectin plus sarolaner; health issues noted were typical of the normal ailments or minor traumatic injuries expected in the general cat population and were similar in both treatment groups. Efficacy against fleas based on geometric (arithmetic) means was 97.2% (95.9%), 99.5% (99.4%), and 99.8% (99.8%) in the selamectin plus sarolaner group and was 79.7% (70.5%), 91.4% (77.3%), and 95.5% (87.4%) in the imidacloprid plus moxidectin group on Days 30, 60, and 90, respectively. Flea counts for the selamectin plus sarolaner group were significantly lower than the counts for the imidacloprid plus moxidectin group at all time-points after treatment administration on Day 0 (P <  0.001). Treatment reduced the clinical signs of flea allergy dermatitis (alopecia, dermatitis/pyodermatitis, erythema, pruritus, scaling, and papules) in affected cats by 86.7%-100% in the selamectin plus sarolaner group and by 66.7%-100% in the imidacloprid plus moxidectin group. In the ear mite study, a single application of selamectin plus sarolaner resulted in the clearance of mites from 87.5% of cats within 14 days and 94.4% of cats within 30 days of treatment. The respective percentages of mite-free cats in the imidacloprid plus moxidectin group were 64.0% and 72.0%. There were significantly more cats with no mites noted in the selamectin plus sarolaner group than in the imidacloprid plus moxidectin group on Day 14 and Day 30 (P ≤  0.018). Selamectin plus sarolaner (Revolution ® Plus/Stronghold ® Plus) administered topically at monthly intervals for three months was well tolerated and highly effective for the treatment and prevention of natural infestations of fleas on cats presented as veterinary patients. Clinical signs of flea allergy dermatitis improved in affected cats following treatment administration. A single topical treatment was also safe and highly effective for the treatment of ear mite infestations in naturally infested cats., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

Background: A spot-on formulation of fluralaner plus moxidectin has been designed to provide long-term protection against fleas and ticks, prevent heartworm disease and treat gastrointestinal nematode infections in cats. The objective of this study was to determine the efficacy of this product against fleas collected from a household with repeated fipronil failures following owner-administered treatments., Methods: Thirty cats were randomized to three equal groups: (A) untreated controls; (B) to receive a single application of fluralaner plus moxidectin (Bravecto ® Plus) at 40 mg/kg and 2 mg/kg body weight, respectively; and (C) three applications at one month intervals with a spot-on formulation of fipronil and (S)-methoprene (Frontline ® Plus) at 0.5 ml manufacturer recommended dose. Flea challenges were completed on Days -6 (for randomization), -1, 7, 14, 28, 42, 56, 70, 77, 84 and 91. Flea counts were completed 48 hours after initial treatment and 48 hours following each subsequent challenge., Results: Fleas were found on all control and all fipronil and (S)-methoprene treated cats at every assessment. From Day 2 to Day 93, all cats in the fluralaner plus moxidectin group were flea-free, with one exception (Day 58; three fleas counted on one cat); control group flea counts ranged between 34-109, and fipronil and (S)-methoprene group counts ranged between 1-79. At each assessment after Day 0, compared to the control group, geometric mean flea counts were significantly lower in the fipronil and (S)-methoprene group (P ≤ 0.04) and in the fluralaner plus moxidectin group (P < 0.001), and mean flea counts in the fluralaner plus moxidectin group were significantly lower than those of the fipronil and (S)-methoprene group (P < 0.001). The efficacy of fluralaner plus moxidectin, based on geometric means, was 100% at each assessment post-Day 0 except on Day 58 when efficacy was 99.7%. In the fipronil and (S)-methoprene group efficacy ranged between 30.6-65.6%., Conclusions: These findings demonstrate complete efficacy of fluralaner plus moxidectin against a flea isolate that was not controlled by fipronil and (S)-methoprene. This study provides confirmation of the consistent, sustained efficacy of topically applied fluralaner in the treatment and control of flea infestations in cats.

Sylvatic plague affects many species in North American prairie ecosystems. Deltamethrin is commonly used to manage fleas in potential outbreak areas. Understanding the role of small mammals and their ectoparasites in sylvatic plague maintenance is pertinent to understanding the ecology of plague and its persistence in nature. This study examined the effects of plague management using deltamethrin on communities of small mammals, their flea faunas, and Yersinia pestis prevalence. We trapped small mammals from 2014 to 2016 on the Lower Brule Indian Reservation (LOBR), South Dakota, and analyzed the effects of deltamethrin treatment on small mammal populations, flea loads, and Y. pestis prevalence. We collected higher flea loads from small mammals on sites not treated with deltamethrin (1.10 fleas per animal) than from deltamethrin-treated sites (1.03 fleas per animal). We observed significant negative trends in mean flea load per animal between pre- and post-treatment collections. We detected no significant effects of deltamethrin treatment on animal captures pre- and post-treatment, but observed significant differences in animal captures by experimental unit. We detected no serological evidence for the presence of Y. pestis antibodies in small mammals and 1.2% Y. pestis prevalence across all sampled fleas. Although there is little overlap in the species of fleas infesting small mammals and prairie dogs, the occurrence of flea spillover has been documented. In our study, treatment with deltamethrin reduced flea loads on small mammals by up to 49%. Our data suggest that although the efficacy of deltamethrin on the LOBR-a mixed-grass system-may not be as high as that found in a comparable study in a short-grass system, deltamethrin is still a useful tool in the management of plague.

To reduce morbidity and mortality caused by visceral leishmaniasis (VL), the Brazilian Visceral Leishmaniasis Control and Surveillance Program promotes the diagnosis and treatment of cases, vector control, euthanasia of seropositive dogs, and health education. Nevertheless, the effectiveness of these measures is questionable as they lead to little reduction in the transmission of the disease. Thus, the effectiveness of strategies such as insecticide-impregnated collars, spot-on insecticides, and immunization of dogs should be assessed. Herein, we evaluated the effectiveness of deltamethrin-impregnated collars on reducing the incidence of Leishmania infantum infection in dogs living in an endemic area of VL. An intervention study was conducted and a total 5,850 dogs were analyzed in baseline. Of these 3,742 seronegative dogs were divided into two groups: collared and uncollared (control). Dogs were followed for 12 months and three interventions were performed. The Cox regression model was used to evaluate the effectiveness of the collar. All analyzes were performed by Intention-to-treat and per-protocol. By intention-to-treat, the incidence rates of L. infantum infection were 7.5 and 7.9 in the collar group, and 6.5 and 13.2 per 1,000 dogs-months in the control group after 6 and 12 months, respectively. In the per-protocol analysis, the incidence rates in the control group were similar to those observed in the intention-to-treat analysis. In the collar group, the incidence rate was 5.1/1,000 dogs-months after 6 and 12 months. The effectiveness by intention-to-treat after adjustment by the multivariate Cox model was 48%. In the analysis per-protocol, the effectiveness increased to 63%. Although collar use was effective when it was evaluated by intention-to-treat, higher effectiveness was found in the per-protocol analysis after one year of follow-up. The data emphasize the importance of the uninterrupted use of deltamethrin-impregnated collars to increase protection against canine VL., Competing Interests: The authors have declared that no competing interests exist.

Background: A spot-on formulation containing fluralaner (280 mg/ml) plus moxidectin (14 mg/ml) (Bravecto® Plus) was developed for the treatment of nematode infections as well as providing 12 weeks of protection against insect and acarine parasites in cats. The effectiveness and safety of this product against feline gastrointestinal nematodes was assessed in naturally-infested, client-owned cats under field conditions in Albania, Bulgaria, Germany and Hungary., Methods: To be eligible for enrollment in this investigator-blinded study cats had to be at least 10 weeks-old, weigh at least 1.2 kg, be clinically healthy, and have a faecal sample testing positive for nematodes no more than eight days prior to treatment. Cats were stratified into blocks of three in order of presentation at each center and randomly allocated in a 2:1 ratio to be treated topically on Day 0 with fluralaner plus moxidectin (minimum dose rates 40 mg/kg and 2 mg/kg, respectively) or emodepside plus praziquantel (minimum dose rates 3 mg/kg and 12 mg/kg, respectively) (Profender®). Faecal samples were collected from cats prior to treatment and 14 ± 4 days later., Results: There were 182 cats randomized to the fluralaner plus moxidectin group, and 91 to the emodepside plus praziquantel group. Prior to treatment the most commonly identified nematode egg was Toxocara cati, found in 79.1 and 82.4% of cats in the fluralaner plus moxidectin and emodepside plus praziquantel groups, respectively. Eggs of Toxascaris leonina were found in 8.2 and 6.6% of cats; of hookworms in 30.8 and 24.2%; and of Capillaria spp. in 7.1 and 4.3%, respectively. After treatment, faecal samples from 98.3% of fluralaner plus moxidectin treated and 96.6% of emodepside plus praziquantel-treated cats were free of nematode ova. Geometric mean faecal egg count reductions for T. cati, the only eggs found in post-treatment faecal samples, were 99.97% and 99.93%, respectively. Treatment with fluralaner plus moxidectin was non-inferior to emodepside plus praziquantel. Both products were safe and well tolerated by cats treated under field conditions., Conclusions: This field study confirms that, in addition to 12-week extended duration flea and tick control, fluralaner plus moxidectin provides broad spectrum treatment of nematodes in cats.

Background: Veterinary clinic transaction records from the USA were examined to determine dog owner purchase patterns for three prescription ectoparasiticides. In-clinic purchases of formulations of fluralaner (with 12-week duration per dose) were compared with dog owner purchases of afoxolaner and spinosad (both with 4 week duration per dose) in a population of 231,565 dogs over a 12 month period. Prior studies in human and animal medicine have suggested that patients more closely adhere to prescriber dosing recommendations when they receive a longer-duration medication., Results: Veterinary clinic transaction records were examined for the period June 2014 through March 2017 using records from approximately 650 veterinary clinics. Ectoparasiticide purchase patterns were compared for two products (afoxalaner and spinosad) with monthly dosing and one product (fluralaner) with an extended (12 week) dosing interval. The average dog owner who obtained fluralaner purchased significantly more months of flea/tick protection (5.7 months) over the 12-month study period than the average dog owner that selected either afoxolaner (4.6 months) or spinosad (3.3 months). The proportion of dog owners who obtained only one dose of ectoparasiticide per 12-month period was 42% for fluralaner, 30% for afoxolaner and 37% for spinosad. The proportion of dog owners who obtained 2 doses or less per 12-month period was 67% for fluralaner, 52% for afoxoalaner and 67% for spinosad. Owners that obtained fluralaner were significantly more likely to obtain 7.0-12.0 months of flea and tick protection and significantly less likely to purchase 1.0-6.9 months compared with dog owners who purchased afoxolaner or spinosad., Conclusions: Dog owners who obtained a flea and tick medication with a longer duration of action acquired significantly more months of protection in a year than dog owners who obtained shorter duration (1 month) products. Dog owners were better able to adhere to veterinary recommendations on ectoparasites control with a longer-acting flea/tick medication.

Sylvatic plague poses a substantial risk to black-tailed prairie dogs ( Cynomys ludovicianus) and their obligate predator, the black-footed ferret ( Mustela nigripes). The effects of plague on prairie dogs and ferrets are mitigated using a deltamethrin pulicide dust that reduces the spread of plague by killing fleas, the vector for the plague bacterium. In portions of Conata Basin, Buffalo Gap National Grassland, and Badlands National Park, South Dakota, US, 0.05% deltamethrin has been infused into prairie dog burrows on an annual basis since 2005. We aimed to determine if fleas ( Oropsylla hirsuta) in portions of the Conata Basin and Badlands National Park have evolved resistance to deltamethrin. We assessed flea prevalence, obtained by combing prairie dogs for fleas, as an indirect measure of resistance. Dusting was ineffective in two colonies treated with deltamethrin for >8 yr; flea prevalence rebounded within 1 mo of dusting. We used a bioassay that exposed fleas to deltamethrin to directly evaluate resistance. Fleas from colonies with >8 yr of exposure to deltamethrin exhibited survival rates that were 15% to 83% higher than fleas from sites that had never been dusted. All fleas were paralyzed or dead after 55 min. After removal from deltamethrin, 30% of fleas from the dusted colonies recovered, compared with 1% of fleas from the not-dusted sites. Thus, deltamethrin paralyzed fleas from colonies with long-term exposure to deltamethrin, but a substantial number of those fleas was resistant and recovered. Flea collections from live-trapped prairie dogs in Thunder Basin National Grassland, Wyoming, US, suggest that, in some cases, fleas might begin to develop a moderate level of resistance to deltamethrin after 5-6 yr of annual treatments. Restoration of black-footed ferrets and prairie dogs will rely on an adaptive, integrative approach to plague management, for instance involving the use of vaccines and rotating applications of insecticidal products with different active ingredients.

Background: Mosquitoes transmit many vector-borne infectious diseases including malaria, dengue, chikungunya, yellow fever, filariasis, and Japanese encephalitis. The insecticidal δ-endotoxins Cry4, Cry11, and Cyt produced from Bacillus thuringiensis have been used for bio-control of mosquito larvae. Cry δ-endotoxins are synthesised as inactive protoxins in the form of crystalline inclusions in which they are processed to active toxins in larval midgut lumen. Previously, we demonstrated that the activated Cry4Ba toxin has to alter the permeability of the peritrophic membrane (PM), allowing toxin passage across PM to reach specific receptors on microvilli of larval midgut epithelial cells, where the toxin undergoes conformational changes, followed by membrane insertion and pore formation, resulting in larval death. A peritrophic membrane (PM)-binding calcofluor has been proposed to inhibit chitin formation and enhance baculovirus infection of lepidopteran Trichoplusia ni., Methods: In this study, Aedes aegypti larvae were fed with the calcofluor and Cry4Ba toxin to investigate the effect of this agent on the toxicity of the Cry4Ba toxin., Results: Calcofluor displayed an enhancing effect when co-fed with the Cry4Ba wild-type toxin. The agent could restore the killing activity of the partially active Cry4Ba mutant E417A/Y455A toward Ae. aegypti larvae. PM destruction was observed after larval challenge with calcofluor together with the toxin. Interestingly, calcofluor increased Cry4Ba toxin susceptibility toward semi-susceptible Culex quinquefasciatus larvae. However, calcofluor alone or in combination with the toxin showed no mortality effect on non-susceptible fresh-water fleas, Moina macrocopa., Conclusions: Our results suggest that PM may contribute to the resistance of the mosquito larvae to Cry4Ba toxin. The PM-permeability alternating calcofluor might be a promising candidate for enhancing insect susceptibility, which will consequently improve Cry4Ba efficacy in field settings in the future.

Plague (Yersinia pestis) and zoonotic cutaneous leishmaniasis (Leishmania major) are two rodent-associated diseases which are vectored by fleas and phlebotomine sand flies, respectively. In Central Asia, the great gerbil (Rhombomys opimus) serves as the primary reservoir for both diseases in most natural foci. The systemic insecticide fipronil has been previously shown to be highly effective in controlling fleas and sand flies. However, the impact of a fipronil-based rodent bait, on flea and sand fly abundance, has never been reported in Central Asia. A field trial was conducted in southeastern Kazakhstan to evaluate the efficacy of a 0.005% fipronil bait, applied to gerbil burrows for oral uptake, in reducing Xenopsylla spp. flea and Phlebotomus spp. sand fly abundance. All active gerbil burrows within the treated area were presented with ~120 g of 0.005% fipronil grain bait twice during late spring/early summer (June 16, June 21). In total, 120 occupied and 14 visited gerbil colonies were surveyed and treated, and the resulting application rate was minimal (~0.006 mg fipronil/m2). The bait resulted in 100% reduction in Xenopsylla spp. flea abundance at 80-days post-treatment. Gravid sand flies were reduced ~72% and 100% during treatment and at week-3 post-treatment, respectively. However, noticeable sand fly reduction did not occur after week-3 and results suggest environmental factors also influenced abundance significantly. In conclusion, fipronil bait, applied in southeastern Kazakhstan, has the potential to reduce or potentially eliminate Xenopsylla spp. fleas if applied at least every 80-days, but may need to be applied at higher frequency to significantly reduce the oviposition rate of Phlebotomus spp. sand flies. Fipronil-based bait may provide a means of controlling blood-feeding vectors, subsequently reducing disease risk, in Central Asia and other affected regions globally., Competing Interests: DMP, ZTP, RMP, and LP are employed by Genesis Laboratories, Inc. The authors have declared that no competing interests exist.

Background: Fluralaner (Bravecto®, Merck Animal Health, Madison, NJ, USA) is a novel isoxazoline that provides up to 12 weeks flea and tick control when administered orally to dogs. Two assessor-blinded studies, one in dogs, the other in cats evaluated the sustained efficacy of a topical fluralaner formulation against fleas in a simulated home environment (SHE)., Methods: Animals were ranked and blocked into groups of two using flea counts completed 24 hours following Ctenocephalides felis infestations placed on dogs on Day -64, and on cats on Day -36. Within blocks animals were randomized to a treatment group, 10 animals per group, one group to receive fluralaner spot-on (minimum dose rate for dogs, 25 mg/kg; for cats, 40 mg/kg), the other to be a sham-treated control. Animals were then placed into their SHE, one animal per pen or cage and then infested with 100 C. felis at weekly intervals. Dogs were infested from Day -56 through -21 and cats on Days -28 and -21. Fleas were counted and removed from each dog and cat on Day -1. Study animals were then held in clean pens/cages until treatment on Day 0. One day later, after treatment, all animals were returned to their home environment (SHE). Additional 50-flea challenges were placed on each animal on Days 22, 50 and 78. Fleas were counted and replaced on all animals on Day 1 and weekly thereafter for 12 weeks., Results: Arithmetic mean counts in control-group animals exceeded 10 fleas at all post-treatment assessments except on Days 1, 7 and 14. All control-group animals remained infested at each assessment from Day or 28 through Day 84, thereby validating the challenge methodology. Fluralaner efficacy was 100% on all occasions except for 2 fleas found on 1 dog on Day 1, and 3 fleas on 1 dog on Day 14. One flea was recovered from 1 fluralaner treated cat on Day 1. There were no treatment-related adverse events., Conclusion: A single application of a topical formulation of fluralaner is well tolerated and highly effective in the prevention of flea infestations of dogs and cats throughout the 12 weeks following treatment.

The human flea, Pulex irritans, is the most important ectoparasite of humans. Intensive use of pyrethroids for its control has led to insecticide resistance. Monitoring pyrethroid resistance and its underlying mechanisms is essential for flea control. The aims of this study were to identify the susceptibility status of human flea to permethrin and to detect the presence of knockdown resistance (kdr) mutation and its frequency in populations of P. irritans. Adults of P. irritans were collected from Zanjan Province, northwest of Iran, during 2013-2017. Different populations of this flea were exposed to permethrin 0.75% for one and 8 h and then the mortality rate, as well as KD 50 and KD 95 times were calculated. Total RNA and gDNA of samples were extracted, and the fragments of cDNA encoding the partial voltage-gated sodium channel (VGSC) peptides were amplified using degenerated primers. Specific PCR and TaqMan real-time assays were conducted to characterize the vgsc gene and to detect the presence of mutation and genotyping of the populations. Mortality rates were in the range from 32% to 67% for one-hour and 73% to 90% for eight-hour exposure to permethrin 0.75%. KD 50 and KD 95 times varied in a range from 46 to 241 and 177 to 899 min, respectively. Sequencing of 70 amplified fragments of gDNA resulted in a 578-bp product. These fragments contained two introns (92 and 63 bp) and three exons (141, 189, and 92 bp) encoding 138 amino acids that encompassed IIS4-IIS6 and the partial linker between domains II and III of VGSC. All the studied populations showed L1014F mutation, substitution of CTT for TTT at the 1014 allele. The result of TaqMan assay for 624 samples showed 96.6% homogenous and 3.36% heterozygous mutant. The development of permethrin resistance and the presence of the L1014F mutation at high frequency in flea populations indicate that pyrethroids are likely ineffective in controlling human flea. Therefore, novel alternative control methods are needed to combat this human ectoparasite., (Copyright © 2018 Elsevier Inc. All rights reserved.)

At Valles Caldera National Preserve in New Mexico, US, infusing Gunnison's prairie dog ( Cynomys gunnisoni) burrows with an insecticide dust containing 0.05% deltamethrin killed fleas which transmit bubonic plague. The reduction in the number of fleas per prairie dog was significant and dramatic immediately after infusions, with a suggestion that the reduction persisted for as long as 12 mo. Despite the lower flea counts, however, a plague epizootic killed >95% of prairie dogs after 3 yr of infusions (once per year). More research is necessary for a better understanding of the efficacy of insecticide dusts at lowering flea counts and protecting prairie dogs from plague.

Background: Preclinical studies have shown that the novel isoxazoline, lotilaner (Credelio™, Elanco) administered orally to dogs, produces rapid flea and tick knockdown and sustained speed of kill for at least a month post-treatment with a wide safety margin. A field study was undertaken to validate pre-clinical results., Methods: Dogs were enrolled at 10 veterinary clinics across the United States. Qualifying households containing up to three dogs and one primary dog with at least 10 fleas were randomized 2:1 to receive lotilaner (Credelio™, Elanco) at the recommended minimum dose of 20 mg/kg, or afoxolaner (Nexgard®, Merial), administered per label, to give a minimum dose of 2.5 mg/kg. Treatments were dispensed on Days 0, 30 and 60 for administration by owners; all household dogs received the same treatment as the primary dog. Post-enrollment flea and tick counts were made on primary dogs on Days 30, 60 and 90, and all dogs were assessed for tablet palatability and safety., Results: For efficacy assessments, data were used from 111 lotilaner-treated dogs and 50 afoxolaner-treated dogs; for safety, 197 and 86 dogs, respectively. Percent reductions from baseline in geometric mean flea counts for the lotilaner group were 99.3, 99.9 and 100% on Days 30, 60 and 90, respectively, and for afoxolaner 98.3, 99.8 and 99.8% (P < 0.001, both groups, all days). On Day 90, 100% of lotilaner-treated dogs and 93% of afoxolaner-treated dogs were flea-free. Too few ticks were present to allow assessment. There were no differences in palatability between products (P = 0.2132), with, respectively, 94% and 96% of lotilaner and afoxolaner treatments accepted when offered by hand, in an empty food bowl or with food. Both treatments were well tolerated, alleviating clinical signs of flea allergy dermatitis (FAD) in dogs affected at enrollment., Conclusion: A single owner-administered lotilaner treatment was greater than 99% effective in reducing mean flea counts within 30 days. Three consecutive monthly lotilaner treatments resulted in a 100% reduction in flea infestations, and a substantial reduction in signs of FAD. Lotilaner flavored tablets were readily accepted under field conditions. The absence of treatment-related adverse events confirms the safety of lotilaner in dogs.

Background: Lotilaner is a novel isoxazoline developed for oral administration to dogs. In laboratory studies, lotilaner was shown to be safe and to produce a rapid flea and tick knockdown, with a sustained speed of kill for at least a month post-treatment. A study was undertaken to demonstrate the efficacy, safety and palatability of three monthly doses of lotilaner flavoured chewable tablets (Credelio™, Elanco) in controlling fleas under field conditions in Europe., Methods: Dogs were enrolled at 17 veterinary clinics across Germany, Hungary and Portugal. Qualifying households having no more than three dogs and one primary dog with at least five fleas was randomised 2:1 to a lotilaner (minimum dose rate 20 mg/kg) or a topical fipronil group (administered per label). There were 128 and 64 households allocated to the lotilaner and fipronil groups, respectively. Treatments were dispensed to owners on Days 0, 28 and 56; supplementary household dogs received the same treatment as the primary dog. Post-enrollment flea counts and flea allergy dermatitis (FAD) assessments were made on primary dogs on Days 14, 28, 56 and 84. Efficacy calculations were based on geometric mean percent reductions of live flea counts versus pre-treatment counts on Day 0. The safety and palatability of lotilaner tablets were also assessed., Results: Lotilaner efficacy was 99.1, 99.5, 99.9 and 99.8% on Days 14, 28, 56 and 84, respectively. Corresponding reductions for fipronil were 93.4, 91.2, 94.4 and 97.0%. Lotilaner was superior to fipronil at all post-Day 0 assessments (t (186)  ≥ 3.43, P ≤ 0.0007). At every post-treatment assessment, at least 90% of lotilaner-treated dogs were flea-free (98.4% on Day 84); fewer than 90% of fipronil group dogs were flea-free on the same time points. Lotilaner flavoured chewable tablets were palatable, and both products were well tolerated. Lotilaner alleviated or eliminated clinical signs of FAD, including pruritus., Conclusions: Under field conditions in Europe, lotilaner flavoured chewable tablets were greater than 99% effective in eliminating fleas from dogs at the first post-treatment assessment (Day 14). Efficacy was maintained through Day 84, with corresponding improvements in FAD. Lotilaner tablets were palatable and safe and provided superior flea control to fipronil.

Background: The present study assessed the activity of a combination of dinotefuran and pyriproxyfen (Vectra® Felis) for long-term control (3 months) of allergic dermatitis (AD) in privately-owned cats under common household conditions in Ile-de-France region., Methods: This was an open pre-treatment vs post-treatment study. Twenty-eight client-owned cats with clinical signs of AD were enrolled in the study. They received topical application of the combination of dinotefuran and pyriproxyfen on days 0, 28, 56 and 84. Two parameters (clinical signs and pruritus severity) were used to assess the animals' condition on days 0, 28 and 84. Fleas were counted if they were observed., Results: Of the 28 cats initially enrolled, 26 were presented on day 28 and 20 for the final evaluation on day 84. A significant improvement in clinical signs and pruritus was observed in cats for which fleas and/or flea feces were detected on day 0. Globally, the post-treatment AD clinical scores on days 28 and 84 were different from that of the pre-treatment on day 0, with a reduction of 30% and 71%, respectively. For cats with fleas and/or flea feces, the reduction on days 28 and 84 was 33% and 85%, respectively. The improvement of clinical signs and pruritus was not significant in cats with no visible fleas and no flea feces at the beginning of the trial (n = 8)., Conclusions: The present study indicated that the treatment with a combination of dinotefuran and pyriproxyfen should be considered as useful in controlling fleas on cats without additional environmental treatment and useful for long-term control of clinical signs and pruritus in allergic cats.

Background: An in-home investigation of naturally flea infested dogs was conducted in West Central Florida, USA to evaluate and compare the effectiveness of two different oral flea adulticides to control flea infestations, minimize dermatologic lesions and reduce pruritus over an 8-week period., Methods: Twenty-nine dogs living in 19 homes and another 26 dogs residing in 16 different homes were orally administered either a sarolaner or spinosad chewable, respectively on day 0 and once between days 28-30. Products were administered by study personnel according to label directions. Flea populations on dogs were estimated using visual area counts and flea infestations in the indoor premises were assessed using intermittent-light flea traps on days 0, 7, 14, 21 and once between days 28-30, 40-45, and 56-60. Assessments of dermatologic lesions were conducted monthly during the study and severity of pruritus was evaluated throughout the study on the same schedule as flea counts were conducted. Concurrent treatments for existing skin disease were not allowed., Results: The administration of sarolaner or spinosad reduced flea populations on dogs by 99.0% and 97.3%, respectively within 7 days. Flea infestations on the sarolaner- and spinosad-treated dogs were reduced by > 99% at every counting period from day 14 post-treatment through the end of the 8-week study. At the end of the study 96.4 and 92.0% of the dogs treated with sarolaner and spinosad, respectively were flea-free. Flea populations in the indoor premises were also markedly reduced the end of the study, with 100 and 99.8% reductions in flea trap counts in the sarolaner and spinosad treatment groups, respectively. FAD lesion scores, atopic dermatitis lesions scores (CADESI-4) and pruritus severity scores were also markedly improved with both formulations., Conclusions: An in-home clinical field study conducted during the summer of 2016 in subtropical Florida demonstrated that two-monthly administrations of either sarolaner or spinosad chewables almost completely eliminated flea infestations on dogs and in private residences, while markedly reducing dermatology lesions and pruritus.

Background: The efficacy and safety of a novel isoxazoline compound, sarolaner (Simparica ® , Zoetis) and spinosad (Comfortis ® , Elanco) as a positive control were evaluated for the treatment and control of natural flea infestations on dogs in two randomised, blinded, multi-centric clinical trials conducted in 11 veterinary clinics in northeastern and southeastern states of Australia., Methods: A total of 162 client-owned dogs (80 in northern study and 82 in southern study) from 105 households were enrolled. Each household was randomly allocated to receive either sarolaner (Simparica ® , Zoetis) or spinosad (Comfortis ® , Elanco). Dogs were dosed on Days 0, 30 and 60 and physical examinations and flea counts were conducted on Days 0, 14, 30, 60 and 90. Efficacy assessments were based on the percentage reduction in live flea counts post-treatment compared to Day 0., Results: In the northern study, at enrolment, primary dogs had flea counts ranging from 5 to 772. At the first efficacy assessment on Day 14, sarolaner resulted in 99.3% mean reduction in live flea counts relative to Day 0, compared to 94.6% in the spinosad group. On Day 30, the sarolaner-treated group had mean efficacy of 99.2% compared to 95.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.8%. In the southern study, at enrolment, primary dogs had flea counts ranging from 5 to 156. Both sarolaner and spinosad resulted in ≥ 96.7% mean reduction in live flea counts on Day 14. On Day 30, the sarolaner-treated group had mean efficacy of 99.5% compared to 89.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.6%. No treatment-related adverse events were observed in either study., Conclusions: A single monthly dose of sarolaner (Simparica ® ) administered orally at 2-4 mg/kg for three consecutive months was well tolerated and provided excellent efficacy against natural infestations of fleas under a range of Australian field conditions including different climatic and housing conditions. Similar efficacy was observed with spinosad (Comfortis ® ) after the second and third monthly treatments.

Background: A spot-on spinetoram formulation (Cheristin ® ) was developed to eliminate fleas from infested cats. This paper describes three spinetoram studies: two for registration (Studies 1 and 2), and one comparing residual speed of kill (SOK) with topically applied fipronil/(S)-methoprene (FSM) and imidacloprid (Study 3)., Methods: Cats were randomized to treatment based on flea counts from infestations placed within 2 weeks prior to treatment. In Studies 1 and 2, groups were untreated control and spinetoram; in Study 3, groups were untreated control, spinetoram, FSM and imidacloprid, all applied per label on Day 0. Cats were infested the day before treatment. In Studies 1 and 2, counts were completed 48 h post-treatment and after weekly challenges through 5 weeks. In Study 3, infestations were completed weekly through Day 28, with counts 1, 4, 8 and 12 h after treatment or post-infestation (PI). Efficacy was determined on geometric mean flea count reductions compared with controls, and in Study 3 mean flea counts in spinetoram-groups were compared with those in FSM and imidacloprid groups., Results: In Studies 1 and 2, spinetoram effectiveness was 100% against existing infestations, and at least 96% through Day 37. In Study 3 mean counts were not significantly different from controls in any group until 8 h post-treatment when imidacloprid counts were significantly lower than spinetoram counts, which were in turn significantly lower than FSM counts (P < 0.05). At 1 h PI spinetoram-group counts were significantly lower (P < 0.05) than counts in: controls, all days; imidacloprid, Days 7, 14, and 28; FSM, Days 14 and 28. At 4 h PI, spinetoram mean counts were significantly lower (P < 0.05) relative to: controls, all days; imidacloprid, Days 7, 14 and 21; FSM, Days 7, 14, 21 and 28 (P < 0.05). On multiple occasions, at 8 and 12 h PI, mean counts were significantly lower (P < 0.05) for spinetoram than for imidacloprid and FSM; at no point were FSM or imidacloprid significantly more effective than spinetoram against new infestations. All treatments were well tolerated., Conclusions: Spinetoram was highly effective for at least 1 month post-treatment and provided more rapid month-long residual SOK than FSM or imidacloprid.

Acaricidal (tick) and insecticidal (flea) efficacy of systemically and cutaneously distributed ectoparasiticide products for dogs are compared based on permethrin and fluralaner as representative molecules. Results of efficacy studies against fleas and ticks are reviewed that show generally good to excellent results. Both externally and systemically distributed treatments have benefits and weaknesses in potentially preventing pathogen transmission by these arthropod vectors.Four general properties are considered related to the goal of providing optimal reduction in the risk of vector-borne pathogen transmission. These are: 1. Owner adherence to the recommended treatment protocol; 2. Rapid onset of activity following administration; 3. Uniform efficacy over all areas of the treated dog at risk for parasite attachment; 4. Maintenance of high efficacy throughout the retreatment interval. In considering these four factors, a systemically distributed acaricide can offer an option that is at least as effective as a cutaneously administered acaricide with regard to the overall goal of reducing the risk of vector-borne pathogen transmission.

Background: A study was conducted to evaluate and compare the effectiveness of two different oral flea and tick products to control flea infestations, reduce pruritus and minimize dermatologic lesions over a 12 week period on naturally infested dogs in west central FL USA., Methods: Thirty-four dogs with natural flea infestations living in 17 homes were treated once with a fluralaner chew on study day 0. Another 27 dogs living in 17 different homes were treated orally with an afoxolaner chewable on day 0, once between days 28-30 and once again between days 54-60. All products were administered according to label directions by study investigators. Flea populations on pets were assessed using visual area counts and premise flea infestations were assessed using intermittent-light flea traps on days 0, 7, 14, 21, and once between days 28-30, 40-45, 54-60 and 82-86. Dermatologic assessments were conducted on day 0 and once monthly. Pruritus assessments were conducted by owners throughout the study. No concurrent treatments for existing skin disease (antibiotics, anti-inflammatories, anti-fungals) were allowed., Results: Following the first administration of fluralaner or afoxolaner, flea populations on pets were reduced by 99.0 % and 99.3 %, respectively within 7 days. Flea populations on the fluralaner treated dogs were 0 (100 % efficacy) on days 54-60 and 82-86 after the administration of a single dose on day 0. Administration of 3 monthly doses of afoxolaner reduced flea populations by 100 % on days 82-86. Flea numbers in indoor-premises were markedly reduced in both treatment groups by days 82-86, with 100 % and 98.9 % reductions in flea trap counts in the fluralaner and afoxolaner treatment groups, respectively. Marked improvement was observed in FAD lesion scoring, Atopic Dermatitis lesions scoring (CADESI-4) and pruritus scores with both formulations., Conclusions: In a clinical field investigation conducted during the summer of 2015 in subtropical Florida, a single administration of an oral fluralaner chew completely eliminated dog and premises flea infestations and markedly reduced dermatology lesions and pruritus. Three monthly doses of the afoxolaner chewable also eliminated flea infestations in dogs, markedly reduced premises' flea populations and similarly improved dermatology lesions and pruritus.

Background: Bravecto™ Chewable Tablets for Dogs, containing fluralaner as active ingredient, is an innovative treatment for flea and tick infestations that provides safe, rapid and long acting efficacy after a single oral administration in dogs. Topically applied fluralaner provides similar safe, rapid and long acting efficacy, both in dogs and in cats. The pharmacokinetic profile of fluralaner was evaluated in dogs and in cats following either topical or intravenous administration., Methods: Twenty four dogs and 24 cats received three different topical doses, with the mid-dose based on the respective minimum recommended dose, and one intravenous dose. Plasma samples were collected for 112 days and fluralaner concentrations were quantified using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method. Pharmacokinetic parameters were calculated using non-compartmental methods., Results: In dogs, fluralaner was readily absorbed from the topical administration site into the skin, subjacent tissues and blood. Fluralaner plasma concentrations showed an apparent plateau between ~ day 7 and 63, with individual tmax seen within this time period. After the plasma plateau, concentrations declined slowly and were quantifiable for more than 12 weeks. In cats, fluralaner was readily systemically absorbed from the topical administration site, reaching maximum concentrations (Cmax) in plasma between 3 and 21 days post administration, after which concentrations declined slowly, and were also quantifiable for more than 12 weeks. Systemic exposure, as shown by Cmax and the area under the concentration versus time curve from time 0 to the last measurable concentration (AUC(0→t)) increased proportionally with dose in both species. Following intravenous administration fluralaner showed a relatively high apparent volume of distribution (Vz), a low plasma clearance (Cl), a long terminal half-life (t1/2) and a long mean residence time (MRT); thereby demonstrating a long persistence of fluralaner in both species., Conclusions: The pharmacokinetic characteristics of fluralaner explain its prolonged activity against fleas and ticks on both dogs and cats after a single topical administration.

Four studies were conducted to evaluate the speed of kill, effect on egg production, and efficacy in a simulated infested-home environment of a novel isoxazoline, sarolaner (Simparica™, Zoetis), against fleas on dogs. Individually identified and housed, purpose-bred Beagles were used in each study and were allocated randomly to groups based on pretreatment parasite counts. In two speed of kill studies, groups of dogs infested with 100 fleas prior to treatment were treated orally with placebo or sarolaner tablets providing the minimum dose of 2mg/kg and then re-infested with fleas weekly for five weeks post-treatment. Comb counts were conducted to determine the numbers of viable fleas at one to three, four, eight and 12h after treatment and each subsequent infestation. In the egg production study, sarolaner- and placebo-treated dogs were similarly challenged with fleas and at 48h after each infestation the dogs were housed for 20h in cages allowing the collection and counting of all flea eggs produced during this period. Collected eggs were incubated to evaluate hatch and development to adults. The last study used dogs housed in a flea-infested simulated-home environment. Dogs were allocated to treatment with either placebo or sarolaner tablets providing a dose of 2mg/kg once a month for three treatments. Flea infestations were assessed by comb counts (fleas were replaced on the dogs) on Days 14, 30, 44, 60, 74 and 90. The speed of kill studies demonstrated that a single 2mg/kg oral dose of sarolaner started killing fleas within three to four hours after treatment or subsequent re-infestations for up to a month, and achieved ≥98% control of fleas by eight hours after treatment or re-infestation for 28 days. In the study to assess effects on flea reproduction, a single oral treatment of sarolaner resulted in the complete cessation of egg-laying for 35 days. This rapid kill of fleas and inhibition of reproduction were confirmed in a simulated-home environment where the existing infestations were reduced by >95% within two weeks of the first treatment and eliminated from the dogs after two monthly doses., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

The novel isoxazoline ectoparasiticide, sarolaner, was identified during a lead optimization program for an orally-active compound with efficacy against fleas and ticks on dogs. The aim of the discovery program was to identify a novel isoxazoline specifically for use in companion animals, beginning with de novo synthesis in the Zoetis research laboratories. The sarolaner molecule has unique structural features important for its potency and pharmacokinetic (PK) properties, including spiroazetidine and sulfone moieties. The flea and tick activity resides in the chirally pure S-enantiomer, which was purified to alleviate potential off-target effects from the inactive enantiomer. The mechanism of action was established in electrophysiology assays using CHO-K1 cell lines stably expressing cat flea (Ctenocephalides felis) RDL (resistance-to-dieldrin) genes for assessment of GABA-gated chloride channel (GABACls) pharmacology. As expected, sarolaner inhibited GABA-elicited currents at both susceptible (CfRDL-A285) and resistant (CfRDL-S285) flea GABACls with similar potency. Initial whole organism screening was conducted in vitro using a blood feeding assay against C. felis. Compounds which demonstrated robust activity in the flea feed assay were subsequently tested in an in vitro ingestion assay against the soft tick, Ornithodoros turicata. Efficacious compounds which were confirmed safe in rodents at doses up to 30mg/kg were progressed to safety, PK and efficacy studies in dogs. In vitro sarolaner demonstrated an LC80 of 0.3μg/mL against C. felis and an LC100 of 0.003μg/mL against O. turicata. In a head-to-head comparative in vitro assay with both afoxolaner and fluralaner, sarolaner demonstrated superior flea and tick potency. In exploratory safety studies in dogs, sarolaner demonstrated safety in dogs≥8 weeks of age upon repeated monthly dosing at up to 20mg/kg. Sarolaner was rapidly and well absorbed following oral dosing. Time to maximum plasma concentration occurred within the first day post-dose. Bioavailability for sarolaner was calculated at >85% and the compound was highly protein bound (>99.9%). The half-life for sarolaner was calculated at 11-12 days. Sarolaner plasma concentrations indicated dose proportionality over the range 1.25-5mg/kg, and these same doses provided robust efficacy (>99%) for ≥35days against both fleas (C. felis) and multiple species of ticks (Rhipicephalus sanguineus, Ixodes ricinus and Dermacentor reticulatus) after oral administration to dogs. As a result of these exploratory investigations, sarolaner was progressed for development as an oral monthly dose for treatment and control of fleas and ticks on dogs., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Insect growth regulators (IGRs) methoprene and pyriproxyfen are widely used as topical treatments to pets or applied to the indoor environment to control cat fleas, Ctenocephalides felis (Bouché). The toxicity of methoprene, pyriproxyfen, and combinations of both IGRs to cat flea larvae was determined. The LC 50 of methoprene and pyriproxyfen applied to larval rearing medium was 0.39 and 0.19 ppm, respectively. Combinations of methoprene:pyriproxyfen in ratios of 1:1, 5:1, 10:1, and 20:1 produced LC 50 s of 0.06, 0.09, 0.19, and 0.13 ppm, respectively. The pyriproxyfen synergized the activity of methoprene as indicated by the combination indices (CI). The ratio of methoprene:pyriproxyfen (40:1) provided an LC 50 of 0.42 ppm and the pyriproxyfen was not synergistic. Combinations of pyriproxyfen:methoprene in ratios of 5:1, 10:1, and 20:1 provided LC 50 s of 0.14, 0.20, 0.20 ppm, respectively, and the methoprene did not synergize the activity of pyriproxyfen. The dose-reduction indices (DRIs) indicated that the concentrations of IGRs in the combinations of methoprene:pyriproxyfen (ratios of 20:1 or less) could be reduced by at least one-third of the amount required by methoprene alone to provide similar larval mortality. Combinations of methoprene and pyriproxyfen may be effective in increasing the residual activity on pets and assist in reducing the likelihood of insecticide resistance developing to IGRs., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Over the last decade, the isoxazoline motif has become the intense focus of crop protection and animal health companies in their search for novel pesticides and ectoparasiticides. Herein we report the discovery of sarolaner, a proprietary, optimized-for-animal health use isoxazoline, for once-a-month oral treatment of flea and tick infestation on dogs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The speed of flea knockdown by different products and their duration of effectiveness are factors which affect veterinarian prescribing decisions. To further validate the month-long pulicidal effectiveness of spinosad and determine its rate of flea knockdown to that of afoxolaner, three studies were conducted in two laboratories in the United States, utilizing flea infestations from colonies which are regularly refreshed through introduction of locally caught fleas., Methods: All study assessors were blinded, dogs were ranked by pre-study flea counts and randomized accordingly, and treatments administered on Day 0. All studies included a negative control group; two also included an afoxolaner group. In one study, flea challenges for treated and control dogs (10 per group) were completed 21 and 28 days after treatment and counts were performed 24 h later. In each of two speed-of-knockdown (SOK) studies, 36 dogs were randomized, six dogs per group, to: untreated controls; administered oral afoxolaner (2.6-6.2 mg/kg); or oral spinosad (32.1-59.2 mg/kg). In the SOK studies, live fleas from Day -1 infestations were counted after being combed off at 1 and 3 h after treatment, and after reinfestations on Day 7., Results: There were no treatment-related adverse events. Spinosad was 98.6% effective at 28 days post treatment. For SOK, geometric mean live flea counts for afoxolaner were not different from controls at any assessment. For spinosad, all mean counts were significantly lower than in controls (p ≤ 0.0128) except at 1 h post treatment in both studies. Spinosad was significantly more effective than afoxolaner in both studies at 3 h post treatment (p ≤ 0.0065) and post-Day 7 infestation (p ≤ 0.0054), and at 1 h post treatment (p = 0.0276) and post-Day 7 infestation in one study., Conclusions: These data validate spinosad's faster onset of flea knockdown than afoxolaner against infestations present at the time of treatment, and faster residual speed of flea knockdown for at least 7 days post treatment, and confirm spinosad's extended residual speed of kill for at least 28 days post treatment.

Background: Three flea species, Pulex irritans, Ctenocephalides canis and C. felis parasitize shepherd dogs living on sheep farms in Greece. The aim of this randomized, blinded, placebo-controlled trial was to examine the efficacy of spinosad, when administered three times every 4 weeks, as the only intervention to treat and prevent flea infestations in shepherd dogs living on sheep farms., Methods: Thirty dogs living on sheep farms and infested by at least 24 fleas were randomly allocated into equal groups. Group A dogs received spinosad (45-70 mg/kg body weight), every 4 weeks for three administrations, whereas Group B dogs were placebo-treated. Flea counting was performed at the beginning of the trial (day 0) and after 14, 28, 56 and 84 days. The first five fleas from each dog and 2-6 fleas collected from 5-11 sheep were used for species identification., Results: The percentage of dogs with zero flea counts was significantly higher in group A than in group B at days 14, 28, 56 and 84 and flea counts were significantly lower in group A than in group B at days 14, 28, 56 and 84. In group A, flea counts were significantly lower at days 14, 28, 56 and 84 compared to day 0 whereas there were no changes in flea counts of group B dogs. The percent efficacy of spinosad for the treatment and prevention of flea infestation was higher than 98% (arithmetic means) or higher than 99% (geometric means) throughout the study. No adverse reactions were recorded. C. canis was the predominant flea species of dogs at day 0. In group A the relative abundance of C. felis increased at day14 whereas in group B the relative abundance of P. irritans increased at days 14, 28, 56 and 84., Conclusions: Spinosad is safe and effective for the treatment of C. canis and C. felis infestations and for the prevention of P. irritans, C. canis and C. felis infestations in shepherd dogs living in close proximity to sheep.

The apparent monthly prevalence of endoparasite infections was measured from 20,991 dogs that had fecal examinations performed upon presentation to the Veterinary Hospital of the University of Pennsylvania between 1984 and 2007. In the period from 1984 to 1991, the mean monthly prevalence of endoparasites was 5.32% for ascarids, 9.80% for hookworms, 9.64% for whipworms, 1.84% for tapeworms (Dipylidium caninum), 4.59% for Giardia species, and 3.04% for coccidia. Based on Student's t tests, the prevalence of ascarids (1.99%), hookworms (1.48%), whipworms (2.33%), and tapeworms (0.29%) were found to be significantly lower in the period from 2000 to 2007. Plots of the smoothed monthly averages revealed that the declines in prevalence occurred shortly after the introduction of modern heartworm and flea preventatives to the commercial market. In the latter study period, 79.8% of dogs were on monthly heartworm prevention and 74.0% were on monthly flea prevention. There were no significant differences in the prevalence of either Giardia species or coccidia species between study time periods. Overall, the findings suggest that heartworm and flea preventatives have had cascade effects on endoparasite prevalence in the population of well-cared-for dogs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Canine flea-allergy dermatitis (FAD), a hypersensitivity response to antigenic material in the saliva of feeding fleas, occurs worldwide and remains a common presentation in companion animal veterinary practice despite widespread availability of effective systemic and topical flea-control products., Hypothesis/objectives: To evaluate the clinical response in dogs with FAD treated topically with indoxacarb, a novel oxadiazine insecticide., Animals: Twenty-five client-owned dogs in Queensland, Australia diagnosed with pre-existing FAD on the basis of clinical signs, flea-antigen intradermal and serological tests., Methods: An open-label, noncontrolled study, in which all dogs were treated with topical indoxacarb at 4 week intervals, three times over 12 weeks., Results: Twenty-four dogs completed the study. Complete resolution of clinical signs of FAD was observed in 21 cases (87.5%), with nearly complete resolution or marked improvement in the remaining three cases. Mean clinical scores (Canine Atopic Dermatitis Extent and Severity Index-03) were reduced by 93.3% at week 12. Mean owner-assessed pruritus scores were reduced by 88% by week 12. Mean flea counts reduced by 98.7 and 100% in weeks 8 and 12, respectively., Conclusions and Clinical Importance: Topical indoxacarb treatment applied every 4 weeks for 12 weeks, without concomitant antipruritic or ectoparasiticide therapy, completely alleviated flea infestations in all dogs and associated clinical signs of FAD in a high proportion of this population of dogs in a challenging flea-infestation environment., (© 2014 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and the ACVD.)

Afoxolaner is an isoxazoline compound characterized by a good safety profile and extended effectiveness against fleas and ticks on dogs following a single oral administration. In vitro membrane feeding assay data and in vivo pharmacokinetic studies in dogs established an afoxolaner blood concentration of 0.1-0.2 μg/ml to be effective against both fleas (Ctenocephalides felis) and ticks (Dermacentor variabilis). Pharmacokinetic profiles in dogs following a 2.5mg/kg oral dosage demonstrated uniform and predictable afoxolaner plasma concentrations above threshold levels required for efficacy for more than one month. Dose ranging and a 5-month multi-dose experimental study in dogs, established that the 2.5mg/kg oral dosage was highly effective against fleas and ticks, and produced predictable and reproducible pharmacokinetics following repeated dosing. Mode of action studies showed that afoxolaner blocked native and expressed insect GABA-gated chloride channels with nanomolar potency. Afoxolaner has comparable potency between wild type channels and channels possessing the A302S (resistance-to-dieldrin) mutation. Lack of cyclodiene cross-resistance for afoxolaner was confirmed in comparative Drosophila toxicity studies, and it is concluded that afoxolaner blocked GABA-gated chloride channels via a site distinct from the cyclodienes., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Fluralaner, a new molecular entity of the isoxazoline class, has potent insecticidal and acaricidal activity and can be safely administered orally to dogs., Methods: A randomized, investigator-blinded, multi-centered field study compared the flea- and tick-control efficacy for dogs over a 12-week period with either a single oral dose of Bravecto (fluralaner) formulated as a chewable tablet or with three sequential topical Frontline (fipronil) treatments. Individual dogs were the experimental unit for ticks and households were the experimental unit for fleas. A total of 108 tick-infested dogs were treated with Bravecto (fluralaner) and 54 tick-infested dogs were treated with Frontline (fipronil). Dogs in 115 flea-infested households received Bravecto (fluralaner) and dogs in 61 flea-infested households received Frontline (fipronil). Flea and tick counts were conducted on all dogs at weeks 2, 4, 8, and 12 following initial treatment and efficacy was calculated as the mean percent reduction in tick or flea count at each time point compared with the mean pretreatment initiation count for each treatment group. Additionally, the percentages of tick-free and flea-free households were determined., Results: At weeks 2, 4, 8, and 12, Bravecto (fluralaner) flea-control efficacy in treated households was 99.2%, 99.8%, 99.8%, and 99.9% respectively, while Frontline (fipronil) efficacy was 94.1%, 93.0%, 96.0%, and 97.3%, respectively. Bravecto (fluralaner) tick-control efficacy on treated dogs at weeks 2, 4, 8, and 12 was 99.9%, 99.9%, 99.7%, and 100%, respectively, and Frontline (fipronil) tick efficacy was 97.6%, 93.8%, 100%, and 100%, respectively. Of dogs showing clinical flea allergy dermatitis (FAD) signs at the study start, 85.7% in the Bravecto™ (fluralaner)-treated group and 55.6% in the Frontline (fipronil)-treated group were evaluated at each time point as showing no clinical signs of FAD until study completion., Conclusions: Bravecto (fluralaner) administered once orally to dogs in a chewable tablet was highly effective for 12 weeks against fleas and ticks on privately-owned dogs and was significantly non-inferior (ticks) and superior (fleas) in comparison with topical Frontline (fipronil) administered 3 times sequentially.

Background: Repellents are a common method for preventing flea bites, making an effective system for flea repellent screening advantageous. We describe an improved technique to facilitate repellent activity screening of numerous plant-based Ctenocephalides felis (cat flea) repellents., Results: Two long strips of filter paper were impregnated with test compounds (dissolved in ethanol) and ethanol only, respectively. After drying, the two filter papers were glued together along the long side and inserted into a glass tube containing non-fed cat fleas. The distribution of cat fleas in each half of the filter paper was recorded after 30 min to calculate repellency. Results showed that the essential oil of Cinnamomum osmophloeum (from leaf), Taiwania cryptomerioides (from heartwood) and Plectranthus amboinicus (from leaf) exhibits repellent activity against cat fleas in a dose dependent manner. Moreover, the repellent activities against cat fleas of 2% trans-cinnamaldehyde (the main constituent of Ci. osmophloeum essential oil) and 0.5% thymol (the main constituent of P. amboinicus essential oil) are 97.6% and 90.6%, and can persist for up to 4 and 8 h, respectively. These results are comparable to those of 15% DEET., Conclusion: The proposed screening technique can facilitate the pre-screening of numerous flea repellents for further evaluation on animal or human subjects., (© 2013 Society of Chemical Industry.)

This review defines insecticide/acaricide resistance and describes the history, evolution, types, mechanisms, and detection of resistance as it applies to chemicals currently used against fleas and ticks of dogs and cats and summarizes resistance reported to date. We introduce the concept of refugia as it applies to flea and tick resistance and discuss strategies to minimize the impact and inevitable onset of resistance to newer classes of insecticides. Our purpose is to provide the veterinary practitioner with information needed to investigate suspected lack of efficacy, respond to lack of efficacy complaints from their clients, and evaluate the relative importance of resistance as they strive to relieve their patients and satisfy their clients when faced with flea and tick infestations that are difficult to resolve. We conclude that causality of suspected lack of insecticide/acaricide efficacy is most likely treatment deficiency, not resistance.

The efficacy of spinosad against adult fleas (Ctenocephalides felis) on cats was evaluated in two separate controlled, blinded studies-one to determine flea knockdown and speed of flea kill (SOFK) on experimentally infested cats, another to assess the ability of spinosad to prevent flea infestations in a simulated home environment (SHE) study design. In each study, pre-treatment live flea counts were used as a blocking factor to randomize cats to treatment, and treated in the fed state, with flavored tablets containing either no active ingredient (control) or spinosad (50-100mg/kg in the SOFK study; 50-75 mg/kg body weight in the SHE study). In the SOFK study, 6 cats per group were infested with unfed adult fleas on Day -1. Groups 1-5 received control tablets; groups 6-10 received spinosad tablets. Flea counts were conducted at 0.5, 2, 4, 8 and 24h post-dosing. In the SHE study, 12 flea-free cats per group, treated on Days 0, 30 and 60, were maintained in solid-sided cages with solid carpeted floors. Each cat was infested on Days 1, 7 and 14 with 100 unfed adult fleas. Individual flea comb counts were performed on Days 3, 9, 16, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91 and 95. After each count, except Day 95, up to 300 live fleas were replaced on each cat. To augment flea challenge, the carpeted area in each cage was sprinkled weekly with larval flea growth media (dried blood, yeast). In the SOFK study, reductions in mean flea counts in the spinosad groups were observed at all post-treatment assessments, beginning at 0.5h post-infestation with significant differences (p<0.0001) from vehicle-treated cats from 2h post-treatment when efficacy was >90%, through the final flea counts 24h post-infestation when no fleas were found on spinosad treated cats. In the SHE study, GM post-treatment flea counts in the control group ranged between 38.9 and 107.0 (arithmetic means 58.8-118.1); no live fleas were combed from spinosad-treated cats (100% effectiveness) at any time point post-treatment. No adverse events that were attributable to the treatments were observed in either study. These studies demonstrated that spinosad administered orally to cats is safe and effective, providing >90% efficacy from 2h post-dosing and 100% knockdown at 24h, and preventing infestations over a 95 day study period from a flea-contaminated simulated home environment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

These second edition guidelines, updated from the 2007 version (Marchiondo et al., 2007), are intended to assist the planning and conduct of laboratory and clinical studies to assess the efficacy of ectoparasiticides applied to dogs or cats for the purpose of treating, preventing and controlling flea and tick infestations. Major revisions to this second edition include guidelines on the assessment of systemic flea and tick products, an update of the geographical distribution of the common fleas and ticks species on dogs and cats, determination of flea and tick efficacy based on geometric versus arithmetic means with respect to geographic regulatory agencies, modification of tick categorization in the assessment of efficacy, expanded guidelines on repellency and anti-feeding effects, enhanced practical field study guidance, and considerations on the ranges of flea and ticks for infestations in laboratory studies. The term ectoparasiticide includes insecticidal and acaricidal compounds, as well as insect growth regulators. The range of biological activities from animal treatment that are considered include: repellency and anti-feeding effects, knockdown, speed of kill, immediate and persistent lethal effects, and interference with egg fertility and subsequent development of off-host life cycle stages. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping, interpretation of results and animal welfare. These guidelines are also intended to assist regulatory authorities involved in the approval and registration of new topical or systemic ectoparasiticides, and to facilitate the worldwide adoption of harmonized procedures.

Objective: To compare safety and efficacy of spinosad and selamectin and determine effects of those products on flea allergy dermatitis (FAD) in cats., Design: Randomized clinical trial. Animals-211 client-owned cats., Procedures: Cats with ≥ 5 fleas evaluated at 8 veterinary clinics were allocated to receive spinosad (50 to 100 mg/kg [22.7 to 45.5 mg/lb], PO; n = 139) or selamectin (≥ 6 mg/kg [≥ 2.7 mg/lb], topically; 72) once per month. Flea comb counts and FAD scores were determined on day -1, between days 27 and 33, and between days 85 and 95 (evaluations 1, 2, and 3, respectively); day 0 was the first day of drug administration., Results: The most common adverse event was vomiting (14.3% and 2.4% of spinosad- and selamectin-treated cats, respectively). Evaluation 2 and 3 geometric mean flea counts for spinosad-treated cats were significantly lower than those for selamectin-treated cats. Percentage reductions in flea counts for the spinosad and selamectin groups were 97.5% and 88.8% (evaluation 2) and 99.3% and 97.7% (evaluation 3), respectively. At evaluations 2 and 3, 70.6% and 92.6% of spinosad-treated cats and 29.4% and 64.7% of selamectin-treated cats were free of fleas, respectively. Weighted FAD scores for spinosad- and selamectin-treated cats decreased 94.2% and 80.0% during the study, respectively. Spinosad tablets were successfully administered during 98.1% of treatments., Conclusions and Clinical Relevance: Results of this study indicated spinosad and selamectin both reduced flea counts and FAD scores for cats, although spinosad was more effective. Monthly oral administration of spinosad may be practical for treatment of flea infestations and FAD in cats.

Pyrethroid insecticides containing deltamethrin provide broad spectrum insect control that can adversely affect food supplies of insectivorous birds. I hypothesized that this could result in lowered nest survival for a ground-nesting insectivorous bird, the Mountain Plover (Charadrius montanus), which preferentially nests on prairie dog colonies. I studied Mountain Plover nest survival in 2003-2010 at a small cluster of black-tailed prairie dog (Cynomys ludovicianus) colonies in north-central Montana. Three colonies were treated with deltamethrin to control fleas and limit the spread of plague; four untreated colonies served as controls. I monitored 412 plover nests during the 8 year study (264 on treatment colonies and 148 on control colonies) and found a strong negative effect of deltamethrin treatments on nest survival (β(Dust) = -1.24, 95 % CI was -2.00 to -0.48) in the years following the actual treatment (2004-2006). I conclude that the observed treatment effect most likely occurred because of changes in insect (food) availability for the plover, and this in turn lowered nest survival because adults spent more time off nests or switched to less desirable insect prey. These results lend support to the need to consider the indirect effects of insecticide treatments on non-target species and suggest a potential conflict in current plague management strategies for prairie dogs.

Eucalyptus bleached kraft pulp production, an important sector of the Brazilian national economy, is responsible for generating large volume, high pollutant load effluents, containing a considerable fraction of recalcitrant organic matter. The objectives of this study were to quantify the biological activity of the effluent from a eucalyptus bleached kraft pulp mill, characterize the nature of compounds responsible for biological activity and assess the effect of ozone treatment on its removal. Primary and secondary effluents were collected bimonthly over the course of one year at a Brazilian bleached eucalypt kraft pulp mill and their pollutant loads (biochemical oxygen demand (BOD), chemical oxygen demand (COD), total organic carbon (TOC), adsorbable organic halogen (AOX), lignin, extractives) and biological activity (acute and chronic toxicity and estrogenic activity) quantified. The effluent studied did not present acute toxicity to Daphnia, but presented the chronic toxicity effects of algal growth inhibition and reduced survival and reproduction in Ceriodaphnia, as well as estrogenic activity. Chronic toxicity and estrogenic activity were reduced but not eliminated during activated sludge biological treatment. The toxicity identification evaluation revealed that lipophilic organic compounds (such as residual lignin, extractives and their byproducts) were responsible for the toxicity and estrogenic activity. Ozone treatment (50 mg/L O(3)) of the secondary effluent eliminated the chronic toxicity and significantly reduced estrogen activity.