Efficacy of fluralaner chewable tablets (Bravecto ® ) against Asian longhorned tick (Haemaphysalis longicornis) infestations of dogs

Efficacy of fluralaner chewable tablets (Bravecto ® ) against Asian longhorned tick (Haemaphysalis longicornis) infestations of dogs | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy of fluralaner chewable tablets (Bravecto ® ) against Asian longhorned tick (Haemaphysalis longicornis) infestations of dogs Melissa Petersen, Riaan Maree, Alta Viljoen, Julian E Liebenberg, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2318486/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Feb, 2023 Read the published version in Parasites & Vectors → Version 1 posted 8 You are reading this latest preprint version Abstract Background The parthenogenic reproductive ability of Haemaphysalis longicornis , facilitating quick life cycle completion and rapid geographic spread, and its pathogen vector potential make infestations a risk to human and canine health. Two 90-day studies were initiated to evaluate the efficacy of a single fluralaner administration for the treatment and prevention of H. longicornis infestations on dogs. Methods Dogs were randomly assigned (10 dogs/group) to either an untreated control group or a group treated once (Day 0) with 13.64% w/w fluralaner chewable tablets (Bravecto®) at the minimum label dose rate of 25 mg/kg. Each dog was infested with approximately 50 H. longicornis ticks on Days − 9 or -6 and on Days − 2, 28, 58, and 88. A different US tick isolate was used in each study. Tick counts were completed on Days − 7 or -4, 2, 30, 60 and 90. The primary efficacy criterion was a 90% reduction in arithmetic mean tick counts between the treated and control groups. For between-group comparisons at any assessment, at least six control dogs were required to retain at least 25% of the infestation dose (13 live ticks). Results Pre-study infestations demonstrated susceptibility of all study dogs to challenge with H. longicornis . At each subsequent assessment in both studies, at least seven untreated control dogs retained ≥ 25% of the challenge, demonstrating adequate infestations for each efficacy calculation. On Days 2, 30, 60 and 90 the mean live tick infestation rate (number of ticks recovered from each dog/infesting challenge of each dog) of untreated control dogs ranged from 27.8 to 60.8%. No live ticks, free or attached, were found on any fluralaner-treated dog in either study. Between-group differences were statistically significant ( P ≤ 0.0002) at each assessment. Conclusion At the minimum recommended label dose rate of 25 mg/kg, fluralaner chewable tablets were 100% effective in eliminating H. longicornis ticks from dogs infested at the time of treatment. Complete efficacy against both US isolates of this tick was maintained through 90 days following a single treatment. Therefore, fluralaner is a treatment of choice for protecting dogs against this invasive tick species. Asian longhorned tick Bravecto dog efficacy fluralaner chewable Haemaphysalis longicornis Background The Asian longhorned tick, Haemaphysalis longicornis , is an invasive species with pathogen vector potential, now spreading within the USA and already established as a threat to human and animal health in Australia and New Zealand [ 1 , 2 ]. Since the first US confirmation on a sheep in New Jersey, infestations have been reported in over 172 counties across 17 states, ranging from New York and Connecticut in the northeast to Arkansas and Missouri in the Midwest and Georgia and the Carolinas in the south [ 3 – 5 ]. Since that New Jersey finding, the USA recording of H. longicornis infestations in over 25 animal species, including dogs, cats, birds, and humans, demonstrates the tick’s broad host range and widening geographic presence [ 4 ]. The suitability of H. longicornis to temperate climates, its parthenogenic and multi-host capability, and an ability to overwinter indicate that its spread in the USA will continue [ 2 ]. Modeling of its potential expansion predicts that within North America, geographic expansion of the range of H. longicornis could extend from the Gulf Coast and southeastern USA to Quebec and Nova Scotia in the east, and from California to the coast of British Columbia in the west [ 6 – 8 ]. Pathogens reported to be carried by H. longicornis include thrombocytopenia syndrome virus, Rickettsia japonica , Anaplasma , Theileria , and Babesia species and possibly Rickettsia rickettsiae , the agent of Rocky Mountain spotted fever [ 9 , 10 ]. That vector potential, the parthenogenic reproduction providing rapid life cycle completion, and the rapid spread of the tick’s geographic distribution make infestations a risk to human and animal health and emphasize the need for effective acaricides [ 5 ]. When administered orally to dogs at the minimum label dose rate of 25 mg/kg the acaricidal isoxazoline compound fluralaner has been shown to provide 8-week efficacy against Amblyomma americanum and 12-week or longer efficacy against Ixodes scapularis , Ixodes ricinus , Ixodes holocyclus , Rhipicephalus sanguineus , Dermacentor reticulatus , and fleas as well as effectiveness against demodectic and sarcoptic mites [ 11 – 15 ]. A dose-ranging study conducted with a Japanese strain of H. longicornis (Okayama) indicated that that the minimum label dose rate would provide high and long-lasting efficacy against this tick for 114 days [ 16 ]. To confirm the results of that study and to establish a fluralaner claim for efficacy, laboratory studies were initiated against two different US isolates of H. longicornis . Methods Each study was a completely randomized design with a fluralaner treated group and an untreated control group. All observations and procedures, including general health observations, tick infestations, and tick counts were performed by masked individuals. Both studies were conducted in accordance with Good Clinical Practices, and the World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of parasiticides against flea and tick infestations of dogs and cats [ 17 , 18 ]. Animals . Prior to beginning each study, 24 dogs in Study 1 and 30 dogs in Study 2 were acclimated to kennel conditions beginning on Day − 10. To be enrolled in either study, dogs were required to be clinically healthy with no pre-existing conditions (e.g., injury, trauma, disease) that could have affected the outcome, at least 6 months of age, not treated with any long-acting anti-flea or anti-tick product within the previous 180 days and have demonstrated susceptibility to tick infestation based on retaining at least 13 live ticks or ≥ 25% of a pre-study infestation. In that pre-study period and then throughout the study dogs were housed in individual cages (except for removal for tick infestations) in a thermostatically controlled environment with an approximate 12-h light/12-h dark cycle, fed a commercial dog food per site practice and allowed ad libitum access to water. Cages were segregated by treatment group to avoid cross exposure of dogs to fluralaner. From the dogs presented for acclimation, in each study 20 were retained for experimental purposes. Dogs selected for Study 1 were Beagles, 11 males and 9 females, aged from 2 to 4 years and weighing from 10.2 to 14.6 kg. Study 2 dogs were Beagles and mixed breed, 7 males and 13 females, aged from 2 to 7 years and weighing from 10.2 to 13.3 kg. Randomization and treatment On Day − 3, study dogs were randomized to treatment groups in a 1:1 ratio using a computer-generated randomization table so that 10 dogs were included in each group. Dogs in Group 1 remained untreated but were handled in the same manner as Group 2 dogs to have a reference time for scheduling post-treatment activities. Group 2 dogs received a single treatment, on Day 0, with 13.64% w/w fluralaner chewable tablets (Bravecto®, Merck Animal Health, Madison, NJ, USA) based on body weights recorded on Day − 2. One or more whole chewable fluralaner tablets were administered, at doses as close as possible to the minimum recommended dose of 25 mg/kg without underdosing. Treatment was administered within 20 minutes after feed had been offered to ensure dosing within the fluralaner label dose (actual doses ranged from 25.2 to 35.9 mg/kg; chews were not shaved, split, or cut). Immediately after treatment, dogs were returned to their cages and observed for approximately 1-h for adverse events and to ensure the treatment was retained. Each dog was observed for general health on the day of treatment administration at 1-h, 3-h, and 6-h post-treatment. Post-treatment observations on all dogs were conducted in a random order of evaluation. Tick infestations and counts At the pre-study infestations on Days − 6 (Study 1) or -9 (Study 2) and on Days − 2, 28, 58 and 88 the 20 dogs included in the study were infested with approximately 50 adult, unfed female H. longicornis ticks. The H. longicornis isolate for Study 1 had been collected in New York during July, 2018 and for Study 2 the isolate was obtained from vegetation in Virginia in October, 2018. Prior to the infestation, each dog was sedated (dexmedetomidine hydrochloride, 0.5 mg/mL Dexdomitor®, Zoetis) and a vial containing the ticks was emptied onto the dog’s back. Each dog was then held individually in an infestation chamber (dimensions: Study 1, 0.9 x 1.1 x 0.9m; Study 2, 0.8 x 0.9 x 0.7m) for a period of up to approximately 4-h to ensure that ticks had established. After the infestation period, the dog was removed from the infestation chamber and returned to its cage. To avoid any cross-animal exposure to fluralaner, from Day 0 forward an infestation chamber was assigned to each dog and used only for that dog for the duration of the study. Before each use, infestation chambers were thoroughly washed with soap and water, rinsed with clean water, and double rinsed with isopropyl alcohol (with air drying between each alcohol rinse). On each count day, each dog was examined for ticks by pushing the hair against its natural nap to expose the skin, covering the entire dog’s body. Any ticks found were gently removed using either forceps or fingers. After this examination was complete the dog was combed (tick comb, approximately 32 teeth per 2.5 cm) to recover any ticks that could have been missed during the visual inspection. Collected live ticks were classified as either free (on the host) or attached, and then discarded. The tick collection procedure on each dog lasted a minimum of 5 minutes. Number of dogs According to the World Association for the Advancement of Veterinary Parasitology (WAAVP) guideline for studies investigating the efficacy of ectoparasiticides, a minimum of 6 dogs is recommended for each treatment group [ 18 ]. A sample size of 10 dogs per treatment group was used in this study to help ensure that an adequate infestation (≥ 13 ticks) was achieved in a minimum of 6 untreated control dogs. Statistical analysis The primary endpoint was based on between-group differences in live tick counts, attached and free on the host, with the experimental unit the individual dog. At least six dogs in the control group were required to be adequately infested (a minimum of 13 live ticks or 25% of the infestation dose) to allow comparisons at any time point. Tick counts were analyzed using a linear mixed model that included treatment group as a fixed effect. The fluralaner group and the control group were compared using a two-sided test at a 5% level of significance. Separate analyses were conducted at each tick infestation day. Arithmetic least squares means were used for treatment comparisons. The null hypothesis was that there was no significant difference between the treated group and the control group. The primary software used for analysis was SAS version 9.3 or higher. Within each infestation schedule, the primary efficacy endpoint was calculated using the formula below, based on arithmetic mean tick counts: Efficacy (%) = [(Group 1 mean counts – Group 2 mean counts)/ Group 1 mean counts] x 100 Results And Discussion The initial infestations (Days − 9 or -6) demonstrated the susceptibility of all study dogs to the laboratory infestations, in Study 1 ranging from 13 to 36 live attached ticks and in Study 2 from 13 to 34 live attached ticks. After inclusion in Study 2 an untreated control group dog was removed (on Day 22) following a seizure. There were no treatment-related adverse events. At each time point in both studies, at least seven dogs in Group 1 (untreated controls) had ≥ 25% of the H. longicornis challenge, demonstrating an adequate tick infestation at each assessment to provide valid between-group comparisons. On Days 2, 30, 60 and 90, the mean live tick infestation rate (number of ticks recovered from each dog/infesting challenge for each dog) of dogs in the negative control group ranged from a low of 27.8% (Study 1) to a high of 60.8% (Study 2) (Table 1 ). Table 1 Haemaphysalis longicornis infestation rate in control dogs Day of count Number (%) of control group dogs with adequate infestations Mean infestation rate (%) ‡ Study 1 Study 2 Study 1 Study 2 2 9/10 (90.0) 10/10 (100.0) 40.4 60.8 30 8/10 (80.0) 7/9 (77.8) 36.8 40.2 60 9/10 (90.0) 8/9 (88.9) 32.2 40.9 90 7/10 (70.0) 8/9 (88.9) 27.8 37.6 ‡ Infestation rate calculated as: (number of ticks recovered from each dog/infesting challenge for each dog) x 100 No live ticks, free or attached, were found on any fluralaner-treated dog in either study. At each post-treatment assessment, the differences in live tick counts between the fluralaner-treated and the control group were statistically significant ( P ≤ 0.0002) (Tables 2 , 3 ). Fluralaner treatment resulted in a 100% reduction against existing tick infestations at 48 hours post administration, and 100% efficacy against H. longicornis infestation was maintained for the full 90-day study period. The fluralaner formulation tested in these studies and a topical fluralaner formulation are the only isoxazoline products labeled to provide up to 12 weeks of acaricidal activity following a single treatment [ 19 , 20 ]. The finding of 100% efficacy of this oral formulation against both tested strains of H. longicornis in these two studies confirms the earlier dose-ranging study and shows that, as against other tick species, fluralaner remains highly effective for at least 12 weeks. That high fluralaner efficacy against both the recent US isolates, as well as against the Japanese strain tested in an earlier study [ 16 ], compares favorably with other investigations of isoxazolines, all requiring monthly retreatments, against H. longicornis . Table 2 Study 1, live Haemaphysalis longicornis tick counts Untreated control dogs (n = 10) Fluralaner-treated dogs (n = 10) % efficacy Test statistic Attached Free Total Attached Free Total Fluralaner vs control Day 2 counts Arithmetic mean 15.8 4.4 20.2 0.0 0.0 0.0 100.0 t 18 = 9.38 P < 0.0001 Standard deviation 10.7 9.3 6.8 0.0 0.0 0.0 Median 18.0 0.0 21.0 0.0 0.0 0.0 Range 0–30 0–23 6–30 0–0 0–0 0–0 Day 30 counts Arithmetic mean 18.4 0.0 18.4 0.0 0.0 0.0 100.0 t 18 = 8.77 P < 0.0001 Standard deviation 6.6 0.0 6.6 0.0 0.0 0.0 Median 18.0 0.0 18.0 0.0 0.0 0.0 Range 10–33 0–0 10–33 0–0 0–0 0–0 Day 60 counts Arithmetic mean 16.1 0.0 16.1 0.0 0.0 0.0 100.0 t 18 = 11.75 P < 0.0001 Standard deviation 4.3 0.0 4.3 0.0 0.0 0.0 Median 17.0 0.0 17.0 0.0 0.0 0.0 Range 5–21 0–0 5–21 0–0 0–0 0–0 Day 90 counts Arithmetic mean 13.9 0.0 13.9 0.0 0.0 0.0 100.0 t 18 = 4.76 P = 0.0002 Standard deviation 9.2 0.0 9.2 0.0 0.0 0.0 Median 17.5 0.0 17.5 0.0 0.0 0.0 Range 0–24 0–0 0–24 0–0 0–0 0–0 Table 3 Study 2, live Haemaphysalis longicornis tick counts Untreated control dogs (n = 9 ‡ ) Fluralaner-treated dogs (n = 10) % efficacy Test statistic Attached Free Total Attached Free Total Fluralaner vs control Day 2 counts Arithmetic mean 30.2 0.2 30.4 0.0 0.0 0.0 100.0 t 18 = 14.99 P < 0.0001 Standard deviation 6.6 0.4 6.4 0.0 0.0 0.0 Median 30.0 0.0 30.5 0.0 0.0 0.0 Range 19–38 0–1 20–38 0–0 0–0 0–0 Day 30 counts Arithmetic mean 20.1 0.0 20.1 0.0 0.0 0.0 100.0 t 17 = 5.09 P < 0.0001 Standard deviation 12.5 0.0 12.5 0.0 0.0 0.0 Median 18.0 0.0 18.0 0.0 0.0 0.0 Range 1–40 0–0 1–40 0–0 0–0 0–0 Day 60 counts Arithmetic mean 20.3 0.1 20.4 0.0 0.0 0.0 100.0 t 17 = 6.79 P < 0.0001 Standard deviation 9.4 0.3 9.6 0.0 0.0 0.0 Median 22.0 0.0 22.0 0.0 0.0 0.0 Range 1–33 0–1 1–33 0–0 0–0 0–0 Day 90 counts Arithmetic mean 18.7 0.1 18.8 0.0 0.0 0.0 100.0 t 17 = 6.75 P < 0.0001 Standard deviation 8.7 0.3 8.8 0.0 0.0 0.0 Median 18.0 0.0 18.0 0.0 0.0 0.0 Range 1–30 0–1 1–30 0–0 0–0 0–0 ‡ 10 dogs on Day 2; one untreated control dog was removed on Day 22 following a seizure The single study reported with afoxolaner indicated that its continuing efficacy against H. longicornis may not be as high as that of other isoxazolines. While at 48-h post treatment efficacy against infestations present at the time of administration was 100%, against subsequent infestations with the Japanese isolate efficacy had declined to 97.7% at 14 days post treatment and 91.9% at 28 days post-treatment [ 21 ]. In that study, calculations were based on geometric means which typically provide a higher efficacy number than do those based on arithmetic mean tick counts. For a single-entity sarolaner formulation, arithmetic mean efficacy against the nymphal stage of a Japanese H. longicornis isolate was 100% through 21 days post-treatment, 98.7% at 28 days post-treatment when two of seven treated dogs (28.5%) were positive, and 95.9% at 35 days post-treatment when three of seven dogs were positive for live ticks [ 22 ]. In another study, 48-h post-lotilaner treatment of dogs infested with a Japanese isolate, the arithmetic mean reduction in longhorned tick numbers was 96.8%, with five of the eight study dogs remaining infested with a single tick. High but incomplete efficacy was then maintained at subsequent weekly infestations placed through 35 days following treatment (94.7 to 99.5%), and up to three dogs were infested with one or two live ticks at each assessment. [ 23 ]. Vigilance and effective tick control measures are important in limiting the expansion of H. longicornis and in maintaining canine health. While no product can reasonably be expected to provide 100% efficacy on 100% of occasions, the consistent and extended high efficacy of fluralaner shown in these studies, including against two separate and recent US isolates, make it a valuable option for the treatment and control of H. longicornis infestations on dogs. For this tick species in particular, such high efficacy is important as its parthenogenic capability means that a single female tick can produce an entire population in a new location [ 24 ]. Conclusion Fluralaner chewable tablets were 100% effective in eliminating H. longicornis ticks from dogs infested at the time of treatment. Complete efficacy was maintained throughout at least 12 weeks following treatment against two H. longicornis strains isolated in the United States. Fluralaner is a treatment of choice for protecting dogs against this invasive tick species. Declarations Acknowledgments The authors thank the technical staff at Clinvet for the conduct of both studies. Funding The study was funded by Merck Animal Health, Madison, NJ, USA. Availability of data and material Data from this study are proprietary and maintained by Merck Animal Health, Madison, NJ, USA. Authors’ contributions All authors contributed to the study design, protocol, and reporting. RM and AV were responsible for the animal phase and data collection for the studies. All authors revised and approved the final version of the manuscript. Ethics approval and consent to participate These studies were conducted in compliance with local and national regulations. Both studies were reviewed and approved by each facilities Institutional Animal Care and Use Committee for animal welfare and ethics. Consent for publication Not applicable. Competing interests MP and FG are employees of Merck Animal Health, Madison, NJ, USA. References Beard CB, Occi J, Bonilla DL, Egizi AM, Fonseca DM, Mertins JW, et al. Multistate infestation with the exotic disease-vector tick Haemaphysalis longicornis — United States, August 2017–September 2018. MMWR. 2018;67:1310‒3. Trout Fryxell RT, Vann DN, Butler RA, Paulsen DJ, Chandler JG, Willis MP, et al. 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Vet Parasitol. 2013;194:84–97. Kondo Y, Kinoshita G, Drag M, Chester TS, Larsen D. Evaluation of the efficacy of afoxolaner against Haemaphysalis longicornis on dogs. Vet Parasitol. 2014;201:229–31. Oda K, Yonetake W, Fujii T, Hodge A, Six RH, Maeder S, et al. Efficacy of sarolaner (Simparica®) against induced infestations of Haemaphysalis longicornis on dogs. Parasit Vectors. 2019;12:509. Otaki H, Sonobe J, Murphy M, Cavalleri D, Seewald W, Drake J, et al. Laboratory evaluation of lotilaner (Credelio TM ) against Haemaphysalis longicornis infestations of dogs. Parasit Vectors. 2018;11:448. FDA NADA 141-426. Corrected Freedom of Information Summary Original Appr.oval May 25, 2014. https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/1502Accessed 13 May 2022. FDA NADA 141-459. Bravecto, fluralaner topical solution dogs and cats. Freedom of Information Summary Original Approval July 20, 2016. https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/945. Accessed 13 May 2022. U.S. Department of Agriculture Animal and Plant Health Inspection Service. Vector-borne diseases. 2021. https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/cattle-disease-information/cattle-vector-borne-diseases. Accessed 6 Apr 2022. Additional Declarations Competing interest reported. MP and FG are employees of Merck Animal Health. Supplementary Files PetersenetalHlongicornisdogvisualabstract.pdf Cite Share Download PDF Status: Published Journal Publication published 08 Feb, 2023 Read the published version in Parasites & Vectors → Version 1 posted Editorial decision: Major revision 09 Dec, 2022 Reviews received at journal 07 Dec, 2022 Reviewers agreed at journal 07 Dec, 2022 Reviewers agreed at journal 28 Nov, 2022 Reviewers invited by journal 28 Nov, 2022 Editor assigned by journal 28 Nov, 2022 Submission checks completed at journal 28 Nov, 2022 First submitted to journal 27 Nov, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2318486","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":155575002,"identity":"4f3a6e8c-1306-4a9d-babd-a528026cbaea","order_by":0,"name":"Melissa Petersen","email":"","orcid":"","institution":"Merck Animal Health","correspondingAuthor":false,"prefix":"","firstName":"Melissa","middleName":"","lastName":"Petersen","suffix":""},{"id":155575003,"identity":"d53a50e3-5ea3-429b-9559-f216de944797","order_by":1,"name":"Riaan Maree","email":"","orcid":"","institution":"Clinvet USA","correspondingAuthor":false,"prefix":"","firstName":"Riaan","middleName":"","lastName":"Maree","suffix":""},{"id":155575004,"identity":"61533579-1c68-4d3d-baa1-60c232e2f828","order_by":2,"name":"Alta Viljoen","email":"","orcid":"","institution":"Clinvet South Africa","correspondingAuthor":false,"prefix":"","firstName":"Alta","middleName":"","lastName":"Viljoen","suffix":""},{"id":155575009,"identity":"5028e7e5-c626-4afe-b5fe-a95b800606cf","order_by":3,"name":"Julian E Liebenberg","email":"","orcid":"","institution":"Clinvet South Africa","correspondingAuthor":false,"prefix":"","firstName":"Julian","middleName":"E","lastName":"Liebenberg","suffix":""},{"id":155575010,"identity":"b334031e-2ede-4796-80aa-5b076d67fd23","order_by":4,"name":"Frank Guerino","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIiWNgGAWjYBAC9gYGBsYGMBNEVdiAWMx4tfAcQNFyJo0kLSBdbYeJ0CJ9+NnDGQy1if3Sh9sefGA7H80vffixAUONTTROLXxp5oYbGI4nzuxLbDecwXM7d2ZfmnECw7G03AYcWux5GMwkHzAcS9xwhrFNmkfidu6GMzzMBxgbDuPUwsPD/g2sZT9Yi8G53P2EtfCYSW5gqEncwAPSknAgdwMPD3MCAS1lkjMMDhjPANoiOeNAcu6MM2zGBgl4/AJ02DbJnoo62f4e9mcSH//Z5fb3MD+W+FBjg1MLBBgcRhNIwKscDOoIKxkFo2AUjIKRCwAS91Y0jE657QAAAABJRU5ErkJggg==","orcid":"","institution":"Merck Animal Health","correspondingAuthor":true,"prefix":"","firstName":"Frank","middleName":"","lastName":"Guerino","suffix":""}],"badges":[],"createdAt":"2022-11-27 19:14:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2318486/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2318486/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13071-023-05664-w","type":"published","date":"2023-02-08T18:45:56+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":44719067,"identity":"e2be986b-2193-4d60-9c55-edb922942ef4","added_by":"auto","created_at":"2023-10-16 18:52:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":412400,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2318486/v1/d252b790-7617-42f0-bac3-d1a4a2b1ff16.pdf"},{"id":29713847,"identity":"4675576f-2c50-4b0c-92e4-161286b0743a","added_by":"auto","created_at":"2022-11-30 11:39:06","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":208804,"visible":true,"origin":"","legend":"","description":"","filename":"PetersenetalHlongicornisdogvisualabstract.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2318486/v1/ab1a16b02f7b1c2a70974e4a.pdf"}],"financialInterests":"Competing interest reported. MP and FG are employees of Merck Animal Health.","formattedTitle":"Efficacy of fluralaner chewable tablets (Bravecto ® ) against Asian longhorned tick (Haemaphysalis longicornis) infestations of dogs","fulltext":[{"header":"Background","content":"\u003cp\u003eThe Asian longhorned tick, \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e, is an invasive species with pathogen vector potential, now spreading within the USA and already established as a threat to human and animal health in Australia and New Zealand [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Since the first US confirmation on a sheep in New Jersey, infestations have been reported in over 172 counties across 17 states, ranging from New York and Connecticut in the northeast to Arkansas and Missouri in the Midwest and Georgia and the Carolinas in the south [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Since that New Jersey finding, the USA recording of \u003cem\u003eH. longicornis\u003c/em\u003e infestations in over 25 animal species, including dogs, cats, birds, and humans, demonstrates the tick\u0026rsquo;s broad host range and widening geographic presence [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The suitability of \u003cem\u003eH. longicornis\u003c/em\u003e to temperate climates, its parthenogenic and multi-host capability, and an ability to overwinter indicate that its spread in the USA will continue [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Modeling of its potential expansion predicts that within North America, geographic expansion of the range of \u003cem\u003eH. longicornis\u003c/em\u003e could extend from the Gulf Coast and southeastern USA to Quebec and Nova Scotia in the east, and from California to the coast of British Columbia in the west [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Pathogens reported to be carried by \u003cem\u003eH. longicornis\u003c/em\u003e include thrombocytopenia syndrome virus, \u003cem\u003eRickettsia japonica\u003c/em\u003e, \u003cem\u003eAnaplasma\u003c/em\u003e, \u003cem\u003eTheileria\u003c/em\u003e, and \u003cem\u003eBabesia\u003c/em\u003e species and possibly \u003cem\u003eRickettsia rickettsiae\u003c/em\u003e, the agent of Rocky Mountain spotted fever [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. That vector potential, the parthenogenic reproduction providing rapid life cycle completion, and the rapid spread of the tick\u0026rsquo;s geographic distribution make infestations a risk to human and animal health and emphasize the need for effective acaricides [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhen administered orally to dogs at the minimum label dose rate of 25 mg/kg the acaricidal isoxazoline compound fluralaner has been shown to provide 8-week efficacy against \u003cem\u003eAmblyomma americanum\u003c/em\u003e and 12-week or longer efficacy against \u003cem\u003eIxodes scapularis\u003c/em\u003e, \u003cem\u003eIxodes ricinus\u003c/em\u003e, \u003cem\u003eIxodes holocyclus\u003c/em\u003e, \u003cem\u003eRhipicephalus sanguineus\u003c/em\u003e, \u003cem\u003eDermacentor reticulatus\u003c/em\u003e, and fleas as well as effectiveness against demodectic and sarcoptic mites [\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A dose-ranging study conducted with a Japanese strain of \u003cem\u003eH. longicornis\u003c/em\u003e (Okayama) indicated that that the minimum label dose rate would provide high and long-lasting efficacy against this tick for 114 days [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. To confirm the results of that study and to establish a fluralaner claim for efficacy, laboratory studies were initiated against two different US isolates of \u003cem\u003eH. longicornis\u003c/em\u003e.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eEach study was a completely randomized design with a fluralaner treated group and an untreated control group. All observations and procedures, including general health observations, tick infestations, and tick counts were performed by masked individuals. Both studies were conducted in accordance with Good Clinical Practices, and the World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of parasiticides against flea and tick infestations of dogs and cats [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eAnimals\u003c/span\u003e.\u003c/p\u003e \u003cp\u003ePrior to beginning each study, 24 dogs in Study 1 and 30 dogs in Study 2 were acclimated to kennel conditions beginning on Day \u0026minus;\u0026thinsp;10. To be enrolled in either study, dogs were required to be clinically healthy with no pre-existing conditions (e.g., injury, trauma, disease) that could have affected the outcome, at least 6 months of age, not treated with any long-acting anti-flea or anti-tick product within the previous 180 days and have demonstrated susceptibility to tick infestation based on retaining at least 13 live ticks or \u0026ge;\u0026thinsp;25% of a pre-study infestation. In that pre-study period and then throughout the study dogs were housed in individual cages (except for removal for tick infestations) in a thermostatically controlled environment with an approximate 12-h light/12-h dark cycle, fed a commercial dog food per site practice and allowed \u003cem\u003ead libitum\u003c/em\u003e access to water. Cages were segregated by treatment group to avoid cross exposure of dogs to fluralaner. From the dogs presented for acclimation, in each study 20 were retained for experimental purposes. Dogs selected for Study 1 were Beagles, 11 males and 9 females, aged from 2 to 4 years and weighing from 10.2 to 14.6 kg. Study 2 dogs were Beagles and mixed breed, 7 males and 13 females, aged from 2 to 7 years and weighing from 10.2 to 13.3 kg.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eRandomization and treatment\u003c/h2\u003e \u003cp\u003eOn Day \u0026minus;\u0026thinsp;3, study dogs were randomized to treatment groups in a 1:1 ratio using a computer-generated randomization table so that 10 dogs were included in each group. Dogs in Group 1 remained untreated but were handled in the same manner as Group 2 dogs to have a reference time for scheduling post-treatment activities. Group 2 dogs received a single treatment, on Day 0, with 13.64% w/w fluralaner chewable tablets (Bravecto\u0026reg;, Merck Animal Health, Madison, NJ, USA) based on body weights recorded on Day \u0026minus;\u0026thinsp;2. One or more whole chewable fluralaner tablets were administered, at doses as close as possible to the minimum recommended dose of 25 mg/kg without underdosing. Treatment was administered within 20 minutes after feed had been offered to ensure dosing within the fluralaner label dose (actual doses ranged from 25.2 to 35.9 mg/kg; chews were not shaved, split, or cut). Immediately after treatment, dogs were returned to their cages and observed for approximately 1-h for adverse events and to ensure the treatment was retained. Each dog was observed for general health on the day of treatment administration at 1-h, 3-h, and 6-h post-treatment. Post-treatment observations on all dogs were conducted in a random order of evaluation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTick infestations and counts\u003c/h2\u003e \u003cp\u003eAt the pre-study infestations on Days \u0026minus;\u0026thinsp;6 (Study 1) or -9 (Study 2) and on Days \u0026minus;\u0026thinsp;2, 28, 58 and 88 the 20 dogs included in the study were infested with approximately 50 adult, unfed female \u003cem\u003eH. longicornis\u003c/em\u003e ticks. The \u003cem\u003eH. longicornis\u003c/em\u003e isolate for Study 1 had been collected in New York during July, 2018 and for Study 2 the isolate was obtained from vegetation in Virginia in October, 2018. Prior to the infestation, each dog was sedated (dexmedetomidine hydrochloride, 0.5 mg/mL Dexdomitor\u0026reg;, Zoetis) and a vial containing the ticks was emptied onto the dog\u0026rsquo;s back. Each dog was then held individually in an infestation chamber (dimensions: Study 1, 0.9 x 1.1 x 0.9m; Study 2, 0.8 x 0.9 x 0.7m) for a period of up to approximately 4-h to ensure that ticks had established. After the infestation period, the dog was removed from the infestation chamber and returned to its cage. To avoid any cross-animal exposure to fluralaner, from Day 0 forward an infestation chamber was assigned to each dog and used only for that dog for the duration of the study. Before each use, infestation chambers were thoroughly washed with soap and water, rinsed with clean water, and double rinsed with isopropyl alcohol (with air drying between each alcohol rinse).\u003c/p\u003e \u003cp\u003eOn each count day, each dog was examined for ticks by pushing the hair against its natural nap to expose the skin, covering the entire dog\u0026rsquo;s body. Any ticks found were gently removed using either forceps or fingers. After this examination was complete the dog was combed (tick comb, approximately 32 teeth per 2.5 cm) to recover any ticks that could have been missed during the visual inspection. Collected live ticks were classified as either free (on the host) or attached, and then discarded. The tick collection procedure on each dog lasted a minimum of 5 minutes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eNumber of dogs\u003c/h2\u003e \u003cp\u003eAccording to the World Association for the Advancement of Veterinary Parasitology (WAAVP) guideline for studies investigating the efficacy of ectoparasiticides, a minimum of 6 dogs is recommended for each treatment group [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A sample size of 10 dogs per treatment group was used in this study to help ensure that an adequate infestation (\u0026ge;\u0026thinsp;13 ticks) was achieved in a minimum of 6 untreated control dogs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe primary endpoint was based on between-group differences in live tick counts, attached and free on the host, with the experimental unit the individual dog. At least six dogs in the control group were required to be adequately infested (a minimum of 13 live ticks or 25% of the infestation dose) to allow comparisons at any time point. Tick counts were analyzed using a linear mixed model that included treatment group as a fixed effect. The fluralaner group and the control group were compared using a two-sided test at a 5% level of significance. Separate analyses were conducted at each tick infestation day. Arithmetic least squares means were used for treatment comparisons. The null hypothesis was that there was no significant difference between the treated group and the control group. The primary software used for analysis was SAS version 9.3 or higher.\u003c/p\u003e \u003cp\u003eWithin each infestation schedule, the primary efficacy endpoint was calculated using the formula below, based on arithmetic mean tick counts:\u003c/p\u003e \u003cp\u003eEfficacy (%) = [(Group 1 mean counts \u0026ndash; Group 2 mean counts)/ Group 1 mean counts] x 100\u003c/p\u003e \u003c/div\u003e"},{"header":"Results And Discussion","content":"\u003cp\u003eThe initial infestations (Days \u0026minus;\u0026thinsp;9 or -6) demonstrated the susceptibility of all study dogs to the laboratory infestations, in Study 1 ranging from 13 to 36 live attached ticks and in Study 2 from 13 to 34 live attached ticks. After inclusion in Study 2 an untreated control group dog was removed (on Day 22) following a seizure. There were no treatment-related adverse events.\u003c/p\u003e \u003cp\u003eAt each time point in both studies, at least seven dogs in Group 1 (untreated controls) had\u0026thinsp;\u0026ge;\u0026thinsp;25% of the \u003cem\u003eH. longicornis\u003c/em\u003e challenge, demonstrating an adequate tick infestation at each assessment to provide valid between-group comparisons. On Days 2, 30, 60 and 90, the mean live tick infestation rate (number of ticks recovered from each dog/infesting challenge for each dog) of dogs in the negative control group ranged from a low of 27.8% (Study 1) to a high of 60.8% (Study 2) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e infestation rate in control dogs\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay of count\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNumber (%) of control group dogs with adequate infestations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMean infestation rate (%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudy 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStudy 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStudy 2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9/10 (90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10/10 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/10 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7/9 (77.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9/10 (90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/9 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/10 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/9 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003eInfestation rate calculated as:\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e(number of ticks recovered from each dog/infesting challenge for each dog) x 100\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNo live ticks, free or attached, were found on any fluralaner-treated dog in either study. At each post-treatment assessment, the differences in live tick counts between the fluralaner-treated and the control group were statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.0002) (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Fluralaner treatment resulted in a 100% reduction against existing tick infestations at 48 hours post administration, and 100% efficacy against \u003cem\u003eH. longicornis\u003c/em\u003e infestation was maintained for the full 90-day study period. The fluralaner formulation tested in these studies and a topical fluralaner formulation are the only isoxazoline products labeled to provide up to 12 weeks of acaricidal activity following a single treatment [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The finding of 100% efficacy of this oral formulation against both tested strains of \u003cem\u003eH. longicornis\u003c/em\u003e in these two studies confirms the earlier dose-ranging study and shows that, as against other tick species, fluralaner remains highly effective for at least 12 weeks. That high fluralaner efficacy against both the recent US isolates, as well as against the Japanese strain tested in an earlier study [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], compares favorably with other investigations of isoxazolines, all requiring monthly retreatments, against \u003cem\u003eH. longicornis\u003c/em\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStudy 1, live \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e tick counts\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUntreated control dogs (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eFluralaner-treated dogs (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e% efficacy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eTest statistic\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAttached\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eFree\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eAttached\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eFree\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eFluralaner vs control\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDay 2 counts\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArithmetic mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003et\u003csub\u003e18\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;9.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDay 30 counts\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArithmetic mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003et\u003csub\u003e18\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;8.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u0026ndash;33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u0026ndash;33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDay 60 counts\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArithmetic mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003et\u003csub\u003e18\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;11.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u0026ndash;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u0026ndash;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDay 90 counts\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArithmetic mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003et\u003csub\u003e18\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;4.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStudy 2, live \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e tick counts\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUntreated control dogs (n\u0026thinsp;=\u0026thinsp;9\u003csup\u003e\u0026Dagger;\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eFluralaner-treated dogs (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e% efficacy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eTest statistic\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAttached\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eFree\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eAttached\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eFree\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eFluralaner vs control\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDay 2 counts\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArithmetic mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003et\u003csub\u003e18\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;14.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u0026ndash;38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u0026ndash;38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDay 30 counts\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArithmetic mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003et\u003csub\u003e17\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;5.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDay 60 counts\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArithmetic mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003et\u003csub\u003e17\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;6.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDay 90 counts\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArithmetic mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003et\u003csub\u003e17\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;6.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003csup\u003e\u003cb\u003e\u0026Dagger;\u003c/b\u003e\u003c/sup\u003e10 dogs on Day 2; one untreated control dog was removed on Day 22 following a seizure\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe single study reported with afoxolaner indicated that its continuing efficacy against \u003cem\u003eH. longicornis\u003c/em\u003e may not be as high as that of other isoxazolines. While at 48-h post treatment efficacy against infestations present at the time of administration was 100%, against subsequent infestations with the Japanese isolate efficacy had declined to 97.7% at 14 days post treatment and 91.9% at 28 days post-treatment [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In that study, calculations were based on geometric means which typically provide a higher efficacy number than do those based on arithmetic mean tick counts. For a single-entity sarolaner formulation, arithmetic mean efficacy against the nymphal stage of a Japanese \u003cem\u003eH. longicornis\u003c/em\u003e isolate was 100% through 21 days post-treatment, 98.7% at 28 days post-treatment when two of seven treated dogs (28.5%) were positive, and 95.9% at 35 days post-treatment when three of seven dogs were positive for live ticks [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In another study, 48-h post-lotilaner treatment of dogs infested with a Japanese isolate, the arithmetic mean reduction in longhorned tick numbers was 96.8%, with five of the eight study dogs remaining infested with a single tick. High but incomplete efficacy was then maintained at subsequent weekly infestations placed through 35 days following treatment (94.7 to 99.5%), and up to three dogs were infested with one or two live ticks at each assessment. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVigilance and effective tick control measures are important in limiting the expansion of \u003cem\u003eH. longicornis\u003c/em\u003e and in maintaining canine health. While no product can reasonably be expected to provide 100% efficacy on 100% of occasions, the consistent and extended high efficacy of fluralaner shown in these studies, including against two separate and recent US isolates, make it a valuable option for the treatment and control of \u003cem\u003eH. longicornis\u003c/em\u003e infestations on dogs. For this tick species in particular, such high efficacy is important as its parthenogenic capability means that a single female tick can produce an entire population in a new location [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFluralaner chewable tablets were 100% effective in eliminating \u003cem\u003eH. longicornis\u003c/em\u003e ticks from dogs infested at the time of treatment. Complete efficacy was maintained throughout at least 12 weeks following treatment against two \u003cem\u003eH. longicornis\u003c/em\u003e strains isolated in the United States. Fluralaner is a treatment of choice for protecting dogs against this invasive tick species.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the technical staff at Clinvet for the conduct of both studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was funded by Merck Animal Health, Madison, NJ, USA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData from this study are proprietary and maintained by Merck Animal Health, Madison, NJ, USA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study design, protocol, and reporting. RM and AV were responsible for the animal phase and data collection for the studies. All authors revised and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThese studies were conducted in compliance with local and national regulations. \u0026nbsp; Both studies were reviewed and approved by each facilities Institutional Animal Care and Use Committee for animal welfare and ethics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMP and FG are employees of Merck Animal Health, Madison, NJ, USA.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBeard CB, Occi J, Bonilla DL, Egizi AM, Fonseca DM, Mertins JW, et al. Multistate infestation with the exotic disease-vector tick \u003cem\u003eHaemaphysalis longicornis\u0026nbsp;\u003c/em\u003e\u0026mdash; United States, August 2017\u0026ndash;September 2018. MMWR. 2018;67:1310‒3.\u003c/li\u003e\n \u003cli\u003eTrout Fryxell RT, Vann DN, Butler RA, Paulsen DJ, Chandler JG, Willis MP, et al. Rapid discovery and detection of \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e through the use of passive surveillance and collaboration: Building a state tick-surveillance network. Int J Environ Res Public Health. 2021;18:7980.\u003c/li\u003e\n \u003cli\u003eRainey T, Occi JL, Robbins RG, Egizi A. Discovery of \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e (Ixodida: Ixodidae) Parasitizing a sheep in New Jersey, United States. J Med Entomol. 2018;55:757‒9.\u003c/li\u003e\n \u003cli\u003eU.S. Department of Agriculture Animal and Plant Health Inspection Service. National \u003cem\u003eHaemaphysalis longicornis\u0026nbsp;\u003c/em\u003e(Asian longhorned tick) situation report, as of July22, 2022. https://www.aphis.usda.gov/animal_health/animal_diseases/tick/downloads/longhorned-tick-sitrep.pdf. Accessed 15 Aug 2022.\u003c/li\u003e\n \u003cli\u003eU.S. Department of Agriculture Animal and Plant Health Inspection Service. Factsheet. 2018. https://www.nj.gov/agriculture/divisions/ah/pdf/longhornedtickfactsheet.pdf. Accessed 4 Apr, 2022.\u003c/li\u003e\n \u003cli\u003eNamgyal J, Couloigner I, Lysyk TJ, Dergousoff SJ, Cork SC. Comparison of habitat suitability models for \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e Neumann in North America to determine its potential geographic range. Int J Environ Res Public Health. 2020;17:8285.\u003c/li\u003e\n \u003cli\u003eRaghavan RK, Barker SC, Cobos ME, Barker D, Teo EJM, Foley DH, et al. Potential spatial distribution of the newly introduced long-horned ticks, \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e, in North America. Sci Rep. 2019;9:498.\u003c/li\u003e\n \u003cli\u003eRochlin I. Modeling the Asian longhorned tick (Acari: Ixodidae) suitable habitat in North America. J Med Entomol. 2019;56:384‒91.\u003c/li\u003e\n \u003cli\u003eStanley HM, Ford SL, Snellgrove AN, Hartzer K, Smith EB, Krapiunaya I, et al. The ability of the invasive Asian longhorned tick \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e (Acari: Ixodidae) to acquire and transmit \u003cem\u003eRickettsia rickettsii\u003c/em\u003e (Rickettsiales: Rickettsiaceae), the agent of Rocky Mountain spotted fever, under laboratory conditions. J Med Entomol. 2020;57:1635‒9.\u003c/li\u003e\n \u003cli\u003eZhao L, Li J, Cui X, Jia N, Wei J, Xia L, et al. Distribution of \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e and associated pathogens: analysis of pooled data from a China field survey and global published data. Lancet Planet Health. 2020;4:e320‒9.\u003c/li\u003e\n \u003cli\u003eWengenmayer C, Williams H, Zschiesche E, Moritz A, Langenstein J, Roepke RK, et al. The speed of kill of fluralaner (Bravecto) against \u003cem\u003eIxodes ricinus\u003c/em\u003e ticks on dogs. Parasit Vectors. 2014;7:525.\u003c/li\u003e\n \u003cli\u003eRanjan S, Young D, Sun F. A single topical fluralaner application to cats and to dogs controls fleas for 12 weeks in a simulated home environment. Parasit Vectors. 2018;11:385.\u003c/li\u003e\n \u003cli\u003eAllen K, Little S, Petersen M, Gruntmeir J, Barrett A, Herrin B, et al. Evaluation of oral fluralaner (Bravecto) for efficacy against nymphs of \u003cem\u003eAmblyomma americanum\u003c/em\u003e and \u003cem\u003eRhipicephalus sanguineus\u003c/em\u003e (sensu lato). Parasit Vectors. 2020;13:315.\u003c/li\u003e\n \u003cli\u003eFourie JJ, Meyer L, Thomas E. Efficacy of topically administered fluralaner or imidacloprid/moxidectin on dogs with generalised demodicosis. Parasit Vectors. 2019;12:59.\u003c/li\u003e\n \u003cli\u003eChiummo R, Petersen I, Plehn C, Zschiesche E, Roepke R, Thomas E. Efficacy of orally and topically administered fluralaner (Bravecto\u003csup\u003e\u0026reg;\u003c/sup\u003e) for treatment of client-owned dogs with sarcoptic mange under field conditions. Parasit Vectors. 2020;13:524.\u003c/li\u003e\n \u003cli\u003eToyota M, Hirama K, Suzuki T, Armstrong R, Okinaga T.P. Efficacy of orally administered fluralaner in dogs against laboratory challenge with \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e ticks. Parasit Vectors. 2019;12:43.\u003c/li\u003e\n \u003cli\u003eUS Food and Drug Administration, Center for Veterinary Medicine VICH GL9. Guidance for industry good clinical practice, VICH GL9 final guidance. 2011. https://www.fda.gov/media/70333/download. Accessed 6 Apr 2022.\u003c/li\u003e\n \u003cli\u003eMarchiondo AA, Holdsworth PA, Fourie LJ, Rugg D, Hellmann K, Snyder DE, et al. World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition: guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestations on dogs and cats. Vet Parasitol. 2013;194:84\u0026ndash;97.\u003c/li\u003e\n \u003cli\u003eKondo Y, Kinoshita G, Drag M, Chester TS, Larsen D. Evaluation of the efficacy of afoxolaner against \u003cem\u003eHaemaphysalis longicornis\u0026nbsp;\u003c/em\u003eon dogs. Vet Parasitol. 2014;201:229\u0026ndash;31.\u003c/li\u003e\n \u003cli\u003eOda K, Yonetake W, Fujii T, Hodge A, Six RH, Maeder S, et al. Efficacy of sarolaner (Simparica\u0026reg;) against induced infestations of \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e on dogs. Parasit Vectors. 2019;12:509.\u003c/li\u003e\n \u003cli\u003eOtaki H, Sonobe J, Murphy M, Cavalleri D, Seewald W, Drake J, et al. Laboratory evaluation of lotilaner (Credelio\u003csup\u003eTM\u003c/sup\u003e) against \u003cem\u003eHaemaphysalis longicornis\u0026nbsp;\u003c/em\u003einfestations of dogs. Parasit Vectors. 2018;11:448.\u003c/li\u003e\n \u003cli\u003eFDA NADA 141-426. Corrected Freedom of Information Summary Original Appr.oval May 25, 2014. https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/1502Accessed 13 May 2022.\u003c/li\u003e\n \u003cli\u003eFDA NADA 141-459. Bravecto, fluralaner topical solution dogs and cats. Freedom of Information Summary Original Approval July 20, 2016. https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/945. Accessed 13 May 2022.\u003c/li\u003e\n \u003cli\u003eU.S. Department of Agriculture Animal and Plant Health Inspection Service. Vector-borne diseases. 2021. https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/cattle-disease-information/cattle-vector-borne-diseases. Accessed 6 Apr 2022.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"parasites-and-vectors","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"parv","sideBox":"Learn more about [Parasites \u0026 Vectors](http://parasitesandvectors.biomedcentral.com/)","snPcode":"13071","submissionUrl":"https://submission.nature.com/new-submission/13071/3","title":"Parasites \u0026 Vectors","twitterHandle":"@bugbittentweets","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Asian longhorned tick, Bravecto, dog, efficacy, fluralaner chewable, Haemaphysalis longicornis ","lastPublishedDoi":"10.21203/rs.3.rs-2318486/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2318486/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe parthenogenic reproductive ability of \u003cem\u003eHaemaphysalis longicornis\u003c/em\u003e, facilitating quick life cycle completion and rapid geographic spread, and its pathogen vector potential make infestations a risk to human and canine health. Two 90-day studies were initiated to evaluate the efficacy of a single fluralaner administration for the treatment and prevention of \u003cem\u003eH. longicornis\u003c/em\u003e infestations on dogs.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eDogs were randomly assigned (10 dogs/group) to either an untreated control group or a group treated once (Day 0) with 13.64% w/w fluralaner chewable tablets (Bravecto\u0026reg;) at the minimum label dose rate of 25 mg/kg. Each dog was infested with approximately 50 \u003cem\u003eH. longicornis\u003c/em\u003e ticks on Days \u0026minus;\u0026thinsp;9 or -6 and on Days \u0026minus;\u0026thinsp;2, 28, 58, and 88. A different US tick isolate was used in each study. Tick counts were completed on Days \u0026minus;\u0026thinsp;7 or -4, 2, 30, 60 and 90. The primary efficacy criterion was a 90% reduction in arithmetic mean tick counts between the treated and control groups. For between-group comparisons at any assessment, at least six control dogs were required to retain at least 25% of the infestation dose (13 live ticks).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePre-study infestations demonstrated susceptibility of all study dogs to challenge with \u003cem\u003eH. longicornis\u003c/em\u003e. At each subsequent assessment in both studies, at least seven untreated control dogs retained\u0026thinsp;\u0026ge;\u0026thinsp;25% of the challenge, demonstrating adequate infestations for each efficacy calculation. On Days 2, 30, 60 and 90 the mean live tick infestation rate (number of ticks recovered from each dog/infesting challenge of each dog) of untreated control dogs ranged from 27.8 to 60.8%. No live ticks, free or attached, were found on any fluralaner-treated dog in either study. Between-group differences were statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.0002) at each assessment.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eAt the minimum recommended label dose rate of 25 mg/kg, fluralaner chewable tablets were 100% effective in eliminating \u003cem\u003eH. longicornis\u003c/em\u003e ticks from dogs infested at the time of treatment. Complete efficacy against both US isolates of this tick was maintained through 90 days following a single treatment. Therefore, fluralaner is a treatment of choice for protecting dogs against this invasive tick species.\u003c/p\u003e","manuscriptTitle":"Efficacy of fluralaner chewable tablets (Bravecto ® ) against Asian longhorned tick (Haemaphysalis longicornis) infestations of dogs","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-30 11:39:01","doi":"10.21203/rs.3.rs-2318486/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-12-09T23:37:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-12-07T20:29:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"28de80be-617d-4822-8802-e5205db36b59","date":"2022-12-07T19:36:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0d49701a-3b55-4a91-90a0-09f2225afe53","date":"2022-11-28T17:49:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-11-28T14:57:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-11-28T09:34:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-11-28T09:25:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Parasites \u0026 Vectors","date":"2022-11-27T19:07:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"parasites-and-vectors","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"parv","sideBox":"Learn more about [Parasites \u0026 Vectors](http://parasitesandvectors.biomedcentral.com/)","snPcode":"13071","submissionUrl":"https://submission.nature.com/new-submission/13071/3","title":"Parasites \u0026 Vectors","twitterHandle":"@bugbittentweets","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"260ee209-dcf5-4542-b4d2-fe6e94232c8a","owner":[],"postedDate":"November 30th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T18:49:48+00:00","versionOfRecord":{"articleIdentity":"rs-2318486","link":"https://doi.org/10.1186/s13071-023-05664-w","journal":{"identity":"parasites-and-vectors","isVorOnly":false,"title":"Parasites \u0026 Vectors"},"publishedOn":"2023-02-08 18:45:56","publishedOnDateReadable":"February 8th, 2023"},"versionCreatedAt":"2022-11-30 11:39:01","video":"","vorDoi":"10.1186/s13071-023-05664-w","vorDoiUrl":"https://doi.org/10.1186/s13071-023-05664-w","workflowStages":[]},"version":"v1","identity":"rs-2318486","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2318486","identity":"rs-2318486","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}