- Email: [email protected]
Evaluation of the efficacy of afoxolaner against Haemaphysalis longicornis on dogs
Veterinary Parasitology 201 (2014) 229–231
Contents lists available at ScienceDirect
Veterinary Parasitology journal homepage: www.elsevier.com/locate/vetpar
Evaluation of the efficacy of afoxolaner against Haemaphysalis longicornis on dogs Yumi Kondo a,∗ , Gen Kinoshita a , Marlene Drag b , Theodore S. Chester b , Diane Larsen b a b
Merial Japan Limited, Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan Merial Limited, 3239 Satellite Boulevard, Duluth, GA 30096-4640, USA
a r t i c l e
i n f o
Keywords: Haemaphysalis longicornis Tick Afoxolaner Dog Efficacy
a b s t r a c t A controlled study to assess the acaricidal efficacy of afoxolaner in dogs after a single oral administration was conducted against Haemaphysalis longicornis ticks. The study was characterized by a negative controlled randomized block design and included sixteen beagle dogs of both sexes. Starting two days before treatment, each dog was infested weekly with 50 ticks over 4 weeks. The number of live ticks was determined 48 h after treatment and then 48 h after each infestation. The mean dose of afoxolaner received by dogs was 3.0 mg/kg (range: 2.5–3.1 mg/kg). Afoxolaner rapidly eliminated pre-existing tick infestations (100% ticks killed within 48 h of treatment) and controlled weekly re-infestations (91.9% prophylactic efficacy at Day 30). © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
1. Introduction Haemaphysalis longicornis is common tick species in Asia and Pacific region, including Japan, China, Korea, Australia and New Zealand (Inokuma, 2013; Shimada et al., 2003; Tenquisf and Charleston, 2001). This species is the major vector of Babesia gibsoni to dogs in Asia (Chomel, 2011; Inokuma, 2013). Canine babesiosis is an important tickborne disease, and the prevention of Babesia transmission is particularly critical given the challenges of appropriate treatment strategies against babesiosis (Beugnet and Franc, 2012; Otranto and Wall, 2008; Otranto et al., 2009a,b; Taboada and Lobetti, 2006). H. longicornis is also a putative vector of Hepatozoon canis and Rickettsia japonica (Inokuma, 2013).
∗ Corresponding author at: Merial Japan Limited, Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan. E-mail address: [email protected] (Y. Kondo).
The present study describes the result of a laboratory study that assessed the efficacy of afoxolaner, administered orally in a chewable formulation (Nexgard® , Merial), against H. longicornis in dogs. 2. Materials and methods Sixteen beagle dogs of both sexes were included in the study, which was designed as a negative controlled randomized block study. All dogs were approximately 10–11 months of age and weighed from 7.2 to 9.0 kg at inclusion. All dogs were healthy and had not been treated with any ectoparasiticides in the 3 months prior to inclusion in the study nor infested by ticks. The health of all dogs was monitored at least once daily and once per hour during the first four hours post treatment. All dogs had free access to water and were fed a commercial diet. The study design was approved by the Merial Institutional Animal Care and Use Committee (USDA, 2008). In the study, two groups of eight dogs were formed randomly, using blocks of two dogs based on decreasing
http://dx.doi.org/10.1016/j.vetpar.2014.02.019 0304-4017/© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/3.0/).
230
Y. Kondo et al. / Veterinary Parasitology 201 (2014) 229–231
pre-treatment tick counts. Dogs in Group 1 were untreated controls. Dogs in Group 2 were treated orally on Day 0 with the appropriate chewable tablets containing afoxolaner. Four sizes of chews were available: 0.5 g, 1.25 g, 3 g and 6 g, containing respectively 11.3 mg, 28.3 mg, 68 mg and 136 mg of afoxolaner. Doses were administered as closely as possible to the minimum effective dose (2.5 mg/kg). In this study, all dogs received 2 chewable tablets of 0.5 g, and the mean dose received by dogs was 3.0 mg/kg of afoxolaner (range: 2.5–3.1 mg/kg). On Days-2, 7, 14, 21, and 28, all dogs were infested with 50 unfed female H. longicornis. The study utilized ticks from laboratory-maintained populations that had been established from ticks collected in field locations in Japan. Ticks were counted 48 h after treatment (Day 2) or after infestations on Days 9, 16, 23, and 30. Counting of ticks on the dogs was performed by parting and feeling through dog’s hair with finger tips. All personnel conducting tick counts and health observations were blinded to treatment groups. The study design was in accordance with the World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestation on dogs and cats (Marchiondo et al., 2013), and was conducted in compliance with VICH GL9 “Good Clinical Practice” (EMEA, 2000). For each tick count, the total count of live ticks was transformed to the natural logarithm (count +1) to calculate the geometric mean for each treatment group. The percent reduction of the live tick counts from treated dogs compared to those from untreated dogs (=percentage efficacy) was calculated using the formula [(C − T)/C] × 100, where C is the geometric mean for the control group and T is the geometric mean for the treated group at the same time point. The log-counts of the live ticks of the treated group were compared to the log-counts of the untreated control group using an F-test adjusted for the allocation blocks used to randomize the animals to the treatment groups at each time point separately. All testing was two-sided at the significance level p = 0.05. 3. Results At each time point, the geometric mean counts of the live ticks in the control group ranged between 13.9 and 23.7 (Table 1). This level of infestation in the control group was adequate for determining efficacy against ticks. The WAAVP guideline recommends that at least 20% of the ticks should be retained from the infestation, meaning an average of 10 ticks per dog out of the 50 used to infest each dogs (Marchiondo et al., 2013). The curative efficacy of afoxolaner against pre-existing tick infestation was 100% at 48 h after treatment (Table 1). The tick efficacy of afoxolaner on weekly re-infestations starting on Day 7 after treatment provided 100% acaricidal efficacy at Day 9 and over 91.9% efficacy at all subsequent time points up to Day 30 (Table 1). The tick counts were significantly different in treated and control dogs at all time points (p < 0.05). One dog in the untreated control group was removed from the study on Day 21 due to mild seizures observed on
Table 1 Geometric tick counts and percent efficacy of afoxolaner oral treatment against Haemaphysalis longicornis after challenges with 50 female ticks. Study daya
2b 9 16 23 30
Geometric mean tick counts (min–max) Control
Treated
23.7 (4–38) 16.7 (8–29) 15.8 (6–37) 13.9 (6–25) 20.2 (15–33)
0.0 (0–0) 0.0 (0–0) 0.4 (0–2) 0.6 (0–6) 1.6 (0–7)
% Efficacy
100 100 97.7 95.5 91.9
a Live H. longicornis were counted 48 h after treatment or infestation. Day 0 is the day of treatment. b Dogs were infested before treatment on Day-2.
Day 17 and Day 21. All data on the dog captured prior to removal were included in the analysis. No adverse reaction to the treatment was observed during this study. 4. Discussion The attachment rate of the ticks was lower than what is usually observed for other tick species infesting dogs such as Rhipicephalus sanguineus (Kunkle et al., 2014). This is known to occur for H. longicornis, which is more adapted to wild ruminants than dogs in the adult stage (Inokuma, 2013; unpublished data). In this experiment, 4 ticks at Day 2 and 6 ticks at Day 16 were recovered from one control dog. It is below the 20% of attachment rate proposed by Marchiondo et al. (2013). Nevertheless the geometric mean count values ranged from 13.9 to 23.7 which were above the 20% attachment rate. The geometric mean counts were used to calculate the percent efficacy, which is therefore valid based on the guidelines (Marchiondo et al., 2013). A single oral treatment with the chewable formulation of afoxolaner achieved 100% curative efficacy for treating preexistent infestation of H. longicornis. It also controlled re-infestation by eliminating >90% of the ticks within the first 48 h after infestation for 4 weeks after treatment. The Day 30 efficacy of afoxolaner seems lower than what has been observed for other tick species (Kunkle et al., 2014; Mitchell et al., 2014). This may be related to a lower attachment rate in the control dogs, but also the variability of each experiment. There are some reports on the efficacy of current veterinary topical products against H. longicornis, e.g. imidacloprid/permethrin, fipronil/(S)-methoprene (Hagimori et al., 2005). However, unlike these topical combinations, ticks are exposed to afoxolaner while feeding on the host’s blood. Afoxolaner is absorbed rapidly by the intestinal mucosa, and its plasma concentration peaks within 2–4 h after administration (Letendre et al., 2014), which ultimately results in rapid uptake of the active ingredient by the ticks and a tick efficacy assessed at 48 h is similar to that of imidacloprid/permethrin or fipronil/(S)methoprene combinations (Hagimori et al., 2005). The systemic distribution offers advantages compared to topical formulations. There is no period after treatmentadministration during which the application site should be avoided by the owners and wetting of the haircoat or any
Y. Kondo et al. / Veterinary Parasitology 201 (2014) 229–231
other topical treatment does not interfere with the product efficacy. Another product for oral administration containing spinosad includes a registered claim for H. longicornis tick curative treatment in Japan (Comfortis1 ); however, this product is not registered for use against ticks elsewhere (Beugnet and Franc, 2012; Snyder et al., 2009). Snyder et al. (2009) reported a limited, short-lasting efficacy of 50 mg/kg spinosad against new tick infestations on dogs with 67.8% efficacy at Day 9, 49.1% at Day 14, dropping to 5% at Day 30, against Rhipicephalus sanguineus by counting ticks 48 h after infestations. In this study, afoxolaner provided both curative and prophylactic efficacy for up to 30 days against H. longicornis. Nexgard® chewable formulation containing afoxolaner represents the first oral ectoparasiticide treatment providing a month-long efficacy against H. longicornis, the main Japanese tick species infesting dogs. Conflict of interest The work reported herein was funded by Merial Limited, GA, USA. All authors are current employees of Merial. Acknowledgments The authors gratefully acknowledge the expert contributions of all collaborators from Nippon Zenyaku Kogyo Co., Ltd. (Fukushima, Japan) and Merial Limited in conducting the study to high standards. The authors gratefully acknowledge Lenaig Halos and Frederic Beugnet, Veterinary Parasitologists, for the scientific editing of the manuscript. References Beugnet, F., Franc, M., 2012. Insecticide and acaricide molecules and/or combinations to prevent pet infestation by ectoparasites. Trends Parasitol. 28, 267–279.
1 ®
ers.
All registered trademarks are the property of their respective own-
231
Chomel, B., 2011. Tick-borne infections in dogs – an emerging infectious threat. Vet. Parasitol. 179, 294–301. EMEA, 2000. Guideline on Good Clinical Practices. VICH Topic GL9 (GCP), EMWA/CVMP/VICH/595/98-Final, http://www.ema. europa.eu/docs/en GB/document library/Scientific guideline/2009/ 10/WC500004343.pdf Hagimori, I., Machida, H., Goi, R., Mencke, N., 2005. Efficacy of imidacloprid/permethrin and fipronil/(S)-methoprene combinations against Haemaphysalis longicornis ticks evaluated under in vitro and in vivo conditions. Parasitol. Res. 97 (Suppl. 1), S120–S126. Inokuma, H., 2013. Panorama of vector borne disease of pets in Asia & Japan. In: Beugnet, F. (Ed.), Guide to Vector Borne Diseases of Pets. Merial, Lyon, France, pp. 94–107. Kunkle, B., Daly, S., Dumont, P., Drag, M., Larsen, D., 2014. Assessment of the efficacy of orally administered afoxolaner against Rhipicephalus sanguineus sensu lato. Vet. Parasitol. 201, 226–228. Letendre, L., Huang, R., Kvaternick, V., Harriman, J., Drag, M., Soll, M., 2014. The intravenous and oral pharmacokinetics of afoxolaner used as a monthly chewable antiparasitic for dogs. Vet. Parasitol. 201, 190–197. Marchiondo, A.A., Holdsworth, P.A., Fourie, L.J., Rugg, D., Hellmann, K.E., Snyder, D.E., Dryden, M.W., 2013. 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. 194, 84–97. Mitchell et al., 2014 (in this issue). Otranto, D., Wall, R., 2008. New strategies for the control of arthropod vectors of disease in dogs and cats. Med. Vet. Entomol. 22, 291–302. Otranto, D., Dantas-Torres, F., Breitschwerdt, E.B., 2009a. Managing canine vector-borne diseases of zoonotic concern: part one. Trends Parasitol. 25, 157–163. Otranto, D., Dantas-Torres, F., Breitschwerdt, E.B., 2009b. Managing canine vector-borne diseases of zoonotic concern: part two. Trends Parasitol. 25, 228–235. Shimada, Y., Beppu, T., Inokuma, H., Okuda, M., Onishi, T., 2003. Ixodid tick species recovered from domestic dogs in Japan. Med. Vet. Entomol. 17, 38–45. Snyder, E., Cruthers, L., Slone, R., 2009. Preliminary study on the acaricidal efficacy of spinosad administered orally to dogs infested with the brown dog tick, Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae). Vet. Parasitol. 166, 131–135. Taboada, J., Lobetti, R., 2006. Babesiosis. In: Craig, E.G. (Ed.), Infectious Disease of the Dog and Cat. Elsevier, Missouri, pp. 722–736. Tenquisf, J.D., Charleston, W.A.G., 2001. A revision of the annotated checklist of ectoparasites of terrestrial mammals in New Zealand. J. R. Soc. N. Z. 31, 481–542. USDA, 2008. Animal Welfare Regulations, 9CFR, http://awic.nal.usda.gov/ government-and-professional-resources/federal-laws/animalwelfare-act
Contents lists available at ScienceDirect
Veterinary Parasitology journal homepage: www.elsevier.com/locate/vetpar
Evaluation of the efficacy of afoxolaner against Haemaphysalis longicornis on dogs Yumi Kondo a,∗ , Gen Kinoshita a , Marlene Drag b , Theodore S. Chester b , Diane Larsen b a b
Merial Japan Limited, Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan Merial Limited, 3239 Satellite Boulevard, Duluth, GA 30096-4640, USA
a r t i c l e
i n f o
Keywords: Haemaphysalis longicornis Tick Afoxolaner Dog Efficacy
a b s t r a c t A controlled study to assess the acaricidal efficacy of afoxolaner in dogs after a single oral administration was conducted against Haemaphysalis longicornis ticks. The study was characterized by a negative controlled randomized block design and included sixteen beagle dogs of both sexes. Starting two days before treatment, each dog was infested weekly with 50 ticks over 4 weeks. The number of live ticks was determined 48 h after treatment and then 48 h after each infestation. The mean dose of afoxolaner received by dogs was 3.0 mg/kg (range: 2.5–3.1 mg/kg). Afoxolaner rapidly eliminated pre-existing tick infestations (100% ticks killed within 48 h of treatment) and controlled weekly re-infestations (91.9% prophylactic efficacy at Day 30). © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
1. Introduction Haemaphysalis longicornis is common tick species in Asia and Pacific region, including Japan, China, Korea, Australia and New Zealand (Inokuma, 2013; Shimada et al., 2003; Tenquisf and Charleston, 2001). This species is the major vector of Babesia gibsoni to dogs in Asia (Chomel, 2011; Inokuma, 2013). Canine babesiosis is an important tickborne disease, and the prevention of Babesia transmission is particularly critical given the challenges of appropriate treatment strategies against babesiosis (Beugnet and Franc, 2012; Otranto and Wall, 2008; Otranto et al., 2009a,b; Taboada and Lobetti, 2006). H. longicornis is also a putative vector of Hepatozoon canis and Rickettsia japonica (Inokuma, 2013).
∗ Corresponding author at: Merial Japan Limited, Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan. E-mail address: [email protected] (Y. Kondo).
The present study describes the result of a laboratory study that assessed the efficacy of afoxolaner, administered orally in a chewable formulation (Nexgard® , Merial), against H. longicornis in dogs. 2. Materials and methods Sixteen beagle dogs of both sexes were included in the study, which was designed as a negative controlled randomized block study. All dogs were approximately 10–11 months of age and weighed from 7.2 to 9.0 kg at inclusion. All dogs were healthy and had not been treated with any ectoparasiticides in the 3 months prior to inclusion in the study nor infested by ticks. The health of all dogs was monitored at least once daily and once per hour during the first four hours post treatment. All dogs had free access to water and were fed a commercial diet. The study design was approved by the Merial Institutional Animal Care and Use Committee (USDA, 2008). In the study, two groups of eight dogs were formed randomly, using blocks of two dogs based on decreasing
http://dx.doi.org/10.1016/j.vetpar.2014.02.019 0304-4017/© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/3.0/).
230
Y. Kondo et al. / Veterinary Parasitology 201 (2014) 229–231
pre-treatment tick counts. Dogs in Group 1 were untreated controls. Dogs in Group 2 were treated orally on Day 0 with the appropriate chewable tablets containing afoxolaner. Four sizes of chews were available: 0.5 g, 1.25 g, 3 g and 6 g, containing respectively 11.3 mg, 28.3 mg, 68 mg and 136 mg of afoxolaner. Doses were administered as closely as possible to the minimum effective dose (2.5 mg/kg). In this study, all dogs received 2 chewable tablets of 0.5 g, and the mean dose received by dogs was 3.0 mg/kg of afoxolaner (range: 2.5–3.1 mg/kg). On Days-2, 7, 14, 21, and 28, all dogs were infested with 50 unfed female H. longicornis. The study utilized ticks from laboratory-maintained populations that had been established from ticks collected in field locations in Japan. Ticks were counted 48 h after treatment (Day 2) or after infestations on Days 9, 16, 23, and 30. Counting of ticks on the dogs was performed by parting and feeling through dog’s hair with finger tips. All personnel conducting tick counts and health observations were blinded to treatment groups. The study design was in accordance with the World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestation on dogs and cats (Marchiondo et al., 2013), and was conducted in compliance with VICH GL9 “Good Clinical Practice” (EMEA, 2000). For each tick count, the total count of live ticks was transformed to the natural logarithm (count +1) to calculate the geometric mean for each treatment group. The percent reduction of the live tick counts from treated dogs compared to those from untreated dogs (=percentage efficacy) was calculated using the formula [(C − T)/C] × 100, where C is the geometric mean for the control group and T is the geometric mean for the treated group at the same time point. The log-counts of the live ticks of the treated group were compared to the log-counts of the untreated control group using an F-test adjusted for the allocation blocks used to randomize the animals to the treatment groups at each time point separately. All testing was two-sided at the significance level p = 0.05. 3. Results At each time point, the geometric mean counts of the live ticks in the control group ranged between 13.9 and 23.7 (Table 1). This level of infestation in the control group was adequate for determining efficacy against ticks. The WAAVP guideline recommends that at least 20% of the ticks should be retained from the infestation, meaning an average of 10 ticks per dog out of the 50 used to infest each dogs (Marchiondo et al., 2013). The curative efficacy of afoxolaner against pre-existing tick infestation was 100% at 48 h after treatment (Table 1). The tick efficacy of afoxolaner on weekly re-infestations starting on Day 7 after treatment provided 100% acaricidal efficacy at Day 9 and over 91.9% efficacy at all subsequent time points up to Day 30 (Table 1). The tick counts were significantly different in treated and control dogs at all time points (p < 0.05). One dog in the untreated control group was removed from the study on Day 21 due to mild seizures observed on
Table 1 Geometric tick counts and percent efficacy of afoxolaner oral treatment against Haemaphysalis longicornis after challenges with 50 female ticks. Study daya
2b 9 16 23 30
Geometric mean tick counts (min–max) Control
Treated
23.7 (4–38) 16.7 (8–29) 15.8 (6–37) 13.9 (6–25) 20.2 (15–33)
0.0 (0–0) 0.0 (0–0) 0.4 (0–2) 0.6 (0–6) 1.6 (0–7)
% Efficacy
100 100 97.7 95.5 91.9
a Live H. longicornis were counted 48 h after treatment or infestation. Day 0 is the day of treatment. b Dogs were infested before treatment on Day-2.
Day 17 and Day 21. All data on the dog captured prior to removal were included in the analysis. No adverse reaction to the treatment was observed during this study. 4. Discussion The attachment rate of the ticks was lower than what is usually observed for other tick species infesting dogs such as Rhipicephalus sanguineus (Kunkle et al., 2014). This is known to occur for H. longicornis, which is more adapted to wild ruminants than dogs in the adult stage (Inokuma, 2013; unpublished data). In this experiment, 4 ticks at Day 2 and 6 ticks at Day 16 were recovered from one control dog. It is below the 20% of attachment rate proposed by Marchiondo et al. (2013). Nevertheless the geometric mean count values ranged from 13.9 to 23.7 which were above the 20% attachment rate. The geometric mean counts were used to calculate the percent efficacy, which is therefore valid based on the guidelines (Marchiondo et al., 2013). A single oral treatment with the chewable formulation of afoxolaner achieved 100% curative efficacy for treating preexistent infestation of H. longicornis. It also controlled re-infestation by eliminating >90% of the ticks within the first 48 h after infestation for 4 weeks after treatment. The Day 30 efficacy of afoxolaner seems lower than what has been observed for other tick species (Kunkle et al., 2014; Mitchell et al., 2014). This may be related to a lower attachment rate in the control dogs, but also the variability of each experiment. There are some reports on the efficacy of current veterinary topical products against H. longicornis, e.g. imidacloprid/permethrin, fipronil/(S)-methoprene (Hagimori et al., 2005). However, unlike these topical combinations, ticks are exposed to afoxolaner while feeding on the host’s blood. Afoxolaner is absorbed rapidly by the intestinal mucosa, and its plasma concentration peaks within 2–4 h after administration (Letendre et al., 2014), which ultimately results in rapid uptake of the active ingredient by the ticks and a tick efficacy assessed at 48 h is similar to that of imidacloprid/permethrin or fipronil/(S)methoprene combinations (Hagimori et al., 2005). The systemic distribution offers advantages compared to topical formulations. There is no period after treatmentadministration during which the application site should be avoided by the owners and wetting of the haircoat or any
Y. Kondo et al. / Veterinary Parasitology 201 (2014) 229–231
other topical treatment does not interfere with the product efficacy. Another product for oral administration containing spinosad includes a registered claim for H. longicornis tick curative treatment in Japan (Comfortis1 ); however, this product is not registered for use against ticks elsewhere (Beugnet and Franc, 2012; Snyder et al., 2009). Snyder et al. (2009) reported a limited, short-lasting efficacy of 50 mg/kg spinosad against new tick infestations on dogs with 67.8% efficacy at Day 9, 49.1% at Day 14, dropping to 5% at Day 30, against Rhipicephalus sanguineus by counting ticks 48 h after infestations. In this study, afoxolaner provided both curative and prophylactic efficacy for up to 30 days against H. longicornis. Nexgard® chewable formulation containing afoxolaner represents the first oral ectoparasiticide treatment providing a month-long efficacy against H. longicornis, the main Japanese tick species infesting dogs. Conflict of interest The work reported herein was funded by Merial Limited, GA, USA. All authors are current employees of Merial. Acknowledgments The authors gratefully acknowledge the expert contributions of all collaborators from Nippon Zenyaku Kogyo Co., Ltd. (Fukushima, Japan) and Merial Limited in conducting the study to high standards. The authors gratefully acknowledge Lenaig Halos and Frederic Beugnet, Veterinary Parasitologists, for the scientific editing of the manuscript. References Beugnet, F., Franc, M., 2012. Insecticide and acaricide molecules and/or combinations to prevent pet infestation by ectoparasites. Trends Parasitol. 28, 267–279.
1 ®
ers.
All registered trademarks are the property of their respective own-
231
Chomel, B., 2011. Tick-borne infections in dogs – an emerging infectious threat. Vet. Parasitol. 179, 294–301. EMEA, 2000. Guideline on Good Clinical Practices. VICH Topic GL9 (GCP), EMWA/CVMP/VICH/595/98-Final, http://www.ema. europa.eu/docs/en GB/document library/Scientific guideline/2009/ 10/WC500004343.pdf Hagimori, I., Machida, H., Goi, R., Mencke, N., 2005. Efficacy of imidacloprid/permethrin and fipronil/(S)-methoprene combinations against Haemaphysalis longicornis ticks evaluated under in vitro and in vivo conditions. Parasitol. Res. 97 (Suppl. 1), S120–S126. Inokuma, H., 2013. Panorama of vector borne disease of pets in Asia & Japan. In: Beugnet, F. (Ed.), Guide to Vector Borne Diseases of Pets. Merial, Lyon, France, pp. 94–107. Kunkle, B., Daly, S., Dumont, P., Drag, M., Larsen, D., 2014. Assessment of the efficacy of orally administered afoxolaner against Rhipicephalus sanguineus sensu lato. Vet. Parasitol. 201, 226–228. Letendre, L., Huang, R., Kvaternick, V., Harriman, J., Drag, M., Soll, M., 2014. The intravenous and oral pharmacokinetics of afoxolaner used as a monthly chewable antiparasitic for dogs. Vet. Parasitol. 201, 190–197. Marchiondo, A.A., Holdsworth, P.A., Fourie, L.J., Rugg, D., Hellmann, K.E., Snyder, D.E., Dryden, M.W., 2013. 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. 194, 84–97. Mitchell et al., 2014 (in this issue). Otranto, D., Wall, R., 2008. New strategies for the control of arthropod vectors of disease in dogs and cats. Med. Vet. Entomol. 22, 291–302. Otranto, D., Dantas-Torres, F., Breitschwerdt, E.B., 2009a. Managing canine vector-borne diseases of zoonotic concern: part one. Trends Parasitol. 25, 157–163. Otranto, D., Dantas-Torres, F., Breitschwerdt, E.B., 2009b. Managing canine vector-borne diseases of zoonotic concern: part two. Trends Parasitol. 25, 228–235. Shimada, Y., Beppu, T., Inokuma, H., Okuda, M., Onishi, T., 2003. Ixodid tick species recovered from domestic dogs in Japan. Med. Vet. Entomol. 17, 38–45. Snyder, E., Cruthers, L., Slone, R., 2009. Preliminary study on the acaricidal efficacy of spinosad administered orally to dogs infested with the brown dog tick, Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae). Vet. Parasitol. 166, 131–135. Taboada, J., Lobetti, R., 2006. Babesiosis. In: Craig, E.G. (Ed.), Infectious Disease of the Dog and Cat. Elsevier, Missouri, pp. 722–736. Tenquisf, J.D., Charleston, W.A.G., 2001. A revision of the annotated checklist of ectoparasites of terrestrial mammals in New Zealand. J. R. Soc. N. Z. 31, 481–542. USDA, 2008. Animal Welfare Regulations, 9CFR, http://awic.nal.usda.gov/ government-and-professional-resources/federal-laws/animalwelfare-act