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Efficacy of combination products containing sarolaner, moxidectin and pyrantel (Simparica Trio™) or afoxolaner and milbemycin (NexGard Spectra®) against induced infestations of Ixodes holocyclus in dogs

Parasites & Vectors volume 13, Article number: 448 (2020) Cite this article

Abstract

Background

The Australian paralysis tick, Ixodes holocyclus, causes tick paralysis in dogs and cats in the eastern coastal regions of Australia. Prevention is the best option to protect dogs against this potentially fatal disease and sarolaner provides rapid and sustained efficacy against I. holocyclus. In this laboratory study, the efficacy of two combination endectocides containing sarolaner + moxidectin + pyrantel (Simparica Trio™) and afoxolaner + milbemycin (NexGard Spectra®) was evaluated against an artificial infestation of I. holocyclus.

Methods

Twenty-four (n =24) foxhounds were randomly allocated to three treatment groups and artificially infested with 30 adult female viable ticks on Days − 1, 7, 14, 21, 28 and 35. On Day 0, dogs in each treatment group were treated with either Drontal® (control group), Simparica Trio™ at the label dose to provide minimum doses of sarolaner (1.2 mg/kg), moxidectin (24 µg/kg) and pyrantel (5 mg/kg) or NexGard Spectra® to provide minimum doses of afoxolaner (2.5 mg/kg) and milbemycin (0.5 mg/kg). Live tick counts were performed at 48 and 72 hours after treatment and after each re-infestation on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for control dogs based on geometric means.

Results

Against an existing infestation, efficacy of both Simparica Trio™ and NexGard Spectra® was 99.6% and 100% at 48 and 72 h time points, respectively (P = 1.000). Against subsequent weekly infestations, treatment with Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 97.7% and ≥ 95.5% (P ≥ 0.0911), respectively at the 48 h time point and at the 72 h time point, Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 99.0% and ≥ 98.4% (P ≥ 0.0511), respectively. There were no treatment-related adverse events in the study.

Conclusions

Single doses of Simparica Trio™ and NexGard Spectra® were highly efficacious and provided comparable efficacy against the Australian paralysis tick, I. holocyclus for up to 35 days.

Background

The isoxazoline class of ectoparasiticides such as sarolaner, afoxolaner, fluralaner and lotilaner are highly efficacious and have broader spectrum activity against ticks, fleas and/or mites [1,2,3,4,5,6,7,8,9]. The combination of the isoxazolines with one or more additional active ingredients has provided activity against other parasites, such as heartworm and gastrointestinal nematodes [10,11,12,13,14]. Heartworm disease caused by Dirofilaria immitis is endemic in Australia [15,16,17,18]. Currently, the majority of heartworm cases in dogs are reported in the tropical regions of Australia, such as Far North Queensland [19] where an abundance of heartworm reservoirs and vectors are present [20, 21]. Gastrointestinal nematode infections are one of the most common diseases in dogs and endemic throughout Australia [15, 22,23,24,25].

Ixodes holocyclus, also known as the Australian paralysis tick, is the major cause of tick paralysis in dogs in Australia. It is widely distributed along the eastern coastal regions of Australia from North Queensland to Lakes Entrance of Victoria [26,27,28,29]. Another ixodid tick, Ixodes cornuatus, is also reported to cause clinically significant paralysis in some parts of south-eastern Australia [29, 30]. Clinical manifestations of tick paralysis caused by I. holocyclus in dogs have been well documented [31, 32]. Treatment of tick paralysis involves removal of attached ticks to prevent further envenomation and administration of tick anti-sera to neutralise the circulating free holocyclotoxins while stabilising the secondary cardio-pulmonary complications [33, 34]. Prognosis of tick paralysis cases depends on various factors such severity of clinical signs at the time of presentation, seasonality and potency of the anti-sera [31, 34]. Prevention is therefore the best option to protect dogs and cats against this fatal disease [35]. Since the introduction of isoxazolines in Australia, the incidence of tick paralysis related insurance claims appears to be declining which is a testimony to their efficacy [36].

These parasites are also zoonotic in nature and can potentially infect humans. Zoonotic diseases caused by Toxocara canis, Ancylostoma caninum and Echinococcus granulosus in humans are well understood [37,38,39,40]. Tick paralysis caused by I. holocyclus [41] and heartworm infections in humans have also been reported [42, 43]. Ixodes holocyclus is also suspected to act as a vector for transmission of Borrelia burgdorferi (sensu stricto) [44] and Rickettsia australis in humans [45, 46]. Hence, these combination products, with a broad spectrum of activity, not only protect dogs against these diseases, but also are important for human health thus supporting the ‘One Health paradigm’ [47, 48].

Here we report on a laboratory study to evaluate and compare the efficacy of two combination endectocides containing sarolaner + moxidectin + pyrantel (Simparica Trio™, Zoetis, Australia) and afoxolaner + milbemycin (NexGard Spectra®, Boehringer Ingelheim Animal Health, Australia) against an artificial infestation of I. holocyclus. Simparica Trio™ is approved in Australia for the treatment and control of fleas, ticks (I. holocyclus and R. sanguineus) and gastrointestinal worms (hookworms and roundworms) as well as the prevention of heartworm disease caused by D. immitis in dogs.

Sarolaner (Simparica™, Zoetis) chewable tablet dosed at 2 mg/kg body weight, a potent ecto-parasiticide, has excellent efficacy against ticks, fleas and mites [6] and has been demonstrated to provide rapid and sustained efficacy against I. holocyclus [49]. To broaden the spectrum of activity, a new novel oral chewable combination product delivering 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (Simparica Trio™, Zoetis) has been approved in USA, Canada, Europe and Australia. Simparica Trio™ has been shown to be efficacious against various tick species and fleas in the USA and Europe [50,51,52,53,54].

Methods

This was a blinded, negative-controlled, randomised laboratory efficacy study conducted in New South Wales (NSW), Australia. Study procedures were 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 [55] and complied with the principles of Good Clinical Practice [56]. The study was conducted according to the Australian Pesticides and Veterinary Medicines Authority (APVMA) guidelines [57]. The protocol was reviewed and approved by the Wongaburra Research Centre Animal Ethics Committee, NSW, Australia. Blinding of the study was assured through the separation of functions. All personnel conducting observations, or performing infestations and counts were blinded to treatment allocation.

Animals

Twenty-four (n = 24) pure and crossbred Foxhound dogs of both sexes (14 females and 10 males), aged between 3 and 8 years were enrolled in the study. Each dog was individually identified by a unique electronic transponder. All dogs had undergone an adequate wash-out period for at least 90 days to ensure that no residual ectoparasiticide efficacy remained from any previously administered treatments which was confirmed by the tick carrying capacity tests conducted on day − 8. Dogs were individually housed in indoor runs such that no physical contact was possible between them and they were acclimatised to these conditions for at least 14 days prior to treatment. Dogs were fed an appropriate maintenance ration of a commercial dry canine feed for the duration of the study. Water was available ad libitum. All dogs were given a physical examination to ensure that they were in good health at enrolment and suitable for inclusion in the study. General health observations were performed three times daily throughout the study.

Design

The study followed a randomised complete block design, with pairs of dogs as the experimental unit. Dogs enrolled in the study were immunised to the tick toxin-holocyclotoxin as described previously [58]. Prior to treatment on Day 0, dogs were ranked according to pre-treatment tick counts into four blocks of six (three pairs of dogs). Within each block, one pair of dogs was randomly allocated to one of three treatment groups. Dogs in the control group were treated with praziquantel (175 mg) + pyrantel (174.4 mg) + febantel (875 mg) combination (Drontal® Bayer, Australia) for the control of pre-existing gastrointestinal worm burden, as per the label dose (1 tablet per 35 kg). As Drontal® does not have any acaricidal effect, this group functioned as the negative control group for the assessment of tick counts in this study. Dogs in the other two groups were treated with combination products containing either sarolaner + moxidectin + pyrantel (Simparica Trio™, Zoetis, Australia) or afoxolaner + milbemycin (NexGard Spectra®, Boehringer Ingelheim Animal Health, Australia).

Treatment

Body weights recorded on the treatment day were used to calculate the appropriate dose of each treatment and the enrolled dogs weighed between 28.7 and 42.2 kg. All dogs were fasted overnight prior to Day 0 and the first feed was offered approximately 4 h after treatment administration. Dogs received their respective treatments according to the label instructions. The dogs in the Simparica Trio™-treated group received sarolaner at minimum 1.2 mg/kg (actual doses ranged from 1.30 to 1.71 mg/kg), moxidectin at minimum 24 µg/kg (26.0–34.1 µg/kg) and pyrantel at minimum 5 mg/kg (5.42–7.11 mg/kg). The dogs in the NexGard Spectra®-treated group received afoxolaner at minimum 2.5 mg/kg (actual doses ranged between 2.61–4.63 mg/kg) and milbemycin at minimum 0.5 mg/kg (0.52–0.93 mg/kg). All doses were administered by hand pilling to ensure accurate and complete dosing. Each dog was observed for at least 2 min after treatment to ensure the dose was swallowed and for 2 h for evidence of vomiting. Vomiting was recorded only in one dog treated with Drontal® in the study. The dogs were monitored for clinical signs approximately 1, 3, 6 and 24 h post-treatment.

Tick infestation and assessment

Wild-caught, unfed adult female I. holocyclus ticks collected from Queensland and the Northern Rivers region of New South Wales, Australia were used in the study. The ticks were stored in dark conditions at around 12 °C and high humidity [58] for approximately 9 months prior to the start of the study. Prior to each infestation, dogs were examined to ensure they were free of ticks. Each dog was infested with 30 adult female unfed, viable ticks on each of Days − 1, 7, 14, 21, 28 and 35 at pre-defined locations (head, shoulders, dorsal midline of the body and tail base) on the dogs as described previously [58]. Following Day − 1 infestation, tick counts were performed at 48 and 72 h after treatment on Day 0 to evaluate the immediate efficacy of treatment and all other tick counts were performed at 48 and 72 h after each weekly infestation to evaluate the persistent efficacy. Tick assessments at 48 h time points were performed without removing the ticks from the dogs. After counting at the 72 h time point, all ticks were removed. Both free and attached ticks were characterized as either live or dead as described previously [58]. Moribund ticks were characterized and included in the live counts as previously described [49]. All the tick counts and assessments were performed by laboratory technicians who were experienced and trained on validated laboratory methods of tick counting and assessments.

Statistical analysis

The primary outcome measure was live tick counts. Data for post-treatment live (free plus attached) tick counts were summarised with arithmetic (AM) and geometric (GM) means by treatment group and time point. Tick counts were transformed by the loge(count + 1) transformation prior to analysis in order to stabilise the variance and normalise the data. Using the PROC MIXED procedure (SAS 9.4, SAS Institute Inc., Cary, NC, USA), transformed counts were analysed using a mixed linear model for repeated measures for the 48 and 72 h time points separately. The fixed effects were treatment, time point and the interaction between time point and treatment. The random effects included block, pair, animal, block by treatment by time point interaction, and error. Testing was two-sided at the significance level α= 0.05, with tests based on contrasts between treatment least squares means from the fitted models.

The assessment of efficacy for live ticks was based on the percent reduction in the AM and GM live tick counts for the treated groups relative to control, as suggested by the most recent guidelines of the WAAVP for systemic acaricides [35], and was calculated using Abbott’s formula:

$${\text{\% Reduction}} = 100 \times \frac{{{\text{Mean count }}\left( {\text{control}} \right){-}{\text{Mean count }}\left( {\text{treated}} \right)}}{{{\text{Mean count }}\left( {\text{control}} \right)}}$$

As the distribution of parasite counts within each group was likely be skewed, comparison between groups was primarily based on GM live tick counts [55].

Results and discussion

Safety

Three dogs in the Simparica Trio™-treated group were treated for dermatitis or lick granuloma and three dogs in the NexGard Spectra®-treated group were treated for trauma, lick granuloma and/or gastrointestinal upset. None of these adverse events were considered as treatment-related.

Efficacy

Dogs in the control group maintained good tick infestations throughout the study with individual tick counts ranging from 16 to 31 and geometric mean counts between 20 to 26 (Tables 1 and 2).

Table 1 Mean live Ixodes holocyclus counts and efficacy relative to control at 48 h after treatment and after weekly re-infestations for dogs treated with a single oral dose of Simparica Trio™ or NexGard Spectra® on Day 0
Full size table
Table 2 Mean live Ixodes holocyclus counts and efficacy relative to control at 72 h after treatment and after weekly re-infestations for dogs treated with a single oral dose of Simparica Trio™ or NexGard Spectra® on Day 0
Full size table

Against an existing infestation, at the 48 and 72 h time points, treatment with Simparica Trio™ and NexGard Spectra® resulted in significantly lower GM tick counts compared to the control group (14.37 ≤ tdf ≤ 28.97 where 34 ≤ df ≤ 51, P < 0.0001). Against the existing infestation, both Simparica Trio™ and NexGard Spectra® provided 99.6% and 100% efficacy at 48 and 72 h post-treatment, respectively. The comparable efficacy results at the 48 h time point were consistent with those previously reported [49] (Tables 1 and 2). Based on arithmetic mean counts, the efficacy of both Simparica Trio™ and NexGard Spectra® against an existing infestation at the 48 h and 72 h time points was 99.4% and 100%, respectively.

Against subsequent weekly infestations at the 48 h time point, treatment with Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 97.7% and ≥ 95.5%, respectively. At the 72 h time point, Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 99.0% and ≥ 98.4%, respectively. At all time points, both treatments resulted in significantly lower GM tick counts compared to the control group (11.76 ≤ tdf ≤ 29.10 where 33 ≤ df ≤ 51, P < 0.0001). However there were no significant differences in the GM tick counts between the two treatments at any time point (-2.00 ≤ tdf ≤ 1.71 where 33 ≤ df ≤ 73, P ≥ 0.0511). Based on arithmetic mean counts, the efficacy of Simparica Trio™ and NexGard Spectra® against subsequent weekly infestations was ≥ 96.9% and ≥ 92.9%, respectively, at the 48 h time points and ≥ 97.8% for both products at the 72 h time points.

Single doses of Simparica Trio™ and NexGard Spectra® resulted in the rapid reduction of an existing infestation and subsequent re-infestations of live I. holocyclus ticks for up to 5 weeks. Although the onset of clinical signs of tick paralysis does not occur until 4 or 5 days after tick attachment, the sooner the attached ticks can be killed, the lower the chance of tick paralysis [59,60,61]. The rapid and sustained speed of kill of Simparica Trio™ after a single oral dose will minimise the risk of tick paralysis. Similar efficacy of Simparica Trio™ has also been demonstrated against ixodid ticks in Europe (Ixodes ricinus and Ixodes hexagonus) and the USA (Ixodes scapularis), respectively [51, 53].

Conclusions

Single doses of Simparica Trio™, containing sarolaner, moxidectin and pyrantel and NexGard Spectra® containing afoxolaner and milbemycin provided comparable efficacy against the Australian paralysis tick, I. holocyclus for up to 35 days. These two combination products with a broader spectrum of activity will provide effective control of the most important parasites in dogs including the Australian paralysis tick, fleas, heartworm, roundworms and hookworms of zoonotic significance, thus offering a holistic one health treatment option to the pet owners.

Availability of data and materials

The dataset supporting the conclusions of this article is included within the article.

Abbreviations

AM:

arithmetic mean

GM:

geometric mean

WAAVP:

World Association for the Advancement of Veterinary Parasitology

References

  1. Beugnet F, de Vos C, Liebenberg J, Halos L, Larsen D, Fourie J. Efficacy of afoxolaner in a clinical field study in dogs naturally infested with Sarcoptes scabiei. Parasite. 2016;23:26.

    PubMed  PubMed Central  Google Scholar 

  2. Becskei C, De Bock F, Illambas J, Cherni JA, Fourie JJ, Lane M, et al. Efficacy and safety of a novel oral isoxazoline, sarolaner (Simparica™), for the treatment of sarcoptic mange in dogs. Vet Parasitol. 2016;222:56–61.

    PubMed  CAS  Google Scholar 

  3. Lebon W, Beccati M, Bourdeau P, Brement T, Bruet V, Cekiera A, et al. Efficacy of two formulations of afoxolaner (NexGard® and NexGard Spectra®) for the treatment of generalised demodicosis in dogs, in veterinary dermatology referral centers in Europe. Parasit Vectors. 2018;11:506.

    PubMed  PubMed Central  Google Scholar 

  4. Six RH, Becskei C, Mazaleski MM, Fourie JJ, Mahabir SP, Myers MR, et al. Efficacy of sarolaner, a novel oral isoxazoline, against two common mite infestations in dogs: Demodex spp and Otodectes cynotis. Vet Parasitol. 2016;222:62–6.

    PubMed  CAS  Google Scholar 

  5. Taenzler J, Liebenberg J, Roepke RKA, Frénais R, Heckeroth AR. Efficacy of fluralaner administered either orally or topically for the treatment of naturally acquired Sarcoptes scabiei var canis infestation in dogs. Parasit Vectors. 2016;9:392.

    PubMed  PubMed Central  Google Scholar 

  6. McTier TL, Chubb N, Curtis MP, Hedges L, Inskeep GA, Knauer CS, et al. Discovery of sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogs. Vet Parasitol. 2016;222:3–11.

    PubMed  CAS  Google Scholar 

  7. Shoop WL, Hartline EJ, Gould BR, Waddell ME, Mcdowell RG, Kinney JB, et al. Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs. Vet Parasitol. 2014;201:179–89.

    PubMed  CAS  Google Scholar 

  8. Gassel M, Wolf C, Noack S, Williams H, Ilg T. The novel isoxazoline ectoparasiticide fluralaner: Selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity. Insect Biochem Mol Biol. 2014;45:111–24.

    PubMed  CAS  Google Scholar 

  9. Cavalleri D, Murphy M, Gorbea RL, Seewald W, Drake J. Laboratory evaluations of the immediate and sustained effectiveness of lotilaner (Credelio™) against three common species of ticks affecting dogs in Europe. Parasit Vectors. 2017;10:527.

    PubMed  PubMed Central  Google Scholar 

  10. Kryda K, Six RH, Walsh KF, Holzmer SJ, Chapin S, Mahabir SP, et al. Laboratory and field studies to investigate the efficacy of a novel, orally administered combination product containing moxidectin, sarolaner and pyrantel for the prevention of heartworm disease (Dirofilaria immitis) in dogs. Parasit Vectors. 2019;12:445.

    PubMed  PubMed Central  Google Scholar 

  11. Becskei C, Kryda K, Fias D, Follis SL, Wozniakiewicz M, Mahabir SP, et al. Field efficacy and safety of a novel oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against naturally acquired gastrointestinal nematode infections in dogs presented as veterinary patients in Europe and the USA. Parasit Vectors. 2020;13:70.

    PubMed  PubMed Central  CAS  Google Scholar 

  12. Becskei C, Kryda K, Thys M, Holzmer S, Bowersock L, Fernandes T, et al. Efficacy of a new oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced ascarid infections in dogs. Parasit Vectors. 2020;13:71.

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Becskei C, Thys M, Kryda K, Meyer L, Martorell S, Geurden T, et al. Efficacy of Simparica Trio™, a novel chewable tablet containing sarolaner, moxidectin and pyrantel, against induced hookworm infections in dogs. Parasit Vectors. 2020;13:99.

    PubMed  PubMed Central  CAS  Google Scholar 

  14. McTier TL, Six RH, Pullins A, Chapin S, Kryda K, Mahabir SP, et al. Preventive efficacy of oral moxidectin at various doses and dosage regimens against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs. Parasit Vectors. 2019;12:444.

    PubMed  PubMed Central  Google Scholar 

  15. Brown B, Copeman D. Zoonotic importance of parasites in wild dogs caught in the vicinity of Townsville. Aust Vet J. 2003;81:700–2.

    PubMed  CAS  Google Scholar 

  16. Carlisle CH. The incidence of Dirofilaria immitis (heartworm) in dogs in Queensland. Aust Vet J. 1969;45:535–8.

    PubMed  CAS  Google Scholar 

  17. Carlisle CH. Observations on the treatment of Dirofilaria immitis infection in dogs in Brisbane. Aust Vet J. 1970;46:185–9.

    PubMed  CAS  Google Scholar 

  18. Carlisle C, Atwell R. A survey of heartworm in dogs in Australia. Aust Vet J. 1984;61:356–60.

    PubMed  CAS  Google Scholar 

  19. Nguyen C, Koh WL, Casteriano A, Beijerink N, Godfrey C, Brown G, et al. Mosquito-borne heartworm Dirofilaria immitis in dogs from Australia. Parasit Vectors. 2016;9:535.

    PubMed  PubMed Central  Google Scholar 

  20. Smout FA, Skerratt LF, Butler JR, Johnson CN, Congdon BC. Dingoes (Canis dingo Meyer, 1793) continue to be an important reservoir host of Dirofilaria immitis in low density housing areas in Australia. Vet Parasitol. 2016;215:6–10.

    PubMed  Google Scholar 

  21. Meyer Steiger DB, Ritchie SA, Laurance SGW. Mosquito communities and disease risk influenced by land use change and seasonality in the Australian tropics. Parasit Vectors. 2016;9:387.

    PubMed  PubMed Central  Google Scholar 

  22. Dunsmore JD, Thompson RCA, Bates IA. Prevalence and survival of Toxocara canis eggs in the urban environment of Perth. Australia. Vet Parasitol. 1984;16:303–11.

    PubMed  CAS  Google Scholar 

  23. Jenkins DJ. Toxocara canis in Australia. Adv Parasitol. 2020;109:873–8.

    PubMed  Google Scholar 

  24. Jenkins DJ, Lievaart JJ, Boufana B, Lett WS, Bradshaw H, Armua-Fernandez MT. Echinococcus granulosus and other intestinal helminths: current status of prevalence and management in rural dogs of eastern Australia. Aust Vet J. 2014;92:292–8.

    PubMed  CAS  Google Scholar 

  25. Morrison P, Stanton R, Pilatti E. Echinococcus granulosus infection in wild dogs in south-eastern New South Wales. Aust Vet J. 1988;65:97–8.

    PubMed  CAS  Google Scholar 

  26. Eppleston KR, Kelman M, Ward MP. Distribution, seasonality and risk factors for tick paralysis in Australian dogs and cats. Vet Parasitol. 2013;196:460–8.

    PubMed  CAS  Google Scholar 

  27. Greay TL, Oskam CL, Gofton AW, Rees RL, Ryan UM, Irwin PJ. A survey of ticks (Acari: Ixodidae) of companion animals in Australia. Parasit Vectors. 2016;9:207.

    PubMed  PubMed Central  Google Scholar 

  28. Jackson J, Beveridge I, Chilton NB, Andrews RH. Distributions of the paralysis ticks Ixodes cornuatus and Ixodes holocyclus in south-eastern Australia. Aust Vet J. 2007;85:420–4.

    PubMed  CAS  Google Scholar 

  29. Barker D, Barker SC. Survey of cases of tick-paralysis and the presence of the eastern paralysis tick, Ixodes holocyclus, and the southern paralysis tick, Ixodes cornuatus, in the Greater Melbourne Area. Aust Vet J. 2020;98:2–10.

    PubMed  CAS  Google Scholar 

  30. Barker SC, Walker AR, Campelo D. A list of the 70 species of Australian ticks; diagnostic guides to and species accounts of Ixodes holocyclus (paralysis tick), Ixodes cornuatus (southern paralysis tick) and Rhipicephalus australis (Australian cattle tick); and consideration of the place of Australia in the evolution of ticks with comments on four controversial ideas. Int J Parasitol. 2014;44:941–53.

    PubMed  Google Scholar 

  31. Westwood MN, Emery DL, Dhand NK. Clinical presentation and treatment of tick paralysis in dogs and cats in Sydney (2001–2010). Aust Vet J. 2013;91:491–8.

    PubMed  CAS  Google Scholar 

  32. Holland CT. Asymmetrical focal neurological deficits in dogs and cats with naturally occurring tick paralysis (Ixodes holocyclus): 27 cases (1999–2006). Aust Vet J. 2008;86:377–84.

    PubMed  CAS  Google Scholar 

  33. Webster RA, Mills PC, Morton JM. Indications, durations and outcomes of mechanical ventilation in dogs and cats with tick paralysis caused by Ixodes holocyclus: 61 cases (2008–2011). Aust Vet J. 2013;91:233–9.

    PubMed  CAS  Google Scholar 

  34. Atwell RB, Campbell FE, Evans EA. Prospective survey of tick paralysis in dogs. Aust Vet J. 2001;79:412–8.

    PubMed  CAS  Google Scholar 

  35. Padula AM, Leister EM, Webster RA. Tick paralysis in dogs and cats in Australia: treatment and prevention deliverables from 100 years of research. Aust Vet J. 2020;98:53–9.

    PubMed  CAS  Google Scholar 

  36. Awad M. The decline in tick paralysis cases. Centre for Veterinary Education Control & Therapy Series. 2016;5571:30–1.

    Google Scholar 

  37. Prociv P, Croese J. Human enteric infection with Ancylostoma caninum: hookworms reappraised in the light of a “new” zoonosis. Acta Trop. 1996;62:23–44.

    PubMed  CAS  Google Scholar 

  38. Bowman DD, Montgomery SP, Zajac AM, Eberhard ML, Kazacos KR. Hookworms of dogs and cats as agents of cutaneous larva migrans. Trends Parasitol. 2010;26:162–7.

    PubMed  Google Scholar 

  39. Macpherson CN. The epidemiology and public health importance of toxocariasis: a zoonosis of global importance. Int J Parasitol. 2013;43:999–1008.

    PubMed  Google Scholar 

  40. Jenkins DJ, Power K. Human hydatidosis in New South Wales and the Australian Capital Territory, 1987–1992. Med J Aust. 1996;164:18–21.

    PubMed  CAS  Google Scholar 

  41. Grattan-Smith PJ, Morris JG, Johnston HM, Yiannikas C, Malik R, Russell R, et al. Clinical and neurophysiological features of tick paralysis. Brain. 1997;120:1975–87.

    PubMed  Google Scholar 

  42. Simón F, Siles-Lucas M, Morchón R, González-Miguel J, Mellado I, Carretón E, et al. Human and animal dirofilariasis: the emergence of a zoonotic mosaic. Clin Microbiol Rev. 2012;25:507–44.

    PubMed  PubMed Central  Google Scholar 

  43. Diaz JH. Increasing risks of human dirofilariasis in travelers. J Travel Med. 2014;22:116–23.

    PubMed  Google Scholar 

  44. Mayne P, Song S, Shao R, Burke J, Wang Y, Roberts T. Evidence for Ixodes holocyclus (Acarina: Ixodidae) as a vector for human lyme borreliosis infection in Australia. J Insect Sci. 2014;14:271.

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Graves S, Unsworth N, Stenos J. Rickettsioses in Australia. Ann N Y Acad Sci. 2006;1078:74–9.

    PubMed  Google Scholar 

  46. Graves S, Jackson C, Hussain-Yusuf H, Vincent G, Nguyen C, Stenos J, et al. Ixodes holocyclus tick-transmitted human pathogens in north-eastern New South Wales. Australia. Trop Med Infect Dis. 2016;1:4.

    Google Scholar 

  47. Fisman DN, Laupland KB. The ‛One Healthʼ paradigm: time for infectious diseases clinicians to take note? Can J Infect Dis Med Microbiol. 2010;21:111–4.

    PubMed  PubMed Central  Google Scholar 

  48. Destoumieux-Garzón D, Mavingui P, Boetsch G, Boissier J, Darriet F, Duboz P, et al. The one health concept: 10 years old and a long road ahead. Front Vet Sci. 2018;5:14.

    PubMed  PubMed Central  Google Scholar 

  49. Packianathan R, Hodge A, Bruellke N, Davis K, Maeder S. Comparative speed of kill of sarolaner (Simparica®) and afoxolaner (NexGard®) against induced infestations of Ixodes holocyclus on dogs. Parasit Vectors. 2017;10:98.

    PubMed  PubMed Central  Google Scholar 

  50. Becskei C, Fias D, Mahabir SP, Farkas R. Efficacy of a novel oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against natural flea and tick infestations on dogs presented as veterinary patients in Europe. Parasit Vectors. 2020;13:72.

    PubMed  PubMed Central  CAS  Google Scholar 

  51. Becskei C, Liebenberg J, Thys M, Mahabir SP. Efficacy of a novel chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against four common tick species infesting dogs in Europe. Parasit Vectors. 2020;13:100.

    PubMed  PubMed Central  CAS  Google Scholar 

  52. Kryda K, Mahabir SP, Carter L, Everett WR, Young DR, Meyer L, et al. Laboratory studies evaluating the efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) for the treatment and control of flea infestations on dogs. Parasit Vectors. 2020;13:57.

    PubMed  PubMed Central  CAS  Google Scholar 

  53. Kryda K, Mahabir SP, Chapin S, Holzmer SJ, Bowersock L, Everett WR, et al. Efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of five common tick species infesting dogs in the USA. Parasit Vectors. 2020;13:77.

    PubMed  PubMed Central  CAS  Google Scholar 

  54. Kryda K, Mahabir SP, Inskeep T, Rugg J. Safety and efficacy of a novel oral chewable combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against natural flea infestations in client-owned dogs in the USA. Parasit Vectors. 2020;13:98.

    PubMed  PubMed Central  CAS  Google Scholar 

  55. Marchiondo AA, Holdsworth PA, Fourie LJ, Rugg D, Kellmann K, Snyder DE. World Association for the Advancement of Veterinary Parasitology (WAAVP) 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;194:84–97.

    PubMed  CAS  Google Scholar 

  56. EMEA. Guideline on good clinical practices. VICH Topic GL9 2001. https://vichsec.org/en/guidelines/pharmaceuticals/pharma-efficacy/good-clinical-practice.html. Accessed 23 May 2020.

  57. Australian Pesticides and Veterinary Medicines Authority (APVMA). The WAAVP guideline for fleas and ticks on dogs and cats. https://apvmagovau/node/1040. 2019.

  58. Fisara P, Webster M. A randomized controlled trial of the efficacy of orally administered fluralaner (Bravecto) against induced Ixodes holocyclus (Australian paralysis tick) infestations on dogs. Parasit Vectors. 2015;8:257.

    PubMed  PubMed Central  Google Scholar 

  59. Ilkiw JE, Turner DM, Howlett CR. Infestation in the dog by the paralysis tick Ixodes holocyclus. 1. Clinical and histological findings. Aust Vet J. 1987;64:137–9.

    PubMed  CAS  Google Scholar 

  60. Ross IC. Tick paralysis in the dog. Aust Vet J. 1934;10:182–3.

    Google Scholar 

  61. Ross IC. An experimental study of tick paralysis in Australia. Aust Vet J. 1927;4:310–29.

    Google Scholar 

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Acknowledgements

The staff of Invetus Australia are gratefully acknowledged for their dedication to the study execution. Authors also would like to thank Drs John Messer and Megan Lui of Zoetis Australia Pty Ltd for reviewing this manuscript.

Funding

Funding for the design, conduct of the study and data collection was provided by Zoetis Australia Research & Manufacturing Pty Ltd.

Author information

Authors and Affiliations

  1. Zoetis Australia Research and Manufacturing Pty Ltd, Veterinary Medicine Research and Development, Level 6, 5 Rider Boulevard, Rhodes, NSW, 2138, Australia

    Raj Packianathan, Andrew Hodge, Natalie Bruellke & Steven Maeder

  2. Invetus, 495 Ellangowan Road, Yorklea, NSW, 2470, Australia

    Chrissie Jackson

Authors
  1. Raj Packianathan
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  2. Andrew Hodge
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  3. Natalie Bruellke
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  4. Chrissie Jackson
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  5. Steven Maeder
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Contributions

All authors assisted with the design and conduct of the study and interpretation of the data. Manuscript was written by RP and AH. NB, CJ and SM contributed to drafting. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Raj Packianathan.

Ethics declarations

Ethics approval and consent to participate

An animal ethics approval was obtained from the Wongaburra Research Centre Animal Ethics Committee on 26 February 2018 prior to the commencement of the study. The animal ethics approval number was ZOE C 17145 W. This study did not report on any data related to humans. All dogs enrolled in the study were owned by the Invetus who conducted this study.

Consent for publication

Not applicable.

Competing interests

RP, AH, NB and SM are current employees of Zoetis. CJ was a contracted study investigator.

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Packianathan, R., Hodge, A., Bruellke, N. et al. Efficacy of combination products containing sarolaner, moxidectin and pyrantel (Simparica Trio™) or afoxolaner and milbemycin (NexGard Spectra®) against induced infestations of Ixodes holocyclus in dogs. Parasites Vectors 13, 448 (2020). https://doi.org/10.1186/s13071-020-04323-8

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Keywords

  • Isoxazoline
  • Ixodes holocyclus
  • NexGard Spectra®
  • Simparica Trio™