SMALL I CONTINUING EDUCATION Canine and feline parasite control – too much choice?

Sue Paterson MA VetMB DVD DipECVD FRCVS, RCVS and European Specialist in Veterinary Dermatology, and veterinary director, Virtual Vet Derms Ltd, discusses the most important ectoparasitic conditions in primary care veterinary practice and considers the different products available for treatment

INTRODUCTION to have contributed to the worrying decline in populations of Routine ectoparasite control forms an important part of any small invertebrates in river systems), are due to their topical health protocol for dogs and cats and is essential as part of use on pets. However, there have been calls for research to the investigation and management of pruritic skin disease. be undertaken to investigate the potential direct and indirect In order to be able to select a suitable ectoparasiticide, it is environmental exposure pathways for dog parasiticide important that the veterinary surgeon has an appreciation of products in relation to the eect of veterinary use on levels of the mode of action of the plethora of dierent products that are in the environment. available and their spectrum of activity. This review will briefly discuss the most important ectoparasitic conditions in primary ECTOPARASITE CONTROL care veterinary practice (in the UK) and consider the dierent Fleas (Ctenocephalides felis) products available for treatment. This will include their current The most common species of flea encountered on dogs and licensed indications plus any evidence around their suitability cats in the UK is Ctenocephalides felis. All will react for therapy of fleas, , harvest , lice, Cheyletiella spp. to flea bites but where individuals are not sensitised to flea Sarcoptes scabiei, and Demodex spp. in the dog and cat. bites, the irritation is generally transient and does not lead to Over the last 12 months there have been changes in clinical signs. Where dogs are hypersensitive to flea salivary ectoparasiticide availability. Several products have switched antigens injected intradermally during flea feeding, they will distributors, a few such as have been discontinued, develop much more severe and widespread clinical signs. and drugs such as the neonicotinoids, although still available for Dogs with flea allergic dermatitis (FAD) develop signs of use in small animals, has been banned in farming. There is, at pruritic skin disease principally aecting the caudo-dorsal this present time, no hard evidence to suggest that chemicals lumbosacral area and often with extension of signs onto like and imidocloprid in water sources (that are thought the dorsal tail head, caudomedial thighs, abdomen and

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flanks. Lesions include pruritic, papular, crusting eruptions relies on them being identified at an early stage, which with secondary erythema and self-inflicted trauma. In cats, is not always possible in a dog or cat with a thick pelage flea bite hypersensitivity is the most common cause of and, therefore, prophylactic therapy as part of a holistic pruritic skin disease and presents in a myriad of dierent ectoparasite programme is preferable. Many of the earliest ways including miliary dermatitis, self-inflicted alopecia or treatments such as fipronil, avermectin (selamectin), as part of the eosinophilic granuloma complex. In addition milbemycin (moxidectin) and derivatives to causing skin disease C. felis has been shown to act as a (, , ) are still available and vector for numerous pathogens including Rickettsia spp., are useful against ticks in dogs. Although many are also Bartonella spp., Mycoplasma spp. and the intermediate host licensed for cats, including flumethrin as a component of of the cestode Dipylidium caninum.1 a flea and tick collar, other and are In the last 20 years, a wide range of have been toxic in this species and are best avoided. Drugs such as registered as flea products either as mono or combined the isoxazolines represent newer licensed products with therapies. Most of the actives such as fipronil, , excellent tick activity. , , permethrin and registered prior to 1997 are still available and, despite Harvest mites (Neotrombicula autumnalis) anecdotal reports suggesting otherwise, resistance to The parasitic larva of the harvest (Neotrombicula these products is uncommon. According to the autumnalis) is responsible for causing an irritating pruritic Pesticide Resistance database there have, to date, only been eruption on ground-skin contact areas in dogs, it can also be reports of C. felis resistance to organochlorines, , found around the ears of outdoor cats. The larva is usually , pyrethroids and pyrethrin. Drugs picked up by the pet while out for a rural walk or while out such as fipronil and imidacloprid have been rejuvenated hunting in the autumn. Little is licensed to treat harvest by being released as generics; other have benefited from mite infestations and although many products have good changes in formulation, application technology and by being eicacy against the parasitic larvae, few produce prolonged combined with other actives.2 Most insecticides licensed for residual protection. This means during high-risk periods veterinary use are available as prescription-only medication animals can become quickly re-infested once they return to – veterinarian (POM-V) products. Drugs such as mono a contaminated environment. Selamectin has been shown formulations of imidacloprid and fipronil are available without to be useful for therapy of harvest mites in dogs and cats. 3 veterinary prescription (as non-food producing animal – Fipronil, in a combination product with permethrin4 has veterinarian, pharmacist, SQP [NFA-VPS]). been used in dogs. Anecdotally, the author’s preference While a high degree of eicacy and persistence is essential for prevention and treatment of harvest mites is the oral for any flea product, the speed of kill (SOK) is also important isoxazolines. Although not licensed for use, they do seem to reduce feeding time which is important in animals with protect against and reduce re-infestation. flea-bite hypersensitivity. Lice (Trichodectes canis, Linognathus setosus) Ticks ( spp.) Lice are highly host-specific parasites. The two species Both hard (Ixodidae) and soft () ticks occur in the found on dogs in the UK are the biting louse, Trichodectes UK but it is the hard ticks Ixodes spp. (ricinus, hexagonus, canis and the sucking louse Linognathus setosus. Feline lice canisuga) that principally aect dogs, cats are rarely infested. infestations are rare but when they occur are caused by Dermacentor reticulatus and Haemaphysalis punctata are the biting louse Felicola subrostratus. Lice infestations are also occasionally found. Ticks tend to attach to a non- uncommon in the UK and when they occur, animals may haired, thin-skinned area such as around the face. As blood be asymptomatic or highly pruritic leading to marked signs feeders the feeding activity of numerous ticks can lead to of self-inflicted trauma. Products that are licensed for the anaemia but commonly it is the wound created by the tick treatment of flea infestations can be used in the treatment bite that leads to local irritation particularly if the tick is of lice. Selamectin, fipronil and imidocloprid are specifically removed after it has attached and the mouth warts are left licensed for the treatment of biting lice, although isoxazolines in the skin. With the increase of reports in the veterinary should also be useful. literature of tick-borne disease in the UK over the last few years, tick control has become a much more important part Browsing mite (Cheyletiella spp.) of routine ectoparasite control. Ticks are known to carry a Cheyletiella spp. is a browsing mite that feeds on the surface of range of bacterial, rickettsial, viral and protozoal diseases. the skin leading to mild pruritic dermatitis, usually manifesting The most common tick-borne disease in the UK is Lyme a dorsal scaling with erythema and crust. Cheyletiella yasguri disease (Borrelia burgdorferi) transmitted by Ixodes ticks, is the species often found on dogs, and Cheyletiella blakei on however babesiosis (Babesia canis) has been recognised cats. However, the mite is not host specific and Cheyletiella very recently _ in June 2020 _ (MRCVS Online) in the parasitovorax may also be identified on pets. Few products are south of England in dogs with no history of travel abroad. licensed for the treatment of Cheyletiella, so flea products with The babesia parasite was thought to be transferred by D. acaricidal activity in the form of sprays, spot-ons or oral drugs reticulatus ticks. While ticks can be manually removed, this are therefore usually employed. Selamectin, moxidectin and

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Mode of action Examples Canine formulation Age and Ectoparasite spectrum of minimum weight activity Chloride channel activators Selamectin (A) Spot-on treatment Dogs >6 weeks Licensed for fleas, ear Dogs <2.5kg mites, Sarcoptes scabiei, Trichodectes canis Avermectins (A)/Milbemycins (M) are agonists Moxidectin (M) Spot-on combined Dogs >7 weeks Licensed for fleas, biting lice, to glutamate-gated chloride channels in flea with imidocloprid Dogs >1kg Otodectes cynotis, Sarcoptes causing blockage of neurotransmission and (slight variation on scabiei, Demodex canis paralysis licensed use may vary between products) Oral product with Dogs >8 weeks Licensed for fleas, ticks, pyrantel and Dogs >1.25kg Chitin biosynthesis inhibitors (juvenoid/IGR) Benzoylphenylurea derivative that inhibits Lufenuron Tablet with and Lufenuron only Licensed for fleas flea development through blocking chitin without milbemycin Dogs weaned production and egg hatch oxime puppies Dogs >2.3kg 2GABA-gated chloride channel antagonist Fipronil Spot-on or spray – Dogs >8 weeks Slight variation in licensed available as numerous Dogs >2kg indications most licensed for 1) Phenylpyrazole that blocks invertebrate different products fleas, ticks, biting lice GABA and glutamate gated chloride channels Also combined with juvenoids (S)- needed for inhibition of nerve impulses leading methoprene and to hyperexcitability and neurotoxicity pyriproxyfen (see juvenoids)

2) Isoxazoline potent antagonist of invertebrate Tablet Dogs >8 weeks Licensed for use against fleas, GABA and glutamate gated chloride channels Dogs >2kg ticks, Demodex spp. Sarcoptes (receptor binding more potent than fipronil) scabiei Tablet and spot-on Tablet and spot Licensed for use against fleas, on ticks, Demodex spp. Sarcoptes Dogs >8 weeks scabiei Dogs >2kg Lotilaner Tablet Dogs >8 weeks Licensed for fleas and ticks Dogs >1.3 kg Sarolaner Tablet Dogs >8 weeks Licensed against fleas, ticks, Dogs >1.3kg Otodectes cynotis, Demodex spp. and Sarcoptes scabiei Juvenile hormone mimetic (juvenoid/IGR) Pyriproxyfen Spot-on, shampoo, Combined with Licensed for fleas, ticks, topical spray, collars fipronil (trio Mimics of juvenile hormones to prevent larvae and environmental product with from completing metamorphosis spray below) Dogs >10 weeks Dogs >2kg Methoprene Spot-on, shampoo, Combined with Slight variation in licensed topical spray and fipronil indications most licensed for environmental spray Dogs >8 weeks fleas, ticks, biting lice Dogs >2kg Nicotinic acetylcholine receptors agonist Furanicotinyl and chloronicotinyl Dinotefuran Spot-on Combination Combination product licensed (neonicotinoids) insecticides binds to post product with for fleas, ticks, also fly repellent synaptic nicotinic acetyl choline receptors pyriproxyfen and activity resulting in inhibition of cholinergic permethrin transmission and paralysis of parasites Dogs >7 weeks Dogs >1.5kg Imidocloprid Spot-on as Monotherapy licensed for fleas monotherapy or in Monotherapy and biting lice combination with Dogs >8 weeks Combination products have moxidectin or as Dogs <4kg broader activity and different collar or spot on with guidance flumethrin Nitenpyam Tablet Dogs no age Licensed for fleas specified Dogs >11kg Spinosyn derivatives activate nicotinic acetyl Spinosad Tablet Dogs >14 weeks Licensed for fleas choline receptors. Causes hyperactivity due to Dogs >1.3kg disrupting binding of acetyl choline in nicotinic acetyl choline receptors at postsynaptic cell that prevents repolarisation of the cell

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Mode of action Examples Canine formulation Age and Ectoparasite spectrum of minimum weight activity Sodium channel modulator Chloride channel activators Deltamethrin Collar Dogs >7 weeks Different products vary in license indications variably Selamectin (A) Spot-on treatment Dogs >6 weeks Licensed for fleas, ear licensed for control of fleas, Dogs <2.5kg mites, Sarcoptes scabiei, ticks, sandflies and mosquitoes Trichodectes canis Flumethrin Collar combined with Dogs >7 weeks Licensed for control of fleas, Avermectins (A)/Milbemycins (M) are agonists Moxidectin (M) Spot-on combined Dogs >7 weeks Licensed for fleas, biting lice, imidacloprid ticks, biting lice, sandflies to glutamate-gated chloride channels in flea with imidocloprid Otodectes cynotis, Sarcoptes Dogs >1kg Permethrin Spot-on also in (see Dinotefuran) Combination product licensed causing blockage of neurotransmission and (slight variation on scabiei, Demodex canis Pyrethroid group of drugs that work by combination with for fleas, ticks, also fly repellent paralysis licensed use may vary prolongation of opening of voltage-gated between products) other products, topical sodium channels in invertebrates, resulting in and environmental activity Oral product with Dogs >8 weeks Licensed for fleas, ticks, increased action potentials and neurotoxicity spray With imidocloprid Different products vary in pyrantel and sarolaner Dogs >1.25kg Dogs >7 weeks license indications variably Chitin biosynthesis inhibitors (juvenoid/IGR) Dogs >1.5kg licensed for control of fleas, ticks, biting lice and repellent Benzoylphenylurea derivative that inhibits Lufenuron Tablet with and Lufenuron only Licensed for fleas activity sandflies, mosquitoes, flea development through blocking chitin without milbemycin Dogs weaned stable flies production and egg hatch oxime puppies Dogs >2.3kg With Licensed for control of fleas, Dogs >8 weeks ticks 2GABA-gated chloride channel antagonist Dogs >1.2kg Fipronil Spot-on or spray – Dogs >8 weeks Slight variation in licensed Voltage dependent sodium channel blockers available as numerous Dogs >2kg indications most licensed for different products fleas, ticks, biting lice Inhibits sodium ion entry into nerve cells which Indoxacarb Spot-on also available Monotherapy Licensed for fleas 1) Phenylpyrazole that blocks invertebrate results in impaired nerve function, cessation of combined with Dogs >8 weeks GABA and glutamate gated chloride channels Also combined with juvenoids (S)- parasite feeding, paralysis and death permethrin Dogs >1.5kg needed for inhibition of nerve impulses leading methoprene and to hyperexcitability and neurotoxicity pyriproxyfen (see juvenoids) fipronil have been shown to be useful treatments. The selection investigation. In the dog it can be juvenile onset, which is of therapy often depends on the age of the animal and the usually found in dogs less than three years of age and adult 2) Isoxazoline potent antagonist of invertebrate Afoxolaner Tablet Dogs >8 weeks Licensed for use against fleas, GABA and glutamate gated chloride channels Dogs >2kg ticks, Demodex spp. Sarcoptes thickness of the coat. The biggest treatment challenges are onset, which is seen in older dogs and usually associated (receptor binding more potent than fipronil) scabiei generally found in puppies and kittens where the minimum age with some form of immunosuppression. Therapy for Fluralaner Tablet and spot-on Tablet and spot Licensed for use against fleas, and weight of administration of a licensed product influences demodicosis has evolved rapidly over the last few years. on ticks, Demodex spp. Sarcoptes treatment choice. While localised juvenile onset disease will resolve with Dogs >8 weeks scabiei Dogs >2kg minimal treatment in most cases, providing the dog or cat Lotilaner Tablet Dogs >8 weeks Licensed for fleas and ticks Sarcoptic mange (Sarcoptes scabiei) is systemically well, the more severe forms of the disease Dogs >1.3 kg This is a common highly pruritic, contagious ectoparasitic have in the past needed extended course of topical therapy Sarolaner Tablet Dogs >8 weeks Licensed against fleas, ticks, disease of dogs. It is a zoonosis and can be passed from with . Milbemycins, which includes moxidectin, Dogs >1.3kg Otodectes cynotis, Demodex dog to owner. These obligate parasites burrow through spp. and Sarcoptes scabiei (not avermectins), have activity against Demodex spp. the skin causing intense irritation, dramatic scaling and Several moxidectin products are licensed to treat demodex Juvenile hormone mimetic (juvenoid/IGR) usually severe self-inflicted trauma. The severity of the in the dog. Current recommendations suggest that lime Pyriproxyfen Spot-on, shampoo, Combined with Licensed for fleas, ticks, topical spray, collars fipronil (trio lesions is thought in part to be due to a hypersensitivity sulphur and amitraz have the biggest evidence base to Mimics of juvenile hormones to prevent larvae and environmental product with reaction to mite allergens in the skin. Lesions tend to be support their use in feline demodicosis. 5 Isoxazolines in the from completing metamorphosis spray dinotefuran below) located on relatively hairless areas such as the ear tips and form of afoxalaner, fluralaner and sarolaner are licensed Dogs >10 weeks the extensor aspects of the joints. S. scabiei is known to be indications for the therapy of canine demodicosis and Dogs >2kg highly prevalent in the fox population, as the mite is viable for recommended for use in therapy. 5 Fluralaner and sarolaner Methoprene Spot-on, shampoo, Combined with Slight variation in licensed topical spray and fipronil indications most licensed for several weeks o their host, fomite spread from fox to dog is as licenced feline ectoparasiticides may also have activity environmental spray Dogs >8 weeks fleas, ticks, biting lice thought to be a common means of transmission. The most against feline demodicosis. Dogs >2kg eective ectoparasiticides are those with a systemic mode of Nicotinic acetylcholine receptors agonist CLASSES OF ECTOPARASITICIDES AND THEIR action. Selamectin and moxidectin both have proven eicacy Furanicotinyl and chloronicotinyl Dinotefuran Spot-on Combination Combination product licensed SPECTRUM OF ACTIVITY (neonicotinoids) insecticides binds to post product with for fleas, ticks, also fly repellent and are licensed to treat scabies. The newer isoxazolines Chloride channel activators synaptic nicotinic acetyl choline receptors pyriproxyfen and activity in the form of afoxalaner, fluralaner and sarolaner are also resulting in inhibition of cholinergic permethrin This principal ectoparasiticide in this group is selamectin. transmission and paralysis of parasites Dogs >7 weeks licensed for the therapy of S. scabiei. Selamectin has a broad spectrum of activity against both Dogs >1.5kg endo and ectoparasites and has been demonstrated to Imidocloprid Spot-on as Monotherapy licensed for fleas Demodectic mange (Demodex spp.) monotherapy or in Monotherapy and biting lice be safe and eicacious in the control of naturally acquired combination with Dogs >8 weeks Combination products have Demodectic mange in the dog is principally caused by the flea infestations on dogs and cats presented as veterinary moxidectin or as Dogs <4kg broader activity and different obligate parasite Demodex canis. Other less common collar or spot on with guidance patients in Europe.6 It has also been shown to be highly flumethrin canine species of the parasite have been identified as eective in the treatment and prevention of flea infestations, Nitenpyam Tablet Dogs no age Licensed for fleas Demodex cornei a short surface-dwelling variant and without the need for supplementary environmental control specified Demodex injai a long serpent-shaped form. In the cat Dogs >11kg measures.7 However, its SOK is inferior to some licensed infestation is caused by Demodex cati and Demodex gatoi. Spinosyn derivatives activate nicotinic acetyl Spinosad Tablet Dogs >14 weeks Licensed for fleas adulticides and would not therefore be the author’s first Dogs >1.3kg Demodicosis is found in two forms either as localised choline receptors. Causes hyperactivity due to choice for flea allergic animals. Selamectin is licensed for disrupting binding of acetyl choline in nicotinic disease or generalised disease. It is a rare disease in the treatment of biting lice, ear mites and S. scabiei. In acetyl choline receptors at postsynaptic cell the cat but should still be eliminated as part of any skin that prevents repolarisation of the cell addition, clinical studies have shown it is eective as an o

Veterinary Ireland Journal I Volume 11 Number 1 41

Vet January 21.indd 41 23/12/2020 15:01 FOCUS > EQUINE

INTRODUCING Respira Bb

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Nobivac® Respira Bb suspension for injection for dogs contains Bordetella bronchiseptica fimbriae (88 - 399 Antigenic mass ELISA units) and is indicated for active THERE’S NOW AN EASIER immunisation of dogs against Bordetella bronchiseptica to reduce clinical signs of upper respiratory tract disease and bacterial shedding post infection. Legal category: ROI: POM NI: POM-V For further information about side effects, precautions, warnings and contra-indications please consult the product SPC, packaging, leaflets or: WAY TO PROTECT DOGS MSD Animal Health, Red Oak North, South County Business Park, Leopardstown, Dublin 18, Ireland. Tel: +353 (0)1 2970220. Email: [email protected] Web: www.msd-animal-health.ie AGAINST CANINE COUGH USE MEDICINES RESPONSIBLY SA-20-210 IE-NOV-201100003 NOV 2020 IE-NOV-201100003 SA-20-210 Protection unites us. NOV 2020 IE-NOV-201100003 SA-20-210

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COMPATIBLE: Can be given concurrently with many other Nobivac® vaccines, and a single dose can be used to boost immunity in Convenience dogs previously vaccinated with Nobivac® KC LONG LASTING: 12 months duration of immunity after primary and flexibility vaccination with Nobivac® KC

Contact your MSD Animal Health account manager to learn more about Nobivac® Respira Bb and our complete canine respiratory vaccine portfolio.

Nobivac® Respira Bb suspension for injection for dogs contains Bordetella bronchiseptica fimbriae (88 - 399 Antigenic mass ELISA units) and is indicated for active THERE’S NOW AN EASIER immunisation of dogs against Bordetella bronchiseptica to reduce clinical signs of upper respiratory tract disease and bacterial shedding post infection. Legal category: ROI: POM NI: POM-V For further information about side effects, precautions, warnings and contra-indications please consult the product SPC, packaging, leaflets or: WAY TO PROTECT DOGS MSD Animal Health, Red Oak North, South County Business Park, Leopardstown, Dublin 18, Ireland. Tel: +353 (0)1 2970220. Email: [email protected] Web: www.msd-animal-health.ie AGAINST CANINE COUGH USE MEDICINES RESPONSIBLY SA-20-210 IE-NOV-201100003 NOV 2020 IE-NOV-201100003 SA-20-210 Protection unites us. NOV 2020 IE-NOV-201100003 SA-20-210

Nobivac Respira DPS VIJ Ad.indd All Pages Vet January 21.indd 43 23/12/202021/12/2020 15:0111:11 SMALL ANIMAL I CONTINUING EDUCATION Table 2: Products available for the prevention and treatment of ectoparasites in cats. Mode of action Examples Feline formulation Age and minimum Ectoparasite spectrum of weight activity Chloride channel activators Selamectin (A) Spot-on treatment >6 weeks Licensed for fleas, Otodectes Avermectins (A)/Milbemycins (M) are agonists – several licensed >2.5kg cynotis, Felicola subrostratus to glutamate-gated chloride channels in flea products, (available causing blockage of neurotransmission and combined with paralysis sarolaner as a spot on see below) Moxidectin (M) Spot-on combined >9 weeks Licensed for fleas, Otodectes with imidocloprid >1kg cynotis, Notoedres cati (slight variation on licensed use may vary between products) Spot-on combined >9 weeks >1.2kg Combined product fleas, ticks, with fluralaner Otodectes cynotis Chitin biosynthesis inhibitors (juvenoid/IGR) Benzoylphenylurea derivative that inhibits Lufenuron Two sizes of injection 40mg cats and Licensed for fleas and flea development through blocking chitin 40mg and 80mg weaned kittens treatment of flea allergic production and egg hatch (oral solution to be <4kg dermatitis withdrawn) 80mg cats and weaned kittens >4kg 2GABA-gated chloride channel antagonist 1) Phenylpyrazole that blocks invertebrate Fipronil Spot-on or spray – Spot on GABA and glutamate gated chloride channels available as numerous >2months needed for inhibition of nerve impulses leading different products >1kg Slight variation in licensed to hyperexcitability and neurotoxicity with differing age and Spray >2 days indications most licensed for weight guidance fleas, ticks, biting lice Several spot-on >8 weeks products combined >0.5-1kg with juvenoid (S)- methoprene and (see juvenoids) Spot-on combined >10 weeks with juvenoid >1kg pyriproxyfen (see juvenoids) 2) Isoxazoline potent antagonist of invertebrate Fluralaner Spot on >9 weeks Licensed for fleas, ticks and GABA and glutamate gated chloride channels >1.2kg Otodectes cynotis (receptor binding more potent than fipronil) Combined product with moxidectin Lotilaner Tablet >8 weeks Licensed for fleas and ticks >0.5kg Product not recommended against ticks in cats <5 months Sarolaner Spot-on combined >8 weeks Licensed for fleas, ticks, with selamectin >1.25kg Otodectes cynotis, Felicola subrostratus Juvenile hormone mimetic (juvenoid/IG) Mimics of juvenile hormones to prevent larvae Pyriproxyfen Spot-on combined >10 weeks Licensed for fleas, ticks from completing metamorphosis with fipronil >1kg Spot-on combined >7 weeks Licensed for fleas with dinotefuran >0.6kg Methoprene Numerous spot-on >8 weeks Slight variation in licensed combinations with >0.5-1kg indications most licensed for fipronil (differing weight fleas, ticks, biting lice recommendations

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Nicotinic acetylcholine receptors agonist Furanicotinyl and chloronicotinyl Dinotefuran Spot-on combined >10 weeks Licensed for fleas (neonicotinoids) insecticides binds to post with pyriproxyfen >1kg synaptic nicotinic acetyl choline receptors resulting in inhibition of cholinergic transmission and paralysis of parasites Imidocloprid Spot-on monotherapy >8 weeks Licensed for fleas and biting lice Numerous products > 9 weeks Licensed for fleas, Otodectes combined with >1kg cynotis, Notoedres cati moxidectin slight variations in licensing Collar combined with >10 weeks Licensed for fleas and ticks flumethrin Tablet >4 weeks Licensed for fleas >1kg Spinosyn derivatives activate nicotinic acetyl Spinosad Tablet >14 weeks Licensed for fleas choline receptors. Causes hyperactivity due to >1.2kg disrupting binding of acetyl choline in nicotinic acetyl choline receptors at postsynaptic cell that prevents repolarisation of the cell Sodium channel modulator Pyrethroid group of drugs that work by Flumethrin Collar combined with >10 weeks Licensed for fleas, ticks prolongation of opening of voltage-gated imidacloprid sodium channels in invertebrates, resulting in increased action potentials and neurotoxicity. Only flumethrin is considered safe in cats Voltage dependent sodium channel blockers Inhibits sodium ion entry into nerve cells which Indoxacarb Spot-on >8 weeks Licensed for fleas results in impaired nerve function, cessation of >0.6kg parasite feeding, paralysis and death

licensed against sucking lice, Neotrombibula autumnalis and used as component of ectoparasiticide collars. While collars Cheyletiella spp.3,8 may be easy ways to achieve ectoparasite control both actives used in collars have good activity against fleas but Nicotinic acetylcholine receptor agonists a slow onset of action, making them better for routine flea Nicotinic acetylcholine receptor agonists (NARAs) control rather than for flea-allergic animals.12 include the neonicotinoids (dinotefuran, imidocloprid and nitenpyam) as well as the spinosyn derivatives (spinosad, GABA gated chloride channel antagonists spinetoram). All of the products in this group have a rapid This group of drugs contains the older phenylpyrazoles which SOK and are excellent rapid acting flea adulticides. 9 Their includes fipronil and the newer class of isoxazolines containing rapid SOK makes them good choices for flea allergic the actives afoxolaner, fluralaner, lotilaner and sarolaner. Fipronil animals. However, they are relatively narrow spectrum with as a monotherapy has a slow SOK. In one study it achieved no acaricidal action, they are therefore often combined a speed of kill of only 46.5% in eight hours9 and in another it with other actives to give a broader spectrum ectoparasitic took a full 12-18 hours to reach 100% eicacy.13 cover (see Table 1). The isoxazoline group of drugs was launched in 2014 in Indoxacarb is the flea adulticides within this class of drugs. the US with afoxolaner. This was closely followed by oral Indoxacarb has excellent adulticide activity against fluralaner, sarolaner, topical fluralaner and lotilaner. While C. felis to control flea infestation and clinical signs in a high the precise labelling for each product diers in its license proportion of dogs and cats with flea allergy dermatitis applications as far as spectrum of activity, minimum age (FAD) without the need for other drugs.10 It also provides of administration, method of administration, minimum superior and effective environmental flea control in body weight and dosing interval (see Table 2) all of the heavily infested environments compared to fipronil (S) products within this group are approved for treatment and methoprene topical formulations.11 It has no acaricidal prevention of flea infestations and for ticks in dogs and activity as a monotherapy but is available with permethrin cats. The safety of all of these products and their ability to for dogs giving an increased licensed indication for ticks. treat fleas has been well documented. Afoxalaner has been shown to be eective in killing C. felis14-16 and C. canis.17 Sodium channel modulators Fluralaner has shown similar benefits as both an oral 18 and This group of drugs contain actives such as permethrin, topical19 formulation to control flea infestations and also the deltamethrin and flumethrin. The latter two drugs are usually signs of flea allergic dermatitis in dogs and cat.19-21 A study

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undertaken by Dryden (2016) compared the activity of convenience of oral dosing also makes the isoxazolines afoxalaner and fluralaner to control flea populations, reduce excellent choices for the therapy of mite infestations. pruritus and minimize dermatological lesions in naturally infested dogs and found both were highly eicacious with This article refers to the UK situation, which is broadly little dierence between the two.22 Sarolaner has been similar to Ireland. shown to be eective in the treatment of fleas in pets 23,24 and flea allergic dermatitis25 as has lotilaner.26-28 Isoxazalines are REFERENCES absorbed systemically, the onset of action of all products is 1. Abdullah S, Helps C, Tasker S, Newbury H, Wall R. two to four hours with close to 100% of fleas killed within eight Pathogens in fleas collected from cats and dogs: hours.29 Their speed of kill together with their safety profile and distribution and prevalence in the UK. Parasit Vectors. persistence makes these the drugs of choice in the author’s 2019;12(1):71. hands for FAD in the dog and cat. 2. Rust MK. The Biology and Ecology of Cat Fleas and Advancements in Their Pest Management: A Review. Although there is evidence in the literature that all have good Insects. 2017;8(4). activity against mites only afoxalaner, fluralaner and sarolaner 3. Fisher MA, Shanks DJ. A review of the off-label use of are currently licenced as acaracides.30-33 However, all four drugs selamectin (Stronghold/Revolution) in dogs and cats. represent on the basis of supporting literature, useful choices Acta Vet Scand. 2008;50:46. for a wide range of ectoparasites in dogs and cats. 4. Lecru LA, Combarros D, Castilla-Castano E, Navarro C, Cadiergues MC. Treatment of Harvest Mite Infestation Juvenoids in Dogs Using a Permethrin 54.5% and Fipronil Two form of juvenoids or insect growth regulators (IGRs) 6.1% (Effitix®) Topical Spot-On Formulation. Vet Sci. are available for the management of flea infestations 2019;6(4). in the dog. These are the chitin biosynthesis inhibitors 5. Mueller RS, Rosenkrantz W, Bensignor E, Karas-Tecza (lufenuron) and the juvenile hormone mimetics J, Paterson T, Shipstone MA. Diagnosis and treatment (methoprene and pyriproxyfen). As numerous studies have of demodicosis in dogs and cats: Clinical consensus shown, products such as the isoxazolines and the NARAs guidelines of the World Association for Veterinary have a rapid and complete SOK before fleas can feed and Dermatology. Vet Dermatol. 2020;31(1):5-27. lay eggs, hence breaking the life cycle, the use of juvenoids 6. Benchaoui HA, Clemence RG, Clements PJ, Jones RL, Watson P, Shanks DJ, et al. Efficacy and safety of as part of a flea control programme may seem superfluous. selamectin against fleas on dogs and cats presented as However recent studies have shown a marked synergism veterinary patients in Europe. Vet Parasitol. 2000;91(3- between IGRs and adulticides.34 It would seem that 4):223-32. IGRs reduce the time required to control fleas within the 7. Shanks DJ, Rowan TG, Jones RL, Watson P, Murphy environment and also lessen the likelihood that MG, Smith DG, et al. Efficacy of selamectin in the 35 resistance may develop. Several studies have shown that treatment and prevention of flea (Ctenocephalides felis drugs such as lufenuron,36 methoprene and pyriproxyfen37 felis) infestations on dogs and cats housed in simulated produce significant increases in adult mortality as well home environments. Vet Parasitol. 2000;91(3-4):213-22. as preventing flea development. Therefore, because of 8. Gunnarsson L, Christensson D, Palmer E. Clinical the multiple effects that IGRs have on both immature and efficacy of selamectin in the treatment of naturally adult fleas, the incorporation of an IGR into any treatment acquired infection of sucking lice (Linognathus regime will increase the efficacy over the use of an setosus) in dogs. J Am Anim Hosp Assoc. adulticide alone.2 2005;41(6):388-94. 9. Schenker R, Tinembart O, Humbert-Droz E, Cavaliero T, Yerly B. Comparative speed of kill between nitenpyram, SUMMARY fipronil, imidacloprid, selamectin and cythioate against The veterinary surgeon has more choice of ectoparasite adult Ctenocephalides felis (Bouche) on cats and dogs. treatments than ever before. With such a bewildering Vet Parasitol. 2003;112(3):249-54. selection of tablets, collars, sprays and spot-ons, it is 10. Fisara P, Sargent RM, Shipstone M, von Berky A, von difficult to know which are the best products to prescribe. Berky J. An open, self-controlled study on the efficacy Many aspects should be considered when selecting of topical indoxacarb for eliminating fleas and clinical therapy. As well as the obvious reasons, such as safety signs of flea-allergy dermatitis in client-owned dogs in and efficacy; features, such as cost, ease of application Queensland, Australia. Vet Dermatol. 2014;25(3):195- and convenience, can influence owner compliance, e49. which is important in sustaining a treatment programme. 11. Dryden MW, Payne PA, Smith V, Chwala M, Jones E, Products such as fipronil and imidocloprid are available Davenport J, et al. Evaluation of indoxacarb and fipronil as NFA-VPS and still represent good low-cost options for (s)-methoprene topical spot-on formulations to control flea control. However, more recent adulticides such as flea populations in naturally infested dogs and cats in the nicotinic acetylcholine receptors agonists (NARAs) private residences in Tampa FL. USA. Parasit Vectors. and the isoxazalines with their rapid SOK are superior in 2013;6:366. 12. Horak IG, Fourie JJ, Stanneck D. Efficacy of slow-release the control of FAD. The broad spectrum of action and the collar formulations of imidacloprid/flumethrin and

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deltamethrin and of spot-on formulations of fipronil/ 25. Six RH, Geurden T, Packianathan R, Colgan S, Everett (s)-- methoprene, dinotefuran/pyriproxyfen/permethrin WR, Grace S, et al. Evaluation of the effectiveness of a and (s) -methoprene/amitraz/fipronil against novel oral formulation of sarolaner (Simparica) for the Rhipicephalus sanguineus and Ctenocephalides felis treatment and control of fleas on dogs. Vet Parasitol. felis on dogs. Parasit Vectors. 2012;5:79. 2016;222:18-22. 13. Cruthers L, Slone RL, Guerrero AJ, Robertson-Plouch 26. Karadzovska D, Chappell K, Coble S, Murphy M, C. Evaluation of the speed of kill of fleas and ticks with Cavalleri D, Wiseman S, et al. A randomized, controlled Frontline Top Spot in dogs. Vet Ther. 2001;2(2):170-4. field study to assess the efficacy and safety of lotilaner 14. Beugnet F, deVos C, Liebenberg J, Halos L, Fourie flavored chewable tablets (Credelio) in eliminating J. Afoxolaner against fleas: immediate efficacy and fleas in client-owned dogs in the USA. Parasit Vectors. resultant mortality after short exposure on dogs. 2017;10(1):528. Parasite. 2014;21:42. 27. Cavalleri D, Murphy M, Seewald W, Drake J, Nanchen 15. Dryden MW, Smith V, Chwala M, Jones E, Crevoiserat L, S. A randomised, blinded, controlled field study to McGrady JC, et al. Evaluation of afoxolaner chewables assess the efficacy and safety of lotilaner tablets to control flea populations in naturally infested dogs in (Credelio) in controlling fleas in client-owned dogs in private residences in Tampa FL, USA. Parasit Vectors. European countries. Parasit Vectors. 2017;10(1):526. 2015;8:286. 28. Cavalleri D, Murphy M, Seewald W, Nanchen S. A 16. Hunter JS, 3rd, Dumont P, Chester TS, Young DR, randomized, controlled field study to assess the Fourie JJ, Larsen DL. Evaluation of the curative and efficacy and safety of lotilaner (Credelio) in controlling preventive efficacy of a single oral administration fleas in client-owned cats in Europe. Parasit Vectors. of afoxolaner against cat flea Ctenocephalides felis 2018;11(1):410. infestations on dogs. Vet Parasitol. 2014;201(3-4):207- 29. Datz C. Isoxazolines. Plumb's therapeutic brief. 11. 2018;April 2018:65-7. 17. Dumont P, Gale B, Chester TS, Larsen DL. Curative 30. Lebon W, Beccati M, Bourdeau P, Brement T, Bruet and preventive efficacy of orally administered V, Cekiera A, et al. Efficacy of two formulations of afoxolaner against Ctenocephalides canis infestation afoxolaner (NexGard(R) and NexGard Spectra(R)) for in dogs. Vet Parasitol. 2014;201(3-4):212-5. the treatment of generalised demodicosis in dogs, 18. Meadows C, Guerino F, Sun F. A randomized, in veterinary dermatology referral centers in Europe. blinded, controlled USA field study to assess the Parasit Vectors. 2018;11(1):506. use of fluralaner tablets in controlling canine flea 31. Petersen I, Chiummo R, Zschiesche E, Karas-Tecza J, infestations. Parasit Vectors. 2014;7:375. Rapti D, Roepke R, et al. A European field assessment 19. Ranjan S, Young D, Sun F. A single topical fluralaner of the efficacy of fluralaner (Bravecto((R))) chewable application to cats and to dogs controls fleas for 12 and spot-on formulations for treatment of dogs weeks in a simulated home environment. Parasit with generalized demodicosis. Parasit Vectors. Vectors. 2018;11(1):385. 2020;13(1):304. 20. Fisara P, Shipstone M, von Berky A, von Berky J. A 32. Six RH, Becskei C, Mazaleski MM, Fourie JJ, Mahabir small-scale open-label study of the treatment of canine flea allergy dermatitis with fluralaner. Vet SP, Myers MR, et al. Efficacy of sarolaner, a novel oral Dermatol. 2015;26(6):417-20, e97-8. isoxazoline, against two common mite infestations 21. Crosaz O, Chapelle E, Cochet-Faivre N, Ka D, in dogs: Demodex spp. and Otodectes cynotis. Vet Hubinois C, Guillot J. Open field study on the efficacy Parasitol. 2016;222:62-6. of oral fluralaner for long-term control of flea allergy 33. Snyder DE, Wiseman S, Liebenberg JE. Efficacy of dermatitis in client-owned dogs in Ile-de-France lotilaner (Credelio), a novel oral isoxazoline against region. Parasit Vectors. 2016;9:174. naturally occurring mange mite infestations in 22. Dryden MW, Canfield MS, Kalosy K, Smith A, dogs caused by Demodex spp. Parasit Vectors. Crevoiserat L, McGrady JC, et al. Evaluation of 2017;10(1):532. fluralaner and afoxolaner treatments to control 34. Rust MK, Hemsarth WLH. Synergism of Adulticides flea populations, reduce pruritus and minimize and Insect Growth Regulators Against Larval Cat dermatologic lesions in naturally infested dogs in Fleas (Siphonaptera: Pulicidae). J Med Entomol. private residences in west central Florida USA. Parasit 2019;56(3):790-5. Vectors. 2016;9(1):365. 35. Blagburn BL, Dryden MW. Biology, treatment, and 23. Becskei C, De Bock F, Illambas J, Mahabir SP, control of flea and tick infestations. Vet Clin North Am Farkas R, Six RH. Efficacy and safety of a novel oral Small Anim Pract. 2009;39(6):1173-200, viii. isoxazoline, sarolaner (Simparica) in the treatment 36. Dean SR, Meola RW, Meola SM, Sittertz-Bhatkar H, of naturally occurring flea and tick infestations in Schenker R. Mode of action of lufenuron in adult dogs presented as veterinary patients in Europe. Vet Ctenocephalides felis (Siphonaptera: Pulicidae). J Med Parasitol. 2016;222:49-55. Entomol. 1999;36(4):486-92. 24. Cherni JA, Mahabir SP, Six RH. 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