Practical Parasitology: The Flea-Infested Pet Dealing with flea-infested pets has never been easier-or more complicated. At this time, atleast 20 active ingredients are commonly used in prescription flea control products in the unitedStates, with numerous other ingredients appearing in various over-the-counter products. Despitethis wealth of options, providing practical and effective suggestions for flea control to clients canstill be a frustrating and overwhelming experience. This article provides an overview of some ofthe clinically relevant features of currently available flea control agents (Table 1). A subsequentarticle will discuss how to use client and patient information to help select an optimal treatmentcontrol program.Oct - Nov 2020 08

PYRETHRIN AND PYRETHROIDS be avoided completely for dogs that live with cats or as environmental treatments in homes withThese are the oldest flea control products cats.4currently in common use. Both pyrethrin andpyrethroids work by disrupting insect nerve Resistance to pyrethrins and pyrethroids has beensodium channels.1 They are active against adult reported in both colonized flea strains and wild-fleas but have no efficacy against immature stages. caught fleas.6,7 Resistance may be associated withPyrethrin is derived from the chrysanthemum mutations in a gene coding for neural sodiumplant.2 It is generally very safe when applied channels.8 These mutations, which are commonlyproperly, even in young cats.1 Pyrethrin has a very referred to as kdr (knockdown resistance) or superquick “knock-down” effect but minimal residual kdr mutations, are widely distributed throughoutactivity. It is readily removed by water exposure. flea colonies and in field-collected fleas.9 As aPyrethrin products are often formulated to include result, the effectiveness of this class ofa synergist, such as piperonyl butoxide. These compounds may be reduced in some areas,synergists are typically well tolerated in dogs and especially when they are not combined with othercats when used at label doses. therapeutic agents.However, pyrethrins and many synergists may be NEONICOTINOIDShighly toxic to other pet species, such as fish andamphibians.2,3 This class of agents acts by binding to insect acetylcholine receptor sites.1 This inducesPyrethroids are synthetic pyrethrins. Compared inhibition of insect nervous system function, withwith pyrethrin, these products have a slightly subsequent paralysis and death.slower onset of action but significantly betterresidual and repellent effects. Examples of this Imidaclopridclass include permethrin and cyphenothrin. This product has a rapid onset of action.10,11 ItPyrethroids are often combined with other agents primarily targets adult fleas, and it is oftento take advantage of the pyrethroids’ repellent combined with an insect growth regulator toeffects and efficacy against ticks. Examples of provide efficacy against immature flea stages.1these products include K9 Advantix (bayerdvm Imidacloprid is available as a spoton product,.com), Certifect, Vectra 3D (vectrapet.com), and either by itself or in combination with permethrinActivyl Tick Plus (us.activyl.com). As a general (K9 Advantix),flumethrin (Seresto collar;rule, pyrethroids have relatively poor resistance to seresto.com), or moxidectin (Advantage Multi;water exposure. bayerdvm.com). Imidacloprid is generally very well tolerated by most individuals. ProductsUnfortunately, most pyrethroids are extremely containing imidacloprid alone (or imida-toxic to cats.1 Notable exceptions include cloprid/insect growth regulator alone) can beflumethrin and etofenprox, which appear to be applied up to once weekly for aggressive fleawell tolerated by most cats. Signs of pyrethroid control.1 In my experience, imidacloprid has poorintoxication include depression, coma, seizures, water resistance and must be reapplied afterhypersalivation, muscle twitching or tremors, and bathing or water immersion. The imidaclopridhyperthermia. Severe or untreated intoxication flumethrin collar appears to replenish the productmay be fatal.4 Many cases of pyrethroid on the pet, making this product better suited forintoxication come from mistaken or intentional patients that are bathed or swim regularly.12application of dog-only flea control formulations. However, this does shorten the expected lifespanHowever, a few cases of toxicity have been of the collar. The efficacy of the collar is generallyreported in cats that came into contact with treated very good, which represents a substantialdogs soon after application.5 For this reason, improvement over most older flea collars (typicallyclient education is critical when dispensing containing organophosphates), whichpyrethroid-containing products to households demonstrated low efficacy.13,14 the olderthat include cats. Alternatively, these products may formulation. Oct - Nov 2020 08

Nitenpyram Spinosad should not be given with extralabel dosesThis agent is available as a no flavored oral tablet of ivermectin because coadministration has been(Capstar). It has a very rapid onset of activity associated with seizures, ataxia, twitching, andagainst adult fleas but a short duration of action other neurologic signs.16(approximately 24 to 48 hours).1 Because of thespeed of onset, it is well suited for rapid Spinetoram is a semisynthetic insecticidedecontamination of animals before or after produced by chemical modification of thehospitalization or boarding or after trips to areas naturally occurring spinosyns J and L.17 It issuch as dog parks. The short duration of action labeled for use in cats only (Cheristin;makes it poorly suited for use as a primary flea cheristin4cats.com).18 It is provided as a spotoncontrol agent, but it can be used as often as daily if formulation, which may be easier for some clientsdesired.1 For this reason, it is sometimes used daily to administer than oral tablets. It is normally wellfor a short period to get a “head start” on flea tolerated, although it may be associated withdepopulation in heavily contaminated vomiting in some cats. Application-site dermatitisenvironments. It has no larvicidal or ovicidal has been reported, although this is less commonproperties.1 than with the older formulation.Dinotefuran ISOXAZOLINESThis agent is primarily active against adult fleas.1 Itis available in a spot-on formulation in These products selectively inhibit insect gamma-combination with an insect growth regulator aminobutyric acid (GABA)- and glutamate-gatedeither with (Vectra 3D) or without (Vectra) chloride channels. This induces hyperexcitationpermethrin. It is labeled for application once and uncontrolled central nervous system activity,monthly. This agent has moderate to good resulting in death of the insect.1 There areresistance to water, although it is suggested that currently three agents in this category: afoxolaner,the pet not be bathed or allowed to swim forseveral hours after application.15 Nonetheless, it is uralaner, and sarolaner. Because the agents areprobably not ideal for a dog that swims or is very similar in many respects, they will bebathed very frequently. discussed together.Spinosad/Spinetoram Afoxolaner (NexGard; nexgardfordogs.com),These two products are closely related. Spinosad is fluralaner (Bravecto; us.bravecto.com), anda naturally occurring mixture of spinosyns A and sarolaner (Simparica; simparica.com) are allD, which are produced by Saccharopolyspora available as flavored chewable oral tablets labeledspinosa, a soil-dwelling actinomycete for dogs only; fluralaner is also available in a topicalbacterium.16 It is available as a flavored (pork) formulation for both cats and dogs.20–22tablet. It should be given with food.16 The same Afoxolaner and sarolaner are given monthly,formulation (Comfortis; comfortis.com) is used in whereas fluralaner is given every 3 months.20–22cats and dogs, although the feline version reflects Because these tablets are flavored with food-basedthe need for a higher dose per body weight than in ingredients (soy or pork), they are not suitable fordogs (50 mg/kg vs 30 mg/kg, respectively). It is administration during food allergy elimination dietlabeled for once-monthly administration. trials, and they may or may not be tolerated by food-allergic individuals. However, because ofThe major side effect in both species is vomiting, fluralaner’s extended duration of action, it may bewhich can be treatment limiting in some given at the beginning of an elimination diet, withindividuals.16 efficacy expected to continue through the 10- to 12-week duration of the trial.Spinosad should be administered with caution (oravoided entirely) in dogs with preexisting seizure Afoxolaner and sarolaner may be given with ordisorders because seizures have been associated without food, but the bioavailability of fluralanerwith administration of this drug in these dogs.16 is best when the agent is given with food.20However, this effect has not been reported in cats. All 3 agents have very good efficacy against adult fleas and may also have clinically significant Oct - Nov 2020 08

inhibition of flea reproduction. They are also Fipronilefficacious against many species of ticks, including This agent belongs to the phenylpyrazole class.1Ixodes scapularis, Dermacentor variabilis, Like the isoxazolines, it acts by blocking GABA- andRhipicephalus sanguineus, and Amblyomma glutamate-gated chloride channels, causingamericanum.20–22 However, fluralaner must be hyperexcitation and death. It is available as both agiven every 2 months for maximal efficacy against spray and a spot-on. Fipronil is available inA americanum.20 Sarolaner also has efficacy numerous formulations, many of which includeagainst A maculatum.22 other agents (such as permethrin or amitraz). It is labeled for once-monthly use. Fipronil kills adultAll of the agents appear to have very good efficacy fleas and is typically formulated with an insectagainst canine demodicosis.23–25 Evidence growth regulator. Some reports suggest that thisshows that they are also effective against agent may be losing efficacy, at least against certainSarcoptes, although whether this is reliable enough strains of fleas.31 Fipronil is somewhat waterto permit diagnostic therapy remains to be resistant but may not hold up if the patient requiresseen.26–28 Sarolaner has also been demonstrated frequent bathing or swims frequently.to be efficacious against Otodectes species.25 IndoxacarbOverall, the 3 agents are well tolerated, with This agent belongs to the oxadiazine pesticide class.vomiting being the most common adverse It is considered a pro-insecticide because it requireseffect.20–22 Afoxolaner should be given with activation by insect enzymes to become effective.1caution in animals with preexisting seizure Once activated, it blocks sodium channels, resultingdisorders, as breakthrough seizures have been in flea paralysis and death. Indoxacarb has goodreported.21 Seizures, ataxia, and trembling have water resistance but may not be sufficient in patientsbeen reported with sarolaner and with topical (but that require very frequent bathing or swimnot oral) fluralaner in dogs.20,22 Similar reactions frequently. Indoxacarb is available as a spot-onhave not been reported in cats with topical formulation, both on its own (Activyl) and withfluralaner. permethrin (Activyl Tick Plus). This product is normally well tolerated, but there have beenThe oral formulations of all agents are expected to anecdotal reports of seizures, neurologic signs, andbe waterproof. Topical fluralaner is expected to be occasional application-site dermatitis (of varyingvery water resistant after 3 days.20,* severity) in both cats and dogs.MISCELLANEOUS ACTIVE Insect Growth/Development RegulatorsINGREDIENTS Two classes of insect growth/development regulators have been registered for use as flea controlSelamectin products: juvenile hormone analogs (methoprene,This agent is an avermectin, similar to pyriproxyfen) and chitin synthesis inhibitorsivermectin.1,29 It activates insect glutamate-gated (lufenuron).1 These agents have no adulticidalchloride channels, which causes paralysis and effects but prevent the development or maturationeventual death of the fleas. It is marketed as a spot- of immature flea stages. They are not well suited foron product for both cats and dogs. It is primarily use as sole flea control products but are commonlyused for its heartworm preventive and flea control added to formulation of agents with adulticidalproperties but also has label claims against therapy to provide broad, multi–life stage control.Otodectes, Dermacentor, and Sarcoptes species indogs and Otodectes, Toxocara, and Ancylostoma CONCLUSIONSspecies in cats.29 It inhibits development of Today’s veterinary practitioner has more choicesimmature flea stages.30 Unlike some other than ever before when it comes to flea control.avermectins, selamectin can be administered to Nonetheless, there is still no single product that isivermectin-sensitive dogs (although salivation and ideal for use under all circumstances. effectiveataxia have been reported with extralabel dose formulation of a flea control program requires aadministration in these breeds).29 Selamectin is thorough understanding of the available productssystemically absorbed and is essentially and of the individual client and patient situation. Inwaterproof after 2 hours. the next article, I will discuss key factors that will allow the practitioner to select the right product for the patient.