How Do Flea Control Products Kill Fleas?

You have asked...There are so many products available for flea control; what are the differences between topical and oral therapeutics?

Topical and oral therapeutics have revolutionized flea control for domestic cats and dogs. In many cases, these new products have eliminated the need to treat indoor and outdoor environments; helped manage flea-allergic dermatitis; and controlled other arthropods, such as ticks and mites. This article expands on reviews of topically and orally administered flea products<sup1–3sup> (Table 1) and discusses whether the active ingredients must be ingested or come into direct contact with fleas.

CONTACT VS INGESTIONMore traditional treatments (such as shampoos, dusts, and sprays) contain carbaryl, permethrin, and synergized pyrethrins and insect growth regulators (ie, methoprene and pyriproxyfen) and are designed to work by contact. Some of these treatments are directed at fleas; with others, the fleas contact residual deposits and are killed.

However, in the past 10 years new chemistries have provided the clinician and pet owner with additional choices (Table 2). Speed of kill and the inhibition of feeding by adult fleas are especially important as they relate to fast knockdown and prevention of flea feeding. The faster an active ingredient inhibits feeding and kills the fleas, the more likely it will prevent flea-allergic dermatitis.

Although many articles have discussed the efficacy of various products, relatively few have addressed whether these therapies kill fleas through contact (ie, topical activity) or ingestion of the toxicant.

TOPICAL AGENTSTopical applications of dinotefuran, fipronil, imidacloprid, metaflumizone, and pyriprole spread rapidly over the hair coat within 24 to 48 hours (Figure 1). They are distributed in the skin and stored in the sebaceous glands. The hair coat is toxic to fleas for 30 to 60 days, depending on the active ingredient.

F

ipronil & ImidaclopridThese insecticides are extremely active against adult fleas; typically < 1 ng is required to kill 50% of adult fleas. Studies with a radiolabeled fipronil showed that it was found mainly in the sebaceous glands and epithelial layers.⁴ Other studies also support the premise that the active ingredient is on the skin and hair. Levels of imidacloprid in serum were below the lowest effective concentration of 0.1 mg/L5; analyses of hair and skin showed metaflumizone values 3 orders of magnitude higher than levels in plasma.<sup6 sup> 

Some studies suggest that repeated or long-term exposures to fipronil or imidacloprid may pose health risks to individuals coming into contact with treated pets.^7,8 However, a recent study at the University of California–Riverside showed that fipronil transfer to humans from treated hair coats was undetectable in human urine.⁹

Figure 1. Migration of a fluorescent dye added to fipronil to the neck of a dog: Application (A), 5 hours after application (B), and 24 hours after applicaton (C)

SelamectinSelamectin is also delivered by topical application, but this novel avermectin is absorbed and found in the plasma. Concentrations peak at a mean (standard deviation) of 12.72 ± 5.13 mcg/mL for male dogs and 0.87 ± 0.85 ng/mL for female dogs in about 5 days.¹⁰ It is also effective in killing the chewing lice Trichodectus canis (dogs) and Felicola subrostratus (cats), which might suggest some activity upon contact. Treated hair is toxic to fleas, albeit very slowly.¹¹ The agent may be absorbed in the basal layer of the epidermis and released with natural oils onto the skin.

ORAL TREATMENTSOrally administered treatments include lufenuron (an insect growth regulator), nitenpyram, and spinosad. These agents’ modes of action differ considerably.

LufenuronLufenuron is taken up during feeding and disrupts the reproductive capabilities of adult fleas; adult females fail to produce viable eggs. The unabsorbed lufenuron passes through the flea digestive system and is excreted in the fecal blood droplets. This treated fecal material is toxic to developing larvae.

Nitenpyram & SpinosadIn contrast, nitenpyram and spinosad are toxic to adult fleas. Plasma concentrations of the neonicotinoid nitenpyram peak within 30 minutes in cats and dogs.¹² Ingestion produces rapid cessation of feeding and knockdown of fleas. The effects persist for up to 48 hours after treatment. Spinosad, a fermentation product of the actinomycete Saccharopolyspora spinosa, contains the active ingredients spinopsyns A and D; unlike nitenpyram, it is effective for 30 days. Topical sprays and pour-on treatments are active against chewing lice on cattle (Bovicola bovis), suggesting that there may be some contact activity as well.¹³

THERAPEUTIC MODES OF ACTIONThe ability of topical and oral therapies to control fleas depends on their unique properties and modes of action. The mode of action of the active ingredients dictates the speed at which fleas are immobilized and feeding is inhibited, not necessarily the route by which the ingredients are delivered. The wide range of active ingredients in these revolutionary therapies ensures that we will have effective flea control products for years to come.

HOW DO FLEA CONTROL PRODUCTS KILL FLEAS? • Michael K. Rust

References

1. Toxicology of newer pesticides for use in dogs and cats. Hovda LR, Hooser SB. Vet Clin Small Anim 32:455-467, 2002.2. Advances in the control of Ctenocephalides felis (cat flea) on cats and dogs. Rust MK. Trends Parasitol 21:232-336, 2005.

1. Biology, treatment and control of flea and tick infestations. Blagburn BL, Dryden MW. Vet Clin Small Anim 39:1173-1200, 2009.4. Skin distribution of fipronil by microautoradiography following topical application to the beagle dog. Cochet P, Birckel P, Bromet-Pettit M, et al. Eur J Drug Metab Pharmacokinet 22:211-216, 1997.

2. Flea Biology and Control. Krämer F, Mencke N—Berlin: Springer, 2001.

3. Pharmacokinetics of metaflumizone and amitraz in the plasma and hair of dogs following topical application. DeLay RL, Lacoste E, Mezzasalma T, Blond-Riou F. Vet Parasitol 150:251-257, 2007.

4. Human exposure to fipronil from dogs treated with Frontline. Jennings KA, Canerday TD, Keller RJ, et al. Vet Human Toxicol 44:301-303, 2002.8. Human exposure to imidacloprid from dogs treated with Advantage. Craig MS, Gupta RC, Candery TD, Britton DA. Toxic Mechanisms Methods 15:287-291, 2005.9. Determinants of human exposure to fipronil following use as a topical flea and tick treatment of companion animals [PhD dissertation]. Dyk MB. Riverside, California: University of California–Riverside, 2009.10. Pharmacokinetics of selamectin following intravenous, oral and topical admistration in cats and dogs. Sarasola P, Jernigan AD, Walker DK, et al. J Vet Pharmacol Ther 25:265-272, 2002.11. Evaluation and development of spinosyns to control ectoparasites on cattle and sheep. Kirst HA, Creemer LC, Naylor SA, et al. Curr Top Medicinal Chem 2:675-699, 2002.

5. Efficacy of nitenpyram as a systemic flea adulticide in dogs and cats. Dobson P, Tinembart O, Fisch RD, Junquera P. Vet Rec 147:709-713, 2000.13. Efficacy of selamectin against biting lice on dogs and cats. Shanks DJ, Gautier R, McTier IL, et al. Vet Rec 152:234, 2003.