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InFocus Flea control offers better protection for pets, humans from diseases Advancements in technology enable veterinarians, owners to eliminate fleas at most stages of development By Lora Ballweber, DVM, MS CONTRIBUTING AUTHOR t one time fleas were an every day fact of life – human infestations were a result of living in close proximity to livestock and other animals as well as generally unkempt environments that attracted rats and other vermin.Humans were quite accustomed to,although maybe not happy about infestions with these ectoparasites,even going so far as to write poems about them. Encountering fleas in many of today’s societies, however, is more a byproduct of keeping pets,rather than an inescapable fact of life.Without pets, it is quite possible to never meet a flea despite the presence of well over 2,000 species. A Diseases associated with fleas Photo: Volpak USA Fleas are the most common ectoparasitic problem in dogs and cats throughout most of the world.Ctenocephalides felisis usually the species encountered and is the least host specific, as many cat or dog owners returning home from vacation to a house alive with Fleas serve as vectors for a variety of human pathogens. hungry fleas can attest to.Clinical signs of infestation in our pets can be mild and resolve once fleas are removed.However,uncontrolled infestations can lead to pruritis,self-inflicted trauma and pyoderma.Certain animals are also allergic to salivary proteins of fleas,which are released each time the flea feeds.The allergic reaction also leads to pruritis,self-trauma and secondary infections. In humans, papular urticaria is often produced when a flea bites. These bites are usually found around the ankles and wrists and tend to just be itchy. However, some humans, just like some dogs and cats,are allergic to the flea’s saliva and severe, painful boil-like lesions may occur. In addition,zoonotic diseases may be transmitted to humans through fleas.Fleas are the intermediate host for the tapeworm, Dipylidium caninum. The definitive hosts for this parasite are cats and dogs,but humans can become infected if an infected flea is ingested. Obviously, the high-risk group is children who tend to not notice what they put in their mouths. Fleas are also vectors for a variety of other human pathogens as well,including the agents of murine typhus (Rickettsia typhi),sylvatic epidemic typhus (Rickettsia prowazekii), cat scratch disease (Bartonella henselae),plague (Yersinia pestis),and,a relatively new-comer on the scene,murine typhuslike disease (Rickettsia felis). The effects of fleas on the health of our pets, as well as our own health,has led to a billion dollar industry centered on flea control products.Recent advances in our understanding of flea biology and in product development has provided veterinarians with many highly effective and safe flea control products with which to combat these voracious pests. Types of activity The latest developments in flea control center primarily on products that are given to the animal.Most Continued on next page In Focus june 2002 21 InFocus The drug does not need to be ingested to be effective;rather,it acts primarily as a contact poison passing through the exoskeleton of the flea. The time to peak effect is six to 12 hours when used for the first time and less than four hours in subsequent applications. Adults are generally killed before they can lay eggs. Fipronil has also been combined with methoprene, an IGR that is directly and indirectly ovicidal,embryocidal and larvicidal.Female fleas exposed to methoprene do not produce viable eggs and developing stages exposed in the environment do not continue to develop. Fipronil is also effective against ticks (Rhipicephalus sangineus (brown dog tick); Dermacentor variabilis(American dog tick); Amblyomma americanum (lone star tick); Ixodes ricinus(deer tick) killing them within 24-48 hours.This can be beneficial in controlling certain tick transmitted diseases such as Lyme disease. Photo: Volpak USA of these products have adulticidal activity, which is the lethal effect on fleas present on the animal at the time of treatment. Some of these products also have indirect larvicidal and ovicidal activity; that is,when trace amounts are transferred to the animal’s surroundings through dermal debris, larvae and ova contacting the debris are also killed. Other products are insect growth regulators (IGR). Some IGRs inhibit chitin synthesis which disrupts the normal formation of cuticle and other chitnous structures. Others are juvenile hormone analogs, binding to insect juvenile hormone receptors and preventing the flea from molting from one stage to the next.Finally,some products also have anthelmintic properties or have been combined with anthelmintics to provide more broad spectrum parasite control. C. felis( left) and C. canis (right). Compounds Fipronil: Fipronil is a phenylpyrazole compound that binds to gama-aminobutyric acid (GABA) receptors of insects. GABA is an inhibitory neurotransmitter in both vertebrates and invertebrates. By blocking GABA receptors,fipronil acts as an antagonist inhibiting the flux of chloride ions into the nerve cell resulting in hyperexcitation of the nervous system and death. The configuration of these receptors in insects is different than that in mammals making this a very safe compound for use in dogs and cats. Fipronil is applied topically. The drug dissolves in sebum,distributes through the epidermis, and accumulates in the sebaceous glands from which it is slowly released by way of the follicular ducts. This reservoir provides a long residual activity allowing for monthly treatment intervals. 22 june 2002 Imidacloprid : Imidacloprid is a chloronicotinyl nitroguanidine that binds to the postsynaptic nicotinic acetylcholine receptor thus preventing acetylcholine from binding.It is not degraded by acetylcholinesterase, therefore, transmission of nerve impulses is prevented resulting in paralysis and death of the insect.It is a safe compound because there is a higher concentration of nicotinic acetylcholine receptors in insect nervous tissue than in the central nervous system (CNS) of mammals and it has a higher affinity for insect receptors than vertebrate receptors. Imidacloprid is applied topically to a single site in dogs and cats, although application of the dose to multiple sites in dogs over 55 pounds is recommended. It is translocated within eight hours and dries as a microcrystal close to the follicles.Within 24 hours, it is completely distributed over the body without any systemic absorption. This drug also does not need to be ingested, but acts as a contact poison. The time to peak effect is under 12 hours in first time applications, within two hours in subsequent applications and adults are generally killed before they can lay eggs.Monthly applications are recommended. Imidacloprid also has larvicidal activ- ity.Larvae that contact dermal debris from treated dogs will not develop and this inhibitory effect has been shown to last for more than four weeks. Selamectin: Selamectin is a semi-synthetic avermectin compound that binds with postsynaptic glutamate receptors. This causes the chloride channel to remain open and chloride ions to flow into the nerve cell blocking neurotransmission resulting in paralysis.The blood brain barrier is generally effective in preventing the large molecule from passing into the CNS, even in dogs with dose-related sensitivity to ivermectin, making this a safe drug. Selamectin is applied topically.It is absorbed from the skin into the bloodstream and redistributes into sebacious glands of the skin. This compound also does not need to be ingested by the flea, but acts as a contact poison. The time for peak effect is 24 to 36 hours in dogs and 12 to 24 hours in cats with duration of activity good for one month.Not only are adults killed,but eggs which may be laid prior to death of the selamectin-exposed flea tend to not develop and hatch. Additionally, dermal debris from treated dogs exhibits ovicidal activity for 21 days, larvicidal activity for 30 days and adulticidal activity for seven days. Selamectin also has activity against other parasites. It is approved for use in the prevention of heartworms (Dirofilaria immitis) and the treatment and control of ear mites (Otodectes cynotis) in dogs and cats. It is also approved for the treatment and control of sarcoptic mange (Sarcoptes scabei) and the control of the American dog tick (D. variabilis) in dogs and the treatment of intestinal roundworm (Toxocara cati) and hookworm (Ancylostoma tubaeforme) in cats. Lufenuron: Lufenuron is a benzoylphenylurea compound that disrupts the synthesis and deposition of chitin by blocking the enzyme chitin synthetase. Chitin is essential for the survival of both ova and larvae; consequently, this drug has both ovicidal and larvicidal activity. Flea feces, an important component of the larval diet, will contain a sufficient amount of lufenuron to inhibit larval development.Fleas take up www.dvmnewsmagazine.com Product Route of administration Approved for of control* Spectrum Fipronil+methoprene Topical Dogs and cats Adult fleas and eggs, ticks Topical Dogs and cats Adult fleas Topical Dogs and cats Cats: Adult fleas and eggs; heartworms, ear mites, hookworms, roundworms Dogs: Adult fleas and eggs, heartworms, ear mites, sarcoptic mange, ticks Injection Cats Flea eggs Oral Dogs and cats Flea eggs Dogs Flea eggs, heartworms, hookworms, roundworms, whipworms Dogs and cats Adult fleas (Frontline Plus®) Imidacloprid InFocus Table 1: Flea Control Options in 2002 (Advantage®) Selamectin (Revolution®) Lufenuron (Program®/6-month injectable) Lufenuron (Program Flavor Tabs) Lufenuron+milbemycin oxime Oral (Sentinel Flavor Tabs) Nitenpyram Oral (Capstar) Hundreds of products are available to control fleas on pets. This table is a summary of just some of the recently marketed products available for flea control. *See text for specific names of parasites. the drug with the bloodmeal and transfer it to their eggs.It does not have adulticidal activity; consequently, it may take five to eight weeks to achieve good flea control when used alone. Significant reduction in environmental flea burdens can be achieved with development inhibition lasting for up to 45 days after a single dose. Lufenuron is administered orally (cats and dogs) or through subcutaneous injection (cats only). This is a highly lipophilic compound that concentrates in adipose tissues from where it is slowly released into the blood.Oral formulations are given on a monthly basis while the injectable formulation provides six months protection. Given that mammals do not have chitin, this is a very safe compound. A combination product of lufenuron with milbemycin oxime is available for use in dogs.Milbemycin oxime,a macrocyclic anthelmintic,eliminates the tissue stage of heartworm, and the adult stage of hookworm (Ancylostoma caninum),roundworm (Toxocara canis and Toxascaris leonina), and whipworm (Trichuris vulpis). Nitenpyram: Nitenpyram is a neonicoti- noid compound that binds and inhibits nicotinic acetylcholine receptors.It is rapidly absorbed and eliminated with maximum blood levels reached within 1.2 hours in dogs and 0.6 hours in cats. The half-life is about three hours in dogs and about eight hours in cats. Effective blood concentrations are only maintained for approximately one day after administration. This compound has adulticidal activity with most adult fleas killed within four to six hours. This compound is also very safe – it can be administered every 24 hours if necessary.It can also be safely combined with lufenuron. Suggested reading Taylor MA. 2001. Recent developments in ectoparasiticides. The Veterinary Journal 161:253-268. A two-part series by Barragry T. 2001. Pharmacological developments in flea control. Irish Veterinary Journal 54:457-459 and 54:523-529. Ruiz A. 2001. Plague in the Americas. Emerging Infectious Diseases 7:539-540 (conference panel summary giving brief overview of plague). In Focus The future Even with the major advancements in the area of flea control, successful ectoparasite control programs still rely heavily on the use of chemicals.Worry over the possible development of resistance to parasiticides,coupled with human,animal and environmental safety concerns, emphasize the need for continued research into discovery of compounds with novel modes of action or improved formulations of existing compounds. The long developmental time and high costs required to bring new products to market,only stresses the importance of using our current products in a wise and judicious manner.Failure to do so may result in their loss before alternatives become available and, should that happen, we may once again be writing poems to the flea. DVM Dr. Ballweber is an associate professor in the College of Veterinary Medicine at Mississippi State University. She joined the faculty in 1993 where her research focuses on parasites of ruminants and llamas, as well as a variety of wildlife. She also shares responsibility for teaching veterinary parasitology to veterinary students. She received her veterinary degree from Oregon State University in 1992 and a master’s degree in parasitology from the University of Wyoming in 1982 and a master’s degree in veterinary science (epidemiology) from Oregon State University in 1989. june 2002 23