In Small Animal Dermatology (Fourth Edition), 2017
Pediculosis (Lice)
Features
Pediculosis is an infestation caused by host-specific sucking (Linognathus setosus [dogs]) or biting (Trichodectes canis [dogs], Felicola subrostratus [cats]) lice. It is uncommon in dogs and cats, with highest incidence reported in young, neglected, underfed animals.
Symptoms usually include restlessness and pruritus, with secondary seborrhea, alopecia, or excoriations. Thickly matted hairs, small papules and crusts, and, in severe infestations, anemia and debilitation may be present.
Top Differentials
Differentials include fleas, scabies, cheyletiellosis, and hypersensitivity (flea bite, food, atopy).
Diagnosis
1.
Direct visualization of lice (flea combing)
2.
Microscopy (acetate tape impressions, hairs): detection of lice and nits (ova)
Treatment and Prognosis
1.
Affected and all in-contact same-species animals should be treated.
2.
Matted hairs should be clipped away.
3.
Traditional therapy is to topically treat the animal's entire body with 2% lime sulfur, pyrethrin, or pyrethroid (dogs only), shampoo, powder, spray, or dip twice 2 weeks apart.
4.
Alternative treatments include the following:
▪
Ivermectin 0.2 mg/kg PO or SC twice 2 weeks apart.
▪
Selamectin spot-on (as per label), topically twice 2 weeks apart. Treatment administered every 2 weeks at least four times may be more effective.
▪
Doramectin 0.2–0.4 mg/kg administered every week for 3 to 4 weeks.
Severely anemic animals may require blood transfusions and good nursing care.
6.
Bedding, grooming tools, and environment should be cleaned at least once.
7.
Prophylactic use of insecticidal flea collars may protect exposed animals from infestation, but avoidance of infected animals is ideal.
8.
The prognosis is good. Lice are highly contagious from dog to dog and from cat to cat, but they are not considered contagious from dogs or cats to humans.
Author's Note
Fluralaner (Bravecto) administered 25 mg/kg every 30 to 60 days seems to be highly effective and safe (as of this writing).
Historically, products containing amitraz and organophosphates have been used; however, these are toxic, and better options exist.
Lice are host-specific, obligate parasites. Infestations of young dogs and cats are commonly associated with poor nutrition, overcrowding, and direct transmission from infested animals. Biting lice (Trichodectes canis and Felicola subrostratus) are recognized by their relatively broad heads compared with those of sucking lice (Linognathus setosus).
Infested pediatric patients display variable pruritus, progressive alopecia, and scale. Matting, erythematous papules, and anemia may develop in severe infestations. Lice and their eggs (nits) may be grossly visualized (Figure 41-7).
Treatment should be directed at all in-contact dogs or cats. Selamectin administered every 2 weeks for four treatments is safe, effective, and convenient. Alternatives include spot-on formulations, dips, powders, or sprays containing imidacloprid, fipronil, lime-sulfur, pyrethrin, carbaryl, or organophosphates, following manufacturer recommendations. The environment, bedding, and grooming tools of infested animals should be cleaned or replaced.
Lance A. Durden , in Medical and Veterinary Entomology (Third Edition), 2019
Lice of Cats and Dogs
Domestic cats are parasitized by one species of chewing louse, whereas dogs are parasitized by two species of chewing lice and one species of sucking louse. All four species appear to be distributed worldwide, but none of them are common associates of healthy cats or dogs in North America or Europe.
The cat biting louse (Felicola subrostrata) parasitizes both domestic and feral cats. It may occur almost anywhere on the body.
Both the dog biting louse (Trichodectes canis) (Fig. 7.15A) and the dog sucking louse (Linognathus setosus) (Fig. 7.15C) parasitize dogs and closely related wild canids. For example, T. canis also parasitizes coyotes, foxes, and wolves. A second species of chewing louse of dogs is Heterodoxus spiniger (Fig. 7.15B), which evolved in Australasia from marsupial-infesting lice and apparently switched to dingo hosts. It now parasitizes various canids and other carnivores throughout the world. Trichodectes canis usually infests the head, neck, and tail region of dogs, where it attaches to the bases of individual hairs. Linognathus setosus occurs primarily on the head and neck and may be especially common beneath collars. Heterodoxus spiniger can typically be found anywhere on its host.
Figure 7.15. Lice of domestic dogs. (A) Dog biting louse (Trichodectes canis), male. (B) Heterodoxus spiniger, female. (C) Dog sucking louse (Linognathus setosus), female. Stacked images of cleared specimens.
Burton J. Bogitsh , ... Thomas N. Oeltmann , in Human Parasitology (Fifth Edition), 2019
Dipylidium Caninum
D. caninum is a common parasite of dogs, cats, and humans, especially children, throughout the world. The parasite can attain a length of 30 cm and possesses on its scolex a conical, retractible rostellum with one to eight (commonly four to six) rows of hooks (Fig. 13.8). This tapeworm is easily recognizable because each proglottid has two sets of reproductive organs with a genital atrium on each lateral edge. The short inconspicuous uterus atrophies early and, as eggs are produced, they are enclosed in egg capsules each containing 8–25 eggs. The medullary region of a typical gravid proglottid is packed with hundreds of egg capsules.
Figure 13.8. Dipylidium caninum.
(A) Cluster of eggs in a uterine ball. (B) Scolex with armed rostellum. (C) Mature proglottid with two sets of reproductive organs. (D) Gravid proglottid filled with uterine balls.
Life Cycle
The adult tapeworm lives in the small intestine of the definitive host where gravid proglottids, 12 mm long and 3 mm wide, separate from the strobila in groups of 2 or 3. The proglottids are capable of moving upon a substrate and can either creep out of the anus or be passed with feces. Eggs and capsules are ingested by larvae of fleas belonging to the genera Pulex and Ctenocephalides or by the dog louse Trichodectes canis. The oncosphere hatches in the gut of the arthropod, burrows through the wall, and develops into a cysticercoid in the hemocoel when the flea or louse metamorphoses to the parasitic adult stage. When the infected arthropod is ingested by a suitable definitive host, the cysticercoid is liberated in the small intestine and develops to sexual maturity in about 20 days.
Epidemiology
Most human infections are in children younger than 8 years old, with a high percentage falling in the under-6-months age group. This probably is attributable to the fact that a high percentage of dogs are infected, many of which undoubtedly are pets. Transmission to humans usually results from accidental ingestion of infected fleas or lice or from allowing dogs and cats to lick ("kiss") the mouths of children immediately after the pet has bitten an infected arthropod.
Symptomatology and Diagnosis
It is rare for humans to harbor more than a single parasite, and symptoms are seldom apparent. Diagnosis is confirmed by discovery of characteristic proglottids or eggs in the feces.
Lance A. Durden , Nancy C. Hinkle , in Medical and Veterinary Entomology (Third Edition), 2019
Fleas as Intermediate Hosts of Helminths
Certain fleas are intermediate hosts for the cysticercoid stage of three species of tapeworms that occasionally infest humans. The most important of these is the double-pored tapeworm (Dipylidium caninum), the adults of which normally parasitize dogs. Gravid worm-like proglottids (Fig. 10.24) are released by D. caninum adults in the gut of the definitive host. These actively exit the anus, partially dry upon exposure to air, and fall to the ground where they resemble sesame seeds. The subsequently expelled eggs are ingested by flea larvae; the chewing mandibles of the larvae enable them to ingest the eggs whereas the sucking mouthparts of adult fleas do not. Fleas such as C. felis, C. canis, and P. irritans have a significant role as intermediate hosts for this tapeworm. The dog-chewing louse (Trichodectes canis) occasionally ingests D. caninum eggs and also can serve as an intermediate host.
Figure 10.24. Proglottid of the double-pored tapeworm, Dipylidium caninum.
Courtesy, U.S. Public Health Service, Public Health Image Library.
The tapeworm develops slowly in flea larvae but rapidly in flea pupae. Cysticercoids can be seen in the body cavity of larvae and pupae, where they remain through development of the flea to the adult stage. Some flea mortality occurs in the pupal stage due to this helminth. Infestation of human (definitive) hosts occurs when a person incidentally ingests an infested flea. The cysticercoid is liberated from the flea by digestive enzymes, after which it everts and attaches to the gut of its new host. Children playing with pets are especially susceptible to infestation by this tapeworm.
Two other tapeworms that use fleas as intermediate hosts are the rodent tapeworm (Hymenolepis diminuta) and the dwarf tapeworm (Hymenolepis nana). Both infest rodents and occasionally parasitize humans, especially children. The development and transmission mechanisms of these two cestodes are similar to those for D. caninum. Both H. diminuta and H. nana form viable cysticercoids in several species of fleas, especially C. canis, P. irritans, X. cheopis, and N. fasciatus. They can also infest some other arthropods, notably coprophagous beetles.
The zoonotic nematode Trichinella spiralis, which causes trichinosis, has also been found in fleas, although this is assumed to represent an accidental association.
Blaine A. Mathison , Bobbi S. Pritt , in Encyclopedia of Infection and Immunity, 2022
Dipylidium caninum (dipylidiasis, dog tapeworm disease)
Biology and life cycle
Dipylidiasis, also commonly referred to as dog tapeworm disease or double-pored dog tapeworm disease, is caused by the zoonotic cestode, Dipylidium caninum. The disease occurs worldwide, but the sparsity of case reports and the asymptomatic nature of most infections probably belies its true prevalence. Most published reports have come out of the United States, Europe, the Philippines, China, Japan, and Latin America (Cabello et al., 2011). Most case reports have been in diaper-aged children, probably due to astute observations of the parents in combination with diapers being an efficient collection apparatus.
The natural definitive hosts for D. caninum are primarily dogs and cats. Adults live in the small intestine of the definitive host, attached to the intestinal mucosa by the scolex, and gravid proglottids are shed into the environment in the feces. Proglottids, and eggs derived therefrom, are eaten by an insect intermediate host, predominately flea larvae and parasitic lice. Common intermediate hosts are cat and dog fleas (Ctenocephalides spp.), human fleas (Pulex irritans), and dog chewing lice (Trichodectes canis). In the arthropod host, the oncosphere develops into a cysticercoid larvae. Fleas are holometabolous insects, and infected flea larvae harbor the cysticercoid larvae through their metamorphosis to adulthood. Cats and dogs become infected after ingesting infected adult fleas and lice when they groom themselves (Cabello et al., 2011). Humans also become infected from the incidental ingestion of infected insects. Children are of particular risk due to their more intimate associations with pets (e.g., kissing, cuddling pets) and tendency to put things in their mouths.
Pathogenesis, clinical presentation, and treatment
Most infected patients are thought to be asymptomatic, although non-specific symptoms such as diarrhea, restlessness and abdominal discomfort may be noted (Cabello et al., 2011). Older children may complain of anal pain and itching. Treatment is primarily with praziquantel (Medical Letter, 2013). Niclosamide is an alternative anti-helminthic drug.
Diagnosis
The diagnosis of dipylidiasis is primary made by the gross morphology of proglottids shed in stool (Fig. 25). The proglottids are hardier than other intestinal cestodes, so eggs and characteristic egg packets are not commonly seen in wet mounts of stool.
Fig. 25. Dipylidium caninum proglottids (left; markings represent millimeters) and characteristic egg packet (right). Note the presence of a 6-hooked within each egg (arrow).
Adult tapeworms are 10–70 cm long, and proglottids seen in clinical specimens are usually single or in small chains. Gravid proglottids are longer than wide and have two genital pores, one on each lateral margin. Gravid proglottids can be upwards of 23 mm long, but as humans are atypical hosts, proglottids seen in clinical specimens are usually smaller (e.g., a few mm long), and have been described as resembling pumpkin seeds or rice grains (Fig. 25). Proglottids are compartmentalized and contain egg packets. The scolex is not usually recovered in clinical specimens, but in conical and has a retractile armed rostellum (Ash and Orihel, 2007). Proglottids submitted to a laboratory that resemble D. caninum should be dissected to look for characteristic eggs packets (Fig. 25) and to rule out the less common, but morphologically similar, members of the genera Raillietina and Inermicapsifer (Davis et al., 2019).
Egg packets observed in wet mounts of stool or liberated from proglottids contain 8–15 eggs on average. The eggs are thin-shelled and measure 25–40 μm in diameter. The oncosphere contains 6 hooklets (Ash and Orihel, 2007).
Seppo Saari DVM , ... Sven Nikander DVM, PhD , in Canine Parasites and Parasitic Diseases, 2019
Dipylidium caninum, Flea Tapeworm
•
A tapeworm species often referred as a flea tapeworm residing in the small intestine and infect dogs by ingestion of the metacestode larval stage—cysticercoid—of the tapeworm in the tissues of insect intermediate hosts.
•
Up to 50 cm in length; body composed of a large strobila with numerous segments that are longer than wide.
•
Cat flea (Ctenocephalides felis) is the main intermediate host, but also biting lice (Trichodectes canis) can serve as intermediate hosts.
•
D. caninum is rarely associated with clinical signs in dogs.
•
Diagnosis is based on the detection of double-pored proglottids and identifying typical egg packets filled with taeniid eggs with microscope.
Identification
D. caninum is a pinkish or yellowish tapeworm. It lives in the small intestine of a dog (or cat). The adult cestode is up to 50 cm long. Suckers are clearly visible in the scolex of the worm, together with a rostellum with four rows of hooks (Fig. 4.18). The strobila consists of 60–175 proglottids that are wider than their length. The posterior end sheds proglottids with visible genital pores on both sides (Figs. 4.19 and 4.20). Hence, it is sometimes referred as the double-pored dog tapeworm. The proglottides are filled with typical egg pouches 100–200 μm large. They contain 1–30 round eggs of taeniid type. With light microscopy, the embryo and its hooks can be seen inside a single egg (Fig. 4.21).
Fig. 4.18. Head of scolex of the D. caninum in scanning electron microscopy. The hooked rostrum or rostellum is almost totally retracted. Two of the tapeworm's four suckers are visible.
Fig. 4.19. Stained proglottids of Dipylidium caninum in light microscopy and scanning electron microscopy. Genital pores are located laterally at the edges of each proglottid, slightly below the central line. The structures stained darker are the ovaries and pore structures of the genitals. Scanning electron microscopy shows that the proglottids are located so that each anterior proglottid slightly extends over the subsequent posterior one.
Fig. 4.20. A mature proglottid of D. caninum in light microscopy. The proglottid is stained for better visibility of the organs. The genital pores at the both sides of the proglottid and the tubule structures leading into them are clearly seen in the photo. Ovaries are seen as structures that are stained darker red. There are numerous testes. They are light, transparent bulbous structures, filling two quarters at the center and extending through the whole proglottid.
Fig. 4.21. The egg package full of taeniid eggs, typical for D. caninum.
Morphology of Dipylidium caninum
D. caninum belongs to midsized Cyclophyllidea cestodes. The worm is able to retract its holdfast organ, the rostellum, to the safety of the scolex. Rostellum has three or four rows of thorn-shaped hooks. Apart from the rostellum, attachment is facilitated by four pairs of suckers. There are several proglottids (Fig. 4.20), and these are arranged in a chain referred as craspedote so that each slightly extends over the subsequent one. Especially the segments at the tail end of the worm are longer that their width. The genitals are paired. The genital pores are situated laterally at both edges of each proglottid just below the midline. The cirrus sac is pear-shaped. There are many testes. Ovaries are paired. The vitelline glands are located posterior to the ovaries and the vagina is at the ventral or posterior side of the cirrus sac. In the gravid proglottids, the uterus forms pouches and capsules with 1–30 taeniid eggs (Fig. 4.21) inside each of them.
Life Cycle
The tapeworm is attached to the intestinal wall with the scolex hooks and suckers. Gravid and egg-filled mature proglottids are being released from the posterior part of the worm and moved out in fecal mass. The proglottids are also capable to some extent of autonomic moving, and they can be seen writhing at the proximity of the anus. The life cycle of the Dipylidium tapeworm requires an intermediate host. The most important intermediate host of the worm is the cat flea (C. felis), which is infective to dogs too. Adult fleas and proglottides of Dipylidium rarely meet, but the flea larvae like to ingest the egg packages protruding from desiccated cestode proglottids. It is likely that also the canine chewing louse (T. canis) can act as an intermediate host. In other flea species (for instance dog flea, Ctenocephalides canis), the development of the larval stage stops and never reaches the stage needed for infection a dog. Outside the host, the proglottid of the tapeworm dries quickly, but remains infectious to the intermediate host. The eggs remain infective at 30°C for about 2.5 months and at 15°C for 3.5 months. In refrigeration, in physiological saline the larval stage stays infective for about a week. In the intermediate host, the larval stage is released from the egg and it penetrates the intestinal tract of the flea larva with the aid of the hooks and the enzymes it secretes. The larval stage infective for the dog is called cysticercoid and develops in the body cavity of the intermediate host. The development of the cysticercoid takes 9–15 days in a warm environment (about 30°C), and longer in colder conditions. If the environment is cool, the intermediate host must be in contact with the warm-blooded mammalian skin for about a week. The dog is infected when it eats an infected flea or louse with the cysticercoids. The development into an adult tapeworm takes about 3 weeks in the dog. Its life cycle is shown in Fig. 4.22.
Fig. 4.22. Life cycle of D. caninum: (1) the adult tapeworm, attached to the canine intestinal wall with the scolex hooks and suckers, sheds mature proglottids from the posterior part of the worm, and they move out in the fecal mass; (2) the proglottides are to some extent capable of independent movement. The proglottids contain egg packages trapped inside uterine folds, each usually holding 1–30 eggs; (3) an intermediate host, the cat flea, is needed for the life cycle of the flea flatworm. The flea larva feed on the proglottids of the tapeworm and the egg packages within; (4) the larval stage, the flatworm, is released from the eggshell in the intermediate host and it penetrates the flea larva intestinal tract using its hooks and secreted enzymes; (5) the larval stage infectious for the dog, cysticercoid, grows in the body cavity of the intermediate host; and (6) the dog is infected when it eats the flea with its cysticercoid. The development into an adult flatworm takes about 3 weeks in a dog.
Dipylidiosis Is a Zoonosis
The flea tapeworm is capable of developing in adulthood also in the human gut. The infection requires that a human ingests an infected flea (intermediate host) or a cysticercoid from the flea. Dipylidiosis is most common in little children who are in close contact with a dog. If the dog has recently crushed a flea with its teeth, cysticercoids may be present in the dog's saliva. Since the worms reach adulthood in the human, alive and writhing cestode proglottids may be found in the soiled nappy or perianal area. The human infection is usually accidental and typical human dipylidiosis is caused by a single worm. The infection is usually subclinical. Abdominal pain, diarrhea, general irritability, and itching of the anal region have been described in the literature.
Distribution
Since fleas are found everywhere in the world, D. caninum is ubiquitous. It is also one of the most important and prevalent feline cestodes. It is also found in humans, albeit rarely.
Importance to Canine Health
Single cestodes very rarely cause clinical signs in canines. The most common signs are itching caused by proglottids moving in the anal area and other irritation. The discomfort leads into rubbing of the caudal area and subsequent trauma. Massive Dipylidium infections are very rare. They may be associated with gastro-intestinal signs such as diarrhea or constipation.
Diagnosis
Diagnosis is based on the recognition of species-specific proglottids and egg packets. The Dipylidium proglottids are elongated and oval, resembling cucumber seeds. A proglottid is placed on the objective glass with a drop of water, covered with a cover slip, and viewed in a microscope. The proglottid releases into the water between the glass surfaces egg packages typical to the species. A fecal sample examined parasitologically by flotation method gives almost always a negative result for D. caninum.
Treatment and Prevention
Most anticestode drugs are efficacious against worms found in the gut of the primary host. These substances include praziquantel, epsiprantel, and nitroscanate. The intermediate host plays an important role in D. caninum infection. The dog will be quickly reinfected unless the anticestode treatment is complemented with an efficient flea control.
P. Jeschke , R. Nauen , in Comprehensive Molecular Insect Science, 2005
5.3.10 Applications in Nonagricultural Fields
Because of the high insecticidal efficacy together with its nonvolatility and stability under storage conditions, imidacloprid (Premise®) has been successfully applied as a termiticide (Jacobs et al., 1997a; Dryden et al., 1999), and has also been used for control of turf pests such as white grubs (Elbert et al., 1991). Furthermore, imidacloprid is the active ingredient of the insecticide Merit®, and is commonly incorporated into fertilizers for early control of grubs in turf (Armbrust and Peeler, 2002). In addition, imidacloprid was the first neonicotinoid to be used in a gel bait formulation for cockroach control. The imidacloprid gel showed outstanding activity even after 27 months' under various conditions (Pospischil et al., 1999). As an endoparasiticide imidacloprid exerted activity against the gastrointestinal nematode Haemonchus contortus in sheep only at higher concentrations (Mencke and Jeschke, 2002). Synergistic mixtures containing imidacloprid are patented and these are useful against textile-damaging insects, such as moth (Tineola bisselliella, Tinea pellionella) and beetles (Attagenus, Anthrenus) (Mencke and Jeschke, 2002). Salmon-parasitizing crabs are controlled by addition of 100 ppm imidacloprid to seawater (Mencke and Jeschke, 2002). Due to its toxicological properties – favorable mammalian safety characteristics (Yamamoto et al., 1995) (Table 6), the absence of eye/skin irritation and skin sensitization potential – imidacloprid has been developed for control of lice in humans (Mencke and Jeschke, 2002) and veterinary medicine (Werner et al., 1995). Imidacloprid (worldwide trademark: Advantage®) is the first neonicotinoid to have been developed for topical application in animals (Griffin et al., 1997) (see Section 5.3.10.1).
Nitenpyram (Capstar®), a fast-acting, orally administered flea treatment, is absorbed into blood of the host animal, and is thus readily available for uptake by feeding fleas (Rust et al., 2003). Therefore, administration of nitenpyram is effective in eliminating adult fleas for up to 48 h after treatment.
5.3.10.1 Imidacloprid as a Veterinary Medicinal Product
The cat flea (Ctenocephalides felis), the primary ectoparasite of companion animals worldwide, will feed on a wide variety of animals in addition to cats and dogs (Rust and Dryden, 1997), although it is not equally well adapted to all hosts (Williams, 1993). Fleas threaten the health of humans and animals due to bite reactions and transmission of diseases (Krämer and Mencke, 2001), and in addition are major nuisance pests. Therefore, flea control, is necessary.
In veterinary medicine, fleas are the primary cause for flea allergic dermatitis. This dermatitis results when the adult flea injects saliva into the host during blood feeding, which accelerates immunological response, leading to secondary infections of the skin.
The last aspect of veterinary importance is the role of fleas in disease, for example, transmission of the cestode Dipylidium caninum. The role of fleas in human disease transmission has been known since historic times. The Oriental rat flea (Xenopsylla cheopis) is the major transmitter of Yersinia pestis, the bacterium that causes the bubonic plague in humans. The cat flea is also capable of transmitting Y. pestis, and human plague cases and even deaths associated with infected cats and dogs have been occasionally reported (Rust et al., 1971).
Furthermore, a variety of bacteria and viruses have been reported to be transmitted by the dog flea (C. canis) as well as the cat flea (C. felis) (Krämer and Mencke, 2001). Moreover, cat owners have a high incidence of cat scratch fever, a zoonotic disease caused by the Gram-negative bacterium Bartonella henselae. Recent research showed that flea feces are the major means of disease transmission between cats, and from cats to humans (Malgorzata et al., 2000).
5.3.10.1.1 Insecticidal efficacy in veterinary medicine
Recommendations for the treatment of fleas on companion animals, and the selection of an insecticide and its formulation, are generally based upon the species and age of the animal to be treated, the level of infestation, the rate of potential reinfestation, and the thoroughness of environmental treatment. However, the selection of an insecticide formulation by a pet owner is actually based on economics and the product's ease of use (Williams, 1993). Another factor in the choice of a flea treatment by pet owners is the safety and toxicology of the insecticide (Krämer and Mencke, 2001).
Imidacloprid, 10% spot-on, was designed to offer a dermal treatment, which means it is applied externally onto a small dorsal area (a spot) of the animal's skin. Criteria for the selection of an appropriate topical flea formulation are good solubility of the compound, good adhesion to the skin, good spreading properties, good local and systemic tolerance, stability, and compatibility with legal standards. The imidacloprid spot-on formulation, which meets all these requirements, contains 10 g a.i. in 100 ml nonaqueous solution. The efficacy of this formulation for flea control on cats and dogs has been reported (Krämer and Mencke, 2001). Imidacloprid applied at the target therapeutic dosage of 10.0 mg kg−1 killed 99% of the fleas within 1 day of treatment, and continued to provide 99–100% control of further flea infestation for at least 4 weeks (Hopkins et al., 1996; Arther et al., 1997) (Figure 25).
Figure 25. Flea control achieved with imidacloprid 10% spot-on as confirmed by a dose-confirmation study in flea infested dogs (Hopkins et al., 1996).
Studies using flea-infested cats (Jacobs et al., 1997b) proved that imidacloprid possess considerable potency against adult fleas on cats, and retains a high level of activity for 4–5 weeks. Imidacloprid was effective for both immediate relief from an existing flea burden (the therapeutic effect), and for longer-term flea control (the prevention or prophylactic effect) (Table 9). Imidacloprid spreads and acts using animal skin as the main carrier. The compound was shown to be localized in the water-resistant lipid layer of the skin surface, produced by sebaceous glands, and spread over the body surface and onto the hair (Mehlhorn et al., 1999). Insecticide spread over the skin surface was also reported from a clinical study that observed fast onset of flea control, as early as 6 h posttreatment (Everett et al., 2000). Therefore if the superficial fatty layer of the skin is removed by repeated swabbing with alcohol fleas consumed the same amount of blood in treated and untreated dogs. Thus imidacloprid localized in the lipid layer of the skin acts on adult fleas by contact. It was reported that imidacloprid is not taken up by the flea during blood feeding, but is absorbed via the flea's smooth, nonsclerotized intersegmental membranes that are responsible for the insect's mobility. Mehlhorn et al. (1999) concluded that this seems reasonable because of imidacloprid's lipophilicity renders it incapable of passing through the sclerotized cuticle. Moreover, initial damage was seen in the ganglia close to the ventral body side (i.e., in subesophageal and thoracic ganglia). Fleas affected by imidacloprid treatment showed characteristic pathohistological changes (Mehlhorn et al., 1999). Muscle fibers and tissue around the subesophageal ganglion were damaged, with the mitochondria and axons showing intensive vacuolization (Figure 26). Imidacloprid's mode of action corresponded with the structural findings (Mehlhorn et al., 1999), which showed overall destruction of the mitochondria, damage of the nerve cells, and disintegration of the insect muscles (Figure 26).
Table 9. Geometric mean flea counts of two groups of cats, an untreated control and a group treated with imidacloprid 10% spot-on at a dosage of 10.0 mg kg−1 bw at day 0 of the study
Weeks after treatment
After 1 day
After 2 days
Control
Treated
Reduction (%)
Control
Treated
Reduction (%)
0
36.7
0.01
99.8
31.7
0.0
100.0
1
34.1
0.0
100.0
2
31.0
0.2
99.3
27.3
0.0
100.0
3
32.1
1.0
97.0
28.9
0.1
99.7
4
36.2
5.0
86.1
27.8
0.9
96.7
5
33.8
9.5
71.9
26.8
3.1
88.3
6
28.1
20.1
28.4
24.8
10.6
57.3
Reproduced from Jacobs, D.E., Hutchinson, M.J., Krieger, K.J., 1997b. Duration of activity of imidacloprid, a novel adulticide for flea control, against Ctenocephalides felis on cats. Vet. Rec. 140, 259–260.
Figure 26. Transmission electron micrograph of a section through an adult cat flea exposed to imidacloprid for 1 h in vitro. Note the extensive damage at the level of muscle fibers and the subesophagal ganglion (vacuoles). CV, cellular cover of the ganglion; DA, degenerating axon; DC, degenerating nerve cell; DM, degenerating mitochondrion; FI, Fibrillar layer of connective tissue; Mu, Muscle fiber; TR, tracheole. Magnification ×25 000. (Reproduced with permission from Mehlhorn, H., Mencke, N., Hansen, O., 1999. Effects of imidacloprid on adult and larval stages of the cat flea Ctenocephalides felis after in vivo and in vitro experiments: a light- and electronmicroscopy study. Parasitol. Res. 85, 625–637.)
Imidacloprid's activity on ectoparasitic insects results from its presence within the lipid layer of the host body surface. Since this lipid layer is always present, imidacloprid remains available for a prolonged time (Hopkins et al., 1996; Mehlhorn et al., 2001a), and reduces the likelihood of its removal during water exposure (Mehlhorn et al., 1999).
The spectrum of imidacloprid activity to ectoparasites is not confined to fleas. It has also proven to be highly effective against both sucking lice (Linognathus setosus), and biting or chewing lice (Trichodectes canis) (Hanssen et al., 1999). Furthermore imidacloprid acted rapidly on all motile stages of sheep keds (Mehlhorn et al., 2001b). Sheep keds of the species Melophagus ovinus are wingless parasitic insects belonging to the dipteran family Hippobiscidae. Besides skin infection, which results in the loss wool quality and meat production, sheep keds are also known to transmit diseases, such as trypanosomiasis. However, ticks did not prove to be sensitive to complete control by imidacloprid (Young and Ryan, 1999).
5.3.10.1.2 Larvicidal activity
Apart from the fast-acting adulticidal activity of imidacloprid on flea populations, its larvicidal effects have also been investigated. Reinfestation of animals, from earlier deposited eggs, larvae, and preemerged adult fleas, can be overcome by the use of effective larvicidal compounds or insecticides acting on both the adult and the immature stages of fleas. In early studies using imidacloprid, larvicidal activity was observed in the immediate surrounding of treated dogs (Hopkins et al., 1997). Skin debris collected from treated dogs, when mixed into flea rearing media, showed high flea larva mortality. In repeated tests using the skin debris samples, collected at day 7 posttreatment, the larval mortality remained high at 100% even after 51 days (Arther et al., 1997). In in vitro studies, flea larvae survived for only 6 h when placed on clipped hair from imidacloprid treated dogs (Mehlhorn et al., 1999). Similar results have also been reported for cats (Jacobs et al., 2000). Adult flea emergence was reduced by 100%, 84%, 60%, and 74% in the first, second, third, and fourth week postimidacloprid treatment, in comparison to untreated controls (Figure 27). This persistent larvicidal activity is important, because in the absence of any larvicidal effect of an applied adulticide, reinfestation would occur from eggs deposited prior to treatment (Jacobs et al., 2001). Furthermore, cats wander freely outdoors, and thus may visit sites shared with other flea-infested domestic or wild animals.
Figure 27. Emergence of adult fleas from flea eggs incubated on blankets used by untreated (control) or imidacloprid treated cats. (Reproduced from Jacobs, D.E., Hutchinson, M.J., Ewald-Hamm, D., 2000. Inhibition of immature Ctenocephalides felis felis (Siphonaptera: Pulicidae) development in the immediate environment of cats treated with imidacloprid. J. Med. Entomol. 37, 228–230.)
5.3.10.1.3 Flea allergy dermatitis (FAD)
FAD is a disease in which a hypersensitive state is produced in a host in response to the injection of antigenic material from flea salivary glands (Carlotti and Jacobs, 2000). Synonyms for FAD include flea bite allergy and flea bite hypersensitivity. In cats, the disease is also known as feline miliary dermatitis and feline eczema. FAD is one of the most frequent causes of skin conditions in small animals, and a major clinical entity in dogs. FAD is the commonest nonroutine reason for pet owners to seek veterinary advice. Hypersensitivity to flea bites is not only of importance to domestic pets, but is also an important cause of the common skin disease in humans, termed papular urticaria. Detailed investigations carried out on patients exposed to flea-infested pets have shown that the incidence of such reactions is quite high.
Several field studies have been conducted, focusing on the efficacy of imidacloprid on cats and dogs with clinical signs of FAD (Krämer and Mencke, 2001). The efficacy of imidacloprid in flea removal, and the resolution of FAD was tested in dogs and cats from single- and multiple-animal households (Genchi et al., 2000). Flea infestation was examined and FAD dermatitis lesions were ranked according to severity of typical clinical signs. Flea numbers dropped significantly after treatment of animals from both single- and multiple-animal households. In dogs clinical signs of FAD prior to treatment, decreased from 38% to 16% by day 14, and 6% by day 28, thus verifying a rapid adulticidal and high residual activity that lasted at least 4 weeks. There was an effective control of parasites, with rapid improvement of allergy until almost complete remission up to 28 days following the first application. Recently studies on the effect of imidacloprid on cats with clinical signs of FAD confirmed field data published by Genchi et al. (2000). Clinical signs of FAD, especially alopecia and pruritus were resolved after monthly treatment using imidacloprid (Keil et al., 2002) (Figure 28). Furthermore, controlling FAD is enhanced when blood feeding of fleas is reduced. This so-called "sublethal effect" or "antifeeding effect" was reported using very low concentrations of imidacloprid (Rust et al., 2001, 2002).
Figure 28. Resolution of signs of flea allergy dermatitis (FAD) in cats treated with imidacloprid over a 84-day study period (Keil et al., 2002).
5.3.10.1.4 Imidacloprid as combination partner in veterinary medicinal products
The ability of acaricides to repel or kill ticks, before they attach to a host and feed, is important for the prevention of transmission of tick born pathogens (Young et al., 2003). K9 Advantix™, an effective tick control agent (Spencer et al., 2003, Mehlhorn et al., 2003), is a spot-on product containing 8.8% (w/w) imidacloprid and 44% (w/w) permethrin. The mixture repels and kills four species of ticks, including Ixodes scapularis, for up to 4 weeks. It also repels and kills mosquitoes, and kills flea adults and larvae. Furthermore, a combination containing imidacloprid 10% (w/v) and permethrin 50% (w/v) in a spot-on formulation, has repellent and insecticidal efficacy, against the sand fly species (Phlebotomus papatasi) (Mencke et al., 2003), ticks (I. ricinus, Rhipicephalus sanguineus), and flea (C. felis felis) (Epe et al., 2003) on dogs.
Another combination product, (Advantage Heart™ (10% w/v imidacloprid plus 1% w/v moxidectin), a macrolide antihelmintic, has been developed as a spot-on for dermal application to kittens and cats (Arther et al., 2003). It is intended for monthly application for control of flea infestations and intestinal nematodes, and for prevention of feline heartworm disease. It controls and treats not only established adult gastrointestinal parasites, but also developmental stages, including fourth instar larvae and immature adults of Toxocara cati in cats (Hellmann et al., 2003; Reinemeyer and Charles, 2003). Furthermore, the spot-on combination is safe and highly efficacious against T. canis and Ancylostomatidae in naturally infested dogs (Hellmann et al., 2003), as well as against Sarcoptes scabiei var. canis on dogs (Fourie et al., 2003).
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