Therapy of Flea Allergy Dermatitis�SOTAL
Didier-No�l Carlotti France
State of the Art Lecture
Didier-Noel Carlotti, Doct.Vet, Dip ECVD
Thursday, August 9, 2001 (14:45 - 15:30 hr)
Dr. Didier No�l Carlotti graduated from Toulouse University in 1977, and has been a private practitioner in Bordeaux, Aquitaine, France since 1979. He decided to dedicate himself exclusively to veterinary dermatology in January 1998. He has been a full member of the American Academy of Veterinary Dermatology (AAVD) since 1985 and was the President of the French Small Animal Dermatology Study Group (GEDAC) from 1985 to 1991.
The GEDAC is a specialized group of the French Small Animal Veterinary Association (CNVSPA/AFVAC), of which he was the representative at WSAVA from 1985 to 1993, Vice-President from April 1989 until April 1993 and Secretary General from 1993 to 1999. He is currently the President of CNVSPA/AFVAC. He was also the Chairman of the Federation of European Companion Animal Veterinary Associations (FECAVA) from May 1990 to June 1995. He is a Founder Member and a Past-President (1988-1990) of the European Society of Veterinary Dermatology (ESVD). He is a Diplomate (and currently the President) of the European College of Veterinary Dermatology (ECVD). He has published about 50 papers and has given numerous lectures in the field of Veterinary Dermatology.
Pruritus due to Ctenocephalides felis infestation (pulicosis) is usually mild. However, in some individuals, exposure to fleas eventually leads to the more serious condition of flea allergy dermatitis (FAD) with severe pruritus and lesions initiated by just a small number of bites. Appropriate therapy will be required.
Symptomatic antipruritic therapy
Except in case of severe pruritus, it is probably better to avoid the use of symptomatic antipruritic therapy for monitoring the progress of an antiparasitic strategy. If necessary, pruritus may be controlled in dogs with short-term oral glucocorticoids unless bacterial folliculitis is present. In cats, glucocorticoids are better tolerated in both oral and long-acting injectable forms. Generally, oral antihistamines are not very effective in dogs but chlorpheniramine can be effective in cats.� For localised lesions (erythema, excoriations, pyotraumatic dermatitis), topical steroids or non-steroidal topical agents may be used. In fact, symptomatic therapy is of variable efficacy and may be poorly tolerated.
Palliative specific therapy
Spontaneous desensitization in an infested environment is not commonly seen in dogs and cats. Any casual approach to FAD control, with or without symptomatic treatment, is therefore unlikely to provide lasting benefit. Immunotherapy (desensitisation, hyposensitisation) is primarily effective against type-1 hypersensitivity reactions (as seen, for example, in atopic dermatitis) and these, unfortunately, form only part of the complex pathogenesis of FAD. A number of clinical studies have been performed to evaluate the benefit of immunotherapy in FAD.� It is difficult to draw conclusions from these as few included placebo controls, and because a variety of experimental designs was employed. The result of two double-blind studies in dogs and one in cats was clear-cut: no benefit was derived from treatment. However, encouraging results were recently reported in a carefully designed double-blinded placebo controlled trial using rush immunotherapy with Ct. felis flea salivary antigens in 22 dogs with FAD. Preventing the sensitized animal from being bitten by fleas remains the only therapeutical option of FAD.
Approach to flea control in case of FAD
Eradication of fleas requires considerable commitment and expense. Consequently, a definitive diagnosis is desirable. Intradermal reactions to flea extracts provide a useful diagnostic tool for use in dogs, but are less reliable in cats. Response to flea control will in fact contribute to the diagnosis of FAD. However, dogs with FAD are often simultaneously affected with atopy and corresponding clinical signs may persist.
The presence of eggs, larvae and pupae in the domestic environment will ensure that the treated animal soon becomes reinfested by newly emerged host-seeking fleas. The modern home with fitted carpets and central heating provides ideal conditions for the development of these life-cycle stages. Fleas are prolific egg-layers, producing on average 27 eggs per day, which soon drop off the animal. Larvae hatch out and crawl deep into the weave of carpets and upholstery, under furniture and appliances, and into cracks and crevices. New adult fleas may appear within two weeks, but emergence from the pupa can be delayed for more than five months, so reinfestation will occur as soon as the residual effects of the insecticide have disappeared. The creation of a totally flea-free environment has to be the objective for FAD control through a three stage process: initial elimination of fleas from animals, protection from reinfestation, and elimination of the environmental reservoir. Consequently, veterinarians are still largely dependent on chemicals for effective management of FAD.
Adulticides used in flea control
Many insecticidal compounds have been developed for flea control on animals but the majority belongs to a relatively small number of chemical groups: organochlorines, organophosphates, carbamates, natural pyrethrins, synthetic pyrethroids, rotenones, phenylpyrazoles, chloronicotinyl nitroguanidines, and avermectines.
Biological and therapeutic characteristics are generally inherent in the molecules but may be modified by formulation. They have been extensively covered in the literature. Care is therefore needed to select a product appropriate both for the particular circumstances of each individual case and the control objectives set. For example, on highly sensitive animals, newly arrived adult fleas must be killed quickly to minimise the number of flea bites; while for in-contact, non-allergic animals, the primary consideration is to kill adult fleas before they start to lay eggs.
Adulticidal efficacy is the lethal effect of a product on those fleas present on an animal at the time of treatment. If applied as a spray, or spot-on or tablet at the correct dose-rate, most modern products will give close to 100% adulticidal efficacy.
Following treatment of an animal, the lethal effect of a product on a flea population may start within minutes or may take up to 48 hours. Speed of kill, which declines with time following treatment, is of practical significance in three separate contexts:
When animals harbour a large resident flea burden (relief from the irritant effects of that infestation).
In the case of hypersensitive animals (minimal exposure to flea bite antigens).
To kill newly arrived fleas before they start to lay eggs at 24 to 36 hours after taking their first blood meal.
�Knock-down� is a term that, in pest control jargon describes the ability of aerosol formulations to bring down flying insects while on the wing. The effect need not be lethal but can be achieved by temporary paralysis. It is therefore incongruous to use this term �knock-down� to describe the cumulative insecticidal efficacy of a pulicide over 24 hours (the first observation point in most efficacy studies). Furthermore, for non-flying biting insects, it should indicate a rapid lethal or paralysing effect capable of controlling feeding activity. Fleas normally initiate feeding within an hour of finding a host. There are few published data on speed of kill, but some formulations containing dichlorvos or permethrin are acknowledged to have a particularly rapid onset (e.g., 15 minutes) whereas imidacloprid acts in a few hours.
There are two forms of repellency. In the first, fleas are deterred by the vapour phase of a compound whereas in the other form, the flea has first to come into physical contact with the substance and then moves away. In pest control jargon, this is known as a �flushing effect� and is the mechanism exhibited by some synthetic pyrethroids. This effect probably contributes to the knock-down potency of permethrin.
When controlling FAD, particularly in highly sensitive animals, there is an obvious advantage in selecting treatments with an anti-feeding effect. Permethrin and dichlorvos/fenitrothion preparations prevent feeding well, whereas relatively little antifeeding activity is observed with fipronil and imidacloprid.
Persistent efficacy is a valuable adjunct to short term adulticidal activity as it protects against reinfestation and reduces egg production for a prolonged period (preventive effect). The duration of activity of adulticidal compounds varies from a few hours to several weeks. Residual action is generally more prolonged in dogs than cats. Persistence may result from the active compound binding to hair or skin, being released slowly from a body reservoir (for example, the sebaceous glands in the case of fipronil), or from a special formulation (a collar or microencapsulated particles). Preparations such as fipronil, imidacloprid and some formulations containing permethrin have considerable residual activity extending four weeks, or sometimes more, from the time of treatment. A high percentage of host-seeking fleas arriving on a treated animal during this period will be killed. However, the speed of kill will decline with time and vary with compound. Trace amounts of some adulticidal preparations may be transferred from an animal to its immediate surroundings in quantities sufficient to have larvicidal effects. Last but not least, products recommended for flea control should be safe to use and well tolerated by the treated pet.
Insect growth regulators
Insect Growth Regulators (IGRs) differ from adulticides in that their primary action is to disrupt developmental processes. They fall into two categories: the Juvenile Hormone Analogues (JHAs) and Insect Development Inhibitors (IDIs).� IGR efficacy can persist for a prolonged period on the animal, depending on formulation and dose-level.
Formulation not only influences the biological and therapeutic properties of a compound but provides the veterinarian with a choice of methods of administration. Client compliance is extremely important in FAD cases.
Insecticidal shampoos are not useful in FAD since rinsing removes insecticide with most. Collars are not always completely effective. Systemic formulations (spot-on or oral adulticides, oral or injectable IGRs) are useless in FAD since exposure depends on fleas biting, but IGRs can be a useful adjunct to adulticide treatment.
Effective formulations for the treatment of FAD are lotions, powders, sprays, pump-sprays, foams, and spot-ons/line-ons. Lotions (dips) are inexpensive but may be malodorous. With powders, there is a risk of build-up in the coat if more than one dose is given. Sprays (aerosols) may be difficult to use with nervous animals. So, preference is often shown for pump-sprays, foams, and spot-ons. Pump-sprays have a good residual action but are relatively expensive. Foams are particularly suitable for cats. Spot-ons and line-ons are a recent innovation and are widely used.
Treatment of an infested environment
Control of fleas in the domestic environment by applying chemicals directly onto surfaces where eggs, larvae, pupae and emergent adults might be found can be very effective if all potential �hotspots� are covered.
Veterinary insecticidal powders can be used indoors on small surfaces but they are impractical, messy and not very effective. Powders containing mineral insecticides (e.g., diatomaceous earth) are suitable for use outdoors. Inside, sodium polyborate is remarkably effective. Aerosols are effective to treat the environment (small areas); these include veterinary and general household insect sprays. Most contain an IGR combined with an adulticide. This is also the case with foggers which are aerosols supplied in pressurised containers that, once triggered, rapidly emit all of their contents. They are easy to use and particularly suited for carpeted areas but additional treatment of particular �hot spots� is recommended.
Pump-sprays are convenient to use in any location and are better than aerosols for treating large areas. They are less practical than foggers and tend to be used outside and for the treatment of �hot-spots� in rooms with tiled floors. For large non-carpeted areas (kennels, garages, cellars, wine-cellars, attics, boxrooms etc), large sized pump-sprays (5-10 litres) may be used containing either emulsions used as lotions or, especially, suspensions of wettable powders (such as permethrin formulations used in stables to control flies). Outdoor areas (sand, gravel, terraces) can also be treated in dry weather. Preparations may be specially formulated for use with devices, such as one that can be fixed to a garden-hose, designed to facilitate application to outside areas.
On-animal environmental control
The recent development of new long-acting adulticidal and IGR treatments has enabled alternative methods to be developed that utilise animal treatments to break the flea life cycle. Theoretically, stringent control of adult fleas on all animals in a household will prevent any eggs from dropping to the ground, but in fact, a low environmental infestation may persist. Actually, it is possible to recover small numbers of viable eggs from cats infested in the third and fourth weeks following fipronil or imidacloprid treatment. This suggests that a treatment interval shorter than the recommended month or that a combination with an IGR may be needed.
IGRs can also be used for depleting the environmental reservoir of flea infestation. The use of oral or injectable lufenuron for this purpose is now well established. In cases of simple pulicosis, lufenuron has the advantage of simplicity in a domestic hygiene programme. It may keep a flea population in check or even eradicate it in closed environments (which are exceptional in an urban or suburban setting). Topical use of pyriproxyfen or methoprene may also make substantial reductions in flea fertility. The sensitivity of eggs decreases with time after they are laid and so topical treatments have the advantage that the eggs are exposed to the IGR during the period of greatest vulnerability. Also, sufficient pyriproxyfen may be transferred from the pelage of a treated animal to its bedding.
Future flea vaccination could provide a convenient way of reducing the number of fleas in a household, but the flea has to bite to become exposed to the antibody. This will limit the usefulness of flea vaccine in the control of FAD.
Strategies for FAD control
Cases vary so much with regard to environmental conditions, presence of in-contact animals, type of allergic animal (dog or cat, breed, behaviour towards in-contacts, reactions to treatment, etc.), that it is impossible to propose an ideal universal therapeutic plan; every case is unique. Control objectives and a strategy for their attainment have to be carefully defined and explained to the owners. The first step is the initial elimination of fleas from animals with a good adulticide. Reinfestation with adult fleas may be acquired from the environment and sometimes by direct contact with other animals.
Protection from reinfestation can be provided in a number of ways and choice of product will be determined by factors such as the possible or likely challenge pressure and degree of hypersensitivity of animals at risk. Agents with a good antifeeding effect, such as permethrin or dichlorvos/fenitrothion should be selected in cases of persistent exogenous infestation or for highly sensitive individuals. Some permethrin formulations claim to combine good antifeeding and long residual effects. Moderately sensitive individuals (i.e., those able to tolerate a few bites) can be treated with slower acting insecticides, such as fipronil and imidacloprid which kill fleas within a few hours and give long term benefits by reducing the flea population and hence antigenic challenge over time. For in-contact animals not sensitized to fleabites, the use of a slower acting preparation or an insecticidal collar may also be sufficient. In cases of FAD, highly effective and long-acting insecticidal formulations such as pump-spray, spot-on, line-on or, for cats, foam preparations are indicated. Systemic treatments such as cythioate (which is no longer available in all countries) should not be used for FAD cases, but are useful in non-allergic cats living in contact with allergic dogs.
The requirements for a successful eradication programme are a good communication with the client, including comprehensive questioning and an appropriate follow-up; an appropriate selection of topical products for allergic and non-allergic animals; the treatment of all in-contact animals; and the appropriate treatment of the environment (indoor and outdoor) with particular care to identify and treat all hot spots. Consequently, there are a lot of possible causes of failure, for example, incomplete compliance with recommendations, one of several household pets not being treated, product efficacy being reduced by bathing/shampooing, animals becoming infested outside the home, untreated animals entering from outside, etc. In addition, if on-animal treatments are used for environmental control, long acting adulticides may be necessary in heavily infested premises for the duration of the �pupal window.�
As yet, insecticide resistance in fleas is not recognised as a major problem in Europe, but authenticated cases are reported in North America. Many suspected cases are unfounded, either because the product was incorrectly used, or because the treated animal was exposed to overwhelming numbers of newly emerged adults. Prevention of resistances can be achieved by the use of effective adulticides at the correct and minimal dose (to minimise selection pressure) and at appropriate intervals, without relying on one chemical group for extended periods, but also in designing control programmes that utilise chemical groups with different modes of action, for example combining a long acting adulticide and an IGR.
The only effective curative and preventative treatment for FAD currently available is to protect the animal from fleas. An integrated approach is necessary which avoids overdependence on chemical control and minimises the risk of insecticidal resistance developing. To achieve this aim it is essential to have a good knowledge of flea biology and epidemiology of flea infestation, the properties of available insecticides and IGRs (both the compounds and their formulations), and the principles underlying flea eradication strategies.
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