Pilot study to assess the effects of early flea exposure on the development of flea hypersensitivity in cats

This pilot study was to determine if early oral flea exposure reduces the incidence of flea allergy dermatitis (FAD) in cats. Eighteen kittens, assigned to three groups, received no flea exposure, oral flea exposure or flea infestation for 12 weeks. Then all the kittens were exposed continually to fleas for 31 weeks. Sensitization was monitored using intradermal testing (IDT), in vitro measurement of anti-flea saliva immunoglobulin E (IgE) and development of FAD. There was no statistically significant difference between groups in IDT reactions, in vitro data or clinical scores. The development of FAD was not associated with the presence of anti-flea saliva IgE. However, the development of a delayed reaction to flea bite was associated with symptoms after flea exposure. Although not statistically significant, the FAD scores in the oral group were lower than in the controls. Further studies are required to determine the role of oral flea exposure in the development of FAD in cats.     

Flea bite hypersensitivity: new aspects on the involvement of mast cells

A study was performed to test the effect of sensitization to flea antigen, followed by exposure to fleas on mast cells (MCs), their subtypes, and IgE+ cells. Biopsies were taken from flea-sensitized dogs (n=28) and non-sensitized dogs (n=5) that had been exposed to fleas. Control groups consisted of flea-sensitized (n=12) and non-sensitized dogs (n=9) that were not exposed to fleas. Biopsies, taken before, 24 and 72 h after local flea exposure, were stained with haematoxylin and eosin (H&E), toluidine blue, a double labelling technique for MC chymase and tryptase and anti-IgE. An intradermal test for flea antigen was performed and serum titres of allergen-specific IgE and IgG were measured. Significantly higher numbers (P<0.001) of double labelled MCs compared to toluidine blue stained MCs were detectable in flea-sensitized dogs independent of flea exposure. In contrast, in non-sensitized dogs, the number of toluidine blue stained MCs and the number of double labelled MCs did not differ. In flea-sensitized dogs after flea exposure the percentage of C-MC was significantly increased at day 1 (P<0.001) and day 3 (P<0.001), whereas the percentage of TC-MCs decreased significantly at day 1 (P<0.001) and day 3 (P<0.05). The percentage of T-MCs decreased (P<0.05 day 0 versus day 1; P<0.05 day 0 versus day 3). No significant difference was detectable after toluidine blue staining and staining for IgE+ cells between the groups nor between the MC density and the number of IgE+ cells. All flea-sensitized dogs had positive skin tests to flea antigen and high serum titres of flea-specific serum IgE and IgG antibodies. In non-sensitized dogs, these results were negative. Our data provide strong evidence for an upregulation of MC proteases during the process of sensitization and a generalized selective release of mast cell tryptase after exposure to the antigen.     

IgE and IgG antibodies to flea antigen in differing dog populations

A radioimmunoassay was developed for the detection of IgG and IgE canine antibodies against partially purified flea antigen. Low background levels were found in flea naive dogs, but high levels of both IgE and IgG antibodies were found in many sera from dogs with clinical flea hypersensitivity. In sera from non-allergic dogs exposed chronically to fleas, IgE levels differed little from background, and levels of IgG anti-flea antibodies were much lower than those from the flea allergic group. The results suggest that chronic flea exposure may result in partial or complete tolerance rather than hyposensitization in the commonly accepted sense.     

Immune dysregulation in flea allergy dermatitis--a model for the immunopathogenesis of allergic dermatitis

BACKGROUND: Flea allergy dermatitis (FAD) is a common skin disease in dogs and can be induced experimentally. It often coexists with other allergic conditions. So far no studies have investigated the quantitative production of cytokine mRNA in skin biopsies and peripheral blood mononuclear cells (PBMC) in flea allergic dogs. OBJECTIVE: The aim of our study was to improve the understanding of the immunopathogenesis of allergic dermatitis as a response to fleabites. MATERIAL AND METHODS: Allergic and non-allergic dogs were exposed to fleas. Before and after 4 days of flea exposure mRNA was isolated from biopsies and PBMC. Production of chymase, tryptase, IL-4, IL-5, IL-13, TNF-alpha and IFN-gamma mRNA was measured by real-time RT-PCR. The inflammatory infiltrate in the skin was scored semi-quantitatively. The number of eosinophils, mast cells (MC) and IgE+ cells/mm2 was evaluated to complete the picture. RESULTS: FAD was associated with a higher number of MC before flea exposure and with a significant increase of eosinophils after flea exposure as compared to non-allergic dogs. The number of IgE+ cells was higher in allergic dogs before and after flea exposure. In allergic dogs mRNA for most cytokines and proteases tested was higher before flea exposure than after flea exposure. After exposure to fleas an increased mRNA production was only observed in non-allergic dogs. In vitro stimulation with flea antigen resulted in a decreased expression of most cytokines in allergic dogs before flea exposure. In contrast, in PBMC, only increased levels of IL-4 and IL-5 mRNA were observed in allergic dogs before flea exposure. However, after flea exposure and additional stimulation with flea antigen the production of mRNA for all cytokines tested was significantly increased in allergic dogs. CONCLUSION: We demonstrated that the response in biopsies and PBMC is different and that FAD is associated with a TH2 response.     

Monoclonal anti-IgE antibodies in the diagnosis of dog allergy

The availability of anti-dog IgE monoclonal antibodies has enabled development of highly specific ELISA assays for measuring antigen-specific IgE in dog serum. In this article the authors propose criteria for evaluation of these monoclonals and demonstrate that some anti-human IgE monoclonals recognize dog IgE. Combinations of two or more monoclonal antibodies can enhance assay sensitivity; for example, a mixture of DE38.HRPO and 4F4.HRPO conjugates detect total dog IgE in the range 10–10000 ng/mL. Results are reported from nine clinical studies conducted in Europe, Japan and Australia involving more than 400 dogs in which serologic IgE determinations performed using the CMG IMMUNODOT strip system for house dust mites, storage mites, flea, grass pollens and moulds were compared with immediate skin test findings. House dust mites were identified as the common major dog allergen throughout these areas although regional reactions to food allergens were observed. These results confirm that the CMG IMMUNODOT system is a valuable and reliable diagnostic test for dog allergy.     

Putative salivary allergens of the cat flea, Ctenocephalides felis felis.

The cat flea, Ctenocephalides felis felis, is the major initiator of flea bite hypersensitivity in dogs. Previous analyses of whole extracts of the flea and flea salivary secretions have failed to identify the allergens responsible. We dissected >2000 salivary glands from adult female fleas, extracted them into buffered saline containing protease inhibitors and fractionated the extract using gel permeation HPLC. Dogs were classified as hypersensitive to fleas (flea-feeding positive, FF+) or insensitive (flea-feeding negative, FF-) using a provocative test with live fleas. The allergenicity of the components of the salivary gland extract was tested by intradermal injection of samples of the column eluates. Dogs were also injected intradermally with a sample of whole salivary gland extract, and with histamine as a positive control. Negative control injections consisted of eluate from the column collected prior to fractions containing any protein. The skin of FF- dogs either did not respond or had a minimal response (a bleb approximately 2 mm larger than the injection blebs at the negative control injection sites) to all fractions and to the whole extract; histamine control injections produced positive responses (defined as wheals 5 mm greater than the blebs at the negative control injection sites) in all dogs. The skin of three of the nine FF+ dogs reacted positively to injection of a fraction containing protein/s with apparent MW 40k. Five other FF+ dogs reacted positively to the fractions containing proteins with apparent MW 12-8k. A single dog responded with very large, red wheals to injection of both the approximately MW 40k and MW12-8k fractions. These findings suggest that proteins with apparent MW 40k and MW 12k-8k are important in flea bite hypersensitivity. This work also supports a previous finding that mice which had been exposed to flea bites had antibodies to proteins with approximately MW 40k that were detected in salivary secretions of the flea.     

FC-53 Serologic allergy testing in horses with insect hypersensitivity

The usefulness of the intradermal test (IDT) and the serological allergy test (SAT) for detecting antigen-specific IgE in allergic cats has not yet been established. In this study, we compared the results of IDT with those of SAT and evaluated the clinical usefulness of the two tests for detecting possible allergens in allergic cats. IDT and SAT using eight antigens were performed on 22 cats with intense pruritus after excluding ectoparasites and performing diet elimination tests. Approximately 50% of the cats reacted to at least one allergen by either IDT or SAT, and 36.4% of the cats reacted on both IDT and SAT. In contrast, seven healthy cats did not show any reactions on IDT or SAT. The most commonly detected allergen in both tests was house dust mites (IDT, 36.4%; SAT, 40.9%). Five cats reacted to one allergen and the others reacted to more than one allergen with IDT. Three cats reacted to one allergen with SAT. The following percentage agreement between the results of the two tests was calculated: house dust mites (86.4%), cat fleas (63.6%), grass mix (86.4%), common mugwort (81.8%), cat epithelia (90.9%), ragweed (86.4%), Japanese cedar (90.9%), and plantain (81.8%). The overall mean percentage agreement was 83.5%. In summary, the present study showed good agreement between IDT and SAT for cats, and SAT may be more sensitive than IDT, but less specific for detecting sensitized allergens.
Funding: Self-funded.     

Efficacy of selamectin in the treatment and control of clinical signs of flea allergy dermatitis in dogs and cats experimentally infested with fleas

OBJECTIVE: To determine whether treatment with selamectin would reduce clinical signs of flea allergy dermatitis (FAD) in dogs and cats housed in flea-infested environments. DESIGN: Randomized controlled trial. ANIMALS: 22 dogs and 17 cats confirmed to have FAD. PROCEDURE: Animals were housed in carpeted pens capable of supporting the flea life cycle and infested with 100 fleas (Ctenocephalides felis) on days -13 and -2 and on alternate weeks with 10 to 20 fleas. On day 0, 11 dogs and 8 cats were treated with selamectin (6 mg/kg [2.7 mg/lb]). Dogs were retreated on day 30; cats were retreated on days 30 and 60. All animals were examined periodically for clinical signs of FAD. Flea counts were conducted at weekly intervals. RESULTS: Throughout the study, geometric mean flea counts exceeded 100 for control animals and were < or = 11 for selamectin-treated animals. Selamectin-treated cats had significant improvements in the severity of miliary lesions and scaling or crusting on days 42 and 84, compared with conditions on day -8, and in severity of excoriation on day 42. In contrast, control cats did not have any significant improvements in any of the clinical signs of FAD. Selamectin-treated dogs had significant improvements in all clinical signs on days 28 and 61, but in control dogs, severity of clinical signs of FAD was not significantly different from baseline severity at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical administration of selamectin, even without the use of supplementary environmental control measures and with minimal therapeutic intervention, can reduce the severity of clinical signs of FAD in dogs and cats.     

Control of immature stages of the flea Ctenocephalides felis (Bouché) in carpets exposed to cats treated with imidacloprid

Fleas cause allergic dermatitis in cats and dogs and therefore warrant control. It has been demonstrated previously that there is marked inhibition of the development of the immature stages of the cat flea Ctenocephalides felis on fleece blankets exposed to cats treated with imidacloprid. This study reports on the efficacy of imidacloprid in suppressing adult flea emergence in carpet exposed to treated cats. Circular discs of carpet pre-seeded with flea eggs and larvae were exposed to 6 untreated control and 6 topically treated (imidacloprid 10% m/v) cats 1 to 2 days after treatment and subsequently fortnightly for 6 weeks. Exposure times on alternate days were either 1 or 6 hours. Adult flea yield from carpets was determined 35 days after exposure. Differences between flea yield on control carpets and those exposed for 1 hour were significant only for days +1 and +14. For the 6-hour exposure, differences were significant at all times except on Day +43. The ability of imidacloprid to suppress the yield of adult fleas on carpets (6-hour exposure) steadily declined from 82 % (Day +2) to 12% (Day +43). For the 1-hour exposure it varied inconsistently between 0 and 83% over the 6-week study period.     

Diagnosis of flea allergy dermatitis: comparison of intradermal testing with flea allergens and a FcepsilonRI alpha-based IgE assay in response to flea control

The objective of this study was to evaluate the accuracy of in vivo and in vitro tests in the diagnosis of flea allergy dermatitis in comparison with history, clinical signs and response to flea control. Intradermal testing using four different sources of flea allergens and FcepsilonRIalpha-based immunoglobulin (Ig)E assays were performed in 15 flea-allergic dogs, 15 atopic dogs and 15 dogs infested with fleas but showing no clinical signs of skin disease. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were calculated for all five tests and results varied greatly. Sensitivity, specificity and overall accuracy were 27, 83 and 64%, respectively, for one extract (Isotec), 67, 90 and 82% for another extract (Greer), 93, 90 and 91% for flea saliva, 40, 90 and 73% for the recombinant Cte f 1 both produced by Heska Corp. and 87, 53 and 64% for a FcepsilonRIalpha-based IgE assay. These results indicate that intradermal testing with flea extracts is more accurate in the diagnosis of flea allergy dermatitis than in vitro tests. Moreover, pure flea saliva used as a reagent for intradermal testing provided the best results in terms of sensitivity, specificity and overall accuracy although the Greer extract, a whole body flea extract, also allowed a good correlation between intradermal testing results and clinical approach to flea allergy dermatitis diagnosis.     

The biology of Dipylidium caninum. Part 2

From 198 cats and 182 dogs in Austria 9,134 fleas were collected. Ctenocephalides felis is the main flea of our cats (98.5%) and dogs (77.5%). Demonstration of cysticercoids of Dipylidium caninum through bleaching of fleas failed. Dissection of fleas gave, however, positive results. Each 44th flea from cats and 61st flea from dogs harbours cysticercoids. Infection intensity rates were 2.3% for C. felis (cats), 1.2% for C. felis (dogs), and 3.1% for C. canis (dogs). Male fleas are more extensively, but less intensively infected than female fleas. Cysticercoids form fleas of feline origin are more infective to cats than those from fleas found on dogs. The longest patency in cats lasted 3 years.     

Hypersensitivity of dog skin to fleas-a clinical report

The results of an examination of the clinical signs, epidemiology and histopathology of dogs presented with flea bite dermatitis at two Dublin clinics are given. Whilst the majority of Dublin dogs are infested with fleas only some develop a reaction to flea saliva.
It is concluded that on the evidence available, flea dermatitis is a hypersensitive reaction to flea saliva and elimination of fleas from the environment of affected animals remains the best method of controlling the disease.     

Comparison of intradermal and serum testing for allergen-specific IgE using a Fcepsilon RIalpha-based assay in atopic dogs in the UK

Atopic dermatitis in dogs is a common allergic skin disease that affects substantial numbers of dogs in the UK. The purpose of this study was to compare the results of an intradermal test (IDT) and an in vitro test in a large cohort of dogs. Dogs were intradermal tested with Greer allergens (Greer Labs Inc, Lenoir, NC, USA) using standard techniques. At the same time blood samples were drawn and submitted for evaluation by ELISA using the ALLERCEPT Definitive Allergen Panels for allergen-specific IgE, a commercial assay that uses a biotinylated recombinant extracellular domain of the high affinity Fc-epsilon receptor alpha chain protein (Fcepsilon RIalpha). The allergens used in the two tests included grass, tree and weed pollens, moulds, flea saliva/whole flea extract and house dust mite species. The optical density readings from the ELISA for each allergen were compared with the results of the IDT for 265 dogs. The prevalence of positive reactions in the ELISA was equal to or greater than the results of the IDT in the case of almost all of the allergens, but two notable exceptions were the house dust mites Dermatophagoides farinae and Dermatophagoides pteronyssinus. These two allergens were the most common positive reactions by IDT (prevalence D. farinae 78.9%, D. pteronyssinus 66.4%). The results of the two tests were significantly different (McNemar's test, P<0.05) for 16 of the 22 allergens. The sensitivities of the ELISA compared to the IDT (where there were more than 3 dogs with positive reactions in both tests) varied between 19.3 and 77.1% (D. pteronyssinus 19.3% and D. farinae 67.9%) and the specificities varied between 64.2 and 96.6% (D. pteronyssinus 96.6% and D. farinae 89.3%).     

Flea species infesting dogs in Florida and Bartonella spp. prevalence rates

Several Bartonella spp. associated with fleas can induce a variety of clinical syndromes in both dogs and humans. However, few studies have investigated the prevalence of Bartonella in the blood of dogs and their fleas. The objectives of this study were to determine the genera of fleas infesting shelter dogs in Florida, the prevalence of Bartonella spp. within the fleas, and the prevalence of Bartonella spp. within the blood of healthy dogs from which the fleas were collected. Fleas, serum, and EDTA-anti-coagulated whole blood were collected from 80 healthy dogs, and total DNA was extracted for PCR amplification of Bartonella spp. The genera of fleas infesting 43 of the dogs were determined phenotypically. PCR amplicons from blood and flea pools were sequenced to confirm the Bartonella species. Amplicons for which sequencing revealed homology to Bartonella vinsonii subsp. berkhoffii (Bvb) underwent specific genotyping by targeting the 16S–23S intergenic spacer region.A total of 220 fleas were collected from 80 dogs and pooled by genus (43 dogs) and flea species. Bartonella spp. DNA was amplified from 14 of 80 dog blood samples (17.5%) and from 9 of 80 pooled fleas (11.3%). B. vinsonii subsp. berkhoffii DNA was amplified from nine dogs and five of the flea pools. Bartonella rochalimae (Br) DNA was amplified from six dogs and two flea pools. One of 14 dogs was co-infected with Bvb and Br. The dog was infested with Pulex spp. fleas containing Br DNA and a single Ctenocephalides felis flea. Of the Bvb bacteremic dogs, five and four were infected with genotypes II and I, respectively. Of the Bvb PCR positive flea pools, three were Bvb genotype II and two were Bvb genotype I.Amplification of Bvb DNA from Pulex spp. collected from domestic dogs, suggests that Pulex fleas may be a vector for dogs and a source for zoonotic transfer of this pathogen from dogs to people. The findings of this study provide evidence to support the hypothesis that flea-infested dogs may be a reservoir host for Bvb and Br and that ectoparasite control is an important component of shelter intake protocols.     

Efficacy of Pyriprole Topical Solution against the Cat Flea, Ctenocephalides felis, on Dogs

Three studies evaluating various aspects of the performance of pyriprole against the cat flea, Ctenocephalides felis, on dogs demonstrated that 12.5% pyriprole applied as a spot-on provides rapid, long-lasting efficacy against adult cat fleas, even under severe flea challenge. Speed of kill data indicate treatment with this product can interrupt an already established adult flea infestation, whereas monthly treatment can prevent reinfestation. Pyriprole disrupts the flea life cycle by killing adult fleas before they lay eggs for at least 30 days after treatment. The residual effect of pyriprole on debris from treated dogs (dander, hair, scales, and flea feces) resulted in a decreased ability of cat flea larvae to complete development to the adult stage for 2 weeks after application. Based on the results of these studies, 12.5% pyriprole represents a valuable new tool in the control of the cat flea, C. felis, on dogs.     

Insecticidal activity of temephos against Ctenocephalides felis on dogs and cats.

Dogs and cats were treated with 2% temephos [0,0'-(thiodi-p-phenylene) 0,0',0'-tetramethyl bis (phosphorothioate)] powder to evaluate its insecticidal activity against the cat flea (Ctenocephalides felis). Dogs and cats were infested each week with approximately 100 unfed, unsexed fleas less than 14 days old. Live-flea counts were made each day. The experiment was terminated when all dogs and cats retained live fleas for 6 days or more. The 2% temephos powder resulted in excellent flea control on dogs and cats for 2 weeks, partial control for 3 to 4 weeks, and no effective control beyond 4 weeks.     

Efficacy of an adulticide used alone or in combination with an insect growth regulator for flea infestations of dogs housed in simulated home environments.

OBJECTIVE: To determine the effect of an adulticide on flea populations of dogs and to evaluate efficacy of combined use of the adulticide and an insect growth regulator (IGR) in dogs with experimentally induced flea infestations. ANIMALS: 40 adult Beagles. PROCEDURE: Each group of 5 dogs was housed in a separate room. Each dog was infested 3 times with 50 fleas, and fleas were counted beginning on day -21. Groups of dogs and treatments (initiated on day 0) were as follows: 1, adulticide once; 2, adulticide on days 0 and 7; 3, adulticide on days 0, 3, and 7; 4, sham treatment; 5, IGR monthly; 6, IGR monthly plus adulticide once weekly for 6 weeks; 7, IGR monthly plus adulticide twice weekly for 6 weeks; 8, sham treatment. Flea counts were compared between treated and control dogs. RESULTS: By 24 hours after initial treatment, all adult fleas but 1 were dead in treated dogs. In groups 1 and 3, populations increased to 15 to 20 fleas/dog 2 months after treatment, compared with 48 fleas/dog in group 4. After treatment, mean flea counts were significantly lower for groups 1, 2, and 3, relative to group 4. Efficacy of treatment for group 5, relative to group 8, was > 94% after day 84. Efficacy of treatment for groups 6 and 7 was 99% after day 28. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with adulticide alone or in combination with an IGR had better efficacy, compared with sham treatment or IGR alone. Administration of adulticide twice weekly was not more efficacious than treatment once weekly.     

A rodent model for allergic dermatitis induced by flea antigens

There have been very few reports of experimentally induced animal models of allergic dermatitis, an immunologic disorder. This report describes the induction of histopathology confirmed allergic dermatitis in C57BL/6 mice along with the consistent clinical sign of alopecia following the administration of flea antigens emulsified in complete Freund's adjuvant (CFA). By comparing different strains of mice, routes of injection, types of adjuvants and different dosages of flea antigens, C57BL/6 mice were found to be most susceptible to flea antigens administered intramuscularly (i.m.) and subsequently developed dermatologic excoriations and local alopecia. The level of specific IgE reactive to flea antigens in C57BL/6 mice after the onset of clinical signs was significantly higher than such levels in mice without clinical signs, suggesting that flea antigen-specific IgE level can be correlated to the severity of allergic hyper-reaction. CD4(+) T lymphocytes and IL-4 rather than IL-10, or IFN-gamma were found to be the predominant cytokines associated with the clinical onset of allergic symptoms in C57BL/6 mice. Further, histopathologic analysis indicated that not only mast cells had infiltrated into the area of the skin lesion, but the damage was found to be at a stage where mast cells were degranulating causing considerable exacerbation of the local injury. In conclusion, this murine allergic dermatitis model induced by flea antigens may provide a useful means to evaluate vaccines or immunodulatory drugs; thus providing researchers with a tool to study allergy-related disorders and other parameters needed in the area of allergic investigations.     

A survey of fleas on dogs in southern Italy

A survey aimed at studying the presence and distribution of fleas on dogs was conducted in an area of southern Italy. Between February 2005 and 2006, dogs were examined for fleas at four private veterinary clinics, with a twice-weekly frequency. Fleas were detected on 246 (17.9%) out of the 1376 tested dogs. A total of 960 fleas were sampled and two species were identified, namely Ctenocephalides felis felis (16.3% of the tested dogs) and Ctenocephalides canis (1.5% of the tested dogs). The results of the logistic regression model showed a significant association between the flea positivity and the following independent variables: housed with other dogs or cats and utilization, i.e. increasing prevalence from pets to guard, hunting, and stray dogs. Clinical symptoms (pruritus, alopecia, and flea allergic dermatitis) were also observed in some of the flea positive dogs. Flea infestation was detected throughout the year, although the prevalence was higher during the period between June and October.     

Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides felis felis) on dogs and cats

Selamectin, a novel avermectin, was evaluated in two controlled studies (one in Beagles, one in domestic shorthaired cats) to determine an appropriate topical dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on dogs and cats for 1 month. For each study, animals were allocated randomly to four treatments. One treatment consisted of the inert formulation ingredients (vehicle) administered as a negative control, and the other three treatments consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each study, selamectin was administered as a topical dose applied to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11, 18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21, and 30, a comb count to determine the number of viable fleas present on each animal was performed. Efficacy of selamectin on day 30 was used to select an appropriate dose. For dogs and cats, percentage reductions in geometric mean flea comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days 7, 14, and 21, compared with the negative-control treatment. On day 30, reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8, 98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1), respectively. For day 30 flea comb counts for dogs and cats, analysis of variance showed that the three selamectin treatments resulted in significantly (P< or =0.05) lower counts than did the negative-control treatment. For dogs and cats, geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1) were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1) treatment dosages combined. There were no significant differences in flea counts between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear-plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult fleas for both dogs and cats, as estimated by the turning point (plateau) in the dose response curve, was 6mgkg(-1).