Effects of lufenuron treatment in cats on the establishment and course of Microsporum canis infection following exposure to infected cats

OBJECTIVE: To determine effects of lufenuron treatment in cats on the establishment and course of Microsporum canis infection following exposure to infected cats. DESIGN: Experimental trial. ANIMALS: 24 healthy juvenile domestic shorthair cats. PROCEDURE: 8 cats were given lufenuron PO (133 mg/cat/mo, equivalent to a dose of 100 to 130 mg/kg [45 to 59 mg/lb] at the beginning of the study and 25 to 35 mg/kg [11 to 16 mg/lb] at the end of the study), and 8 were given lufenuron SC (40 mg every 6 months). The remaining 8 were used as untreated control cats. After 4 months, cats were challenged by the introduction of cats with mild, experimentally induced M canis infection into the rooms where cats were housed. Extent of resulting infections in the na?ve cats was monitored for 22 weeks by physical examination and fungal culture. RESULTS: All lufenuron-treated and control cats became infected with M canis. Cats treated with lufenuron had significantly lower infection scores, compared with control cats, during the early weeks following exposure, and there was a more prolonged initial progression phase of the infection. Once infections reached peak intensity, they resolved over similar periods in lufenuron-treated and control cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that oral or SC administration of lufenuron to cats, at the dosages used and under the conditions of this study, did not prevent establishment of dermatophytosis following exposure to infected cats. Infection was established more slowly among cats treated with lufenuron, but once established, infection resolved in approximately the same amount of time in lufenuron-treated as in control cats.     

P-15 Identification of Malassezia spp. isolated from a cat and cattle, including a new species, M. nana

Preliminary studies showed that lufenuron inhibits chitin synthesis, a dermatophyte cell wall constituent, and may be effective in the treatment of dermatophytosis. Our purpose was to evaluate the efficacy of lufenuron in the treatment of feline dermatophytosis. Forty-six cats (Persians and mixed-breed cats from 1-month to 4-years old) naturally infected with Microsporum canis were included in this study. Fifteen cats were treated isolated in cages in the veterinary hospital and 31 were treated in their home environment (some with access to the outdoors). Dermatophyte skin lesions were seen in 29 animals while 17 other cats were asymptomatic carriers. Wood's lamp, direct microscopic examination of hairs, fungal culture and skin biopsies were used for the diagnosis. Affected cats and all in-contact animals received lufenuron at a dose of 120 mg/kg every 21 days for four treatments. Of the 29 symptomatic cats treated with lufenuron, 70% recovered within 21 days and 28% within 42 days of initiation of therapy. One cat had only partial recovery and another was euthanized. Negative fungal culture was recorded only after the fourth dose of lufenuron in 98% of affected cats and 100% of asymptomatic carriers. There was no difference in clinical response to lufenuron between the cats treated in their home environment and those treated in the veterinary hospital. Side effects were not observed, thus the drug proved to be safe and effective for the treatment of dermatophytosis.
Funding: Novartis.     

Safety and immunologic effects after inoculation of inactivated and combined live-inactivated dermatophytosis vaccines in cats

OBJECTIVE: To determine antidermatophyte immunologic effects of an experimental combined live-inactivated dermatophytosis vaccine (CLIDV) and a commercial inactivated dermatophytosis vaccine (IDV) in cats and to evaluate adverse effects associated with administration of these vaccines. ANIMALS: 20 healthy juvenile domestic shorthair cats. PROCEDURE: Cats were injected with 2 doses of CLIDV at the standard dosage or 1 dose of CLIDV at 10 times the standard dosage; IDV was administered at the manufacturer-recommended dosage. Cats were observed for illness and reactions at inoculation sites. Periodically, samples were obtained for fungal culture, lymphocyte blastogenesis test (LBT) as an indicator of cell-mediated immunity against dermatophyte antigens, and antidermatophyte IgG titers. Following vaccination, cats were challenge-exposed by topical application of Microsporum canis macroconidia and examined weekly for clinical signs of dermatophytosis. RESULTS: of 10 cats given CLIDV developed focal crusts at the injection site that resolved without treatment; these were areas of dermatophyte infection with the vaccine strain. Antidermatophyte IgG titers increased significantly with all vaccination protocols. Cellular immunity against M canis increased slightly and variably during the vaccination period and did not differ significantly between vaccinated and control cats. All cats developed dermatophyte infection after challenge exposure. Vaccination with CLIDV or IDV was associated with slightly reduced severity of initial infection. CONCLUSIONS AND CLINICAL RELEVANCE: Noculation with IDV or CLIDV did not provide prophylactic immunity against topical challenge exposure with M canis. Inoculation with either vaccine did not provide a more rapid cure of an established infection.     

A lufenuron pre-treatment may enhance the effects of enilconazole or griseofulvin in feline dermatophytosis?

The effectiveness of enilconazole (4 weekly rinses with a 0.2% solution) or griseofulvin (50mg/kg twice daily for 40 days) following a pre-treatment with oral lufenuron (100mg/kg by-weekly for 8 weeks) was tested on 25 (11+14) Microsporum canis infected cats. Control animals were treated with lufenuron, griseofulvin and enilconazole alone. At day 150 pre-treated animals were culturally negative and clinically cured. While lufenuron alone was found to be ineffective against M canis infection, an immunomodulatory effect of the drug can be suggested, as reported in literature. Its use could be reserved to long-lasting infections, unsuccessfully treated with conventional drugs. Further studies are required to clearly establish the possible adjuvant effect of this molecule when used prior to enilconazole or griseofulvin.     

Evaluation of the efficacy of oral lufenuron combined with topical enilconazole for the management of dermatophytosis in catteries

The efficacy of oral lufenuron, a chitin synthetase inhibitor, combined with topical enilconazole, was evaluated for the management of Microsporum canis infection in 100 cats housed in two catteries in France. The cats were treated with weekly rinses with enilconazole (0.2 per cent) for four weeks and, in each cattery, one group (A) was also treated with micronised griseofulvin (25 mg/kg administered orally twice a day for five weeks) and a second group (B) was treated with 60 mg/kg lufenuron administered orally once on day 0 and again after 30 days. All the cats were examined individually for cutaneous lesions and mycological cultures were made when the treatment began and after 15, 30, 60 and 90 days. In the first cattery, the cats' clinical scores after 30 and 60 days were significantly lower in group B than in group A. In both catteries and both treatment groups, the mean number of fungal colonies decreased rapidly during the first 15 days of treatment, remained stable for the following 45 days but increased from day 60 to the end of the experiment on day 90.     

Use of lufenuron for treating fungal infections of dogs and cats: 297 cases (1997-1999)

OBJECTIVE: To evaluate use of lufenuron for treating cutaneous fungal infections in dogs and cats. DESIGN: Retrospective study. ANIMALS: 156 dogs and 201 cats with dermatophytosis or superficial dermatomycoses. PROCEDURE: Medical records were reviewed for dogs and cats that had been treated for dermatophytosis or other fungal infections by administration of lufenuron and 18 dogs and 42 cats that were not treated and served as a control group. RESULTS: Dogs were treated once by oral administration of lufenuron tablets at doses ranging from 54.2 to 68.3 mg/kg (24.6 to 31.0 mg/lb) of body weight. Samples of skin, scrapings, and hair were obtained daily from 14 dogs with dermatophytosis; mean durations from time of treatment to time of negative fungal culture results and resolution of gross lesions were 14.5 and 20.75 days, respectively. In all treated dogs, gross lesions resolved within approximately 21 days. Cats were treated once by oral administration of lufenuron suspension in doses ranging from 51.2 to 266 mg/kg (23.3 to 120.9 mg/lb). Samples were obtained daily from 23 cats; mean durations from time of treatment to time of negative fungal culture results and resolution of gross lesions were 8.3 and 12 days, respectively. Time to resolution of lesions in most untreated control animals was approximately 90 days. Adverse effects of treatment were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that lufenuron provides an effective, convenient, and rapid method for treating fungal infections in dogs and cats.     

Use of lime sulphur and itraconazole to treat shelter cats naturally infected with Microsporum canis in an annex facility: an open field trial

Dermatophytosis is the most common contagious and infectious skin disease of cats. It is of particular importance in animal shelters because it is a known zoonosis, highly contagious, and easily transmitted. In this open clinical trial, 58 cats with confirmed Microsporum canis dermatophytosis and 32 uninfected bonded pairs or littermates were treated with a combination of 21 days of oral itraconazole (10 mg kg(-1)) and twice weekly lime sulphur rinses until cured. Cats were not clipped in this treatment programme. Fungal cultures were obtained once weekly on all cats, and cats were considered cured when they had two consecutive negative weekly fungal cultures. Cats were held in the facility and received continued topical treatment until the fungal cultures were finalized. None of the cats developed oral ulcerations as a result of grooming the lime sulphur rinses. Oral ulcerations only developed in cats with clinical signs associated with upper respiratory disease. None of the uninfected cats living in contact with infected cats became culture positive or developed skin lesions. When data were examined retrospectively and the number of days to finalize the cultures was subtracted (21 days) from the total number of days the cats were housed in the annex, the mean number of days of treatment required for cure was 18.4 +/- 9.5 SEM (range 10-49 days). Cats with more severe infections required longer therapy. In this shelter, the combination of oral itraconazole and topical lime sulphur rinses for the treatment of dermatophytosis was effective and safe.     

Incidence, immunity and treatment of feline dermatophytosis

Feline dermatophytosis is a superficial skin infection characterized by the invasion of cornified tissues such as hair and nails.This infection is nearly always caused by Microsporum canis. Infected animals release infective spores in the environment which will then contaminate other animals or humans. Infected animals usually develop immunity so the infection will spontaneously disappear after a few weeks to months. Long haired and immunocom-promised cats do not have the same ability to acquire resistance and spontaneous recovery does usually not occur. The treatment of such an infection will require topical and systemic treatment of all contaminated and in-contact cats. The use of desinfectants such as bleach or enilconazole has been proven effective to destroy the spores in the environment. In addition, the efficacy of topical and systemic treatments with azole derivates or allylamines has also been demonstrated in several studies. On the contrary, dermatophyte vaccination has never been proven effective in well controlled studies. Regular follow-up and fungal cultures are mandatory to ensure succesfull treatment.     

Drug efficacy of terbinafine hydrochloride (Lamisil) during oral treatment of cats,experimentally infected with Microsporum canis

Cats represent a primary source of Microsporum canis infections in humans. Terbinafine hydrochloride (Lamisil) is commonly used in the treatment of microsporosis in humans as its fungicidal action permits short periods of treatment. The aim of the present study was to estimate the efficacy of the drug in cats. Nine cats were experimentally infected with M. canis and treated with terbinafine hydrochloride at a dose of 10-20 mg/kg (once daily, SID; low-dose group, LDG). Another nine cats were similarly infected and treated with 30-40 mg/kg SID (high-dose group, HDG) and a further nine cats were also infected and left untreated (control group, CG). The general condition of the cats was observed daily and their clinical symptoms evaluated weekly. The cats recovery was monitored using the Wood's lamp illumination test and microscopic and fungal culture examinations. The general condition of the cats during the study was good. The cure rates of the LDG were not significantly different from the CG at any period during the treatment. However, the HDG cure rates differed significantly from the other two groups. After 109 days of treatment, when all nine cats of the HDG were healed, seven cats of the LDG and all the cats in the CG were still M. canis-positive. This study shows that dosages of 10-20 mg/kg SID of terbinafine hydrochloride are not sufficient to terminate an experimental M. canis infection in cats within an acceptable period of time. Terbinafine hydrochloride can be used to treat dermatophytosis in cats, but a higher dosage, 30-40 mg/kg SID, should be used to achieve a cure.     

Evaluation of topically applied enilconazole for the treatment of dermatophytosis in a Persian cattery

Many Persian catteries have long-standing dermatophyte infections and are particularly difficult to treat. Enilconazole is a topical antifungal agent that has demonstrated good efficacy in recent studies. Twenty-two Persian cats naturally infected with Microsporum canis in a breeding cattery were treated with topical 0.2% enilconazole and monitored for 180 days. The treatments were repeated every 3 days for a total of eight applications. All the cats improved clinically and became culture negative by day 28. By day 180, four cats had developed clinical dermatophytosis and all cats had positive fungal cultures. In this study, topical 0.2% enilconazole was generally well tolerated but may have caused hypersalivation, idiopathic muscle weakness and slightly elevated serum alanine aminotransferase (ALT) concentrations. This study suggests that enilconazole may be used safely with little risk to the young, aged and gravid animals.     

P‐13 Dermatophytosis in domestic cats: treatment with lufenuron

Preliminary studies showed that lufenuron inhibits chitin synthesis, a dermatophyte cell wall constituent, and may be effective in the treatment of dermatophytosis. Our purpose was to evaluate the efficacy of lufenuron in the treatment of feline dermatophytosis. Forty‐six cats (Persians and mixed‐breed cats from 1‐month to 4‐years old) naturally infected with Microsporumcanis were included in this study. Fifteen cats were treated isolated in cages in the veterinary hospital and 31 were treated in their home environment (some with access to the outdoors). Dermatophyte skin lesions were seen in 29 animals while 17 other cats were asymptomatic carriers. Wood's lamp, direct microscopic examination of hairs, fungal culture and skin biopsies were used for the diagnosis. Affected cats and all in‐contact animals received lufenuron at a dose of 120 mg/kg every 21 days for four treatments. Of the 29 symptomatic cats treated with lufenuron, 70% recovered within 21 days and 28% within 42 days of initiation of therapy. One cat had only partial recovery and another was euthanized. Negative fungal culture was recorded only after the fourth dose of lufenuron in 98% of affected cats and 100% of asymptomatic carriers. There was no difference in clinical response to lufenuron between the cats treated in their home environment and those treated in the veterinary hospital. Side effects were not observed, thus the drug proved to be safe and effective for the treatment of dermatophytosis. Funding: Novartis.     

Evaluation of the comparative efficacy of selamectin against flea (Ctenocephalides felis felis) infestations on dogs and cats in simulated home environments

The comparative efficacy of monthly administration of selamectin or lufenuron against Ctenocephalides felis felis on dogs and cats was evaluated over a 5-month period in flea-infested environments. Twenty-four dogs and 32 cats were randomly allocated to receiving a topical treatment with selamectin or an oral administration of tablets containing lufenuron/milbemycin oxime (for dogs) or lufenuron only (for cats). Each product was administered in accordance with the manufacturer's label recommendations. Eight dogs and four cats served as untreated sentinels. Treatments were administered on days 0, 30, 60, 90, and 120. Each animal received an application of 100 fleas on days -28 and -21, and then weekly applications of 20 fleas from days 91 through 147. Flea comb counts were performed on day -6, and every 2 weeks after day 0. From day 29 (dogs) or day 44 (cats) to day 150, geometric mean flea counts for selamectin were < or =0.4. Mean flea counts for animals assigned to treatment with selamectin were significantly lower (P=0.0001) than for animals assigned to treatment with lufenuron at all assessments after day 0.     

The prevalence of immediate and delayed type hypersensitivity reactions to Microsporum canis antigens in cats

Spontaneous recovery from Microsporum canis infections in cats is thought to be dependent on the development of a competent immune response. The purpose of this study was to determine the prevalence of positive delayed type hypersensitivity reactions in cats with and without dermatophytosis. Four groups of cats were intradermally skin tested with M canis extract and test sites were evaluated both subjectively and objectively at 0, 24 and 48 h after injection. Delayed intradermal testing (IDT) reactions were absent in cats not exposed to dermatophytosis (n=20); infected-recovered cats (n=38 culture negative lesion negative and n=43 lesion negative but culture positive) had significantly larger IDT reactions than unexposed cats and cats that were still actively infected (n=18). Based on the results of this study, IDT with M canis extract can be used to assess the cellular immune response of cats with dermatophytosis.     

Isolation of Microsporum canis from the hair coat of pet dogs and cats belonging to owners diagnosed with M. canis tinea corporis

Microsporum canis has been frequently isolated from human cases of tinea capitis and tinea corporis. The infection may be acquired from infected animals with cutaneous lesions but also from asymptomatic carriers or from the environment. As asymptomatic M. canis carriers are considered to be a critical factor in the epidemiology of dermatophytosis in humans, this study investigated the relationship between the presence of dermatophytes on the hair coats of dogs and cats without cutaneous lesions and the occurrence of the disease in their respective owners. A total of 136 dogs and 248 cats were sampled from January 1999 to January 2005. Seventy-eight animals (22 dogs and 56 cats) belonged to individuals affected by tinea corporis caused by M. canis and 306 (114 dogs and 192 cats) to individuals without dermatophytosis. Age, sex, breed, habitat and season were recorded for each animal and examined as potential risk factors. Dermatophytes were isolated from 20.5% of the dogs and 28.2% of the cats. Microsporum canis was isolated from 36.4% of dogs cohabiting with owners diagnosed with tinea corporis but it was never isolated from dogs whose owners had no lesions. By contrast, M. canis was isolated from 53.6% of cats cohabiting with owners diagnosed with tinea corporis and from 14.6% of cats whose owners had no signs of the disease. These results clearly indicate that both cats and dogs should be considered as a major source of pathogenic dermatophytes for humans even when they do not present clinical signs of dermatophytosis.     

A study of the efficacy of topical and systemic therapy for the treatment of feline Microsporum canis infection.

Microsporum canis infection was induced in 21 healthy SPF-derived cats. Once infection was established (4 weeks after inoculation) the cats were divided into three equal groups housed in separate rooms and monitored for 16 weeks. During this time, group A cats received oral griseofulvin at approximately 50 mg/kg daily and were shampooed twice weekly with a product containing chlorhexidine and miconazole. Group B cats were treated with griseofulvin alone, and group C cats served as untreated controls. The cats were examined on a weekly basis and the severity of lesions was scored semi-quantitatively. In addition, hair samples were collected from each cat on a weekly basis by the MacKenzie brush technique and by the sticky-tape method. A semi-quantitative scoring system was also used for the assessment of fungal (M canis) growth. Generally, significant differences in clinical scores were not seen between the groups although at weeks 3, 4 and 11 there was a significant difference (P< or =0.015) with cats in group A having significantly lower median scores than those in group C. Median times to clinical resolution (return of clinical scores to zero) in groups A, B and C were at treatment weeks 2, 9 and 12, respectively (P>0.05). Median times for mycological resolution (persistently negative culture results) for groups A, B and C were at treatment weeks 2, 9 and 12, respectively, for the MacKenzie brush technique and at weeks 4, 8 and 12 for the sticky-tape technique. For both these results, the groups differed significantly (P< or =0.001) and in both instances group A had significantly more rapid resolution than groups B or C. Median culture scores were significantly different between the three groups using one or both of the sampling techniques at week 2 through to week 12 of treatment with median scores for either group A alone, or groups A and B being significantly lower than group C (P< or =0.026). These results showed a benefit from the addition of twice-weekly chlorhexidine-miconazole shampooing to systemic griseofulvin therapy alone in the treatment of M canis infected cats.     

Use of a sustained release preparation of clotrimazole to treat dermatophytosis in a siamang (Hylobates syndactylus).

In November 2004, an adult male siamang (Hylobates syndactylus) from The Tisch Family Zoological Gardens-Jerusalem Biblical Zoo (Israel) presented with skin lesions on various body parts. Lesions consisted of alopecia and dry, crusty areas of hyperkeratosis. A diagnosis of dermatophytosis due to Microsporum canis was determined by fungal culture of skin scraping taken from the edge of several lesions. Treatment with various oral and topical antifungal agents such as griseofluvin, itraconozole, and lufenuron resulted in the resolution of most lesions and a decrease in size of the single remaining lesion, which continued to be culture positive for M. canis. The animal was anesthetized and an experimental sustained-release clotrimazole varnish was painted directly on the lesion. Initially there was no change in the lesion, and 2 months later a slightly altered formula was applied under anesthesia. One month later, the lesion began to reduce in size; 3 months after the start of treatment, although 2 years after the onset of clinical signs, the lesion resolved. Minimizing the number of treatments is always an advantage when dealing with exotic animals or zoological collections.     

FC-3 Immunity to bovine trichophytosis

During the last few years, reports have appeared claiming that lufenuron diminished or even cured dermatophyte infections in cats and dogs. As these observations have a rather anecdotal character leading to some ambiguity in the literature, it was decided to test lufenuron in a generally accepted animal model for dermatomycotic infection. The test was carried out in guinea pigs artificially infected with Microsporum canis on scarified dorsal skin and orally treated with lufenuron (Program™). The efficacy of up to five doses of 80 mg/kg was assessed 7 and 14 days after the start of treatment. All animals failed to show any improvement in skin lesions as compared to the vehicle-only treated animals. Clinical symptoms taken into account were scaling, crust formation, erythema, and exudation. Neither the number of treatments (one or five) nor the dose range (40 or 80 mg/kg) made any difference. Itraconazole, tested earlier under identical circumstances, resulted in a clear and consistent improvement at day 7 of the infection at a dose of 15 mg/kg, given either in one dose or spread over several days. The absence of antimycotic activity of lufenuron in this established animal model constitutes a significant element in the discussion on the antifungal potency of lufenuron and supports the fact that there is, as yet, no evidence that benzoylphenyl urea derivative compounds have an effect on chitin synthesis in fungi.
Funding: J&J Pharmaceutical Research and Development, Janssen Animal Health.     

Efficacy of itraconazole as a combined continuous/pulse therapy in feline dermatophytosis: preliminary results in nine cases

This study evaluated the efficacy of itraconazole as a combined continuous/pulse therapy for feline dermatophytosis. Nine cats with dermatophytosis caused by Microsporum canis were treated with itraconazole at 10 mg kg(-1) orally once daily for 28 days and then on an alternate week regimen (1 week off, 1 week on) at the same dosage. Cats were re-evaluated by physical examination and fungal culture at days 28, 42, 56 and 70 if necessary. Treatment was stopped when two consecutive negative fungal cultures were obtained. Eight cats were cured after 56 days, with two negative cultures obtained at days 28 and 42. In one case, a positive culture was obtained at day 28, but negative cultures were achieved at days 42 and 56. This protocol appears to be effective in the treatment of feline dermatophytosis, although these preliminary results should be confirmed by a controlled study.     

Generalized Microsporum canis dermatophytosis in six Yorkshire terrier dogs

Six Yorkshire terrier dogs with generalized, chronic dermatophytosis caused by Microsporum canis were seen over a 3-year period. Specific tests showed that they also had concurrent leishmaniosis (four cases), leishmaniosis and ehrlichiosis (one case) or diabetes mellitus (one case). Although specific therapy for these infectious diseases was instituted and the dogs were treated systemically and topically with appropriate antifungal drugs, only partial clinical resolution of the dermatophytosis was achieved. M. canis infection resolved in the dog with diabetes mellitus after stabilizing the diabetes mellitus. Although immunological studies were not performed in these cases, it is theorized that the immune disregulation caused by leishmaniosis, ehrlichiosis or diabetes mellitus may have favoured generalization of the infection and prevented favourable responses to appropriate treatment of the M. canis infection.     

Dermatophytosis and papular eosinophilic/mastocytic dermatitis (urticaria pigmentosa-like dermatitis) in three Devon Rex cats

PRESENTING SIGNS: Three Devon Rex cats were presented with multiple erythematous papules, occasionally associated with crusting and hyperpigmentation, with a linear distribution on the head, neck, chest and abdomen. One cat also had multifocal alopecia with hyperpigmentation on the dorsum. DIAGNOSIS AND TREATMENT: Clinical and histopathological features were suggestive of papular eosinophilic/mastocytic dermatitis (urticaria pigmentosa-like dermatitis). In all cases, dermatophytosis was diagnosed: in cases 1 and 2 there was histopathological evidence of dermatophytosis, while fungal culture was positive for Microsporum canis in cases 2 and 3. In all cats, lesions disappeared following antifungal treatment. CLINICAL SIGNIFICANCE: Papular eosinophilic/mastocytic dermatitis in Devon Rex cats may represent either an atypical presentation of dermatophytosis or a clinical and histological reaction pattern to various diseases, including dermatophytosis and allergic diseases. Clinical differentiation is crucial as there are important implications regarding treatment and, in particular, the use of glucocorticoids, which are contraindicated in cases of dermatophytosis.