Dermatofitosis Estudios Recientes

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FELINE DERMATOLOGY 0195-5616/95 $0.00 + .

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FELINE DERMATOPHYTOSIS
Recent Advances and Recommendations
for Therapy

Karen A. Moriello, DVM, and Douglas J. DeBoer, DVM

Feline dermatophytosis is an important skin disease of cats and probably


will not lose this dubious honor in the future. This disease is the most common
infectious skin disease of cats and is zoonotic. Within the medical profession,
increasing interest in zoonotic diseases exists most likely because of human
immunodeficiency virus (HIV) infection, improved organ transplant procedures,
and increased longevity of cancer patients because of chemotherapy. These
conditions have created many immunosuppressed individuals who are uniquely
susceptible to opportunistic and zoonotic diseases. Additionally, reports from
other countries on the increasing prevalence of dermatophytosis have increased
the awareness of many physicians to this particular zoonotic disease. 24
For a variety of reasons, cat ownership is increasing worldwide. With this
increase will undoubtedly come an escalation in the number of children and
adults contracting Microsporum canis from kittens and cats. Veterinarians have a
responsibility to provide accurate information to physicians and owners with
respect to disease transmission, risk factors, contagion, and current treatments
for cats. The goal of this article is to summarize current research findings in the
area of feline dermatophytosis and to update treatment recommendations.

EPIDEMIOLOGIC ASPECTS

The most commonly isolated fungal pathogen from the skin and hair coat
of cats is Microsporum canis. Though other pathogens such as M. gypseum and
Trichophyton mentagrophytes have been isolated from cats with clinical-lesions,
they are rare; this discussion focuses on M. canis.

From the School of Veterinary Medicine, University of Wisconsin-Madison, Madison,


Wisconsin

VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE

VOLUME 25 • NUMBER 4 • JULY 1995 901


902 MORIELLO & DeBOER

Fungal Flora of Cat Hair

In both the veterinary and medical literature, cats are often cited as the
reservoirs of M canis. The implication that cats are the "natural hosts" of M.
canis suggests that this organism is part of the natural flora of cat hair. Several
convincing reports on the prevalence of M. canis isolates from cats support this
opinion. For instance, up to 35% of clinically normallonghaired cats sampled at
a cat show in England carried spores on their hair coats. 36 In another study, the
prevalence of M. canis carriage was only 6.5%,48 and in another widely cited
study the prevalence of M. canis isolation from clinically normal cats was 88%. 49
What is important to consider when examining this data is that these studies
were conducted in different countries (England, New Zealand, and Brazil),
climates, and housing conditions for the cats (shows, shelters, free-roaming).
Whether or not cats are "reservoirs" of infection may depend on climatic,
geographic, and socioeconomic factors of pet ownership in a particular region
or country.
The following summarizes a series of studies on the prevalence of M. canis
on the hair coat of pet cats, cattery cats, and stray cats in the United States. In
these studies, the toothbrush culture technique was used and all of the sapro-
phytic and def!Ilatophytic fungi isolated from the cats sampled were identified.

Pet Cats
One hundred seventy-two clinically healthy pet cats were examined and
sampled. 28 These cats were a mixture of long- and shorthaired individuals
with ~door and outdoor lifestyles from single- and multiple-cat households.
Interestingly, M. canis was never isolated from any of the cats. In this study,
several potential pathogens were isolated from the hair coat of cats including
M. gypseum (n=1), M. vanbreuseghemii (n=1), and T. rubrum (n=14). The latter
is an important human pathogen and is the organism associated with tinea
cruris and tinea pedis. The most commonly isolated fungi from the hair coat of
pet cats were common saprophytes: Alternaria, Cladosporium, Penicillium, and
Aspergillus spp: The findings in this study were similar to a large prospective
study conducted in England in which 181 cats examined for nondermatologic
problems at the veterinary hospital at the University of Bristol were sampled.
In that study, M. canis was isolated from only four cats or 2.2% of the population.
All four of these cats were from households with more than three cats and all
were allowed to roam free outside. 42

Cattery Cats
In another similar study, the hair coat of cats from catteries with and
without a history of dermatophytosis was sampled. 29 One hundred seventy-six
cats from seven catteries were examined and cultured using the same toothbrush
culturing technique. The study included long- and shorthaired cats, juvenile and
adult cats, and breeding and show cats. All of the adult cats were clinically
healthy, signs of dermatophytosis were seen only in kittens.
Using the fungal culture data, the catteries were divided into either M.
canis-negative catteries (n = 4) or M. canis-positive catteries (n = 3). In the four
catteries with no previous history of dermatophytosis, M. canis was never
isolated. This was true for both long- and shorthaired cat breeds. The fungal
flora of these catteries was similar to that of pet cats. In the three catteries with
a previous history of dermatophytosis, M. canis was isolated. Depending on the
FELINE DERMATOPHYTOSIS 903

duration of the infection in the facility, the isolate patterns were distinctly
different. In one of the catteries dermatophytosis had been present for greater
than 1 year. In this facility, M. canis was isolated from all of the cats irregardless
of clinical signs and M. canis was the only organism that grew on the fungal
culture plates. In the two other catteries, the infection had only been present for
a short period, less than 30 days, and we found culture results supporting the
history that the infection was relatively recent. In contrast to the cattery with
the long-standing infection, not all of the cats had positive fungal cultures. In
cats with obvious lesions of dermatophytosis, M. canis was isolated and, again,
it was the only fungal organism cultured from the hair coat. In cats that were
free of clinical signs we found either mixed isolates (M. canis and saprophytes)
or cultures that were negative for M. canis. Pending culture results, the owners
elected not to treat any of the cats. After the results were reported and before
treatment was initiated, all of the cats in these two catteries were recultured; the
infection had been present for 30 to 60 days in each facility. This time all cats
were culture positive for M. canis, and it was the only fungal isolate found on
the plates. When M. canis-positive and M. canis-negative cats were compared,
we found no statistically significant differences in age, sex, or hair length. This
latter finding was interesting because a widely held belief is that longhaired cats
are predisposed to infection. The findings in this study were identical to those
of a smaller study that also failed to isolate M. canis from the hair coat of cattery
cats from facilities that were free of the disease. 44

Stray Cats
In another study, the hair coats of 200 adoptable cats from animal shelters
in two regions of the United States (a cool temperate area (n= 100) and a warm
subtropical area (n = 100)) were cultured. 30 Samples were collected in the fall in
both regions. The goal of this study was to estimate the prevalence of pathogenic
fungi on the hair coat of cats and kittens determined to be suitable for adoption.
In this study, only cats determined by the shelter managers to be adoptable
were examined and cultured. The overall prevalence of dermatophytic fungi
(Microsporum, Epidermophyton, and Trichophyton spp) was 17.5%; for M. canis
alone it was 4%. Interestingly, these findings were similar to those of another
stu~y in which the overall prevalence of M. canis from 199 stray cats sampled
was 6.5%. 48

General Conclusions
These studies do not support the widely held belief that cats, as a species,
are the sole reservoir of M. canis. In other words, M. canis is not part of the
resident flora of cat hair or skin. In all of the studies examining the fungal flora
of cats, the isolation of M. canis was associated with animals at risk for infection
and/ or exposure. The isolation of M. canis from the hair coat of a cat should be
considered a serious finding. Positive cultures obtained via the toothbrush
culture technique imply either active disease or fomite carriage of the organism
from a contaminated environment. In either case, aggressive investigatton of the
clinical situation is indicated.

Zoonotic Considerations

The exact prevalence of feline dermatophytosis in the United States is


unknown because this disease is not reportable. As mentioned previously, the
904 MORIELLO & DeBOER

incidence or recognition of dermatophyte infections is increasing worldwide.


The authors have noted ·a marked increase in the number of physician-to-
veterinarian referrals I consults for treatment or screening of pets, particularly
cats. In many instances, this is a reasonable course of action, particularly if M.
canis has been isolated from the owners or children in the household. Pepin and
Oxemhim33• 34 demonstrated the risk of exposure when they found that 50% of
people exposed to either symptomatic or asymptomatically infected cats devel-
oped lesions, and that in 69.6% of all households with an infected cat at least
one person became infected.
The authors strongly encourage veterinarians to culture any cat suspected
of being the source of infection for humans; however, the vast majority of pet
cats pose little risk to the pet-owning public. The risk factors we believe are
associated with potential exposure include adoption of kittens or cats from
animal shelters or catteries with a known history of dermatophytosis, exposure
to large numbers of other animals (breeding loans, grooming parlors, boarding
kennels, outdoor lifestyle), and age. Young or old animals are much more likely
to become infected.
In some cases of human dermatophytosis, the cat is not the source of
exposure, or at least the organism cannot be cultured from the hair coat. We are
confident that the toothbrush culture technique is a reliable screening tool in
that it can identity both actively infected cats and cats acting as fomite carriers.
What does a veterinarian say to a client when the results are negative? Conceiv-
able, but unlikely, is the possibility that by the time the cat was examined and
cultured, the infection had spontaneously resolved. If this is the case, then the
cat is no longer a source of exposure. Dermatophytosis in people is often
diagnosed via clinical examination and/ or direct examination of scales or hairs
for fungal hyphae and spores. Routine fungal cultures and microscopic identifi-
cation of the dermatophyte species may not have been done; M. canis infection
may not have been definitively diagnosed. The veterinarian should have the
owners request that fungal cultures be performed and the species be docu-
mented. If it is M. canis and the pets are not infected, alternative sources of
exposure should be considered. Though rare, human-to-human transmission of
M. canis is possible. 39• 22 M. canis can also be asymptomatically carried on the
scalps of people acting as a source of contagion for others (possibly cats?). 22

THOUGHTS ON FACTORS THAT MAY AFFECT THE


PATHOGENESIS OF INFECTION

The scope of this article does not allow for a detailed discussion of all of
the intricacies of the pathogenesis of dermatophyte infections; however, we
would like to highlight those points that are relevant to clinical practice and the
development of disease.
The naturally infective stage of M. canis is the arthrospore which is formed
from segmentation and fragmentation of fungal hyphae. Susceptible cats are
exposed either from direct contact with an infected host or from contact with a
contaminated environment. In a home or facility with infected cats, infective
hairs and spores are prevalent in large numbers. What "critical mass" of infec-
tive hairs is required for natural infection is unknown, however we are aware
of fomite transmission of dermatophytosis from contaminated collars, brushes,
and cages; infected hairs can remain viable for at least 12 to 24 months. 42
When infective arthrospores contact the hair coat of cats, many factors
influence whether a successful infection will occur. Studies with our experimen-
FELINE DERMATOPHYTOSIS 905

tal model of feline dermatophytosis have shown that grooming may be an


extremely important natural defense against colonization and infection of cat
hair. 6 During the experiments, experimentally infecting cats was much more
difficult if they were allowed to groom the site where the infective spores were
applied. Interestingly, the first signs of dermatophytosis in kittens usually occur
at, or around, the time they are separated from the queen. Additionally, signs
commonly occur on the face, an area that is difficult for young kittens to groom.
The importance of grooming and the mechanical removal of spores may explain
the common clinical opinion that longhaired cats are more susceptible to or
more commonly infected with M. canis. Obviously, a longhaired cat has more
difficulty in grooming its coat thoroughly than does a shorthaired cat.
Under optimal conditions, infective spores may germinate within 6 hours
of adherence to keratinocytes. 1 Arthrospores adhere strongly to keratin and
the presence of keratinocytes produces favorable conditions for germination. 1
Arthrospores cannot penetrate healthy intact skin and hence some type of
trauma may be necessary to facilitate infection. The amount of trauma necessary
to allow infection is relatively minimal. We and others have been able to
experimentally infect cats with M. canis by applying the spores to areas that
have been traumatized by gentle clipping, rubbing of the skin with a glass rod,
and application of the spores under occlusion. 6• 40 Other factors to consider that
may predispose cattery cats and kittens to infection include microtrauma from
other skin diseases including fleas, lice, and mite infestations.
· Increased hydration and subsequent maceration of the skin is a common
factor in the pathogenesis of human infections that enhances the ability of
dermatophytes to penetrate the skin and favors germination of spores. The
natural barriers to infection are the "desert-like" conditions of the epidermis
and the fungistatic activity of sebum and serum. Additionally, germination of
the spores is temperature dependent. Speculating that the natural activities of
cats such as sun-bathing and grooming may be protective and inhibitory to
fungal germination is interesting. In contrast, excessive bathing and grooming
of cats, for instance, for shows, may predispose them to infection by removing
innate barriers to infection (fungistatic sebum and serum factors), by removing
layers of epidermal cells that may act as a mechanical barrier, and by increasing
the humidity of the hair coat.
· Other predisposing factors include age, immune status, exposure to immu-
nosuppressive drugs, and possibly genetic background. Very young and very
old cats are most commonly infected with dermatophytosis. This probably
reflects a developing or deteriorating immune status, respectively. The presence
of other diseases and infections is well recognized as a predisposing factor;
dermatophytosis has been found 3 times more prevalent in cats with feline
immunodeficiency virus than in uninfected cats. 25 Finally, some evidence sug-
gests that a genetic susceptibility to persistent dermatophytosis may exist in
people and cats.'· 17 When we investigated the immune response of cats to
naturally occurring dermatophytosis, we found that chronic dermatophytosis
was most common in three catteries where members were genetically related.
Additionally, these particular cats had significantly elevated antibody titers and
different in-vitro lymphocyte blastogenesis responses when compared to cats
that were culture negative and had recovered from infection. The prevalence of
chronic dermatophytosis in catteries and in some breeds may be influenced by
genetics; breeders may be selecting for more susceptible individuals when they
breed for certain coat or physical characteristics. Genetic influences would also
explain the reports of greater prevalence in longhaired cats.
906 MORIELLO & DeBOER

STUDIES ON THE IMMUNOLOGY OF FELINE


DERMATOPHYTOSIS

Until recently, the immunology of dermatophytosis had not been studied


in cats, even though they are one of the most commonly affected species.
Previous studies in humans and rodents, using either natural or experimental
infections, found that infection elicits both a humoral and cellular immune
response. These studies generally conclude that the development of a cell-
mediated response is most important in recovery from and immunity to further
infections. Persistent infections in humans with Trichophyton spp are usually
associated with the persistence of a vigorous humoral immune response, as
demonstrated by high antibody titers or strong positive immediate reactions to
intradermal fungal antigen and a less-than-adequate cell-mediated response. 18

Humoral and Cellular Immune Responses of Cats to


Dermatophyte Infections

In a series of studies the immune response of cats to dermatophytosis was


evaluated . using intradermal skin-test antigens, antibody titers, and antigen-
specific lymphocyte blastogenesis tests. These investigations were conducted on
cats with naturally occurring infections and experimental M. canis infections.
Intradermal skin testing with dermatophyte antigens is a common investiga-
tional tool in human medicine. In a pilot study, 15 cats were intradermally skin
tested with fungal antigens.U Ten of the cats were healthy controls with no
history of dermatophytosis and five cats were clinically recovered and Wood's-
lamp negative, but still yielded positive cultures for M. canis. (The environment
was heavily contaminated with spores and the cats probably were fomite carri-
ers.) All o1 the cats were intradermally skin tested with positive and negative
controls, Trichophyton rubrum antigen, M. canis antigen, and ragweed antigen
(irrelevant control). All five previously infected cats had strong immediate
reactions to M. canis compared to only 2 of the 10 control cats. Interestingly,
four of five previously infected cats also had strong immediate reactions to
Trichophyton antigen, suggesting cross-reactivity between the two antigens. At
24 and 48 hours after injection, four of five cats had strong delayed reactions to
M. canis at the site of previous injection. Histologic examination of biopsy
specimens obtained from these sites was consistent with a delayed type-hyper-
sensitivity response to fungal antigens. In a much larger field study, 118 cats in
various stages of infection were intradermally skin tested with M. canis antigen
(Moriello KA, DeBoer DJ, Kuhl K, Greek J: Intradermal skin test reactions to
M. canis antigen in cats with dermatophytosis, unpublished data, 1994). The
preliminary findings in this larger study were similar to those of the pilot study.
Cats that had spontaneously recovered from dermatophytosis developed stroug
immediate and delayed intradermal skin-test reactions to M. canis antigen. In
cats that had recovered via systemic antifungal treatment, immediate reactivity
was noted; however, delayed reactions were often weaker or absent compared
to those of cats that had spontaneously recovered. In cats with clinical lesions,
immediate skin-test reactions were common; however, the presence of delayed
reactions was unpredictable. These data suggest that dermatophytosis in cats is
accompanied by the development of both humoral and cellular immune re-
sponses to the organism. Additionally, the noticeably weaker delayed reactions
in cats with active infections or infections cured via antifungal therapy suggest
FELINE DERMATOPHYTOSIS 907

that cell-mediated immunity may require some yet-to-be-determined length of


time for development.
In another study, the humoral and cellular immune responses of cats recov-
ered from naturally occurring dermatophytosis were evaluated via serum anti-
body titers and antigen-specific cell-mediated immune responses? In this study,
99 cats from catteries throughout the United States were tested. Based on history,
clinical signs, and fungal culture results the cats in this study were initially
divided into two groups: culture-negative cats (n = 83) and culture-positive cats
(n = 16). ·The culture-negative cats consisted of several subsets: exposed but
never infected/lesional, exposed and recovered, and never exposed (control
laboratory breeding colony). Of the culture-positive cats, 13 cats were from
catteries with endemic dermatophytosis and three were actively infected. Periph-
eral blood lymphocytes isolated from cattery cats that were culture positive for
M. canis or from cats that had recovered from M. canis infection showed a
significantly greater mean in-vitro blastogenesis response to M. canis antigen
than did lymphocytes from uninfected cats. Antibodies against dermatophyte
glycoprotein antigen were detected in the plasma of all cats, but were present
in significantly higher titers in the culture-positive group. These results are
similar to those of another group of investigators. 41 The results of these studies
indicate that cats infected with M. canis mount a strong humoral and cellular
immune response to the organism as is seen in other species. Recovery appears
dependent on development of a strong cell-mediated immune response. The
c;ats that were persistently infected had strong humoral immune responses but
weaker cell-mediated responses. The strong antibody response may be caused
by the persistent antigen exposure or by an aberrant and ineffective host immune
response to the organism: a response that does not allow for complete elimina-
tion of the fungus from infected cats. Cats with defective cell-mediated immunity
either as a result of disease 25 (e.g. feline immunodeficiency virus infection)
or excessively high antibody titers that interfere with cellular immunity are
predisposed to persistent infection?
The exact role of the cell-mediated response in the elimination of infection
in cats is yet to be defined. Based on studies in other species, the development
of ·cell-mediated immunity is associated with the resolution of lesions and
resistance to reinfection; immunity to dermatophytosis is relative and reinfection
may occur if the infective dose is large enough and conditions are optimum.
Mechanisms of cell-mediated immunity that may eliminate the infection include
increased epithelial cell turnover in infected tissues and increased permeability
of the epidermal barrier allowing penetration of serum containing antifungal
factors (transferrin) to the infected keratinocytes. 2 • 21

Immune Response of Kittens to an Experimental Killed


Dermatophyte Vaccine

In two studies, we evaluated the immune response of kittens to an experi-


mental killed M. canis vaccine developed at the University of Wisconsin. In the
first study, 12 kittens from a barrier reared facility were used. 10 Pretreatment
complete blood counts, antigen specific lymphocyte blastogenesis tests (LBT),
and antidermatophyte antibody titers were obtained. Beginning at 8 weeks of
age, 6 kittens were vaccinated intradermally every 2 weeks for 10 weeks with a
killed dermatophyte vaccine. The control group received intradermal injections
of saline using the same schedule. At 18 weeks of age, all kittens were challenged
with live M. canis spores. The following characteristics were monitored for 6
908 MORIELLO & DeBOER

months: serum antidermatophyte titers, antigen-specific LBT, complete blood


counts, Wood's lamp examinations, fungal cultures, and clinical signs. The
vaccine induced an antibody titer quantitatively similar to that produced by
infection but less measured cellular immunity than occurred with infection and
recovery. The vaccine was .not protective against challenge exposure. Though
no statistically significant difference was found between the two groups with
respect to lesion observations, in the vaccinated group the lesions developed
sooner, appeared less inflammatory, and were smaller than those of the control
group. All of the kittens were monitored until the infection healed spontane-
ously; infections in both groups resolved at approximately the same time
(60-70 days).
The results of this pilot study were encouraging in that vaccination did
stimulate some degree of cellular and humoral immunity. Not encouraging was
the fact that the vaccine did not appear to be protective against challenge
exposure. Because the experimentally induced challenge infection used a large
number of spores, we performed a second study that simulated field exposure
to more fairly determine if the vaccine was protective. 9 The study design was
similar to the first. Six kittens were vaccinated with either placebo or vaccine
every 2 weeks for 10 weeks. The kittens were housed in groups of six in separate
biohazard rooms that eliminated uncontrolled exposure to M. canis. At the end
of the vaccination period, an asymptomatically infected cat was introduced into
each room of kittens. This cat was positive for M. canis on fungal culture and
had 10 to 15 Wood's lamp-positive hairs scattered throughout its hair coat, but
was otherwise clinically normal. The cats were carefully observed to ensure that
normal social interaction was occurring. The same characteristics as before
were monitored except that we used an additional scoring system for lesion
development. After 3 to 6 weeks lesions consistent with dermatophytosis devel-
oped in both the vaccinated and control cats. These lesions were fungal culture
and Wood's lamp positive and selected hairs showed evidence of fungal
arthrospore invasion. Again, the vaccine-induced cellular and strong humoral
immune responses, but these responses were not of the magnitude of natural
infection.
In conclusion, experimental vaccination with a killed vaccine appears to
produce both a humoral and cellular immune response in M. canis-naive kittens.
However, neither the cellular or humoral immune response induced by this
experimental vaccine is protective against challenge exposure, even when this
exposure is casual. To date, no published information exists on the immune
response induced by the recently released commercial M. canis vaccine (Fel-0-
Vac MC-K, Fort Dodge Company, Fort Dodge, IA). The recommendations for
vaccine use in feline dermatophytosis are discussed later in this article (see
section on Controversial Therapies).

LIMITATIONS OF DIAGNOSTIC TESTS FOR FELINE


DERMATOPHYTOSIS
Diagnostic tests for feline skin diseases are discussed in detail elsewhere in
this issue, however we briefly comment on some of our experiences with Wood's
lamps, fungal cultures, and hair shaft examinations for fungal spores.

Wood's Lamp Examinations


A good Wood's lamp examination should be of at least 3 to 5 minutes
duration after the lamp has been allowed to warm up. When using this tool,
FELINE DERMATOPHYTOSIS 909

remember that the reaction on the hairs may not be visible for several minutes.
The cause of the delay is unclear but is unlikely to be biochemical; a molecule
either does or does not fluoresce. A likely explanation is that the delay in
recognition of the fluorescence is caused by delayed "dark adaptation" of human
eyes. Another interesting observation we have made is that not all fluorescing
strains of M. canis will glow on all cats. Additionally, the presence of fluores-
cence only indicates that fungal metabolites or altered substances are present in
the hair shaft; positive fluorescence does not guarantee that fungal arthrospores
are present. During a treatment trial we noted that hairs would retain their
positive fluorescence long after they were no longer fungal-culture positive.
That the fluorescence is caused by tryptophan metabolites is widely accepted;
however, M. canis does not produce this substance, and the exact nature of the
fluorescence is not known?'

Hair Shaft Examinations for Fungal Elements

Direct examination of hairs for the presence of fungal elements can be


tediGJus and time consuming, however under certain circumstances it can be
helpful. In a busy practice setting, we recommend limiting the examination of
selected hairs to only Wood's lamp-positive hairs. These hairs are most likely
tci yield positive results. Infected hairs appear swollen, pale, and filamentous
when compared to uninfected hairs. Often, known glowing hairs are plucked
and examined, but no evidence of fungal spores can be found microscopically.
This may be an example of a hairshaft coated in the fungal metabolite/altered
substance responsible for the reaction, or the spores may simply be overlooked.
If this occurs, turn the lights off in the laboratory, and, with the slide on the
microscope stage, expose the sample to the Wood's lamp. In most cases, the
hairs will fluoresce and can be found for examination.
Potassium hydroxide (KOH) and chlorphenolac are the most widely used
clea.ring agents for examining hairs. Recently, a technique was described using
calcofluor white and 10% KOH for the rapid identification of fungal elements in
people and animals. 16• 43 In both people and animal specimens, the calcofluor
white and KOH combination was superior to KOH alone and was much easier
to interpret. Calcofluor white is a textile brightener that binds to chitin and
cellulose and on exposure to long-wave ultraviolet light gives an apple-green
fluorescence. Sparkes43 recommends using a working solution comprising cal-
cofluor white and Evans Blue (1:9 ratio) mixed with an equal volume of 20%
KOH. Hair and scale are suspended in this mixture on a microscope slide, cover-
slipped, and allowed to clear for 10 to 20 minutes before being examined with
a fluorescent microscope. The stain highlights fungal spores and hyphae and
glows white. The problem with this technique in general practice is that it
requires a fluorescent microscope; however, one report suggests that it can be
used with a standard light microscope. 16

Fungal Cultures

Fungal cultures are still the gold standard for diagnosing a dermatophyte
infection. Our preferred technique is the toothbrush fungal culture technique as
described elsewhere in this issue. However, some important limitations of this
technique exist that must be considered when interpreting the results.
This technique is an excellent tool for culturing lesional cats and for cultur-
910 MORIELLO & DeBOER

ing and identifying subclinically infected individuals, both humans and animals.
The bristles collect spores from infected hairs that otherwise cannot be identified
by clinical examination. This technique also identifies cats that are fomite carriers
of M. canis spores (on their haircoats). This technique cannot distinguish between
subclinically infected cats or asymptomatic cats (cats with small numbers of
infected hairs) and cats that are fomite carriers of spores. Though not completely
reliable, the following clues may help distinguish between these two types of
cats. First, cats that are acting as fomite carriers tend to be from facilities with
multiple cats with either active dermatophytosis or a history of dermatophytosis.
Culturing the environment may provide supporting evidence that this is the
source of exposure. Second, we have observed that many, but not all, cats that
are acting as fomite carriers have fungal culture results that fluctuate between
positive and negative. Additionally, the number of colonies on the fungal culture
plate may be small-less than 3 to 4. This will, of course, be dependent on the
severity of the environmental contamination. Third, identifying most fomite
carriers is possible by isolating them in a sterile cage for 5 to 10 days and
reculturing them several times during this period. The natural grooming activity
of the cats removes and eliminates the small number of fomite spores from their
hair coats. This technique is most reliable with shorter-haired cats. Many cats or
catteries with "endemic" dermatophytosis that have been previously considered
persistently "infected" may really have an unrecognized environmental contami-
nation problem. However, recognizing that spores and hairs remain infective in
the environment for at least 12 to 24 months and that susceptible people and
cats can become infected is important. The purpose of identifying fomite carriers
is to alert the cattery operator to a reservoir of infective spores.
Finally, all fungal cultures should be examined every other day for growth
and microscopic identification of the organism is mandatory. We have isolated
cultures of M. canis from catteries that do not have classic gross or microscopic
characteristics of typical M. canis colonies. 29 These colonies were small and pale
grossly and did not produce the classic color change on dermatophyte test
medium. After subculturing several times, these colonies "converted" to conven-
tional characteristics. Other investigators have also identified what is termed
"dysgonic isolates" of M. canis.l'· 14• 35 Commonly these subtypes coexist with
normal strains of M. canis. Of concern, however, is that these dysgonic isolates
do not have any of the classic growth characteristics. On both gross and micro-
scopic fungal cultures, these species can resemble saprophytes or appear as
unsporulated hyphae; novice mycologists can easily overlook the existence of
these species. Additionally, these species tend to grow rather rapidly and will
swarm a fungal culture plate masking or inhibiting the growth of normal
colonies. Their biologic behavior is also a problem because they possess the
same propensity for causing disease.

REVISED RECOMMENDATIONS FOR TREATMENT OF


FELINE DERMATOPHYTOSIS

The following recommendations are intended to replace our previous treat-


ment protocols for feline dermatophytosis. 26 We have previously been strong
advocates of topical therapy as the sole treatment for dermatophytosis, however
recent research has shown that these therapies may be of limited usefulness.
The following recommendations are based on recent studies completed at the
University of Wisconsin.
FELINE DERMATOPHYTOSIS 911

Clipping of the Hair Coat

The rationale for clipping of the hair coat is based on the assumption that
clipping removes infected hairs, stimulates new hair growth, and hastens recov-
ery. In several controlled studies, we noted that clipping the hair coat of infected
cats often led to a worsening of signs within 7 to 10 days. 8 • 27 The worsening of
clinical signs was characterized by a marked increase in size of the main
lesion and development of miliary dermatitis-like lesions on the skin where the
haircoat had been clipped. These lesions were Wood's-lamp and fungal-culture
positive. Microscopically, hairs plucked from these lesions were positive for
fungal spores and hyphae. We suspected that the signs of the infection worsen
because of microtrauma and mechanical spread of the spores via clipping. In
one of the studies the cats were bathed twice weekly; this too may have
contributed to the spread of the lesions. Many of the cats increased their groom-
ing habits after clipping; this may also have helped spread spores to suscepti-
ble areas.
Because of the potential for temporarily worsening the clinical signs of
dermatophytosis, clipping may not be indicated in all cases of feline dermato-
phytosis. In cats with limited obvious lesions, clipping the entire haircoat may
not be necessary. To limit contagion, obvious lesions should be clipped with
scissors. In cats with generalized dermatophytosis or in longhaired cats, clipping
of the entire hair coat is still strongly recommended. Clipping the hair coat in
these cases is important to limit the spread of infected spores into the environ-
ment and to limit contagion to people and other animals.
The hair coat should be clipped with blunt scissors or a #10 clipper blade;
chemical or heat sterilization is mandatory for instruments because spores re-
main viable for long periods. The owner should always be warned that a
temporary worsening of lesions may occur after clipping.
In summary, clipping of the hair coat is optional and depends on the
severity of the infection. It is of value in severely lesional animals. In cats with
minimal lesions, it may do more harm than good. If the entire hair coat is
clipped, the cat should be treated with systemic antifungal therapy.

Topical Shampoo and Dip Therapy

For many years, topical therapy has been strongly advocated as the initial
therapy of choice, particularly by the author. 26 This recommendation was based
primarily on the clinical observation that cats receiving topical therapy alone
were cured. Recently, several studies have been conducted that raise serious
doubts about the value of topical therapy as a sole treatment modality.
In one in vivo study, the efficacy of various topical antifungals for the
treatment of experimental dermatophytosis was evaluated. 8 Kittens were experi-
mentally infected with a strongly positive Wood's lamp strain of M. cani$
using a previously established technique. During the infection procedure and
throughout the entire study, kittens were examined once or twice weekly.
Objective data on lesion size, scaling, induration, erythema, Wood's lamp exami-
nation, and fungal cultures were obtained each week. In this study, 24 kittens
were treated and observed for up to 150 days. The topical therapies that were
evaluated included chlorhexidine shampoo followed by a chlorhexidine dip, an
experimental shampoo (glyceryl monolaurate) with strong in vitro antifungal
activity, and a detergent shampoo. To ensure objectivity, the investigators were
prevented from knowing which antifungal agent was used. The results of this
912 MORIELLO & DeBOER

study were unexpected. At the end of 150 days of treatment, there was no
significant difference between the three treatment groups and the untreated
control group. In other Words, topical therapy alone did not alter the course of
infection. During the study, we also noted that many kittens that had received
topical shampoo/dip therapy had a worsening of lesions. This may have been
because of microtrauma from clipping, shampooing, or grooming.
Another interesting finding that we encountered in our studies was the
observation that shampoo therapy may enhance the dispersal of spores. When
semiquantitative M. canis cultures were compared pre- and postshampoo ther-
apy (24 hours post), higher number of colonies were isolated after shampoo or
dip therapy. Again, this suggests that not only are the topical therapies we are
using potentially ineffective but also that the mechanical action of dipping/
shampoo therapy may be detrimental.
In-vitro studies on the efficacy of antifungal solutions have also found that
many commonly recommended topical therapies are inadequate in the treatment
of dermatophytosis47 (Moriello KA, DeBoer DJ, unpublished data, 1993-1994).
Using isolated infected hairs placed in stockinettes, various topical agents with
known or suspected antifungal activity were evaluated for their ability to kill/
inactivate infective spores and hairs. 37 Depending on the "conventional" treat-
ment recommendation, stockinettes were either shampooed or soaked for an
appropriate per~od and then were allowed to dry for 24 hours before hairs
were removed and cultured. Surprisingly, many of the commonly used topical
antifungal solutions and shampoos were not very sporicidal after one or two
treatments, in fact many of them were not effective even after repeated therapy.
Of concern is that in this model, continued spore production within the hair
follicle is not a factor and contact with antifungal solutions is optimal. Of the
numerous compounds tested by the authors, lime sulfur (1:16), enilconazole
(bottle dilution), and miconazole shampoo were superior to other topical anti-
fungal agents tested. These included chlorhexidine dip (1:32), chlorhexidine
shampoo and dip (1:32), chlorhexidine shampoo, bleach (1:10), and glyceral
monolauate shampoo. At this time enilconazole is not approved for use in cats
and conflicting anecdotal information exists about its safety in cats. One of the
authors (KAM) is aware of one cattery in which its use resulted in the death of
several cats. In Europe this product is currently used on dogs; some clinicians
have found it to be safe on cats, while others have found it to be toxic. Currently,
a prospective study is underway in Canada on the safety of this product in cats
and until more information is known about enilconazole's safety in cats it is not
recommended.
Though topical therapy alone may not speed recovery or significantly alter
the course of infection, it still may have some value. Spores that are present on
the distal hairs are only removed via grooming or when the hair is shed into
the environment; systemic therapy acts at the hair-follicle level. The major value
of topical antifungal therapy is to limit environmental contagion by killing
spores on the hair coat that may otherwise be shed into the environment. The
decision to use topical adjuvant therapy should be based on the owner's ability
and willingness to bath or dip their pet and the severity of the lesions.
If adjuvant topical therapy is desired, the lime sulfur (4 to 8 oz/ gal) or
miconazole shampoo is recommended. The higher concentration of lime sulfur
(8 oz/ gal) has great potential to be irritating to cat skin and may cause marked
exfoliation. If ingested this concentration may cause oral ulceration and gastroin-
testinal signs. The lime sulfur dip or the miconazole shampoo should be applied
carefully using gauze sponges and by patting rather than rubbing the skin.
Lathering or rubbing of the hair coat may spread the spores by simple dispersal
FELINE DERMATOPHYTOSIS 913

and/ or the rupturing of infected hairs. This may contribute to a worsening of


lesions. If lime sulfur is used, put an Elizabethan collar on the cat until the lime
sulfur dries· to prevent ingestion of the dip. Irritant reactions, vomiting, and
mild depression have all been reported to the author after ingestion of lime
sulfur dip by cats.
In summary, topical antifungal preparations are no longer recommended as
the sole treatment for feline dermatophytosis.

Local Topical Antifungal Therapy

Another major question that must be answered is what is the value of


topical antifungal creams as adjuvant treatments? We do not routinely use
topical creams, gels, or ointments. These preparations are messy, easily groomed
from the coat by the cat, and encourage owners to only perform "spot therapy."
The efficacy of these products in feline dermatophytosis is unproven. Further-
more, a study using the guinea pig model of dermatophytosis raises serious
questions about the value of this type of therapy'~ (The experimental guinea pig
model of dermatophytosis is accepted as the industry model for evaluation of
human products and is the model we adapted for our cat studies.) In this study,
oral itraconazole was compared to topical bifonazole, a new topical antifungal
agent. The investigators evaluated the efficacy of these two agents against
Trichophyton mentagrophytes and M. canis infection on the glabrous skin and hair
follicles. Both drugs were able to eliminate dermatophytosis when it was limited
to the glabrous skin (that is, the stratum corneum), however a significant differ-
ence occurred in efficacy in the hair follicle. Fungi in the hair sheaths were only
affected by systemic therapy (itraconazole), which not only prevented invasion
of the inner structures but led to a complete clearance of the infection within 7
to 10 days. The topical bifonazole was not able to injure fungi in the hair sheaths
and did not suppress invasion into the hair sheaths. Furthermore, the authors
concluded that the use of topical agents may predispose the host to chronic/
recurrent infections.
This study raises some serious questions about the value of topical antifun-
gals in the treatment of feline dermatophytosis. Many topical products for use
in veterinary medicine (for example, miconazole) are older and are less effica-
cious than some of the newer imidazole creams (for example, bifonazole). Addi-
tionally, cats do not have dermatophyte infections localized to glabrous skin;
the foot pads are the only area in cats that are free of hair follicles. The use of
adjuvant topical agents may not only be ineffective, but may be one of the
reasons that some cats are predisposed to recurrent infections.
In summary, local topical therapy is not recommended for the treatment of
feline dermatophytosis.

Systemic Therapy

In another blinded controlled study, the efficacy of several systemic antifun-


gals drugs was evaluatedP Kittens experimentally infected with a strongly
Wood's lamp-positive strain of M. canis were treated with either itraconazole,
griseofulvin, or a placebo-vehicle control. Each group of kittens was housed in
a separate biohazard containment room and each individual room was
"furnished" so as to simulate a cattery or home with multiple cats. Kittens were
allowed to comingle and had toys, scratching posts, and cat beds. Kittens were
914 MORIELLO & DeBOER

examined daily and objective data on lesion size, scaling, induration, erythema,
Wood's lamp examination, and fungal cultures were obtained once weekly. Cats
were treated for 100 days or until they were cured; a cure was defined as three
consecutive negative fungal cultures at weekly intervals. In this study, cats with
generalized M. canis infections receiving either griseofulvin (50 mg/kg PO) or
itraconazole (10 mg/kg PO) once daily as the sole therapy responded signifi-
cantly better than did the control group. Negative fungal cultures were seen as
early as 3 to 4 weeks after the start of therapy in individual cats receiving
itraconazole or griseofulvin. The itraconazole group (n=5) was cured (three
negative weekly fungal cultures from each cat) after 56 days of therapy and the
griseofulvin group (n = 5) was cured after 70 days of therapy. A significant
difference was present in lesion size, fungal culture scores, and infection scores
between the treatment groups and the vehicle controls. None of the cats in the
vehicle control group became culture negative during the study, though the cats
were clinically normal at the end of the study. All of the vehicle control cats
still had numerous Wood's lamp-positive hairs scattered throughout their coat.
These cats were clipped, however, and we did see a worsening of lesions post-
clipping. This worsening was much milder than that in the cats in the topical
study. Furthermore, in the itraconazole group no increase occurred in the main
lesion size and fewer satellite lesions occurred after clipping.
Griseofulvin ~s a fungistatic drug that has enhanced absorption when ad-
ministered in divided daily doses and with fatty meals. The most common side
effects are vomiting, diarrhea, and anorexia. These can be managed by dividing
the dose or by slightly lowering the dose. Bone marrow depression (neutropenia,
anemia, or pancytopenia) may occur in some patients but is idiosyncratic. This
side effect is most common in cats. Because severe neutropenic reactions have
been associated with feline immunodeficiency virus (FIV), griseofulvin should
not be used in cats with this infection. 38 Ideally, all cats should be tested for
FIV before griseofulvin is administered. Weekly or biweekly blood counts are
recommended for these patients. The use of griseofulvin is contraindicated in preg-
nant cats.
Itraconazole is a newer antifungal that is related to ketoconazole. It is better
tolerated by cats than is ketoconazole. We observed no adverse effects in kittens
treated with this drug. This drug is indicated in cats that cannot tolerate griseo-
fulvin or have failed to respond to griseofulvin therapy. The use of itraconazole is
not recommended in pregnant animals. Embryotoxic and teratogenic effects are
dose related. In rat studies, itraconazole is safe when used at therapeutic doses
and only adversely affects fetal development at toxic doses. However, the
"toxic" and "therapeutic" doses are unknown for the cat. Itraconazole is much
more expensive than griseofulvin and it must be reformulated because it is only
supplied in 100 mg capsules and is difficult to use.
Systemic therapy is the treatment of choice in cats infected with M. canis.
Griseofulvin is the initial drug of choice because it is approved for use in the
cat, is effective, and is much less expensive than itraconazole or other newer
agents. Griseofulvin dosed at 50 mg/kg (microsize) orally or 5 to 10 mg/kg
(ultramicrosize) once daily is used most commonly by the authors. When neces-
sary, the authors use itraconazole at a dose of 10 mg/kg orally once daily. Cats
should be treated until they are mycologically cured-three negative fungal
cultures at weekly intervals. Cats will be clinically cured several weeks before a
mycologic cure is evident. Beginning weekly fungal cultures 3 to 4 weeks after
initiating therapy is recommended.
In summary, systemic therapy is recommended as the treatment of choice
in cats with dermatophytosis. It is effective as a sole therapy; however, it can be
FELINE DERMATOPHYTOSIS 915

combined with prophylactic clipping of the hair coat and selected adjuvant
topical whole-body treatment.

Monitoring Therapy

Cats with dermatophytosis usually self-cure in 60 to 100 days if they have


a competent immune system. Cats receiving systemic therapy usually show
clinical resolution of lesions within 2 to 3 weeks of initiating therapy. Remember
that cats will appear clinically normal long before they are cured and are culture
negative. Infected individuals should be examined every 3 to 4 weeks. A Wood's
lamp can be used to screen for the presence or absence of infection, however its
limitations should be taken into consideration when hairs are examined. Actively
infected hairs tend to glow along the entire shaft or the proximal (hair follicle)
shaft. Individual hairs that are no longer infected may still fluoresce along the
distal portion or just the tips of the hairs. These hairs may or may not be
culture positive. Cats should be treated at weekly intervals until they are culture
negative at least twice and preferably three times. Weekly fungal cultures should
be started after the cat has received 4 to 6 weeks of therapy. The author has the
client perform the toothbrush sampling at home to minimize cost to the client
and. decrease the potential for contamination of the hospital.
False-positive toothbrush fungal cultures can occur in cats that are clinically
recovered and cured of dermatophytosis if they are living in a contaminated
eiwironment. This is most likely to occur in a shelter situation or cattery.
Determining the true status of these cats-asymptomatically infected or fomite
carriers, is difficult. In our experience, these cats frequently have fluctuating
culture results, that is, positive to negative to positive. Additionally, the number
of colonies isolated from fomite carrier cats is usually low-one to five small
colonies. If any doubt exists, the suspect cat should be isolated in a mycologically
sterile cage for a period of 5 to 10 days and recultured to determine its true
status. In many instances, a site visit and cultures of the environment can also
be informative.

Environmental Decontamination

The M. canis-infected cats in our topical and systemic drug studies were
housed in rooms designed to closely resemble either catteries or multiple-cat
households. The floors, ceilings, walls, furniture, cages, bedding, and bowls
were all heavily contaminated with M. canis even though the rooms were
cleaned daily. Each day the rooms were swept to remove hairs, litter, and other
debris. Blankets were changed daily. Once a week, each room was thoroughly
cleaned with hot water and high pressure water hosing of the walls and floors.
Additionally, all nonporous areas were sprayed with a 1:10 solution of house~
hold bleach.
In a small pilot study, we tested the efficacy of several commonly used
disinfectants for their ability to kill infected hairs and spores in the environment
(Moriello KA, DeBoer DJ. unpublished data, 1994). Fungal spores were evenly
dispersed on the floor of biohazard rooms over a grid consisting of squares 1 ft
X 1 ft in size. Each square was equally subdivided into three smaller sections.
One of the sections was used as a control to ensure that that particular square
was contaminated with M. canis. The remaining two sections were treated with
a product commonly used for decontamination of the environment. Fungal
916 MORIELLO & DeBOER

cultures were obtained 2 hours and 24 hours after treatment. Some of the more
commonly used chemicals/products evaluated were commercially available
chlorhexidine products (several dilutions), bleach (several dilutions), commercial
brands One-Stroke and Lysol Brand Disinfectant, enilconazole, and 1% formalin.
Of all the products tested, only concentrated bleach and 1% formalin were
effective in killing all of the spores (0% growth) in all of the test rooms. Bleach
at a dilution of 1:10 was the next most effective product with only 11% of the
rooms having positive growth at 2 hours posttreatment. Thirty-three percent of
rooms treated with enilconazole still harbored viable spores 2 hours after treat-
ment. With the exception of concentrated bleach, none of the products tested
had any residual activity, that is, no growth 24 hours after application. Bleach
1:10 and 1% formalin were equivalent in residual activity with only 22% of
rooms still culture positive 24 hours after application. Thirty-three percent of
rooms treated with enilconazole were culture positive 24 hours after treatment.
This is an important finding because enilconazole is widely used as a fungicide
in poultry houses and is widely used in Europe as a fungal premise spray
for catteries.
We were surprised at the degree of environmental contamination found in
our studies. This is an underrecognized source of exposure and an area of
treatment that many owners neglect. The findings in this pilot study suggest
that expecting any disinfectant to be sporicidal with a single application is
unrealistic. Undiluted bleach and 1% formalin are too dangerous and harsh to
be routinely used in homes. How much environmental contamination occurs
with only a single infected cat in the house is unknown; several infected cats do
represent significant contagion. Informing clients that they should thoroughly
vacuum all surfaces in the home, preferably on a daily basis, is critical. We
recommend the purchase of an inexpensive electric broom for this purpose; the
appliance can be discarded after the infection has been eliminated. Additionally,
all nonporous surfaces in contact with the cats should be cleaned with 1:10
bleach dilution <.m a daily basis. This product is the least expensive and most
readily available. Chlorhexidine should not be used because it was ineffective
in the aqueous formulation that is commercially available to clients.

CONTROVERSIAL THERAPIES

Fixed Treatment Schedules

In human medicine, a great deal of interest exists in the use of limited


treatment courses with antifungal agents. This interest arose because long treat-
ment courses have long been recognized as associated with poor patient compli-
ance. The longer the course of therapy, the more likely the patient is to elect to
discontinue treatment because of inconvenience, adverse effects, and cost. A
search was undertaken to identify a drug(s) that was well tolerated and was
active over a short treatment period. Itraconazole was chosen as the drug to
investigate.
Itraconazole seemed particularly suited for these studies for a number of
reasons. It was more effective than was ketoconazole against many species of
dermatophytes and the minimum inhibitory concentrations were several times
lower than those for ketoconazole. 32 Limited studies in animals also suggested
that it was effective on a limited treatment schedule.'6 Additionally, skin kinetics
of itraconazole indicated that it is excreted in a moderate amount via the sweat
glands, is incorporated to some degree in the basal layer of the epidermis, and
FELINE DERMATOPHYTOSIS 917

is excreted in high quantities with sebum. 4 Levels of itraconazole in the stratum


corneum of the skin are 10 times those of plasma. Therapeutic concentrations of
itraconazole may remain in the epidermis for up to 4 weeks after discontinuing
therapy even though serum levels are no longer detectable. 5 Finally, itraconazole
inhibits the adhesion of fungal spores to keratinocytes of the stratum corneum
to a greater degree than does griseofulvin or ketoconazole. 19
In a summary of a number of multicentric studies conducted throughout
the world, 15- to 30-day fixed treatment schedules for dermatophytosis were
evaluated in open clinical trialsY In these studies, the investigators found that
fixed treatment schedules resulted in an 80% mycologic cure response and a
90% clinical cure response. In comparative studies with griseofulvin, the myco-
logic and clinical response was approximately 20% less.
The authors are aware of anecdotal reports from Europe in which fixed
treatment schedules have been used for the treatment of feline dermatophytosis.
All cats in a cattery receive itraconazole (10 mg/kg orally for 15 days). In
addition, intense treatment of the environment is included in this regimen. The
authors have used or recommended fixed treatment schedules with itraconazole.
Our experience is that 15 days of treatment with itraconazole does speed resolu-
tion .of the infection. Indications for this therapy are limited to instances in
which the options are this treatment or no treatment at all. Fifteen days of
itraconazole can be equally as expensive as conventional griseofulvin therapy;
cost containment is not a justifiable reason to use this experimental therapy.
Another reasonable indication would be a larger cattery with endemic dermato-
phytosis. Fifteen days of itraconazole coupled with whole-body clipping and
intense environmental decontamination may be an effective treatment regimen
for a frustrated cattery operator. Finally, this therapy may be reasonable in a
shelter outbreak of dermatophytosis. Remember that this drug is not approved
for use in the cat and has only been available for a relatively short time. The
full extent of adverse effects may not be known.

Fungal Vaccines

Without question, the most recent development in the treatment of feline


dermatophytosis is the use of killed M. canis fungal vaccines. In this section, we
review briefly the use of these vaccines in other species and our research in the
area and comment on the recently released commercial killed M. canis vaccine.
Impetus for the development of a fungal vaccine has stemmed from anec-
dotal reports of use in cats 31 and from the use of fungal vaccines in the manage-
ment of bovine dermatophytosis in eastern Europe and several Scandinavian
countries. 15• 45 In the cattle studies, a live Trichophyton spp fungal vaccine was
used successfully for control of dermatophytosis. The use of these vaccines has
significantly diminished clinical dermatophytosis in cattle; mycologic cure was
not evaluated.
Many difficulties exist with the development of a protective fungal vaccine.
The desired goal of cat breeders, who unquestionably have the most vested
interest in a fungal vaccine, is prophylactic protection against infection. The type
and degree of protection desired is similar to that provided by routine prophy-
lactic vaccinations for viral diseases such as rabies, panleukopenia, or respiratory
diseases. Our opinion is that this expectation may be unrealistic and impossible
to obtain with current technology and knowledge of immunologic intervention.
The immunology and pathogenesis of infection and the host immune responses
are different for viral versus dermatophyte infections. Antibody titers are im-
918 MORIELLO & DeBOER

portant in the protective mechanisms of viral diseases. In dermatophytosis, high


antibody titers do not appear to be protective; the development of cell-mediated
immunity is critical to resolution of infection. Another complicating factor in the
development of a fungal vaccine for cats is the limitation on the type of vaccine
that can be produced. The cattle vaccines are live vaccines known to induce a
greater immune response. A product that shed live spores into the environment
for any period of time probably would not be licensed in the United States.

Studies at the University of Wisconsin with an Experimental


Microsporum Canis Vaccine
We have conducted two controlled studies using an experimental killed M.
canis vaccine (see above). In the first study, we determined that intradermal
inoculation of this vaccine did stimulate both humoral and cellular immune
responses, though to a lesser degree than did natural disease. However, it was
not protective against challenge exposure nor did its use shorten the clinical
course of the disease as compared to a placebo control group. However, we did
notice that clinical lesions developed slightly sooner and were more inflamma-
tory in vaccinated kittens than in the control group.
Though the failure of the vaccine to protect the cats against challenge was
disappointing, this type of challenge exposure did not mimic natural exposure.
In our second study, which was designed to test the efficacy of a killed M. canis
vaccine for prevention of infection under field conditions (see above), again the
vaccine was not protective against challenge exposure. The development of high
serum titers of antidermatophyte IgG along with a small cell-mediated immune
response against M. canis did not protect cats from challenge infection that
simulated natural transmission.

Commercial Vaccine
In the spring of 1994, Fort Dodge Laboratories received approval for a
killed M. canis vaccine (Fel-0-Vax MC-K). According to the product insert the
indications for use of this vaccine are "as an aid in the prevention and treatment
of clinical signs of disease caused by Microsporum canis. Vaccination has not
been demonstrated to eliminate Microsporum canis organisms from infected cats"
(Product insert. Fel-0-Vax MC-K, Fort Dodge Company, 1994). According to the
company, the vaccine is intended as adjuvant therapy, not sole therapy. 20 The
vaccine is administered subcutaneously in three 1-mL doses on day 0, 12 to 16,
and 26 to 30 of treatment. To date, the manufacturer has not released data on
immunologic studies on this product.
During the efficacy studies, the manufacturer tested this vaccine in a con-
trolled blinded study in 11 catteries. The presence of M. canis was documented
in each cattery via fungal culture. Approximately equal numbers of cats were
randomly vaccinated with the vaccine or a placebo on days 0, 14, and 42 of the
study. The study tracked the approximate size and number of lesions and
presence or absence of fluorescent hairs on the cats. The cats were examined by
a veterinarian and the last date of examination was approximately 2 weeks after
the third dose. "In the vaccinated group, the percentage of cats with clinical
lesions decreased from 97.4% at day 0 to 20.9% at day 56. Fluorescence in the
vaccinated cats decreased from 98% to 26.9%. Within the placebo group, the
percentage of cats with lesions decreased from 98.1% at day 0 to 90.2% at day
56, and fluorescence decreased from 96.1% to 90.0%" (Product insert. Fel-0-Vax
MC-K, Fort Dodge Company, 1994). The field data did demonstrate a 78%
decrease in clinical lesions in the vaccinated group as compared to the unvacci-
nated placebo group. Additionally, a 70% decrease occurred in the observance
FELINE DERMATOPHYTOSIS 919

of Wood's lamp-positive hairs in the treated group. During the study, no other
treatment was allowed. A small number of vaccinated cats who were lesion free
and Wood's. lamp negative at the start of the study were observed not to
develop lesions.
The studies performed by the manufacturer did not include data to evaluate
the vaccine's prophylactic ability, that is, its ability to protect against challenge
exposure. Current claims of "prevention" refer to prevention of clinical signs rather
than prophylactic ability.
The veterinary profession is looking forward to more information on this
vaccine. Many unanswered questions include, but are not limited to:
1. Used on its own, is it capable of consistently inducing a full mycologic
cure in all cats or must it be used along with additional topical and
systemic therapy?
2. Does it have any prophylactic efficacy?
3. What is the duration of immunity produced by the vaccine?
4. How does the vaccine work? Does it stimulate antibody titers or cell-
mediated immunity, or does it work by some other mechanism?
5. Are any unusual, rare, or long-term adverse effects associated with
its use?
The authors have limited clinical experience with this product. We partici-
pated in a safety study conducted by the manufacturer and noted few adverse
reactions to the administration of the vaccine. As reported in the product insert,
we did note several cats with small nodules at the site of inoculation; a few cats
became lethargic after vaccination, and in a few instances cats developed hair
loss at the site of injection. In the infected cats that we vaccinated, we did note
clinical improvement of lesions in some, but not all, cats.
In our practice we believe that this adjuvant therapy may be helpful in
selected cases of dermatophytosis in which large numbers of cats are involved
or in which a refractory infection exists. In a cattery with a large number of
infected cats, the use of the vaccine may enhance healing of lesions when used
in conjunction with systemic therapy, possibly a fixed treatment schedule. This
would serve to decrease infected hairs in the environment. A frustrated owner
that observes a decrease in clinical lesions will be encouraged to continue with
a complete program of treatment. Another potential indication is in the single-
cat situation as an alternative therapy to topical agents. As mentioned above,
few antifungal shampoos/dips are effective and topical ointments may not be
effective. Our experience is that many owners contract M. canis during the
treatment process when they are bathing and/ or dipping the cat or applying an
ointment. Vaccination may be beneficial in decreasing clinical lesions and
thereby decreasing the potential for zoonotic complications.
In summary, biologics are a new and novel approach to disease treatment.
A great deal of excitement exists in this area of research and the value of this
vaccine in a complete treatment program is yet to be determined.

References

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18:231, 1993
920 MORIELLO & DeBOER

2. Berk SH, Penneys NS, Weinstein GD: Epidermal activity in annular dermatophytosis.
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3. Borgers M, Xhonneux B, Van Cutsem J: Oral itraconazole versus topical bifonazole
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4. Cauwenbergh G: Skin Mycoses: Effects of therapy with ketoconazole and itraconazole
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University, Leuven, Germany, 1988
5. Cauwenbergh G, Degree£ H, Heykants J, et al: Pharmacokinetics profile of orally
administered itraconazole in the human skin. JAm Acad Dermatol 18:283, 1988
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Address reprint ~equests to


Karen A. Moriello, DVM
Department of Medical Sciences
School of Veterinary Medicine
University of Wisconsin-Madison
2015 Linden Drive West
Madison, WI 53706

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