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A Persian cat with
sino-orbital aspergillosis affecting the right nasal cavity and orbit, due
to Aspergillus felis infection. The fungus has invaded
from the nasal cavity into the orbit and grown behind the eye, pushing it
forward. This has resulted in swelling (white arrows).
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SAT
has recently featured a number of blogs on fungal disease (mycoses) and those
who study fungi (mycologists). One of the reasons is that fungal diseases are
so neglected when it comes to research funding. But they’re a real issue and
the incidence appears to be increasing, in both humans and animals. Unfortunately I recently lost a non-human companion due to a fungal disease resulting in acute fungal hepatitis. Investigations are continuing.
We
spoke to Dr Vanessa Barrs, a feline specialist who was awarded a PhD in
mycology recently, about the challenges of diagnosing and treating these
diseases in feline patients.
As
a companion animal practitioner, the most common fungal infections I see in
cats are dermatophytes or ringworm. But as a feline specialist you've diagnosed
systemic fungal infections, or mycoses. What are the key systemic mycoses that
affect cats in Australia?
The major ones that
affect cats in Australia are cryptococcosis, aspergillosis and
phaeohyphomycoses. Australia has one of the highest rates of cryptococcal
infection in cats in the world. Until recently ‘crypto ’was the only systemic
mycosis on the radar for most practicing vets, and with the availability of antigen
tests for diagnosis, with high sensitivity and specificity (like the latex
cryptococcal antigen agglutination titre (LCAT) many vets have diagnosed and
managed cases of cryptococosis in vet practices around Australia.
Aspergillosis, on the
other hand, is an emerging mycosis of cats globally. Aspergillosis in cats
generally takes two forms – a focal form restricted to the upper respiratory
tract, or a disseminated form. The latter was diagnosed most commonly twenty or
more years ago in young cats immunosuppressed from panleukopenia infections,
but we don’t see much of this now. Upper
respiratory aspergillosis was rarely diagnosed until recently. Interestingly,
the very first case in a cat was diagnosed in 1982 by Dr. George Wilkinson, the
“grandfather” of feline medicine in Australia, from the University of
Queensland. Then, no Australian cases were reported for many years. Now, in
2015, Australia has recorded the highest number of cases of this disease in the
world.
Phaeohyphomycoses are
the third most common “deep” fungal infection affecting Australian cats. These
fungi are distinctive because they have melanin in their cell walls. They cause
opportunistic infections when they are inoculated into the skin from
penetrating wounds, or inhaled.
With global warming
the prevalence of fungal infections in animals and humans is predicted to
increase, because of more favorable environments for fungi to grow over a wider
geographic range. On that note, we are
starting to see other “unusual” fungal infections in cats presenting to the
Valentine Charlton Cat Centre at the University of Sydney, like scedosporiosis,
which is a filamentous fungus that belongs in the “hyalohyphomycoses” group.
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| Dr Barrs with a feline patient. |
How
did you get involved in researching fungal diseases in cats?
It started back in
2006, when I was referred three unusual feline cases of upper
respiratory tract disease. My investigations revealed they all had
aspergillosis of the nasal cavity and sinuses, with additional orbital
involvement in two cases. In fact those two cases were presented for “a swollen
eye” by their owners, because the fungus had grown behind the eye and pushed it
forward. What was even more interesting is that none of these cases seemed to
be caused by Aspergillus fumigatus. At
that time, it was widely accepted that A.
fumigatus was the most common cause of this disease in cats.
Co-incidental to these three cases turning up, colleagues at the Centre
for Infectious Diseases at Westmead Hospital, including Dr. Catriona Halliday,
had requested submission of samples from cats and dogs with mycoses to evaluate
a new PCR assay that they had developed for diagnosis of fungal infections in people.
The PCR sequences of the fungi from my cats were closely related to but different
to A. fumigatus.
My interest was piqued, and I decided to research this disease in cats
further. I enrolled in a PhD part time. Colleagues at Westmead hospital were extremely
helpful and collaborated on the initial molecular identification studies. It
wasn’t long before we had 23 new cases for study from around Australia, thanks
to the willingness of Australian veterinarians to contribute cases and support
clinical research. I was fortunate to then be awarded an Endeavour Research
Fellowship from the Australian Government that enabled me to continue my
research with Professor Robert Samson’s group at the renowned CBS-Fungal
Biodiversity Centre in Utrecht, The Netherlands. We were able to confirm that a
new species of fungus, Aspergillus felis,
is the most common cause of sino-orbital aspergillosis in cats. Aspergillus felis is inherently more
virulent than A. fumigatus and more
likely to be resistant to antifungal drugs.
My interest in fungal infections in cats (and dare I say it, dogs) is
ongoing. Currently, in my lab, four vets (2 PhD and 2 Masters students) are
investigating multiple different areas including where these fungi live in the
environment, why certain breeds of cats are prone to respiratory aspergillosis,
diagnostic tests and pharmacokinetics of new antifungal drugs.
Why
do cats get systemic mycoses in the first place?
That is a very
interesting question. We have some answers, but there is a long way to go
before this question can be fully answered.
Two things have to
happen for these mycoses to occur – exposure to the fungus, and failure of the
immune-system to eliminate it. The first varies with geographic region. For
example “hot spots” for cryptococcosis are Australia and the Pacific Northwest.
Fungi like Cryptococcus and Aspergillus live in the environment in
places like soil and decaying plant matter BUT they can also be found in air
and water, so it’s not just outdoor cats that are exposed. In fact in one study
of cats with cryptococcosis a quarter of cats were indoor only pets.
There are many
reasons why the immune-system might not be able to eliminate a fungus after it
is inhaled or inoculated, and these depend on a complex interplay between the cat’s
immune-system (host factors) and virulence factors of the fungus. We know that
in Australia certain breeds of cats are more likely to develop these
infections. For example Ragdoll cats appear to be prone to both cryptococcosis
and upper respiratory aspergillosis. Pure-bred cats of Persian lineage (e.g.
Persians, Himalayans, British shorthairs) are susceptible to upper respiratory
aspergillosis. Why is this? Certainly an inherited immune-disorder is possible.
But, these cats also have brachycephalic conformation, which means there nasal
cavity and sinuses are anatomically quite different to other cats. It’s been
proposed that this might make the microenvironment in the nasal cavity more
favorable for fungal colonization. Other
factors like previous viral upper respiratory infections are also implicated.
Cats with suppression
of their immune-system from disease or drugs, are also susceptible to systemic
mycoses. For example, I saw a cat with severe rheumatoid arthritis that was
being treated with immunosuppressive drugs develop a disseminated fungal
infection (a phaeohyphomycoses).
Why
are fungal infections difficult to diagnose?
Fungal infections can
be difficult to diagnose because they can mimic other diseases like cancer, and
testing for them can be complicated. Fortunately, for both cryptococcosis and
aspergillosis, diagnosis is getting easier, thanks to new diagnostic tests.
As I mentioned
earlier antigen tests for cryptococcosis like the LCAT have been around for
many years. They are very reliable and revolutionized our ability to diagnose
this disease in cats. Newer, less expensive cage-side tests like the lateral
flow assay (CrAg® LFA, IMMY) will also help us to rapidly achieve
diagnosis of this disease.
My group evaluated an
antigen test (serum galactomannan) for respiratory aspergillosis in cats. It is
not very reliable and not recommended for routine screening tests. We then
evaluated serum antibody titres (IgG) by ELISA and found that this testing
methodology has an excellent ability to discriminate between cats with upper
respiratory aspergillosis and non-infected cats.
There’s been a fairly
widespread conception that fungi are hard to culture from cats, but this is in
fact not true. Both Cryptococcus and Aspergillus fungi can be readily
cultured – the trick is getting good diagnostic samples. For example, some cats
with cryptococcosis only have infections right at the back of their nasal
cavity, so culture from nasal swabs can be negative. We showed that fungal
cultures were positive in over 95% of cats with upper respiratory tract
aspergillosis.
What
makes them challenging to treat?
These infections are
challenging to treat for lots of reasons. We know little about how antifungal
drugs work in cats, and for some mycoses the best treatments have not been
identified. The treatment period is often much longer than for other
infections, e.g. bacterial infections. Typically, cats require treatment
courses of many months for cure, but it does vary from cat to cat and from
mycosis to mycosis. Treatments can also be expensive. Owners need to be
dedicated and able to keep in regular contact with their veterinarian to
monitor their cat’s recovery.
The prognosis for
cryptococcosis overall is good. The prognosis for aspergillosis depends on the
type of infection. If the infection is just in the nasal cavity, then the
prognosis is favorable. If it’s an orbital infection the prognosis is currently
poor overall, although individual cats have been cured.
Are
there any recent developments that might improve the outcomes for cats with
systemic mycoses?
There are quite a few
new developments in the field of veterinary mycology. We’ve recognised that to
get the best outcome we need to know quite a bit about the fungus that is
causing it. Where possible, identification of the fungus should be performed.
As we’ve discovered, this is not always just a case of sending a sample to the
lab for culture. In many cases in order to identify the fungus, molecular
techniques are required. This means arranging for your vet lab to send the
fungus to a Mycology Reference Centre (e.g. www.mycology.adelaide.edu.au) or to
an institution that specializes in fungal identification. There is new
information coming out about antifungal drugs in cats. We’ve shown that
posaconazole, a newer generation triazole antifungal similar to itraconazole,
is well-tolerated by cats with clinical infections. Researchers at North
Carolina State University have recently published findings on pharmacokinetics
of this drug in dogs, and results from a similar study in cats are anticipated
to be available soon.
My lab is happy to
talk to any vet from around Australia with a feline fungal enquiry (vanessa.barrs@sydney.edu.au).
Thank
you Vanessa. And thank you to all of the mycologists and fungal experts who
have contributed to research on mycoses in Australia. We’re looking forward to
seeing you at the International Society for Human And Animal Mycology congress.
