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Ettinger General - 9th Ed EW > Ch207 - Cryptococcosis > Flashcards

Ch207 - Cryptococcosis Flashcards

1
Q

What is cryptococcosis?

A

Cryptococcosis is a systemic fungal infection found worldwide that affects various mammalian species, including dogs and cats.

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2
Q

What is cryptococcus

A

A dimorphic fungus that exists in a filamentous form in the environment and as an encapsulated budding yeast in the host.

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3
Q

What species of cryptococcus are normally responsible for infections in dogs, cats and humans

A

Cryptococcus neoformans and Cryptococcus gattii

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4
Q

Cryptococcus organisms had been divided into five serotypes - what are these and what were the divisions based on?

A

(A, B, C, D, and AD) based on antibody response to capsular polysaccharide

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5
Q

How are animals infected with cryptococcus?

A
  • Desiccated yeast cells or basidiospores in the environment are inhaled
  • These are primarily deposited into the upper respiratory tract
  • This initial colonization will result in cryptococcal rhinitis in some dogs and cats
  • No clinical signs noted in some exposed individuals.
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6
Q

In some cases the cryptococcus yeast undergoes haematogenous dissemination to which organs?

A

CNS, eyes, lymph nodes, and skin to establish a disseminated infection

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7
Q

Why is the polysaccharide capsule of cryptococcus an important virulence factor?

A
  • It inhibits phagocytosis,
  • depletes complement
  • inhibits the cell-mediated immune response by shifting the host adaptive immune response from a Th1 to a Th2 type response
  • Organisms can also evade the host cell-mediated immune system by altering the cell membrane composition and structure
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8
Q

Does cryptococcus require individuals to be immune-compromised?

A
  • It is usually diagnosed in seemingly immunocompetent individuals
  • Cats concurrently infected with FeLV or FIV may have more severe clinical signs or be slower to respond to treatment
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9
Q

How long does it take clinical signs to develop?

A

Clinical signs can develop between 2 months and 1 year after exposure.

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10
Q

Are cats or dogs more commonly affected?

A

Cats are more commonly affected than dogs.

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11
Q

What are the most commonly infected breeds of cat in Australia?

A

Siamese, Birman, and Ragdoll - this has not been noted in the US

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12
Q

What is the typical clinical presentation of cryptococcus in cats?

A
  • Chronic progressive URT infection with sneezing and mucopurulent to haemaorrhagic nasal discharge
  • 50% cats have nasal swelling or ulcerated cutanseous nasal lesions
  • 50% cats have ulcerative draining sub/cutaneous nodules
  • 1/3 cats have chorioretinitis and optic neuritis (strongly associated with CNS involvement)
  • 20% cats neurological signs
  • Less commonly: Lameness (osteomyelitis) and lower respritary signs (pleural effusion)
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13
Q

Cryptococcus most commomly affected which breeds of dog in Australis and the US?

A

Australia: Great dane, GSD, Doberman pinscher
US: American cocker spaniel

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14
Q

What age are most dogs diagnosed with cryptococcosis?

A

<4years

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15
Q

Are dogs or cats more likely to have disseminated disease with cryptococcosis?

A

Dogs

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16
Q

What percentage of dogs with cryptococcosis have multiple organ systems involved?

A

80%

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17
Q

What clinical signs do dogs with cryptococcosis present with?

A
  • Non specific signs predominate: lethargy, weight loss, hyporexia
  • 75% dogs exhibit neurological sifns that corrolate with lesion localisation (seizure, ataxia, blindness)
  • URT signs - sneezing and nasal discharge
  • Lymphadenomegaly, ulcerated skin lesions, GI signs
  • Ocular signs - granulomatous chorioretinitis
  • Lameness (osteomyelitis)
  • Lower resp signs very rare
  • 50% dogs had subclinical disease - only diagnosed at necropsy
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18
Q

What is this ocular lesion in a Doberman Pinscher diagnosed with nasal and central nervous system cryptococcosis?

A

granulomatous chorioretinitis

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19
Q

What are CSF findings in dogs and cats who have CNS involvement with cryptococcosis?

A
  • Elevated protein and leukocyte concentrations
  • Cytology: mononuclear and neutrophilic inflammation
  • Cryptococcal organisms are observed in up to 90% of infected dogs.
  • Note - CSF collection can result in acute increases in intracranial pressure + clinical decompensation; CSF should not be pursued unless a diagnosis cannot be achieved in other ways
20
Q

What does the image show

A

Impression smear specimen demonstrating the appearance of stained cryptococcal yeast organisms surrounded by a large, non-staining capsule.

21
Q

Although pulmonary cryptococcosis is rare, what would thoracic radiographs show?

A

Interstitial to alveolar pattern or nodular infiltrates. Occasionally, pleural effusion or tracheobronchial lymphadenomegaly.

22
Q

What does CT if the nasal cavity in animals with cryptococcal rhinitis show?

A

Soft tissue mass with evidence of rhinosinusitis and lysis of the nasal bones or cribriform plate

23
Q

Typical MRI findings in dogs and cats with cryptococcosis with CNS involvement

A
  • contrast-enhancing mass lesions that are T2W hyperintense and T1W hypointense
  • May have evidence of edema with surrounding T2 hyperintensity
24
Q

What is the standard for diagnosis cryptococcosis?

A
  • Cytologic or histologic identification of Cryptococcus yeasts.
  • Obtained from nasal swabs, impression smears of ulcerated cutaneous lesions, aspirates of mass lesions, cavitary effusions, or bodily fluids
25
Q

What stains are appropriate to identify cryptococcal organisms? i.e a stained cell surrounded by a non-staining capsule

A

New methylene blue, Romanowsky, and Gram stains

25
Q

How sensitive is cytologic evaluation for detection of organisms?

A

50-75%, a negative test cannot rule out diagnosis

25
Q

How quickly does fungal culture reveal growth of cryptococcus

A

2-10 days

26
Q

Which culture medium does cryptococcus grow readily on?

A

Sabouraud’s dextrose agar

27
Q

Why should fungal culture of cryptococcus not be used for diagnosis alone?

A

Subclinical colonization occurs in the nasal cavity of some animals

28
Q

What is Cryptococcal Antigen Latex Agglutination System (CALAS) or latex cryptococcal antigen test (LCAT)

A

A quantitative serologic test that detects Cryptococcus polysaccharide capsular antigen

29
Q

Which species antigens does the CALAS/LCAT detect?

A

C. neoformans and C. gattii on both serum and CSF

30
Q

What is the sensitivity and specificity of the CALAS/LCAT for detecting cryptococcosis in cats?

A

sensitive (95-100%) and specific (100%)
Sensitivity may be lower in dogs

31
Q

Why should diagnosis be confirmed with cytology/histopathology in in cases of cryptococcus with LCAT/CALAS titers <1:200

A

Subclinical colonization in cats may be responsible for false positive CALAS results, with titers up to 1:200

32
Q

In what scenario can false negatice CALAS results be observed

A

More frequently in dogs than cats, especially with localised ocular, CNS or cutaneous lesions

33
Q

Are pre-treatment CALAS titres associated with mortality or severity?

A

Yes with severity but not with mortality

34
Q

A point of care cryptococcal antigen detection assay (immunochromatographic lateral flow assay CrAg IMMY) widely used in humans has been validated for dogs and cats - what is its sensitivity and specificity compared to CALAS?

A

sensitivity of 92-100% and specificity of 81-93%

35
Q

What is an appropriate treatment for cats with localised nasal cryptococcus?

A
  • Azoles (fluconazole and itraconazole) are efficacious as monotherapy
  • Fluconazole initial treatment of choice
  • Itraconazole used in cats with failure to respond to fluconazole
36
Q

Treatment of disseminated cryptococcus or CNS involvement

A
  • Fluconazole + amphotericin B for 4 weeks
  • If available 5-flucytosine is synergistic with amphotericin B and is optimal for treatment of cats (challenging to obtain, expensive and toxic epidermal necrolysis in dogs)
  • Following 4 weeks induction - azole monotherapy can be continued
37
Q

What newer antifungal drugs used in humans have activity against cryptococcus

A

Voriconazole, posaconazole, terbinafine
Care - voriconazole can be toxic in cats due to impaired hepatic metabolism

38
Q

What can be noted during initial treatment of cryptococcus with antifungals

A

Worsening clinical signs in the first 4 days of treatment (includind neurological status) due to a marked inflammatory response

39
Q

What monitoring should be performed following commencement of treatement with antifungals for cryptococcosis

A

Monthly examination, liver enzyme activity, latex agglutination antibody titre

40
Q

What level of decrease in CALAS titre indicates a positive response?

A

A 4 fold decrease in the first 2 months of treatment

41
Q

What is the treatment duration for cats with cryptococcosis

A

2-12 months with a median of 4 months
Dogs = longer

42
Q

How long should treatment be continued past resolution of clinical signs and negative latex agglutination?

A

2 months

43
Q

When is relapse of disease typically seen follwing treatment for cryptococcus?

A

Typically within first 2 years but up to 10 years later

44
Q

What is the percentage of successful treatment for cryptococcosis in dogs and cats

A
  • Success in 75% of cats
  • 50% with CNS involvement and 84% without CNS involvement
  • Dogs have a more guarded prognosis, with 50% successfully treated in one study.

Ettinger General - 9th Ed EW (7 decks)

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