Feline Crytococcosis

Question 1

Cryptococcus neoformans - etiology

Answer 1

Saprophytic round yeast-like fungus
--not a true yeast
--reproduces by budding 
--yeast form grows in lab culture
Forms heteropolysaccharide capsule 
Only Crypto spp that grows @ 37C

Question 2

Epidemiology

Answer 2

Found in excrement - high nitrogen
Remain viable in bird droppings for 2yr
WW distribution
Most common systemic fungal IFX of cats

Question 3

Pathogenesis

Answer 3

IFX - prob by inhal
–If deposited on nasal epithelium –> granuloma
–if reach alveoli –> lung granuloma
Disseminated by local spread/blood –> CNS
Dissemination depends in immune status
–Cats with CNS dz often have FIV/FeLV

Question 4

CF

Answer 4

No sex/breed predilection
Young adult cats (2-3yr) overrep

Upper resp signs common

• -rare to have other systemic signs
• -Snoring, steroids, inspiratory dyspnea w/ open mouth breathing can occur as ONLY presenting signs (no supf lesions on the nose!)

Question 5

CF #2

Answer 5

Signs of nasopharyngeal mass
Nostril swelling or mass over bridge of nose
Lymphadenopathy
–Major characteristic of systemically infected cats

Question 6

CF #3

Answer 6

Cutaneous lesions - 40% cases
CNS - variable CS
–CN involvement common
–depression, bizarre behavior, sz, circling, head pressing, paresis, head tilt, blindness

Question 7

Ocular Findings

Answer 7

OPTIC SIGNS ALWAYS MARKER OF NEURO DZ

Peripheral blindness - dilated unresponsive pupils
–optic neuritis, granulomatous chorioretinitis

Question 8

Dx Cytology

Answer 8

DiffQuik, Giemsa, Wright, New Methylene Blue best
Cytospin best for CSF but only 60% positive on cytology

Remember that CSF tap dangerous to do in a cat with elevated CSF pressure. Look in the eyes. If eyes involved, so is CNS

Question 9

Dx Serology

Answer 9

Latex Agglutination antigen test

Question 10

Latex agglutination antigen test

Answer 10

Detects ANTIGEN in serum, CSF, urine
90-100% sensitivity, 97-100% specific
May get false positives with talc from latex gloves or rubber blood-tube stoppers
Do serum titer before CSF tap as some cats degenerate after CSF tap DT changes in CSF pressure
Titers can be very high
–1:32,000 not unusual for systemic infection
–Titer of 1:4 can be significant as long as sample not contaminated

Question 11

Dx Tissue Biopsy

Answer 11

Impression smears can provide quick Dx

PAS, silver, masson-fontana stains best

Question 12

Dx Culture/isolation

Answer 12

Easily cultured from exudates, aspirates, fluids
Sabourand’s agar
NOT infectious risk to lab staff

Question 13

Therapy - initial considerations

Answer 13

O must understand time/cost commitment
Immunocompromised P (FeLV/FIV) –> relapses, recurrent IFX
May need sx debunk mass lesions
–often best done after start of drug tx to reduce mass effect
Antifungal agents = mainstay of tx

Question 14

Therapy other azoles

Answer 14

Itraconazole, ketoconazole
Surpassed by fluconazole, AMB, flucytosine
Can use itraconazole if no response to fluconazole

Question 15

Therapy - fluconazole

Answer 15

Excellent penetration into eye, CNS, urinary tract with minimal SE
Can cause GI upsets
–liver tox much less than with ketoconazole
Doesn’t suppress adrenal or sex hormones
Cost used to be a factor but no longer
Best tx for mild dz
Best results if start dosing high

Question 16

Therapy - Flucytosine

Answer 16

Resistance develops if used alone 
Penetrates BBB well 
Use with other drugs - AMB 
--combination with AMB more efficacious than anoles 
Well-tolerated by cats --> NOT DOGS
May use prednisone during very early stages of tx 
--first 3-7d 
Support with feeding tubes if necessary

Question 17

Tx Amphotericin B #1

Answer 17

Most effective drug available 
--only fungicidal agent 
Able to clear CNS infections 
Req parental admin
NEPHROTOX
Optimal tx for severe disseminated dz = AMB, flucytosine 
--esp when CNS involved 
AMB liposomal and lipid complex --> less toxic but not necessarily more effective 
--much more expensive

Question 18

Therapy: AMB #2

Answer 18

Heat-pretx reduces nephrotox
–not everyone believes this!
Give SC or IV 2-3x/wk
–dilute 50mg vial Fungizone w/ 10ml water
–freeze
–thaw in very hot tap water
–Mix each dose in 400mL 0.45% saline/2.5% dextrose
–Admin sq btw shoulder blades in one site –> pooling will absorb over several hours
Monitor for nephrotox

Question 19

How long tx for?

Answer 19

Must have pre-tx serum titer!
Remember!
–pre-tx titer does not correlate with tx success
–serum titer usually correlates with CSF titer
Treat until clinically normal (3-12mo)
Then, measure titer –> usually 4-6 fold decrease suggesting successful tx
If not decreased, change treatment - another round of AMB or add flucytosine even if clinical improvement!
Generally, titer should drop approx 2 fold (1 dilution) per month tx

Question 20

Long-term follow up

Answer 20

Continue tx until titer NEGATIVE
You can see re-occurrences years later if titers are not negative when start tx
REMEMBER! Only AMB is fungicidal so if using -azoles, need CMI to remove fungus
Cat tx with itraconazole alone needs a median of 8mo treatment
Cats tx’d with AMB + flucytosine have quicker response
FeLV/FIV positive cats - check titer Q6mo after stopping tx (when titer is negative)

Question 21

Public Health

Answer 21

Lab culture not a public health risk
Contact with infected pets not a risk to owners
–not really considered zoonotic disease
Common source of exposure = main health hazard
Important opportunistic pathogen of people with HIV