Fungal and algal disease

Question 1

Describe the potential clinical signs associated with cryptoccus infection in cats

Answer 1

• Nasal signs
  
  • Common - sneezing, mucopululent to bloody discharge, facial deformity, pain
  • Enlarged local lymph nodes
  • May progress to cause middle ear signs or pulmonary disease
• Neurological signs
  
  • Direct spread from the nasal cavity
    
    • Optic neuritis, blindness, seizures, behavioural changes
  • Haematogenous spread
    
    • Granulomatous encephalomyelitis
• Ocular signs
  
  • Common
  • Uveitis, chorioretinitis
• Cutaneous disease
  
  • Solitary to multiple cutaneous nodules
  • Subcutaneous nodules suggest dissemination from other primary site
• Systemic signs
  
  • Inappetance, lethargy, weight loss

Question 2

Describe the diagnostic tests useful in confirming a suspected Cryptococcus spp diagnosis

Answer 2

• Cytology
  
  • Direct from lesion
  • In CSF
  • In body fluids such a pleural fluid or from BAL
• LCAT
  
  • Serum, CSF or urine
  • Useful also for monitoring response to treatment
• Other POC tests
  
  • Similar performance in confirming diagnosis with LCAT
• Histopathology
  
  • Similar to cytology but more sensitive
• Culture
  
  • Can be used to identify strain (with follow up PCR) and test for drug resistance

Question 3

Describe the treatment options for cryptococcosis in cats.

What is the prognosis for cats with cryptococcus infection

Answer 3

• The prognosis is generally good as long as the disease is detected early (prior to dissemination) and the prolonged treatment course is adhered to - 68% success in one study
• CNS involvement may carry a more guarded prognosis than the localised nasal form of the disease
• CNS involvement
  
  • Amphotericin B - 0.25 mg/kg IV q 48 hours for a total of 4-16 mg
    
    • Can be given SC also if hospital care is not necessary
  • Monitor renal function frequently - weekly
• Fluconazole - most effective single agent
  
  • Penetrates the CNS
• Itraconazole
  
  • Poor penetration in to the CNS
  • Less well tolerated when compared to FCZ
• Flucytosine
  
  • Generally recommended initially for CNS infection in combination with amphotericin B
  • Combination therapy continues for 6-12 weeks
  • Follow up thereafter with FCZ
• Glucocorticoids
  
  • May be used initially at anti-inflammatory doses for neurological disease

Question 4

Briefly comment on the releavance of immunosuppression on cryptococcus infection in dogs and cats

Answer 4

• Immunosuppression may pre-dispose to infection
• FeLV and FIV have been suggested to increase the incidence/risk
• Been reported in cats undergoing chemotherapy - cause and effect not possible to prove
• Cell mediated immunity is essential for clearing the organisms as humoural immune responses are ineffective
• Infection in dogs tends to progress to systemic and neurological forms of the disease more readily than in cats

Question 5

Describe the potential clinical signs for dogs with nasal Aspergillus infection

Question 6

Briefly document the aetiology of canine sinonasal aspergillosis

Answer 6

• Primarily caused for Aspergillus fumigatus infection
  
  • A niger, A flavus and A nidulans occasionally involved
• Aspergillus is a dichotomously branching (at 45° angles) fungus that form septate, non-pigmented hyphae
• The fungus is a ubiquitous saprophyte that causes opportunistic infection

Question 7

Briefly describe the pathogenesis of SNA in dogs

Answer 7

• Environmental fungus, the conidia of which can remain airborne and are inhaled regularly
• Innate immune mechanisms protect against infection
• Young dogs most commonly affected - median 3 years
• Impaired CMI may play a part and has been documented
  
  • However, most patients are systemically healthy
• SNA can cause extensive osteolysis
  
  • Mediated by extensive infiltration of mixed inflammatory cells

Question 8

List the diagnostic tests that can help investigate a suspected case of nasal aspergillosis in a dog

Answer 8

• Imaging and endoscopy
  
  • CT more sensitive than radiographs
  • Turbinate destruction, mass lesions, contrast enhaning mucosa
  • Endoscopy allows for sample detection
• Cytology / histopathology
  
  • Cytology positive in >93% when prepared from biopsy or visualised brush samples
  • Positive in < 20% with blind sampling or swabs from discharge
  • Histopathology highly sensitive when endoscopically guided
• Culture - endoscopically acquired tissue is best
• Antibody testing
• Antigen detection

Question 9

Describe the diagnostic utility of aspergillus antigen detection testing and Ab testing in the investigation of SNA in dogs

Answer 9

Antibody Testing

• Agar gel double diffusion more reliable than ELISA
• Serological testing had a sensitivity of 67% in a study where culture was 81% sensitive
• Specificity of AGDD was 98%

Antigen Testing

• Based on the detection of galactomanna or other fungal released carbohydrates in serum
• Poor sensitivity and specificity and not recommended

Question 10

Briefly describe the aetiology of canine disseminated aspergillosis

Answer 10

• Caused by Aspergillus terreus, A flavipes, A deflectus and A fumigatus
• Respiratory entry and systemic spread is most likely
• With blood borne spread, common sites of localisation include the IV discs, glomeruli and uveal tracts
• As immunity to systemic Aspergillus infection requires functional CMI, defective CMI responses are likely present in dogs with disseminated aspergillosis
  
  • German Shepherd dogs are predisposed and one study constituted 68% of all patients

Question 11

Note the potential clinical findings in dog with disseminated aspergillosis

Answer 11

• GSD over-represented
• Many are severely ill at the time of diagnosis
• Back pain and neurological deficits are common
• Non-specific signs
  
  • Lethargy / weakness
  • Anorexia / weight loss
  • Pyrexia
  • Vomiting
• Limb pain / lameness
• Lymphadenitis / lymphadenopathy
• Uveitis / endophthalmitis - may occur early in the course of disease

Question 12

Describe the diagnostic tests that may be helpful in the investigation of suspected canine disseminated aspergillosis

Answer 12

• Routine clinical pathology
  
  • Mature neutrophilia +/- eosinophilia and monocytosis
  • Variable increases in liver and renal parameters
  • Increased total protein / globulin
• Imaging - Radiographs, CT, US
  
  • Changes depend on the site of infection
  • Discospondylitis can be seen with radiographs and CT
  • Renal involvement may be suggested by US findings
• Organism detection
  
  • Cytology, culture and histopathological options
  • Urine cytology may be diagnostic
  • Culture requires 5-7 days on Sabouraud’s dextrose agar
• Ab testing
  
  • Not to be used as a solitary test and interpretation of results may be difficult due to the ubiquitous nature of the fungus
• PCR?