Lecture Slides


Actinomycetales
Antifungal Drugs
Aspergillus
Blastomycosis
Candidiasis
Coccidioidomycosis
Cryptococcosis
Dermatophytosis
Fungal Ecology
Histoplasmosis
Mycotic Keratitis
Mycotoxins
Oportunistic Fungal Inf-
ections

Otomycosis
Sporotrichosis
Unusual Pathogens
Zygomycosis

Cryptococcosis

- Caused by the encapsulated yeast Cryptococcus neoformans
- More common in immunocompromised, but can occur in healthy individuals
- Tends to cause insidious meningitis, sometimes skin lesions (esp. in cats)

Distribution and Ecology

- Found worldwide, not restricted to endemic areas
- Prefers to grow in pigeon droppings, which are high in creatinine
- Does not infect pigeons
- Dries out over time, loses capsule, easier to inhale

Cryptococcosis

Dogs and cats
- Infection thought to usually initiate in the lung
- Disseminates to other sites, including CNS, skin and eyes
- Cats - perhaps primary inoculation of skin?
- Horses - usually meningitis
- Cattle - mastitis, by inoculation
- Humans - Inhalation, dissemination to CNS, skin lesions uncommon, strain specific?

Pathogenesis of Cryptococcosis

Thought that dessicated yeast are inhaled
- Innate defenses usually adequate
- If large exposure, or weak CMI, infection progresses
- Capsular polysaccharide - forms in vivo
Infection disseminates to CNS
- Develops slowly
- Few inflammatory cells in CSF
- Difficult to visualize yeast

Virulence mechanisms and Host Defense

- Capsule inhibits phagocytosis
- Capsular polysaccharide - induces T suppressor cells
- Melanin - increases resistance to ROI
- Anti-capsular Ab response - usually weak
- Ab will opsonize, increase killing by neutrophils and macrophages

Treatment of Cryptococcosis

Treatment of CNS infection - blood-brain barrier is a problem
- 5-fluorocytosine - penetrates CSF, but resistance develops, use in combination
- Amphotericin B - difficult to get adequate levels in CSF
- Fluconazole - good drug distribution to CNS, effective
- Ketoconazole ineffective, poor distribution

Diagnosis of Cryptococcosis

- Cytology - somtimes see yeast, but usually few in number
- usually few inflammatory cells - but these may outline capsule
- Culture - grows readily in vitro, urease +
- Serology - often weak Ab response
- Antigen detection - use Abs to detect circulating antigen, can be prognostic

Cryptococcosis

- Initiated by inhalation of desiccated yeast. Multiply in lung, become encapsulated, disseminate to CNS.
- Is NOT dimorphic!
- Can cause disease in healthy animals or people, but is more severe in immunosuppression

Distribution and Ecology

- Found worldwide
- Favored environmental niche is dirt laden with pigeon droppings.
- Creatinine in pigeon droppings encourages growth of C. neoformans. Does NOT infect pigeons. - Urban outbreaks when pigeons roost outside air intakes for a building.

Cryptococcosis

Dogs and cats
- Pulmonary infection
- Thought to be usual portal of entry
- May be mild or inapparent
- Meningitis
- Facial and ocular lesions
- Facial lesions very common in cats - grooming?
- Skin lesions similar to original reports of human cryptococcosis
Horses
- Pulmonary and CNS infection
Cattle
- Not associated with pulmonary and CNS infection
- Infrequent cause of mastitis
- Contaminated milking line or infusion equipment

Case - Canine Cryptococcosis

- Pekingese, 2 yr old, female
- Neurological problems
- loss of balance, can’t climb stairs, severe head tilt, last 3 weeks
- blindness, 3 days earlier
- Total WBC and blood chemsitry normal
- CSF - some increase in eosinophils, see encapsulated yeasts with India ink stain