Fungal Diseases of NSB

Question 1

describe aspergillus spp.
where found, which causes disease, transmission

Answer 1

1. ubiquitous fungi found in soil, vegetation, feed
2. disease caused by A. fumigatus, A. flavus, A. terreus, A. niger
   -all produce mycotoxins, but A. flavus specifically produces aflatoxins
3. transmission:
   -inhalation of ingestion of spores
   -contamination of wound
   -exposure is common!

Question 2

describe pathogenesis of aspergillus

Answer 2

1. conidia are inhaled (usually alveolar macrophages can kill)
2. if spores germinate, hyphae are formed; neutrophils will try to attack and destroy hyphae
3. if alveolar macrophages or neutrophils fail to kill fungus, tissue invasion results
   -produce elastase to help invade

-disease is associated with decreased neutrophil function and number (neutropenia!!)

Question 3

describe aspergillus infection in the cornea

Answer 3

1. common in horses due to external trauma to the cornea when saprophytic fungi invade damaged corneal tissue
2. inflammation is damaging and can cause blindings; corneal scarring is likely
3. diagnosis: corneal scraping using fluorescin stain
4. treatment: longterm (6-8wks) topic antifungal drugs but few are available for eyes
   -use topical 1% itraconazole

Question 4

describe canine disseminated aspergillosus

Answer 4

1. caused by A. terreus, inhaled, causing nasal lesions that disseminate to the CNS
   -immunosuppression is a common predisposing factor
   -more common in german shepherds
2. diagnosis: imaging, biopsy, cytology
3. prognosis: poor

Question 5

describe common features of cryptococcus, blastomyces, and coccidioides

Answer 5

1. infection generally via inhalation; mold spores inhaled and transform into yeast or alternate form in the lung
2. require cell-mediated immunity for protection
3. if immunity inadequate, dissemination throughout body and chronic disease results
   -disease lesions are granulomatous or pyogranulomatous
4. location and travel history important to get in history!
5. treatment: longterm antifungals
6. NO vaccines commercially available for any systemic fungal diseases in animals or humans

Question 6

describe cryptococcus spp.

Answer 6

1. dimorphic fungus; encapsulated in yeast in host
   -C. neoformans is important species
2. birds are reservoirs! carry mold in intestines where bird shit provides essential nutrients for growth (creatinine)
3. basidiospores in environment are inhaled and then transform into yeast in animal host
4. disease is more common in immunosuppressed (cancer, FLV, FEV)

Question 7

describe cryptococcus spp transmission and pathogenic features

Answer 7

1. C. neoformans is present worldwide and prefers to grow in pigeon shit
2. basidiospores (can persist for more than 2 years in environment) inhaled from env germinate in upper resp tract, where encapsulated yeast emerges

pathogenic features: polysaccharide capsule inhibits phagocytosis; capsule is SHED from growing yeast and can induce T cell apoptosis

Question 8

describe clinical disease of cryptococcosis in cats

Answer 8

1. most common systemic fungal disease in cats!
   -infrequent in dogs and horses
2. primarily a localized infection in the upper respiratory tract (nasal cavity, sinuses) where granulomas form
3. yeast may disseminate from upper resp tract to CNS, skin, eyes
   -skin lesions are common in cats and due to hematogenous spread
   -may form cryptococcomas in the brain

Question 9

what causes cryptococcosis to disseminate? how?

Answer 9

1. if host is exposed to a large number of spores or has impaired T cell function (immunosuppressed)
2. can spread through cribriform plate to brain
3. yeast can enter CNS and cause meningitis

Question 10

describe diagnosis of cryptococcosis

Answer 10

1. cytology: stain clinical sample with india ink or giemsa/wright stain
   -capsule does NOT take up india ink stain
   -usually see a few inflammatory cells surrounding the yeast
2. histopathology: micicarmine will stain capsule rose-red and the organism pink
3. culture and capsule serotyping/serology:
   -measurement of cryptococcus antigen by latex agglutination detects CIRCULATING capsule antigen in blood or CSF
   -ANY antigen titer value is significant; can be very high in infected animals

Question 11

describe treatment of cryptococcosis

Answer 11

1. surgically remove fungal granulomas in nasal passages and sinuses
2. anti-fungal therapy:
   -azoles for cutaneous or nasal disease, but some cryptococcus are resistant
   -amphotericin B effectively kills but does NOT penetrate CNS
3. may need to treat for up to 12 months = hella expensive
4. brain form is most difficult to treat
5. monitor capsule antigen levels in CSF to follow response to treatment
   -prognosis is favorable if there is a 10-fold drop in capsule antigen titer two months after therapy initiated
   -treat for 2 months after the antigen titer value is zero!

Question 12

describe blastomycosis dermatidis

Answer 12

1. dimorphic fungus; mold/spores present in moist soil from upper midwest to southeast US (GA) and mississippi river basin
   -distribution appears to be expanding, also occurs in europe, asia, and africa
2. dogs are 10x more susceptible than humans; most infected dogs live within 400 meters of lake/river water

Question 13

describe blastomycosis dermatidis transmission

Answer 13

1. dog inhales microconidia spores
2. yeast sporulate in lungs, enter blood disseminate throughout body

Question 14

describe immune response to blastomycosis dermatitidis

Answer 14

1. cell mediated immunity is protective
   -most exposed dogs develop effected CMI reponses and show no clinical signs aftrer inhaling spores
2. 5% of dogs develop pneumonia and disseminated disease because they generate inappropriate antibody mediated responses or are immunosuppressed

Question 15

describe clinical disease of blastomycosis in dogs

Answer 15

1. pneumonia and respiratory distress
2. skin lesions common
3. ocular disease and bone involvement common with dissemination

Question 16

describe blastomycosis diagnosis

Answer 16

1. cytology/histopathology: visualize broad based budding yeast in clinical sample (BAL, TTW, or FNA)
2. culture: mold form on sabouraud’s agar at 25 degrees C; but biohazard bc hyphae and conidia are infectious

Question 17

describe treatment/control of blastomycosis

Answer 17

1. antifungal treatment:
   -intraconazole will work better if no CNS dissemination and resp disease NOT severe
2. long term treatment (min 2-3 months); recurrence post therapy common
3. prevention: restrict dogs from lakes and creeks known to have infected other dogs

Question 18

describe coccidioides spp.

Answer 18

1. genus with two important species
   -c. immitus: central valley of california
   -c. posadasii: not california
2. dimorphic fungi; MOST virulent fungus in US
3. mold form endemic in soils in
   -SW US: arizona, NM, texas, california
   -mexico, central and parts of south america

Question 19

describe the coccidioides spp life cycle

Answer 19

1. hyphae (mold) grow in soil and fragment to form arthroconidia (spores), which persist in the top layer of soil despite heat and dry conditions
2. spores germinate after monsoon rains to repopulate soil with more spores
3. spores become airborne during dust storms or when soil disrupted (construction) and are inhaled
4. spores transform into spherules inside the lungs of the host; spherules rupture and release endospores inside animal
   -dimorphic but do NOT form a yeast phase (spherules instead)
5. each endospore can then form a new spherule inside a host
6. infected dogs are NOT contagious to other dogs or people, only arthrocnidia are infectious

Question 20

describe valley fever in dogs (caused by coccidioidomycosis)

Answer 20

1. inhaling as few as 10 spores can produce pneumonia
2. 1-3 week incubation period
3. MOST infected dogs asymptomatic bc develop appropriate CMI
4. some dogs develop signs of pneumonia with high fever (104-105) and cough; pneumonia may be followed by dissemination

Question 21

describe diagnosis of coccidioidmycosis

Answer 21

1. clinical signs:
   -suspect if animal has visited/resides in endemic region and has suggestive clinical signs
2. culture: not routinely done bc organism is a biohazard and select agent
3. cytology and histology:
   -fungal spherules and endospores found in exudates/biopsies; are LARGE
4. serology: galactomannan urine or serum antigen test but is not specific for coccidioides
5. A REPORTABLE DISEASE

Question 22

describe treatment and prevention of coccidioidomycosis

Answer 22

1. requires long term antifungal therapy:
   -azoles combined with chitin synthesis inhibitors for up to 1 year
2. prognosis for disseminated disease is poor
3. prevent by limiting exposure of immunosuppressed animals in endemic regions
   -keep away from construction sites and inside during dust storms