Cryptococcosis

Torulosis
European blastomycosis
Busse-Buschke’s disease
 Overview
• Organism
• History
• Epidemiology
• Transmission
• Disease in Humans
• Disease in Animals
• Prevention and Control

Center for Food Security and Public Health, Iowa State University, 2012
THE ORGANISM
 The Organism
• Cryptococcus neoformans
– Encapsulated yeast
– Four serotypes
• Based on capsular antigens
– Cryptococcus neoformans
var neoformans
• Serotypes A and D
• Ubiquitous
• Causes most cases of
cryptococcosis in humans,
especially those in the
immunocompromised

Center for Food Security and Public Health, Iowa State University, 2012
 The Organism
• Cryptococcus neoformans var gattii
– Serotypes B and C
– Less common in environment
– Mostly in immunocompetent hosts
• Cryptococcus laurentii
– Rarely causes disease in humans
– Immunocompromised hosts

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HISTORY
 History
• 1894
– Isolated from tibial lesion of human
patient by Busse and Buschke
– Isolated from peach juice in Italy
• Most early cases associated
with cancer patients
• 1905
– First case of cryptococcal meningitis
reported by Von Hansemann
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EPIDEMIOLOGY
 Geographic Distribution
• C. neoformans var neoformans
– Found worldwide in soil
– Serotype A most common in U.S.
• C. neoformans var gattii
– Often found near
eucalyptus trees
– Tropical and sub-
tropical areas

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 Morbidity and Mortality:
Humans
• C. neoformans var neoformans
– General population
• 0.4-1.3 cases/100,000 persons
– Immunosuppressed people
• AIDS patients
– 2-7 cases/1,000 patients
• Transplant recipients
– 0.3-5.3 cases/100 patients
– Mortality rate
• 12-28% overall
Center for Food Security and Public Health, Iowa State University, 2012
 Morbidity and Mortality:
Animals
• Cases usually sporadic
• Cats most frequently affected
– Immunosuppressed
• Feline leukemia virus
• Feline immunodeficiency virus
– Untreated infections often fatal
• Birds carry organism in
intestinal tract
– Clinical disease rare
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TRANSMISSION
 Transmission
• C. neoformans var neoformans
– Grows naturally in environment
• Soil saprophyte
– Found in pigeons nests, droppings
• Favorable growth environment
• C. neoformans var gattii
– Bark and plant debris under
eucalyptus trees
– Not associated with pigeons
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 Transmission
• Inhalation
– Via environment
• Reactivation of latent infection
• Fomites
– Mastitis in cattle
• Contaminated syringes, cannulas, etc.
• Animal-to-human and human-to-
human transmission very rare

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DISEASE IN HUMANS
 Disease in Humans
• Spectrum of disease
• C. neoformans var neoformans
– Opportunist
– Immunosuppressed patients
• C. neoformans var gattii
– Immunocompetent people
– Initial infection usually in lungs

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 Disease in Humans
• Pulmonary cryptococcosis
– Often asymptomatic
• Coughing, pleuritic chest pain may occur
– Rarely fatal
• Progressive disease most common in
immunocompromised
• Disseminated disease
– Often first sign of
cryptococcosis

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 Disease in Humans
• Disseminated disease
– CNS infections most common
• Meningitis, meningoencephalitis
– Headache, nausea, vomiting
– Changes in mental status
– Untreated infections often fatal
• Subacute presentations common in
AIDS patients
• May have few symptoms or exhibit
nonspecific signs

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 Disease in Humans
• Additional disease forms
– Ocular lesions
• Optic neuritis, chorioretinitis,
endophthalmitis
– Skin lesions
• Papules, vesicles, bullae, ulcers, etc.
• Cellulitis
– Organ transplant recipients
– Other
• Involvement of bone, other organs
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 Diagnosis in Humans
• Detection in tissues or fluids
– Methods
• Direct observation
• Culture
• Imaging (CT, MRI, X-ray)
– Specimens
• CSF, blood, sputum, urine, others
– Yeast characteristics
• Encapsulated, round to oval, clear halo

Center for Food Security and Public Health, Iowa State University, 2012
 Treatment in Humans
• Anti-fungals
– Amphotericin B, fluconazole, others
– Long term therapy may be required
in AIDS patients
• C. neoformans var gattii
– Infections respond slowly to treatment

Center for Food Security and Public Health, Iowa State University, 2012
DISEASE IN ANIMALS
 Species Affected
• Cats • Foxes
• Cattle • Mink
• Dogs • Cheetahs
• Ferrets • Gazelles
• Guinea Pigs • Koalas
• Horses • Wallabies
• Sheep • Porpoises
• Goats • Non-human
• Llamas primates
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 Clinical Signs: Cats
• Upper respiratory
– Most common form of disease in cats
– Sneezing, snoring, dyspnea, nasal
discharge, nasal polyps
• Skin lesions
– Firm nodular lesions
– Face often affected
• CNS
• Other
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 Clinical Signs: Dogs
• Disseminated disease
– Neurologic disease most common
form of cryptococcosis in dogs
• Ocular
– Chorioretinitis, optic neuritis
• Other organs also affected
– Nasal cavity rarely affected

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 Clinical Signs:
Other Animals
• Cows: mastitis
• Sheep and goats: pulmonary disease
• Horses: CNS, pulmonary, other
• Birds
– Disease rare
• Rhinitis and sinusitis may occur
– Shed organism in feces

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 Post Mortem Lesions
• Granulomas or gelatinous masses
– Minimal inflammation
– Any organ system
• Lungs, kidney, lymph nodes, spleen, liver
• CNS involvement
– Meninges congested and thickened
– Brain and spinal cord abscesses
• Ocular lesions

Center for Food Security and Public Health, Iowa State University, 2012
 Diagnosis in Animals
• Detection in tissues or fluids
– Methods
• Direct observation
• Culture
• Serology
– Specimens
• CSF, biopsies, impression smears, aspirates
– Yeast characteristics
• Encapsulated, round to oval, clear halo

Center for Food Security and Public Health, Iowa State University, 2012
 Treatment in Animals
• Anti-fungals
– Amphotericin B
– Flucytosine
– Itraconazole
– Fluconazole

Center for Food Security and Public Health, Iowa State University, 2012
PREVENTION AND
CONTROL
 Prevention and Control
• Environmental exposures
– Difficult to prevent
• C. neoformans var neoformans
– Avoid pigeon droppings
• Carefully remove from
environment
• C. neoformans var gattii
– Avoid eucalyptus trees
• Other exposures sources exist

Center for Food Security and Public Health, Iowa State University, 2012
 Prevention and Control
• Animal-associated exposures
– C. neoformans var neoformans
carried by pet birds in intestinal tract
• Use care when cleaning cages
– No mammal-to-human cases reported
• Use care when handling infected animals
– Immunosuppressed people most at risk
• Anti-fungals may be used for prophylaxis

Center for Food Security and Public Health, Iowa State University, 2012
 Prevention and Control
• Cryptococcal mastitis
– Usually associated with treatment of
mammary gland for another condition
– Take care not to contaminate syringes,
cannulas, or antibiotic preparations
– Clean teat ends before treatment

Center for Food Security and Public Health, Iowa State University, 2012
 Additional Resources
• Center for Food Security and Public Health
– www.cfsph.iastate.edu
• CDC
– www.cdc.gov/fungal/diseases/cryptococcosis-
neoformans/index.html
– www.cdc.gov/fungal/diseases/cryptococcosis-
gattii/index.html

Center for Food Security and Public Health, Iowa State University, 2012
 Acknowledgments
Development of this presentation was made possible
through grants provided to
the Center for Food Security and Public Health at Iowa
State University, College of Veterinary Medicine from
the Centers for Disease Control and Prevention,
the U.S. Department of Agriculture,
the Iowa Homeland Security and
Emergency Management Division, and the
Multi-State Partnership for Security in Agriculture.

Authors: Kerry Leedom Larson, DVM, MPH, PhD, DACVPM; Anna Rovid Spickler, DVM, PhD
Reviewer: Glenda Dvorak, DVM, MPH, DACVPM

Center for Food Security and Public Health, Iowa State University, 2012