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 Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 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 subtropical areas Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 Transmission • Inhalation – Via environment • Reactivation of latent infection • Fomites – Mastitis in cattle • Contaminated syringes, cannulas, etc. • Animal-to-human and human-tohuman transmission very rare Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 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 Cattle Dogs Ferrets Guinea Pigs Horses Sheep Goats Llamas • • • • • • • • Foxes Mink Cheetahs Gazelles Koalas Wallabies Porpoises Non-human primates Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 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 Center for Food Security and Public Health, Iowa State University, 2012 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 – http://www.cdc.gov/fungal/cryptococcosisneoformans/ – http://www.cdc.gov/fungal/cryptococcosisgattii/ 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