Abstract
Cryptococcosis is one of the most serious fungal infection encountered worldwide. The etiologic agent is Cryptococcus neoformans, an environmental yeast species which initiates the infection after inhalation of the organism by the host. Although C. neoformans can cause lesions in almost every organ, the most common clinical manifestation, as well as the most common cause of death, is meningoencephalitis, an infection of the brain. Untreated cryptococcal meningoencephalitis is fatal, and death can result in as little as two weeks from the onset of symptoms or the symptoms may last for up to 13 years before death [1]. Despite the most advanced medical treatment, the fatality rate for cryptococcosis is close to 25% [1]. While cryptococcosis sporadically occurs in normal populations without any underlying condition, the disease primarily affects immunocompromised individuals, especially those with T-lymphocyte depletion or dysfunction such as is the case with HIV-1 patients. In fact, cryptococcosis was designated as the AIDS-defining opportunistic infection, as the HIV-1 epidemic became widely known since the mid 1980s. Infections with C. neoformans have significantly declined in the developed world as a result of antiretroviral therapy that has reduced the reservoir of immunosuppressed HIV-1 infected patient. However, due to an explosion of AIDS-associated cryptococcosis cases in developing countries, the disease still causes 780,000 deaths in the world annually [2].
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Kwon-Chung K J & Bennett J E (1992). Medical Mycology Lea & Febiger, Philadelphia (pps 397–446)
Park B J, Wannemuehler K, Marston B J & et al (2009). Estimating the current global burden of cryptococcal meningitis among persons living with HIV/ AIDS, AIDS, 23, 525–530
Emmons C W (1951. Isolation of Cryptococcus neoformans from soil, J Bacteriol, 62, 685–690
Emmons C W (1955). Saprophytic sources of Cryptococcus neoformans associated with the pigeon (Columba livia), Am J Hyg, 62, 227–232
Busse O (1894). Über parasitäre zelleinschlüsse und ihre züchtung, Zentralbl Bakteriol, 16, 175–180
Sanfelice F (1894). Contributo alla morfologia e biologia dei blastomiceti che si sviluppano nei succhidi alcuni frutti, Ann Igien, 4, 463–495
Emmons C W (1949). Isolation of Histoplasma capsulatum from soil, Pub Hlth Rep, 64, 892–896
Emmons C W (1958). Association of bats with histoplasmosis, Pub Hlth Rep, 73, 590–595
Emmons C W (1960). Prevalence of Cryptococcus neoformans in pigeon habitats, Pub Hlth Rep, 75, 362–364
Casadevall A & Perfect J R (1998). Cryptococcus neoformans, ASM Press, Washington, D C, (pp 541)
Ellis D H & Pfeiffer T G (1990). Natural habitat of Cryptococcus neoformans var. gattii, J Clin Microbiol, 28, 1642–1644
Lazera M S, Pires F D & et al (1996). Natural habitat of Cryptococcus neoformans var. neoformans in decaying wood forming hollows in living trees, J Med Mycol, 34, 127–131
Kidd S E, Hagen F & et al (2004). A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada), Proc Natl Acad Sci USA 101, 17258–17263
McCullough N B, Louria D B, Hilbish T F & et al (1958). Cryptococcosis: Clinical Staff Conference at the National Institutes of Health, Ann Intern Med, 49, 642–661
Hill G J, Butler W T, Szwed C F & et al (1963). Comparison of renal toxicity of two preparations of amphotericin B, Am Rev Respir Dis, 88, 342–346
Bennett J E, Hill G J, Butler W T & et al (1964). Correlation of particle size of intravenous amphotericin B with toxic and chemotherapeutic effects. In: Antimicrobial Agents and Chemotherapy – 1963 (Ed: J C Sylvester), Braun-Brumfield, Ann Arbor (pps 745–752)
Butler W T, Alling D W, Spickard A & et al (1962). Diagnostic and prognostic value of clinical and laboratory findings in cryptococcal meningitis, N Engl J Med, 270, 59–67
Bell N H, Andriole V T, Sabesi S M & et al (1962). On the nephrotoxicity of amphotericin B in man, Am J Med, 33, 64–69
Butler W T & Hill G J (1964). Intravenous administration of amphotericin B in the dog, J Am Vet Med Assoc, 144, 399–402
Butler W T, Bennett J, Hill G J & et al (1964). Electrocardiographic and electrolyte abnormalities caused by amphotericin B in dog and man, Proc Soc Exp Biol Med, 16, 857–863
Utz J, Bennett J, Brandriss M & et al (1964). Amphotericin B toxicity, Ann Intern Med, 61, 334–354
Butler W T, Bennett J, Alling D & et al (1964). Nephrotoxicity of amphotericin B, Ann Intern Med, 61, 175–187
Tynes B S, Utz J P, Bennett J E & et al (1963). Reducing amphotericin B reactions, Am Rev Respir Dis, 87, 264–268
Brandriss M W, Wolff S M & Moores RS F Jr (1964). Anemia induced by amphotericin, JAMA, 189, 663–666
MacGregor R R, Bennett J E & Erslev A A (1978). Erythropoietin concentration in amphotericin B induced anemia, Antimicrob. Agents Chemother, 14, 270–273
Bindschadler D D & Bennett J E (1969). A pharmacologic guide to the clinical use of amphotericin B, J Infect Dis, 120, 427–436
Atkinson A J & Bennett J E (1978). Amphotericin B pharmacokinetics in humans, Antimicrob Agents Chemother, 13, 271–276
Diamond R D & Bennett J E (1974). Prognostic factors in cryptococcal meningitis: a study in 111 cases, Ann Intern Med, 80, 176–181
Bennett J E (1967). Susceptibility of Cryptococcus neoformans to amphotericin B. In: Antimicrobial Agents and Chemotherapy – 1966 (Ed: G L Hobby), American Society for Microbiology, Ann Arbor (pps 405–410)
Diamond R D & Bennett J E (1973). A subcutaneous reservoir for intrathecal therapy of fungal meningitis, N Engl J Med, 288, 186–188
Block E R & Bennett J E (1972). Pharmacologic studies with 5-fluorocytosine, Antimicrob Agents Chemother, 1, 476–482
Bennett J E (1977). Flucytosine, Ann Intern Med, 86, 319–322
Block E R, Jennings A E & Bennett J E (1973). 5-Fluorocytosine resistance in Cryptococcus neoformans, Antimicrob. Agents Chemother, 3, 649–656
Hospenthal D R & Bennett J E (1998). Flucytosine (5-FC) monotherapy of cryptococcosis, Clin Infect Dis, 27, 260–264
Block E R & Bennett J E (1973). The combined effect of 5-fluorocytosine and amphotericin B in the therapy of murine cryptococcosis, Proc Soc Exp Biol Med, 142, 476–480
Bennett J E, DismukesW E, Duma R J & et al (1979). A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis, N Engl J Med, 301, 126–131
Dismukes W E, Cloud G, Gallis H A & et al (1987). Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks, N Engl J Med, 317, 334–341
Washburn R G, Klym D M, Kroll M H & et al (1986). Rapid enzymatic method for measurement of serum flucytosine levels, J Antimicrob Chemother, 17, 673–677
Huang C M, Kroll M H, Ruddel M & et al (1988). An enzymatic method for 5-fluorocytosine, Clin Chem, 34, 59–62
Diasio R B, Bennett J E & Myers C E (1978). Mode of action of 5-fluorocytosine, Biochem Pharmacol, 27, 703–707
Tynes B, Mason K N, Jennings A E & et al (1968). Variant forms of pulmonary cryptococcosis, Ann Intern Med, 69, 1117–1125
Rex J R, Larsen R A, Dismukes W E & et al (1993). Catastrophic visual loss due to Cryptococcus neoformans meningitis, Medicine (Baltimore), 72, 207–224
Park M K, Hospenthal D R & Bennett J E (1999). Treatment of hydrocephalus secondary to cryptococcal meningitis by use of shunting, Clin Infect Dis, 28, 629–633
Hospenthal, D & Bennett J E (2000). Persistence of cryptococcomas on neuroimaging, Clin Infect Dis, 31, 1303–1306
Bennett J E, Hasenclever H F & Tynes B S (1964). Detection of cryptococcal polysaccharide in serum and spinal fluid: Value in diagnosis and prognosis, Trans Assoc Am Physicians, 77, 145–150
Bindschadler D D & Bennett J E (1968). Serology of human cryptococcosis, Ann Intern Med, 69, 45–52
Bennett J & Hasenclever H (1965). Cryptococcus neoformans polysaccharide: studies of serologic properties and role in infection, J Immunol, 94, 916–920
Diamond R D, May J E, Kane M A & et al (1974). The role of the classical and alternate complement pathways in host defenses against Cryptococcus neoformans infection, J Immunol, 112, 2260–2270
Macher A M, Bennett J E, Gadek J E & et al (1978). Complement depletion in cryptococcal sepsis, J Immunol, 120, 1686–1690
Diamond R D, May J E, Kane M A & et al (1974). The role of the classical and alternate complement pathways in host defenses against Cryptococcus neoformans infection, J Immunol, 112, 2260–2270
Diamond R D, Root R K & Bennett J E (1972). Factors influencing killing of Cryptococcus neoformans by human leukocytes in vitro, J Infect Dis, 125, 367–376
Diamond R D & Bennett J E (1973). Growth of Cryptococcus neoformans within human macrophages in vitro, Infect Immun, 7, 231–236
Henderson D K, Bennett J E & Huber M A (1982). Long-lasting, specific immunologic unresponsiveness associated with cryptococcal meningitis, J Clin Invest, 69, 1185–1190
Henderson D K, Kan V L & Bennett J E (1986). Tolerance to cryptococcal polysaccharide in cured cryptococcosis patients: failure of antibody secretion in vitro, Clin Exp Immunol, 65, 639646
Devi S J N, Schneerson R, Egan W & et al (1991). Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization and immunogenicity, Infect Immun, 59, 3700–3707
Wilson D E, Bennett J E & Bailey J W (1968). Serologic grouping of Cryptococcus neoformans, Proc Soc Exp Biol Med, 127, 820–823
Bhattacharjee A K, Bennett J E, Bundle D R & et al (1983) Anticryptococcal type D antibodies raised in rabbits, Mol Immunol, 20, 351–359
Bhattacharjee A K, Bennett J E & Glaudemans C P J (1984). Capsular polysaccharides of Cryptococcus neoformans, Rev Infect Dis, 6, 619–624
Bennett J E, Kwon-Chung K J & Howard D H (1977). Epidemiologic differences among serotypes of Cryptococcus neoformans, Am J Epidemiol, 105, 582–586
Bennett J E, Kwon-Chung K J & Theodore T S (1978). Biochemical differences between serotypes of Cryptococcus neoformans, Sabouraudia, 16, 167–174
Bennett J & Hasenclever H (1965). Evaluation of a skin test for cryptococcosis, Am Rev Respir Dis, 91, 616
Atkinson A J & Bennett J E (1968). Experience with a new skin test antigen prepared from Cryptococcus neoformans, Am Rev Respir Dis, 97, 637–643
Diamond R D & Bennett J E (1973). Disseminated cryptococcosis in man. Decreased lymphocyte transformation to Cryptococcus neoformans, J Infect Dis, 127, 694–697
Bennett J E (1981). Cryptococcal skin test antigen: preparation variables and characterization, Infect Immun, 32, 373–380
Newberry W M, Walter J E, Chandler J W & et al (1967). Epidemiologic study of Cryptococcus neoformans, Ann. Intern. Med., 67, 724–732.
Kwon-Chung K J (1976) Morphogenesis of Filobasidiella neoformans, the sexual state of Cryptococcus neoformans, Mycologia, 68, 822–833
Kwon-Chung K J (1975). A new genus Filobasidiella, the perfect state of Cryptococcus neoformans, Mycologia, 67, 1197–1200
Kwon-Chung K J (1980). Nuclear genotypes of spore chains in Filobasidiella neoformans, Mycologia, 72, 418–422
Kwon-Chung K J (1976). A new species of Filobasidiella, the sexual state of Cryptococcus neoformans serotype B and C, Mycologia, 68, 943–946
Kwon-Chung K J, Polacheck I & Popkin T J (1982). Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice, J Bacteriol, 150, 1414–1421
Kwon-Chung K J & Rhodes J C (1986). Encapsulation and melanin formation as indicators of virulence in Cryptococcus neoformans, Infect Immun, 51, 218–223
Salas S D, Bennett J E, Kwon-Chung K J & et al (1996). Effect of the laccase gene, CNLAC1 on virulence of Cryptococcus neoformans, J Exper Med 184: 377–386
Chang Y C & Kwon-Chung K J (1994). Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence, Mol Cell Biol, 14, 4912–4919
Chang Y C, Penoyer L A & Kwon-Chung K J (1996). The second capsule gene Cryptococcus neoformans, CAP64, is essential for virulence, Infect Immun, 64, 1977–1983
Chang Y C & Kwon-Chung K J (1998). Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans, Infect Immun, 66, 2230–2236
Williamson P R, Wakamatsu K & Ito S (1998). Melanin biosynthesis in Cryptococcus neoformans, J Bacteriol, 180, 1570–1572
Wang Y, Aisen P & Casadevall A (1995). Cryptococcus neoformans melanin and virulence: mechanism of action, Infect Immun, 63, 3131–3136
Chang Y C, Jong A, Huang S, Zerfa P & Kwon-Chung K J (2006). CPS1, a homolog of Streptococcus pneumoniae type 3 polysaccharide synthase gene is important for pathobiology of Cryptococcus neoformans, Infect Immun, 74, 3930–3938
Kwon-Chung K J & Bennett J E (1978). Distribution of alpha and a mating types of Cryptococcus neoformans among natural and clinical isolates, Am J Epidemiol, 108, 337–340
Kwon-Chung K J & Hill W B (1981). Virulence of the two mating types and pathogenicity of Filobasidiella neoformans (Cryptococcus neoformans), In: Sexuality and Pathogenicity of Fungi (Eds: R Vanbreuseghem & C DeVroy) Masson, New York (pp. 243–250)
Kwon-Chung K J, Edman J C & Wickes B L (1992). Genetic association of mating types and virulence in Cryptococcus neoformans, Infect Immun, 60, 602–605
Karos M, Chang Y C, McClelland C M & et al (2000). Mapping of the Cryptococcus neoformans MATalpha locus : presence of mating type-specific mitogen-activated protein kinase cascade homologs, J Bacteriol, 182, 6222–6227
Lengeler K B, Fox D S, Fraser J A & et al (2002) Mating-type locus of Cryptococcus neoformans: a step in evolution of sex chromosomes, Eukaryot Cell, 1, 704–718
Hsueh Y P, Idnurm A & Heitman J (2006). Recombination hotspots flank the Cryptococcus mating type locus: implications for the evolution of a fungal sex chromosome, PLoS Genet, 2, e184
Fraser J A & Heitman J (2004). Evolution of fungal sex chromosomes, Mol Microbiol, 51, 299–306
Loftus B J, Fung E, Roncaglia P & et al (2004). The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans, Science, 307, 1321–1324
Evans E E (1949). An immunologic comparison of 12 strains of Cryptococcus neoformans (Torula histolytica), Proc Soc Exp Biol Med, 71, 644–646
Kwon-Chung K J, Rhodes J C & Bennett J E (1982). Taxonomic studies on Filobasidiella species and their anamorphs, Antonie Van Leeuwenhoek, 48, 25–38.
Kwon-Chung K J, Varma A & Howard D H (1990). Ecology of Cryptococcus neoformans and prevalence of its two varieties in AIDS and non-AIDS associated cryptococcosis. In: Mycosis in AIDS Patients (Eds: H. Vanden Bossche, D W R. Mackenzie, G. Canwenbergh & et al) Plenum Press, New York(pp 103–113)
Kwon-Chung K J & Bennett J E (1984). Epidemiologic differences between two varieties of Cryptococcus neoformans, Am J Epidemiol, 120, 123–130
Kwon-Chung K J & Bennett J E (1984). High prevalence of Cryptococcus neoformans var. gattii in tropical regions, Zentralbl Bakteriol Mikrobiol Hyg A, 257, 213–218
Speed B & Dunt D (1995). Clinical and host differences between infections with the two varieties of Cryptococcus neoformans, Clin Infect Dis, 21, 28–34
Kwon-Chung K J & Varma A (2006). Do major species concepts support one, two or more species of Cryptococcus neoformans? FEMS Yeast Res, 6, 574–587
Kwon-Chung K J, Boekhout T, Fell J W & Diaz M (2002). Proposal to conserve the name Cryptococcus gattii against C. hondurianus and C. bacillisporus (Basidiomycota, Hymenomycetes, Tremellomycetidae), Taxon., 51, 804–806
Diaz M R, Boekhout T, Kiesling T & Fell J W (2005). Comparative analysis of the intergenic spacer regions and population structure of the species complex of the pathogenic yeast Cryptococcus neoformans, FEMS Yeast Res, 5, 1129–1140
Kwon-Chung K J, Polacheck I & Bennett J E (1982). Improved diagnostic medium for separation of Cryptococcus neoformans var. neoformans (serotype A and D) and Cryptococcus neoformans var. gattii (serotypes B and C), J Clin Microbiol 15, 535–537
Curtis F. (1895) Sur un parasite vegetal de l(espece des levures produisant chez l’homme des tumeurs d(aspect myxomateux, Presse Med., Sept.28, 370–371.
Edman J C & Kwon-Chung K J (1990). Isolation of the URA5 gene from Cryptococcus neoformans var. neoformans and its use as a selective marker for transformation, Mol Cell Biol, 10, 4538–4544
Walsh S & Barrell B (1996). The Saccharomyces cerevisiae genome on the World Wide Web, Trends Genet, 12, 276–277
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Kwon-Chung, K.J., Bennett, J.E. (2010). Cryptococcosis: From Discovering the Natural Reservoir of its Etiology to the Genetic Manipulation of Cryptococcus neoformans: Milestones in Cryptococcal Research by Intramural Investigators at NIAID. In: Georgiev, V. (eds) National Institute of Allergy and Infectious Diseases, NIH. Infectious Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-512-5_14
Download citation
DOI: https://doi.org/10.1007/978-1-60761-512-5_14
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-511-8
Online ISBN: 978-1-60761-512-5
eBook Packages: MedicineMedicine (R0)