• John W. Baddley
  • William E. Dismukes


Cryptococcosis is a systemic mycosis caused by the ­encapsulated yeast Cryptococcus neoformans, an organism found in soil and often associated with pigeon droppings. Infection involves most frequently the lungs or central nervous system and, less frequently, the blood, skin, skeletal system, and prostate. Because the incidence of cryptococcosis is greatly increased in immunocompromised patients, especially among patients with AIDS or organ transplant recipients, cryptococcosis is considered an opportunistic fungal infection. Treatment of cryptococcosis is based on anatomic site of disease, severity of disease, and the underlying immune status of the patient. Cryptococcal meningitis is treated with induction therapy of amphotericin B with or without flucytosine, followed by a prolonged course of fluconazole. For pulmonary disease alone, fluconazole is effective therapy in most patients. Chronic maintenance therapy with fluconazole may be required in HIV-infected patients or transplant patients who remain immunosuppressed.


Immune Reconstitution Inflammatory Syndrome Cryptococcal Meningitis Central Nervous System Infection Cryptococcal Antigen Cryptococcal Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    de Hoog G. Atlas of Clinical Fungi. 2nd ed. Washington, DC: American Society for Microbiology Press; 2001.Google Scholar
  2. 2.
    Johnson LB, Bradley SF, Kauffman CA. Fungaemia due to Cryptococcus laurentii and a review of non-neoformans cryptococcaemia. Mycoses. 1998;41:277–80.PubMedCrossRefGoogle Scholar
  3. 3.
    Khawcharoenporn T, Apisarnthanarak A, Mundy LM. Non-neoformans cryptococcal infections: a systematic review. Infection. 2007;35:51–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Kordossis T, Avlami A, Velegraki A, et al. First report of Cryptococcus laurentii meningitis and a fatal case of Cryptococcus albidus cryptococcaemia in AIDS patients. Med Mycol. 1998;36:335–9.PubMedGoogle Scholar
  5. 5.
    Neilson JB, Fromtling RA, Bulmer GS. Cryptococcus neoformans: size range of infectious particles from aerosolized soil. Infect Immun. 1977;17:634–8.PubMedGoogle Scholar
  6. 6.
    Franzot SP, Salkin IF, Casadevall A. Cryptococcus neoformans var. grubii: separate varietal status for Cryptococcus neoformans serotype A isolates. J Clin Microbiol. 1999;37:838–40.PubMedGoogle Scholar
  7. 7.
    Kidd SE, Hagen F, Tscharke RL, et al. A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proc Natl Acad Sci USA. 2004;101:17258–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Chambers C, MacDougall L, Li M, Galanis E. Tourism and ­specific risk areas for Cryptococcus gattii, Vancouver Island, Canada. Emerg Infect Dis. 2008;14:1781–3.PubMedCrossRefGoogle Scholar
  9. 9.
    Byrnes 3rd EJ, Bildfell RJ, Frank SA, Mitchell TG, Marr KA, Heitman J. Molecular evidence that the range of the Vancouver Island outbreak of Cryptococcus gattii infection has expanded into the Pacific Northwest in the United States. J Infect Dis. 2009;199:1081–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS–100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev. 1995;8:515–48.PubMedGoogle Scholar
  11. 11.
    Kwon-Chung KJ, Bennett JE. Epidemiologic differences between the two varieties of Cryptococcus neoformans. Am J Epidemiol. 1984;120:123–30.PubMedGoogle Scholar
  12. 12.
    Kwon-Chung KJ. A new species of Filobasidiella, the sexual state of Cryptococcus neoformans B and C serotypes. Mycologia. 1976;68:943–6.PubMedGoogle Scholar
  13. 13.
    Min KH, Kwon-Chung KJ. The biochemical basis for the distinction between the two Cryptococcus neoformans varieties with CGB medium. Zbl Bakt Mik Hyg. 1986;261:471–80.Google Scholar
  14. 14.
    Levitz SM. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis. 1991;13:1163–9.PubMedGoogle Scholar
  15. 15.
    Emmons CW. Saprophytic sources of Cryptococcus neoformans associated with the pigeon (Columba livia). Am J Hyg. 1955;62:227–32.PubMedGoogle Scholar
  16. 16.
    Girish Kumar KCP, Prabu D, Mitani H, Mikami Y, Menon T. Environmental isolation of Cryptococcus neoformans and Cryptococcus gattii from living trees in Guindy National Park, Chennai, South India. Mycoses. 2010;53:262–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Refojo N, Perrotta D, Brudny M, Abrantes R, Hevia AI, Davel G. Isolation of Cryptococcus neoformans and Cryptococcus gattii from trunk hollows of living trees in Buenos Aires City, Argentina. Med Mycol. 2009;47:177–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Granados DP, Castaneda E. Isolation and characterization of Cryptococcus neoformans varieties recovered from natural sources in Bogota, Colombia, and study of ecological conditions in the area. Microb Ecol. 2005;49:282–90.PubMedCrossRefGoogle Scholar
  19. 19.
    Ellis DH, Pfeiffer TJ. Natural habitat of Cryptococcus neoformans var. gattii. J Clin Microbiol. 1990;28:1642–4.PubMedGoogle Scholar
  20. 20.
    Chen SC, Currie BJ, Campbell HM, et al. Cryptococcus neoformans var. gattii infection in northern Australia: existence of an environmental source other than known host eucalypts. Trans R Soc Trop Med Hyg. 1997;91:547–50.PubMedCrossRefGoogle Scholar
  21. 21.
    Fink JN, Barboriak JJ, Kaufman L. Cryptococcal antibodies in pigeon breeders’ disease. J Allergy. 1968;41:297–301.PubMedCrossRefGoogle Scholar
  22. 22.
    Newberry Jr WM, Walter JE, Chandler Jr JW, Tosh FE. Epidemiologic study of Cryptococcus neoformans. Ann Intern Med. 1967;67:724–32.PubMedGoogle Scholar
  23. 23.
    Hajjeh RA, Conn LA, Stephens DS, Cryptococcal Active Surveillance Group, et al. Cryptococcosis: population-based multistate active surveillance and risk factors in human immunodeficiency virus-infected persons. J Infect Dis. 1999;179:449–54.PubMedCrossRefGoogle Scholar
  24. 24.
    Powell KE, Dahl BA, Weeks RJ, Tosh FE. Airborne Cryptococcus neoformans: particles from pigeon excreta compatible with alveolar deposition. J Infect Dis. 1972;125:412–5.PubMedGoogle Scholar
  25. 25.
    Swinne D, Deppner M, Laroche R, Floch JJ, Kadende P. Isolation of Cryptococcus neoformans from houses of AIDS-associated cryptococcosis patients in Bujumbura (Burundi). AIDS (London). 1989;3:389–90.Google Scholar
  26. 26.
    Duperval R, Hermans PE, Brewer NS, Roberts GD. Cryptococcosis, with emphasis on the significance of isolation of Cryptococcus neoformans from the respiratory tract. Chest. 1977;72:13–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Tynes B, Mason KN, Jennings AE, Bennett JE. Variant forms of pulmonary cryptococcosis. Ann Intern Med. 1968;69:1117–25.PubMedGoogle Scholar
  28. 28.
    Beyt Jr BE, Waltman SR. Cryptococcal endophthalmitis after corneal transplantation. N Engl J Med. 1978;298:825–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Glaser JB, Garden A. Inoculation of cryptococcosis without ­transmission of the acquired immunodeficiency syndrome. N Engl J Med. 1985;313:266.PubMedGoogle Scholar
  30. 30.
    Kanj SS, Welty-Wolf K, Madden J, et al. Fungal infections in lung and heart-lung transplant recipients. Report of 9 cases and review of the literature. Medicine. 1996;75:142–56.PubMedCrossRefGoogle Scholar
  31. 31.
    de Castro LE, Sarraf OA, Lally JM, Sandoval HP, Solomon KD, Vroman DT. Cryptococcus albidus keratitis after corneal transplantation. Cornea. 2005;24:882–3.PubMedCrossRefGoogle Scholar
  32. 32.
    Nosanchuk JD, Shoham S, Fries BC, Shapiro DS, Levitz SM, Casadevall A. Evidence of zoonotic transmission of Cryptococcus neoformans from a pet cockatoo to an immunocompromised patient. Ann Intern Med. 2000;132:205–8.PubMedGoogle Scholar
  33. 33.
    Lagrou K, Van Eldere J, Keuleers S, et al. Zoonotic transmission of Cryptococcus neoformans from a magpie to an immunocompetent patient. J Intern Med. 2005;257:385–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Shrestha RK, Stoller JK, Honari G, Procop GW, Gordon SM. Pneumonia due to Cryptococcus neoformans in a patient receiving infliximab: possible zoonotic transmission from a pet cockatiel. Respir Care. 2004;49:606–8.PubMedGoogle Scholar
  35. 35.
    Pappas PG, Perfect JR, Cloud GA, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis. 2001;33:690–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Vilchez RA, Irish W, Lacomis J, Costello P, Fung J, Kusne S. The clinical epidemiology of pulmonary cryptococcosis in non-AIDS patients at a tertiary care medical center. Medicine. 2001;80:308–12.PubMedCrossRefGoogle Scholar
  37. 37.
    Sun HY, Wagener MM, Singh N. Cryptococcosis in solid-organ, hematopoietic stem cell, and tissue transplant recipients: evidence-based evolving trends. Clin Infect Dis. 2009;48:1566–76.PubMedCrossRefGoogle Scholar
  38. 38.
    Kontoyiannis DP, Peitsch WK, Reddy BT, et al. Cryptococcosis in patients with cancer. Clin Infect Dis. 2001;32:e145–50.PubMedCrossRefGoogle Scholar
  39. 39.
    Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin N Am. 2006;20:507–44.CrossRefGoogle Scholar
  40. 40.
    Hage CA, Wood KL, Winer-Muram HT, Wilson SJ, Sarosi G, Knox KS. Pulmonary cryptococcosis after initiation of anti-tumor necrosis factor-alpha therapy. Chest. 2003;124:2395–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Silveira FP, Husain S, Kwak EJ, et al. Cryptococcosis in liver and kidney transplant recipients receiving anti-thymocyte globulin or alemtuzumab. Transpl Infect Dis. 2007;9:22–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Peleg AY, Husain S, Kwak EJ, et al. Opportunistic infections in 547 organ transplant recipients receiving alemtuzumab, a humanized monoclonal CD-52 antibody. Clin Infect Dis. 2007;44:204–12.PubMedCrossRefGoogle Scholar
  43. 43.
    Munoz P, Giannella M, Valerio M, et al. Cryptococcal meningitis in a patient treated with infliximab. Diagn Microbiol Infect Dis. 2007;57:443–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Lewis JL, Rabinovich S. The wide spectrum of cryptococcal infections. Am J Med. 1972;53:315–22.PubMedCrossRefGoogle Scholar
  45. 45.
    Dismukes WE, Cloud G, Gallis HA, et al. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med. 1987;317:334–41.PubMedCrossRefGoogle Scholar
  46. 46.
    Zonios DI, Falloon J, Huang CY, Chaitt D, Bennett JE. Cryptococcosis and idiopathic CD4 lymphocytopenia. Medicine (Baltimore). 2007;86:78–92.CrossRefGoogle Scholar
  47. 47.
    Duncan RA, von Reyn CF, Alliegro GM, Toossi Z, Sugar AM, Levitz SM. Idiopathic CD4+ T-lymphocytopenia – four patients with opportunistic infections and no evidence of HIV infection. N Engl J Med. 1993;328:393–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Currie BP, Casadevall A. Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. Clin Infect Dis. 1994;19:1029–33.PubMedGoogle Scholar
  49. 49.
    Dismukes WE. Antifungal therapy: from amphotericin B to present. Trans Am Clin Climatol Assoc. 1993;104:166–77. discussion 77–9.PubMedGoogle Scholar
  50. 50.
    Dromer F, Mathoulin S, Dupont B, Laporte A, French Cryptococcosis Study Group. Epidemiology of cryptococcosis in France: a 9-year survey (1985–1993). Clin Infect Dis. 1996;23:82–90.PubMedGoogle Scholar
  51. 51.
    Dromer F, Mathoulin-Pelissier S, Fontanet A, Ronin O, Dupont B, Lortholary O. Epidemiology of HIV-associated cryptococcosis in France (1985–2001): comparison of the pre- and post-HAART eras. AIDS (London). 2004;18:555–62.Google Scholar
  52. 52.
    Mirza SA, Phelan M, Rimland D, et al. The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992–2000. Clin Infect Dis. 2003;36:789–94.PubMedCrossRefGoogle Scholar
  53. 53.
    Chen SC. Cryptococcosis in Australasia and the treatment of cryptococcal and other fungal infections with liposomal amphotericin B. J Antimicrob Chemother. 2002;49 Suppl 1:57–61.PubMedGoogle Scholar
  54. 54.
    Hakim JG, Gangaidzo IT, Heyderman RS, et al. Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS (London). 2000;14:1401–7.Google Scholar
  55. 55.
    Jarvis JN, Boulle A, Loyse A, et al. High ongoing burden of cryptococcal disease in Africa despite antiretroviral roll out. AIDS (London). 2009;23:1182–3.Google Scholar
  56. 56.
    Heyderman RS, Gangaidzo IT, Hakim JG, et al. Cryptococcal meningitis in human immunodeficiency virus-infected patients in Harare, Zimbabwe. Clin Infect Dis. 1998;26:284–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS (London). 2009;23:525–30.Google Scholar
  58. 58.
    Goldman D, Lee SC, Casadevall A. Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat. Infect Immun. 1994;62:4755–61.PubMedGoogle Scholar
  59. 59.
    Kwon-Chung KJ, Kozel TR, Edman JC, et al. Recent advances in biology and immunology of Cryptococcus neoformans. J Med Vet Mycol. 1992;30 Suppl 1:133–42.PubMedCrossRefGoogle Scholar
  60. 60.
    Bolanos B, Mitchell TG. Phagocytosis of Cryptococcus neoformans by rat alveolar macrophages. J Med Vet Mycol. 1989;27:203–17.PubMedCrossRefGoogle Scholar
  61. 61.
    Harrison TS, Levitz SM. Mechanisms of impaired anticryptococcal activity of monocytes from donors infected with human immunodeficiency virus. J Infect Dis. 1997;176:537–40.PubMedCrossRefGoogle Scholar
  62. 62.
    Levitz SM, Mathews HL, Murphy JW. Direct antimicrobial activity of T cells. Immunol Today. 1995;16:387–91.PubMedCrossRefGoogle Scholar
  63. 63.
    Casadevall A. Antibody immunity and invasive fungal infections. Infect Immun. 1995;63:4211–8.PubMedGoogle Scholar
  64. 64.
    Lendvai N, Casadevall A, Liang Z, Goldman DL, Mukherjee J, Zuckier L. Effect of immune mechanisms on the pharmacokinetics and organ distribution of cryptococcal polysaccharide. J Infect Dis. 1998;177:1647–59.PubMedCrossRefGoogle Scholar
  65. 65.
    Rachini A, Pietrella D, Lupo P, et al. An anti-beta-glucan monoclonal antibody inhibits growth and capsule formation of Cryptococcus neoformans in vitro and exerts therapeutic, anti­cryptococcal activity in vivo. Infect Immun. 2007;75:5085–94.PubMedCrossRefGoogle Scholar
  66. 66.
    Buchanan KL, Murphy JW. What makes Cryptococcus neoformans a pathogen? Emerg Infect Dis. 1998;4:71–83.PubMedCrossRefGoogle Scholar
  67. 67.
    Ma H, May RC. Virulence in Cryptococcusspecies. Adv Appl Microbiol. 2009;67:131–90.PubMedCrossRefGoogle Scholar
  68. 68.
    Heitman J, Kozel T, Kwon-Chung J, Perfect J, Casadevall A, editors. Cryptococcus: From human pathogen to model yeast. Washington, DC: American Society for Microbiology Press; 2010.Google Scholar
  69. 69.
    Chang YC, Kwon-Chung KJ. Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol Cell Biol. 1994;14:4912–9.PubMedGoogle Scholar
  70. 70.
    Guerrero A, Jain N, Goldman DL, Fries BC. Phenotypic switching in Cryptococcus neoformans. Microbiology. 2006;152:3–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Bulmer GS, Sans MD. Cryptococcus neoformans. 3. Inhibition of phagocytosis. J Bacteriol. 1968;95:5–8.PubMedGoogle Scholar
  72. 72.
    Levitz SM, Tabuni A, Kornfeld H, Reardon CC, Golenbock DT. Production of tumor necrosis factor alpha in human leukocytes stimulated by Cryptococcus neoformans. Infect Immun. 1994;62:1975–81.PubMedGoogle Scholar
  73. 73.
    Collins HL, Bancroft GJ. Encapsulation of Cryptococcus ­neoformans impairs antigen-specific T-cell responses. Infect Immun. 1991;59:3883–8.PubMedGoogle Scholar
  74. 74.
    Kwon-Chung KJ, Polacheck I, Popkin TJ. Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice. J Bacteriol. 1982;150:1414–21.PubMedGoogle Scholar
  75. 75.
    Wang Y, Aisen P, Casadevall A. Cryptococcus neoformans ­melanin and virulence: mechanism of action. Infect Immun. 1995;63:3131–6.PubMedGoogle Scholar
  76. 76.
    Rittershaus PC, Kechichian TB, Allegood JC, et al. Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformans. J Clin Invest. 2006;116:1651–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Garcia J, Shea J, Alvarez-Vasquez F, et al. Mathematical modeling of pathogenicity of Cryptococcus neoformans. Mol Syst Biol. 2008;4:183.PubMedCrossRefGoogle Scholar
  78. 78.
    Visnegarwala F, Graviss EA, Lacke CE, et al. Acute respiratory failure associated with cryptococcosis in patients with AIDS: analysis of predictive factors. Clin Infect Dis. 1998;27:1231–7.PubMedCrossRefGoogle Scholar
  79. 79.
    Murray RJ, Becker P, Furth P, Criner GJ. Recovery from cryptococcemia and the adult respiratory distress syndrome in the acquired immunodeficiency syndrome. Chest. 1988;93:1304–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Chang WC, Tzao C, Hsu HH, et al. Pulmonary cryptococcosis: comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients. Chest. 2006;129:333–40.PubMedCrossRefGoogle Scholar
  81. 81.
    Kerkering TM, Duma RJ, Shadomy S. The evolution of pulmonary cryptococcosis: clinical implications from a study of 41 patients with and without compromising host factors. Ann Intern Med. 1981;94:611–6.PubMedGoogle Scholar
  82. 82.
    Pappas PG. Therapy of cryptococcal meningitis in non-HIV-infected patients. Curr Infect Dis Rep. 2001;3:365–70.PubMedCrossRefGoogle Scholar
  83. 83.
    Baddley JW, Perfect JR, Oster RA, et al. Pulmonary cryptococcosis in patients without HIV infection: factors associated with ­disseminated disease. Eur J Clin Microbiol Infect Dis. 2008;27:937–43.PubMedCrossRefGoogle Scholar
  84. 84.
    Roebuck DJ, Fisher DA, Currie BJ. Cryptococcosis in HIV ­negative patients: findings on chest radiography. Thorax. 1998;53:554–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Oliveira Fde M, Severo CB, Guazzelli LS, Severo LC. Cryptococcus gattii fungemia: report of a case with lung and brain lesions mimicking radiological features of malignancy. Rev Inst Med Trop São Paulo. 2007;49:263–5.PubMedGoogle Scholar
  86. 86.
    Speed B, Dunt D. Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis. 1995;21:28–34.PubMedGoogle Scholar
  87. 87.
    Khoury MB, Godwin JD, Ravin CE, Gallis HA, Halvorsen RA, Putman CE. Thoracic cryptococcosis: immunologic competence and radiologic appearance. Am J Roentgenol. 1984;142:893–6.Google Scholar
  88. 88.
    Shirley RM, Baddley JW. Cryptococcal lung disease. Curr Opin Pulm Med. 2009;15:254–60.PubMedCrossRefGoogle Scholar
  89. 89.
    Woodring JH, Ciporkin G, Lee C, Worm B, Woolley S. Pulmonary cryptococcosis. Semin Roentgenol. 1996;31:67–75.PubMedCrossRefGoogle Scholar
  90. 90.
    Cameron ML, Bartlett JA, Gallis HA, Waskin HA. Manifestations of pulmonary cryptococcosis in patients with acquired immunodeficiency syndrome. Rev Infect Dis. 1991;13:64–7.PubMedGoogle Scholar
  91. 91.
    Meyohas MC, Roux P, Bollens D, et al. Pulmonary cryptococcosis: localized and disseminated infections in 27 patients with AIDS. Clin Infect Dis. 1995;21:628–33.PubMedGoogle Scholar
  92. 92.
    Saag MS, Powderly WG, Cloud GA, The NIAID Mycoses Study Group and the AIDS Clinical Trials Group, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. N Engl J Med. 1992;326:83–9.PubMedCrossRefGoogle Scholar
  93. 93.
    van der Horst CM, Saag MS, Cloud GA, National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group, et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N Engl J Med. 1997;337:15–21.PubMedCrossRefGoogle Scholar
  94. 94.
    Graybill JR, Sobel J, Saag M, The NIAID Mycoses Study Group and AIDS Cooperative Treatment Groups, et al. Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. Clin Infect Dis. 2000;30:47–54.PubMedCrossRefGoogle Scholar
  95. 95.
    Pappas PG. Managing cryptococcal meningitis is about handling the pressure. Clin Infect Dis. 2005;40:480–2.PubMedCrossRefGoogle Scholar
  96. 96.
    Bicanic T, Brouwer AE, Meintjes G, et al. Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures. AIDS (London). 2009;23:701–6.Google Scholar
  97. 97.
    Fujita NK, Reynard M, Sapico FL, Guze LB, Edwards Jr JE. Cryptococcal intracerebral mass lesions: the role of computed tomography and nonsurgical management. Ann Intern Med. 1981;94:382–8.PubMedGoogle Scholar
  98. 98.
    Charlier C, Dromer F, Leveque C, et al. Cryptococcal neuroradiological lesions correlate with severity during cryptococcal meningoencephalitis in HIV-positive patients in the HAART era. PloS. 2008;3:e1950.Google Scholar
  99. 99.
    Singh N, Lortholary O, Dromer F, et al. Central nervous system cryptococcosis in solid organ transplant recipients: clinical relevance of abnormal neuroimaging findings. Transplantation. 2008;86:647–51.PubMedCrossRefGoogle Scholar
  100. 100.
    Mitchell DH, Sorrell TC, Allworth AM, et al. Cryptococcal disease of the CNS in immunocompetent hosts: influence of cryptococcal variety on clinical manifestations and outcome. Clin Infect Dis. 1995;20:611–6.PubMedGoogle Scholar
  101. 101.
    Popovich MJ, Arthur RH, Helmer E. CT of intracranial cryptococcosis. Am J Roentgenol. 1990;154:603–6.Google Scholar
  102. 102.
    Park MK, Hospenthal DR, Bennett JE. Treatment of hydrocephalus secondary to cryptococcal meningitis by use of shunting. Clin Infect Dis. 1999;28:629–33.PubMedCrossRefGoogle Scholar
  103. 103.
    Liliang PC, Liang CL, Chang WN, Lu K, Lu CH. Use of ventriculoperitoneal shunts to treat uncontrollable intracranial hypertension in patients who have cryptococcal meningitis without hydrocephalus. Clin Infect Dis. 2002;34:E64–8.PubMedCrossRefGoogle Scholar
  104. 104.
    Diamond RD, Bennett JE. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med. 1974;80:176–81.PubMedGoogle Scholar
  105. 105.
    Lu CH, Chang WN, Chang HW, Chuang YC. The prognostic factors of cryptococcal meningitis in HIV-negative patients. J Hosp Infect. 1999;42:313–20.PubMedCrossRefGoogle Scholar
  106. 106.
    Powderly WG, Saag MS, Cloud GA, The NIAID AIDS Clinical Trials Group and Mycoses Study Group, et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992;326:793–8.PubMedCrossRefGoogle Scholar
  107. 107.
    Powderly WG, Cloud GA, Dismukes WE, Saag MS. Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1994;18:789–92.PubMedGoogle Scholar
  108. 108.
    Bicanic T, Wood R, Meintjes G, et al. High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial. Clin Infect Dis. 2008;47:123–30.PubMedCrossRefGoogle Scholar
  109. 109.
    McNeil MM, Nash SL, Hajjeh RA, et al. Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis. 2001;33:641–7.PubMedCrossRefGoogle Scholar
  110. 110.
    Baer S, Baddley JW, Gnann JW, Pappas PG. Cryptococcal disease presenting as necrotizing cellulitis in transplant recipients. Transpl Infect Dis 2009.Google Scholar
  111. 111.
    Pema K, Diaz J, Guerra LG, Nabhan D, Verghese A. Disseminated cutaneous cryptococcosis. Comparison of clinical manifestations in the pre-AIDS and AIDS eras. Arch Intern Med. 1994;154:1032–4.PubMedCrossRefGoogle Scholar
  112. 112.
    Anderson DJ, Schmidt C, Goodman J, Pomeroy C. Cryptococcal disease presenting as cellulitis. Clin Infect Dis. 1992;14:666–72.PubMedGoogle Scholar
  113. 113.
    Casadevall A, Mukherjee J, Yuan R, Perfect J. Management of injuries caused by Cryptococcus neoformans–contaminated ­needles. Clin Infect Dis. 1994;19:951–3.PubMedGoogle Scholar
  114. 114.
    Neuville S, Dromer F, Morin O, Dupont B, Ronin O, Lortholary O. Primary cutaneous cryptococcosis: a distinct clinical entity. Clin Infect Dis. 2003;36:337–47.PubMedCrossRefGoogle Scholar
  115. 115.
    Behrman RE, Masci JR, Nicholas P. Cryptococcal skeletal infections: case report and review. Rev Infect Dis. 1990;12:181–90.PubMedGoogle Scholar
  116. 116.
    Nottebart HC, McGehee RF, Utz JP. Cryptococcus neoformans osteomyelitis: case report of two patients. Sabouraudia. 1974;12:127–32.PubMedGoogle Scholar
  117. 117.
    Stead KJ, Klugman KP, Painter ML, Koornhof HJ. Septic arthritis due to Cryptococcus neoformans. J Infect. 1988;17:139–45.PubMedCrossRefGoogle Scholar
  118. 118.
    Perfect JR. Cryptococcosis. Infect Dis Clin N Am. 1989;3:77–102.Google Scholar
  119. 119.
    Braman RT. Cryptococcosis (torulosis) of prostate. Urology. 1981;17:284–5.PubMedCrossRefGoogle Scholar
  120. 120.
    Crump JR, Elner SG, Elner VM, Kauffman CA. Cryptococcal endophthalmitis: case report and review. Clin Infect Dis. 1992;14:1069–73.PubMedGoogle Scholar
  121. 121.
    Leavitt AD, Kauffman CA. Cryptococcal aortitis. Am J Med. 1988;85:108–10.PubMedCrossRefGoogle Scholar
  122. 122.
    Staib F, Seibold M, L’Age M, et al. Cryptococcus neoformans in the seminal fluid of an AIDS patient. A contribution to the clinical course of cryptococcosis. Mycoses. 1989;32:171–80.PubMedCrossRefGoogle Scholar
  123. 123.
    Larsen RA, Bozzette S, McCutchan JA, Chiu J, Leal MA, Richman DD, et al. Persistent Cryptococcus neoformans infection of the prostate after successful treatment of meningitis. Ann Intern Med. 1989;111:125–8.PubMedGoogle Scholar
  124. 124.
    Bicanic T, Meintjes G, Rebe K, et al. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr. 2009;51:130–4.PubMedCrossRefGoogle Scholar
  125. 125.
    Lortholary O, Fontanet A, Memain N, Martin A, Sitbon K, Dromer F. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS (London). 2005;19:1043–9.Google Scholar
  126. 126.
    Shelburne 3rd SA, Darcourt J, White Jr AC, et al. The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis. 2005;40:1049–52.PubMedCrossRefGoogle Scholar
  127. 127.
    Singh N, Lortholary O, Alexander BD, et al. An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients. Clin Infect Dis. 2005;40:1756–61.PubMedCrossRefGoogle Scholar
  128. 128.
    Shelburne SA, Visnegarwala F, Darcourt J, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS. 2005;19:399–406.PubMedCrossRefGoogle Scholar
  129. 129.
    Singh N, Dromer F, Perfect JR, Lortholary O. Cryptococcosis in solid organ transplant recipients: current state of the science. Clin Infect Dis. 2008;47:1321–7.PubMedCrossRefGoogle Scholar
  130. 130.
    Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med. 1979;301:126–31.PubMedCrossRefGoogle Scholar
  131. 131.
    Aberg JA, Mundy LM, Powderly WG. Pulmonary cryptococcosis in patients without HIV infection. Chest. 1999;115:734–40.PubMedCrossRefGoogle Scholar
  132. 132.
    Campbell CK, Payne AL, Teall AJ, Brownell A, Mackenzie DW. Cryptococcal latex antigen test positive in patient with Trichosporon beigelii infection. Lancet. 1985;2(8445):43–4.PubMedCrossRefGoogle Scholar
  133. 133.
    Tarrand JJ, Guillot C, Wenglar M, Jackson J, Lajeunesse JD, Rolston KV. Clinical comparison of the resin-containing BACTEC 26 Plus and the Isolator 10 blood culturing systems. J Clin Microbiol. 1991;29:2245–9.PubMedGoogle Scholar
  134. 134.
    Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard, 3rd edn., M23-A3. Wayne: Clinical Laboratory Standards Institute, 2008.Google Scholar
  135. 135.
    Brandt ME, Pfaller MA, Hajjeh RA, et al. Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates in the United States: 1992 to 1994 and 1996 to 1998. Antimicrob Agents Chemother. 2001;45:3065–9.PubMedCrossRefGoogle Scholar
  136. 136.
    Pfaller MA, Diekema DJ, Gibbs DL, et al. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: 10.5-year analysis of susceptibilities of noncandidal yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing. J Clin Microbiol. 2009;47:117–23.PubMedCrossRefGoogle Scholar
  137. 137.
    Torres-Rodriguez JM, Alvarado-Ramirez E, Murciano F, Sellart M. MICs and minimum fungicidal concentrations of posaconazole, voriconazole and fluconazole for Cryptococcus neoformans and Cryptococcus gattii. J Antimicrob Chemother. 2008;62:205–6.PubMedCrossRefGoogle Scholar
  138. 138.
    Bartizal K, Gill CJ, Abruzzo GK, et al. In vitro preclinical evaluation studies with the echinocandin antifungal MK-0991 (L-743, 872). Antimicrob Agents Chemother. 1997;41:2326–32.PubMedGoogle Scholar
  139. 139.
    Aller AI, Martin-Mazuelos E, Lozano F, et al. Correlation of fluconazole MICs with clinical outcome in cryptococcal infection. Antimicrob Agents Chemother. 2000;44:1544–8.PubMedCrossRefGoogle Scholar
  140. 140.
    Armengou A, Porcar C, Mascaro J, Garcia-Bragado F. Possible development of resistance to fluconazole during suppressive therapy for AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1996;23:1337–8.PubMedGoogle Scholar
  141. 141.
    Witt MD, Lewis RJ, Larsen RA, et al. Identification of patients with acute AIDS-associated cryptococcal meningitis who can be effectively treated with fluconazole: the role of antifungal susceptibility testing. Clin Infect Dis. 1996;22:322–8.PubMedGoogle Scholar
  142. 142.
    Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Disease Society of America. Clin Infect Dis. 2010;50:291–322.PubMedCrossRefGoogle Scholar
  143. 143.
    Hospenthal DR, Bennett JE. Flucytosine monotherapy for cryptococcosis. Clin Infect Dis. 1998;27:260–4.PubMedCrossRefGoogle Scholar
  144. 144.
    Harrison TS. Amphotericin B plus fluconazole for HIV-associated cryptococcal meningitis. Clin Infect Dis. 2009;48:1784–6.PubMedCrossRefGoogle Scholar
  145. 145.
    Pappas PG, Chetchotisakd P, Larsen RA, et al. A phase II randomized trial of amphotericin B alone or combined with fluconazole in the treatment of HIV-associated cryptococcal meningitis. Clin Infect Dis. 2009;48:1775–83.PubMedCrossRefGoogle Scholar
  146. 146.
    Dromer F, Mathoulin S, Dupont B, Brugiere O, Letenneur L, French Cryptococcosis Study Group. Comparison of the efficacy of amphotericin B and fluconazole in the treatment of cryptococcosis in human immunodeficiency virus-negative patients: retrospective analysis of 83 cases. Clin Infect Dis. 1996;22 Suppl 2:S154–60.PubMedGoogle Scholar
  147. 147.
    Nadrous HF, Antonios VS, Terrell CL, Ryu JH. Pulmonary cryptococcosis in nonimmunocompromised patients. Chest. 2003;124:2143–7.PubMedCrossRefGoogle Scholar
  148. 148.
    Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008;29:141–50.PubMedCrossRefGoogle Scholar
  149. 149.
    Yamaguchi H, Ikemoto H, Watanabe K, Ito A, Hara K, Kohno S. Fluconazole monotherapy for cryptococcosis in non-AIDS patients. Eur J Clin Microbiol Infect Dis. 1996;15:787–92.PubMedCrossRefGoogle Scholar
  150. 150.
    Denning DW, Tucker RM, Hanson LH, Hamilton JR, Stevens DA. Itraconazole therapy for cryptococcal meningitis and cryptococcosis. Arch Intern Med. 1989;149:2301–8.PubMedCrossRefGoogle Scholar
  151. 151.
    Raad II, Graybill JR, Bustamante AB, et al. Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clin Infect Dis. 2006;42:1726–34.PubMedCrossRefGoogle Scholar
  152. 152.
    Perfect JR, Marr KA, Walsh TJ, et al. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis. 2003;36:1122–31.PubMedCrossRefGoogle Scholar
  153. 153.
    Sharkey PK, Graybill JR, Johnson ES, et al. Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996;22:315–21.PubMedGoogle Scholar
  154. 154.
    Coker RJ, Viviani M, Gazzard BG, et al. Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS. AIDS (London, England). 1993;7:829–35.Google Scholar
  155. 155.
    Leenders AC, Reiss P, Portegies P, et al. Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. AIDS (London). 1997;11:1463–71.Google Scholar
  156. 156.
    Hammerman KJ, Powell KE, Christianson CS, et al. Pulmonary cryptococcosis: clinical forms and treatment. A Center for Disease Control Cooperative Mycoses study. Am Rev Respir Dis. 1973;108:1116–23.PubMedGoogle Scholar
  157. 157.
    Husain S, Wagener MM, Singh N. Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome. Emerg Infect Dis. 2001;7:375–81.PubMedCrossRefGoogle Scholar
  158. 158.
    Hospenthal DR, Bennett JE. Persistence of cryptococcomas on neuroimaging. Clin Infect Dis. 2000;31:1303–6.PubMedCrossRefGoogle Scholar
  159. 159.
    Larsen RA, Bozzette SA, Jones BE, et al. Fluconazole combined with flucytosine for treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1994;19:741–5.PubMedGoogle Scholar
  160. 160.
    Mayanja-Kizza H, Oishi K, Mitarai S, et al. Combination therapy with fluconazole and flucytosine for cryptococcal meningitis in Ugandan patients with AIDS. Clin Infect Dis. 1998;26:1362–6.PubMedCrossRefGoogle Scholar
  161. 161.
    Menichetti F, Fiorio M, Tosti A, et al. High-dose fluconazole therapy for cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996;22:838–40.PubMedGoogle Scholar
  162. 162.
    Haubrich RH, Haghighat D, Bozzette SA, Tilles J, McCutchan JA, The California Collaborative Treatment Group. High-dose fluconazole for treatment of cryptococcal disease in patients with human immunodeficiency virus infection. J Infect Dis. 1994;170:238–42.PubMedGoogle Scholar
  163. 163.
    de Gans J, Portegies P, Tiessens G, et al. Itraconazole compared with amphotericin B plus flucytosine in AIDS patients with cryptococcal meningitis. AIDS (London). 1992;6:185–90.Google Scholar
  164. 164.
    Bozzette SA, Larsen RA, Chiu J, California Collaborative Treatment Group, et al. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. N Engl J Med. 1991;324:580–4.PubMedCrossRefGoogle Scholar
  165. 165.
    Saag MS, Cloud GA, Graybill JR, National Institute of Allergy and Infectious Diseases Mycoses Study Group, et al. A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1999;28:291–6.PubMedCrossRefGoogle Scholar
  166. 166.
    Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR. 2009;58:1–207.Google Scholar
  167. 167.
    Mussini C, Pezzotti P, Miro JM, et al. Discontinuation of maintenance therapy for cryptococcal meningitis in patients with AIDS treated with highly active antiretroviral therapy: an international observational study. Clin Infect Dis. 2004;38:565–71.PubMedCrossRefGoogle Scholar
  168. 168.
    Vibhagool A, Sungkanuparph S, Mootsikapun P, et al. Discontinuation of secondary prophylaxis for cryptococcal meningitis in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy: a prospective, multicenter, randomized study. Clin Infect Dis. 2003;36:1329–31.PubMedCrossRefGoogle Scholar
  169. 169.
    Bicanic T, Meintjes G, Wood R, et al. Fungal burden, early fungicidal activity, and outcome in cryptococcal meningitis in antiretroviral-naive or antiretroviral-experienced patients treated with amphotericin B or fluconazole. Clin Infect Dis. 2007;45:76–80.PubMedCrossRefGoogle Scholar
  170. 170.
    Chuck SL, Sande MA. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med. 1989;321:794–9.PubMedCrossRefGoogle Scholar
  171. 171.
    Larsen RA, Leal MA, Chan LS. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial. Ann Intern Med. 1990;113:183–7.PubMedGoogle Scholar
  172. 172.
    Brouwer AE, Rajanuwong A, Chierakul W, et al. Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial. Lancet. 2004;363:1764–7.PubMedCrossRefGoogle Scholar
  173. 173.
    Dromer F, Bernede-Bauduin C, Guillemot D, Lortholary O. Major role for amphotericin B-flucytosine combination in severe cryptococcosis. PloS. 2008;3:2870.Google Scholar
  174. 174.
    Baddour LM, Perfect JR, Ostrosky-Zeichner L. Successful use of amphotericin B lipid complex in the treatment of cryptococcosis. Clin Infect Dis. 2005;40 Suppl 6:S409–13.PubMedCrossRefGoogle Scholar
  175. 175.
    Longley N, Muzoora C, Taseera K, et al. Dose response effect of high-dose fluconazole for HIV-associated cryptococcal meningitis in southwestern Uganda. Clin Infect Dis. 2008;47:1556–61.PubMedCrossRefGoogle Scholar
  176. 176.
    Aberg JA, Price RW, Heeren DM, Bredt B. A pilot study of the discontinuation of antifungal therapy for disseminated cryptococcal disease in patients with acquired immunodeficiency syndrome, following immunologic response to antiretroviral therapy. J Infect Dis. 2002;185:1179–82.PubMedCrossRefGoogle Scholar
  177. 177.
    Zolopa A, Andersen J, Komarow L, et al. Immediate vs. deferred ART in the setting of a randomized strategy trial ACTG A5164. 15th Conference on Retroviruses and Opportunistic Infections. February, 2008. Boston. Abstract 142.Google Scholar
  178. 178.
    Newton PN, le Thai H, Tip NQ, et al. A randomized, double-blind, placebo-controlled trial of acetazolamide for the treatment of elevated intracranial pressure in cryptococcal meningitis. Clin Infect Dis. 2002;35:769–72.PubMedCrossRefGoogle Scholar
  179. 179.
    McKinsey DS, Wheat LJ, Cloud GA, National Institute of Allergy and Infectious Diseases Mycoses Study Group, et al. Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. Clin Infect Dis. 1999;28:1049–56.PubMedCrossRefGoogle Scholar
  180. 180.
    Powderly WG, Finkelstein D, Feinberg J, NIAID AIDS Clinical Trials Group, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. N Engl J Med. 1995;332:700–5.PubMedCrossRefGoogle Scholar
  181. 181.
    Jarvis JN, Lawn SD, Vogt M, Bangani N, Wood R, Harrison TS. Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa. Clin Infect Dis. 2009;48:856–62.PubMedCrossRefGoogle Scholar
  182. 182.
    Tassie JM, Pepper L, Fogg C, et al. Systematic screening of cryptococcal antigenemia in HIV-positive adults in Uganda. J Acquir Immune Defic Syndr. 2003;33:411–2.PubMedGoogle Scholar
  183. 183.
    Nelson MR, Bower M, Smith D, Reed C, Shanson D, Gazzard B. The value of serum cryptococcal antigen in the diagnosis of cryptococcal infection in patients infected with the human immunodeficiency virus. J Infect. 1990;21:175–81.PubMedCrossRefGoogle Scholar
  184. 184.
    Desmet P, Kayembe KD, De Vroey C. The value of cryptococcal serum antigen screening among HIV-positive/AIDS patients in Kinshasa, Zaire. AIDS (London). 1989;3:77–8.Google Scholar
  185. 185.
    Liechty CA, Solberg P, Were W, et al. Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Health. 2007;12:929–35.PubMedCrossRefGoogle Scholar
  186. 186.
    Micol R, Lortholary O, Sar B, et al. Prevalence, determinants of positivity, and clinical utility of cryptococcal antigenemia in Cambodian HIV-infected patients. J Acquir Immune Defic Syndr. 2007;45:555–9.PubMedCrossRefGoogle Scholar
  187. 187.
    French N, Gray K, Watera C, et al. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS (London). 2002;16:1031–8.Google Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Division of Infectious Diseases, Birmingham VA Medical CenterUniversity of Alabama at Birmingham School of MedicineBirminghamUSA

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