Cryptococcus neoformans is a fungus found worldwide. It is commonly associated with bird guano (particularly pigeon) and has been isolated from the heartwood of several species of trees.[1]Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006 Sep;20(3):507-44.
http://www.ncbi.nlm.nih.gov/pubmed/16984867?tool=bestpractice.com
[2]Perfect JR, Casadevall A. Cryptococcosis. Infect Dis Clin North Am. 2002 Dec;16(4):837-74.
http://www.ncbi.nlm.nih.gov/pubmed/12512184?tool=bestpractice.com
[4]Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008 Apr;29(2):141-50.
http://www.ncbi.nlm.nih.gov/pubmed/18365996?tool=bestpractice.com
Cryptococcus neoformans var. grubii (serotype A) is the most common form, accounting for >95% of cases of cryptococcosis.[1]Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006 Sep;20(3):507-44.
http://www.ncbi.nlm.nih.gov/pubmed/16984867?tool=bestpractice.com
Cryptococcus neoformans var. neoformans (serotype D) causes disease in European countries (e.g., Denmark, Germany, Italy, France, and Switzerland), Australasia, and the US. Cryptococcus var. gattii (serotypes B and C) occurs predominantly in tropical and subtropical areas (e.g., Australia, Papua New Guinea, Southeast Asia, Central Africa, and South America) where certain Eucalyptus species grow. However, Cryptococcus var. gattii has been isolated as the causative organism in outbreaks of infection on Vancouver Island, Canada, and in the Pacific Northwest of the US.[5]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 Dec 7;101(49):17258-63.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535360
http://www.ncbi.nlm.nih.gov/pubmed/15572442?tool=bestpractice.com
[6]Lui G, Lee N, Ip M, et al. Cryptococcosis in apparently immunocompetent patients. QJM. 2006 Mar;99(3):143-51.
https://qjmed.oxfordjournals.org/cgi/content/full/99/3/143
http://www.ncbi.nlm.nih.gov/pubmed/16504989?tool=bestpractice.com
[7]Harris JR, Lockhart SR, Debess E, et al. Cryptococcus gattii in the United States: clinical aspects of infection with an emerging pathogen. Clin Infect Dis. 2011 Dec;53(12):1188-95.
https://academic.oup.com/cid/article/53/12/1188/400737
http://www.ncbi.nlm.nih.gov/pubmed/22016503?tool=bestpractice.com
Exposure to Cryptococcus species is common and there is evidence that most people have been exposed to the fungus by 5 years of age.[8]Goldman DL, Khine H, Abadi J, et al. Serologic evidence for Cryptococcus neoformans infection in early childhood. Pediatrics. 2001 May;107(5):E66.
http://www.ncbi.nlm.nih.gov/pubmed/11331716?tool=bestpractice.com
The annual incidence of cryptococcosis in HIV-negative patients is approximately 0.2 to 0.9 per 100,000, depending on the geographic area studied.[9]Hajjeh RA, Conn LA, Stephens DS, et al. Cryptococcosis: population-based multistate active surveillance and risk factors in human immunodeficiency virus-infected persons. J Infect Dis. 1999 Feb;179(2):449-54.
https://academic.oup.com/jid/article/179/2/449/1000299
http://www.ncbi.nlm.nih.gov/pubmed/9878030?tool=bestpractice.com
HIV infection is associated with more than 80% of cryptococcosis cases worldwide.
Patients with HIV and CD4 count of <100 cells/mm³ are at highest risk of infection. It is estimated that among HIV-infected people, there are 223,000 cases of cryptococcal meningitis globally each year, with sub-Saharan Africa accounting for 73% of all cryptococcal meningitis cases. These meningitis cases result in 181,000 deaths globally. Thus, cryptococcal meningitis causes 15% of all AIDS-related deaths.[10]Rajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017 Aug;17(8):873-81.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818156
http://www.ncbi.nlm.nih.gov/pubmed/28483415?tool=bestpractice.com
A male predominance has been shown among HIV-positive and HIV-negative patients with cryptococcosis.[11]Dromer F, Mathoulin-Pelissier S, Fontanet A, et al. Epidemiology of HIV-associate cryptococcosis in France (1985-2001): comparison of the pre-and post-HAART eras. AIDS. 2004 Feb 20;18(3):555-62.
http://www.ncbi.nlm.nih.gov/pubmed/15090810?tool=bestpractice.com
[12]Dromer F, Mathoulin-Pelissier S, Launay O, et al; French Cryptococcosis Study Group. Determinants of disease presentation and outcome during cryptococcosis. PLoS Med. 2007 Feb;4(2):e21.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808080
http://www.ncbi.nlm.nih.gov/pubmed/17284154?tool=bestpractice.com
Cryptococcosis is very uncommon in children, even in those with AIDS.
In immunocompromised patients, the majority of infections are caused by Cryptococcus neoformans, whereas Cryptococcus var. gattii is more commonly identified in HIV-negative populations.[1]Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006 Sep;20(3):507-44.
http://www.ncbi.nlm.nih.gov/pubmed/16984867?tool=bestpractice.com
[4]Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008 Apr;29(2):141-50.
http://www.ncbi.nlm.nih.gov/pubmed/18365996?tool=bestpractice.com
[5]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 Dec 7;101(49):17258-63.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535360
http://www.ncbi.nlm.nih.gov/pubmed/15572442?tool=bestpractice.com
[6]Lui G, Lee N, Ip M, et al. Cryptococcosis in apparently immunocompetent patients. QJM. 2006 Mar;99(3):143-51.
https://qjmed.oxfordjournals.org/cgi/content/full/99/3/143
http://www.ncbi.nlm.nih.gov/pubmed/16504989?tool=bestpractice.com
[13]MacDougall L, Kidd SE, Galanis E, et al. Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. Emerg Infect Dis. 2007 Jan;13(1):42-50.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725832
http://www.ncbi.nlm.nih.gov/pubmed/17370514?tool=bestpractice.com
Cryptococcosis is the third most common invasive fungal infection (8%) in solid-organ transplant patients.[1]Chayakulkeeree M, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2006 Sep;20(3):507-44.
http://www.ncbi.nlm.nih.gov/pubmed/16984867?tool=bestpractice.com
[4]Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008 Apr;29(2):141-50.
http://www.ncbi.nlm.nih.gov/pubmed/18365996?tool=bestpractice.com
[14]Vilchez RA, Fung J, Kusne S. Cryptococcosis in organ transplant recipients: an overview. Am J Transplant. 2002 Aug;2(7):575-80.
http://onlinelibrary.wiley.com/doi/10.1034/j.1600-6143.2002.20701.x/full
http://www.ncbi.nlm.nih.gov/pubmed/12201357?tool=bestpractice.com
[15]Pappas PG, Alexander BD, Andes DR, et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis. 2010 Apr 15;50(8):1101-11.
https://academic.oup.com/cid/article/50/8/1101/449301
http://www.ncbi.nlm.nih.gov/pubmed/20218876?tool=bestpractice.com