Epidemiology

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][2][4]​ Cryptococcus neoformans var. grubii (serotype A) is the most common form, accounting for >95% of cases of cryptococcosis.[1] ​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][6][7]

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] The annual incidence of cryptococcosis in patients without HIV is approximately 0.2 to 0.9 per 100,000, depending on the geographic area studied.[9] HIV infection is associated with more than 80% of cryptococcosis cases worldwide.

Patients with HIV and CD4 count of <100 cells/microliter are at highest risk of infection. It is estimated that there are 223,000 cases of cryptococcal meningitis globally each year in people with HIV, with 73% occurring in sub-Saharan Africa. These meningitis cases result in 181,000 deaths globally. Thus, cryptococcal meningitis causes 15% of all AIDS-related deaths.[10] A male predominance has been shown among people with and without HIV who have cryptococcosis.[11][12]​​ 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 immunocompetent populations.[1][4][5][6][13]​ Cryptococcosis is the third most common invasive fungal infection (8%) in solid-organ transplant patients.[1][4][14][15]

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