This 5-year study will follow the course of disease in previously healthy patients with cryptococcosis who developed the disease for no identifiable reason.

Individuals with a positive culture of Cryptococcus neoformans 18 years of age and older without HIV infection or other condition predisposing to cryptococcosis (such as high-dose corticosteroid therapy, sarcoidosis, or a blood cancer) may be eligible for this study. Candidates who test positive for HIV infection may not participate.

Participants will have a physical examination, medical history, routine blood tests and assessment of disease activity upon entering the study. Patients who may have active cryptococcosis will also have a lumbar puncture (spinal tap) and additional blood tests. Following the initial evaluation, patients receiving treatment for cryptococcosis will come to the NIH Clinical Center as needed to manage their disease, typically no less than every 3 months. Other patients will be seen every 6 to 12 months. The visits will include a medical history, physical examination, and blood and urine tests.

Cryptococcosis is a fungus which causes infection in immunocompromised patients, such as those with the acquired immunodeficiency syndrome, but also in occasional persons who have been previously healthy. The reasons for infection of ostensibly normal persons remain unclear. Nowthat enumeration of lymphocyte subpopulations has become more common, a low number of DC4 cells have been found in some cryptococcosis patients. These patients fit the CDC definition of 1diopathic CD4 Lmphocytopenia (ICL) in that they have CD4 levels below 300/ul, no laboratory evidence of HIV infection and no defined immunodeficiency or therapy associated with depressed CD4 levels (MMWR, July 31, 1992). One of the first five cases of ICL reported in that issue of MMWR was presented with cryptococcal meningitis. According to Dr. Harold Jaffe at CDC, about one fourth of the ICL cases reported to CDC by December, 1992 have presented with cryptococcosis (personal communication.) However the incidence of ICL in cryptococcosis patients is unknown. Also, the long term outcome of patients with cryptococcosis and ICL patients is unclear. For example, it is not known if they are more difficult to cure than other previously normal patients, as would be the case had they been HIV seropositive.

This protocol will bring to NIH patients with cryptococcosis who have no underlying disease, either with or without prior treatment of their mycosis. Those who have ICL will be compared with those not having ICL for response to treatment, prior and future opportunistic infections other than cryptococcosis, and future course of the lymphocyte subpopulations.

• Cryptococcosis
• Lymphopenia

• Rex JH, Larsen RA, Dismukes WE, Cloud GA, Bennett JE. Catastrophic visual loss due to Cryptococcus neoformans meningitis. Medicine (Baltimore). 1993 Jul;72(4):207-24. Review.
• Hospenthal DR, Bennett JE. Flucytosine monotherapy for cryptococcosis. Clin Infect Dis. 1998 Aug;27(2):260-4.
• Zonios DI, Falloon J, Huang CY, Chaitt D, Bennett JE. Cryptococcosis and idiopathic CD4 lymphocytopenia. Medicine (Baltimore). 2007 Mar;86(2):78-92.

• INCLUSION CRITERIA:

Positive culture of Cryptococcus neoformans from any body site;

Age 18 years or older; and

Ability to provide informed consent.

EXCLUSION CRITERIA:

Known HIV positive serology or other condition predisposing to Cryptococcosis, including but not limited to corticosteroid therapy equivalent to prednisone 20 mg per day or more, acidosis or hematologic malignancy.

Dementia impairing informed consent.