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. Now that 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 idiopathic CD4 Lymphocytopenia (ICL) in that they have CD4 levels below 300/microl, no laboratory evidence of HIV infection and no defined immunodeficiency or therapy associated with depressed CD4 levels. 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.

In addition, novel discovery methods such as genome wide association studies (GWAS) of copy number variation (CNV) and single nuclear polymorphisms (SNP's) have been used to identify genes involved in patient diseases. We would thus like to supplement the methods previously used in this protocol with genetic comparisons, maintaining the original objectives of the study.

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.