Cryptococcal meningitis (CM) causes significant morbidity and mortality globally; however, recent national trends have not been described. Incidence and trends for CM-associated hospitalizations in 18 states were estimated using the Agency for Healthcare and Research Quality (AHRQ) State Inpatient Databases (SID) datasets for 1997 through 2009. We identified 30,840 hospitalizations coded for CM, of which 21.6% were among HIV-uninfected patients. CM in-hospital mortality was significant (12.4% for women and 10.8% for men) with a total of 3,440 deaths over the study period. Co-morbidities of CM coded at increased frequency in HIV-uninfected CM hospitalized populations included hydrocephalus and acute/chronic renal failure as well as possible predispositions including transplantation, combined T and B cell defects, Cushing’s syndrome, liver disease and hypogammaglobulinemia. Median hospitalization costs were significant for CM and higher for HIV-uninfected patients (16,803.01 vs. 15,708.07; p<0.0001). Cryptococcal meningitis remains a disease with significant morbidity and mortality in the U.S. and the relative burden among persons without HIV infection is increasing.

Background Cryptococcal meningitis has been described in immunocompromised patients as well as in those for whom no immune defect has been identified. GM-CSF regulates the function of phagocytes and pulmonary alveolar macrophages, critical elements in cryptococcal control. Methods We performed clinical histories, immunological evaluation, and anticytokine autoantibody screening in 4 current patients with cryptococcal meningitis, and identified and tested 103 archived plasma/CSF samples from patients with cryptococcal meningitis. We assessed the ability of anti-GM-CSF autoantibody containing plasmas to inhibit GM-CSF signaling. Results We recognized anti-GM-CSF autoantibodies in an otherwise healthy female with cryptococcal meningitis who later developed pulmonary alveolar proteinosis. Her diagnosis prompted screening of patients with cryptococcal meningitis for anticytokine autoantibodies. We identified 7 HIV uninfected patients with cryptococcal meningitis who tested positive for high-titer anti-GM-CSF autoantibodies. Two of the 7 later developed evidence of PAP. Plasma from all patients prevented GM-CSF-induced STAT-5 phosphorylation and MIP-1α production in normal PBMC. This effect was limited to their IgG fraction. Conclusions Anti-GM-CSF autoantibodies are associated with some cases of cryptococcal meningitis in otherwise immunocompetent patients. These cases need not have associated pulmonary alveolar proteinosis.

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