侵襲性隱球菌感染的危險因子: 病例對照研究

Abstract

Background Cryptococcus neoformans is a widespread environmental fungus that is frequently found in the excrement of pigeons. C. neoformans can invade the central nervous system and cause life-threatening cryptococcal meningitis. Additionally, C. neoformans can invade the bloodstream and cause cryptococcemia, which carries a high risk of mortality. Previously, we conducted the first cohort study on the clinical outcomes of cryptococcemia. Among the 52 cases, the three most common underlying host diseases/conditions were acquired immunodeficiency syndrome (AIDS), immunosuppressive therapy, and decompensated liver cirrhosis. Whether the above-stated factors increase the risk for developing cryptococcosis is unclear. There is still no case-control study that examined the role of these factors in the pathogenesis of invasive cryptococcal diseases. Aims To identify the risk factors for invasive cryptococcal diseases, i.e., cryptococcemia and cryptococcal meningitis, we performed a hospital-based, retrospective, density-sampling case-control study. Methods This retrospective, density-sampling, matched case-control study was conducted at the National Taiwan University Hospital (NTUH). The study procedure was reviewed and approved by the institutional review board of the NTUH (No. 201101083RC). All of the cryptococcemia patients (blood culture-positive) and cryptococcal meningitis patients (cerebral spinal fluid [CSF] culture-proven) at the NTUH from Jan. 1, 2002 to Dec. 31, 2010 were included as cases. The controls were selected from patients hospitalized at the NTUH without a diagnosis of cryptococcemia or cryptococcal meningitis. The controls and cases were individually matched by admission date, age, and gender at a 4:1 ratio (cryptococcemia) or 2:1 ratio (cryptococcal meningitis). Information on gender, age, and the presence of underlying conditions or environmental exposures was systematically collected using a standardized data format. Exact conditional logistic regression was used to analyze the matched case-control data. A stepwise procedure was used for the multivariate regression analyses. Results A total of 101 patients with cryptococcal meningitis (with 266 controls) and 47 patients with cryptococcemia (with 188 controls) were included in this study. Thirty-two patients had both cryptococcal meningitis and cryptococcemia. The multivariate regression analysis showed that AIDS (adjusted odds ratio [OR] = 470.6; 95% confidence interval [CI], 33.4 to >999; p<0.0001), decompensated liver cirrhosis (adjusted OR = 25.5; 95% CI, 3.7 to 174.4; p=0.0009), cell-mediated immunity (CMI)-suppressive therapy (adjusted OR = 36.0; 95% CI, 6.5 to 198.0; p<0.0001), and leukemia/myeloma (adjusted OR = 87.3; 95% CI, 2.9 to >999; p<0.0101) were independent risk factors for cryptococcemia. Additionally, the multivariate regression analysis showed that decompensated liver cirrhosis (adjusted OR = 10.7; 95% CI, 2.3 to 49.4; p=0.0024), AIDS (adjusted OR = 161.9; 95% CI, 21.6 to >999; p<0.0001), and CMI-suppressive therapy (adjusted OR = 9.3; 95% CI, 3.8 to 22.9; p<0.0001) were independent risk factors for cryptococcal meningitis. Cryptococcemia in patients with AIDS was more likely to present with culture-proven meningitis than that in patients with decompensated liver cirrhosis (90% vs. 44.4%, p=0.0079). Patients with decompensated liver cirrhosis were significantly less likely than patients with AIDS to undergo a lumbar puncture for a CSF study (33.3% vs. 0%, p=0.023). Conclusions This study confirmed that decompensated liver cirrhosis, AIDS, and CMI-suppressive therapy are independent risk factors for cryptococcemia and cryptococcal meningitis. Invasive cryptococcal diseases should be included in the differential diagnosis in cases in which patients with the above-stated conditions develop fever and/or symptoms of meningitis.