Risk factors for invasive Cryptococcus neoformans diseases: a case-control study

PLoS One. 2015 Mar 6;10(3):e0119090. doi: 10.1371/journal.pone.0119090. eCollection 2015.


Background: Cryptococcus neoformans is a ubiquitous environmental fungus that can cause life-threatening meningitis and fungemia, often in the presence of acquired immunodeficiency syndrome (AIDS), liver cirrhosis, diabetes mellitus, or other medical conditions. To distinguish risk factors from comorbidities, we performed a hospital-based, density-sampled, matched case-control study.

Methods: All new-onset cryptococcal meningitis cases and cryptococcemia cases at a university hospital in Taiwan from 2002-2010 were retrospectively identified from the computerized inpatient registry and were included in this study. Controls were selected from those hospitalized patients not experiencing cryptococcal meningitis or cryptococcemia. Controls and cases were matched by admission date, age, and gender. Conditional logistic regression was used to analyze the risk factors.

Results: A total of 101 patients with cryptococcal meningitis (266 controls) and 47 patients with cryptococcemia (188 controls), of whom 32 patients had both cryptococcal meningitis and cryptococcemia, were included in this study. Multivariate regression analysis showed that AIDS (adjusted odds ratio [aOR] = 181.4; p < 0.001), decompensated liver cirrhosis (aOR = 8.5; p = 0.008), and cell-mediated immunity (CMI)-suppressive regimens without calcineurin inhibitors (CAs) (aOR = 15.9; p < 0.001) were independent risk factors for cryptococcal meningitis. Moreover, AIDS (aOR = 216.3, p < 0.001), decompensated liver cirrhosis (aOR = 23.8; p < 0.001), CMI-suppressive regimens without CAs (aOR = 7.3; p = 0.034), and autoimmune diseases (aOR = 9.3; p = 0.038) were independent risk factors for developing cryptococcemia. On the other hand, diabetes mellitus and other medical conditions were not found to be risk factors for cryptococcal meningitis or cryptococcemia.

Conclusions: The findings confirm AIDS, decompensated liver cirrhosis, CMI-suppressive regimens without CAs, and autoimmune diseases are risk factors for invasive C. neoformans diseases.

Publication types

  • Clinical Trial

MeSH terms

  • Acquired Immunodeficiency Syndrome / complications
  • Acquired Immunodeficiency Syndrome / epidemiology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Cryptococcus neoformans*
  • Female
  • Fungemia / epidemiology*
  • Fungemia / etiology
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / epidemiology*
  • Male
  • Meningitis, Cryptococcal / epidemiology*
  • Meningitis, Cryptococcal / etiology
  • Middle Aged
  • Registries*
  • Retrospective Studies
  • Risk Factors

Grant support

The authors have no support or funding to report.