Serologic biomarkers in Candida and Aspergillus infections of the central nervous system: A comparison of galactomannan, mannan and β-1,3-D-gucan testing from serum and cerebrospinal fluid.

Abstract

The incidence of Aspergillus and Candida CNS infection, which are characterised by high mortality rates, is underestimated. This underdiagnosis presumably results from the limitations of available diagnostic tools and the need for invasive sampling. Little is known about the role of serologic biomarkers in the setting of CNS aspergillosis and candidiasis. Serum and cerebrospinal fluid (CSF; 10) samples of 19 patients, whose CNS specimens yielded growth of Aspergillus or Candida, were analysed for different biomarkers for fungal infection, that is galactomannan (GM), galactomannoprotein (GP), mannan, anti-mannan-antibodies and β-1,3-D-glucan (BDG). Serum and CSF specimens of time-matched patients (two each for every case of fungal CNS infection) were included as controls. Galactomannan, GP and BDG seropositivity was found in one, two and three of five cases of CNS aspergillosis. BDG and mannan/anti-mannan-antibody sensitivity in proven CNS candidiasis was 40% and 20%, respectively. Applying the serum cut-off, sensitivity in CSF testing was 100% for GM and BDG and 50% for mannans. While serum specificity for all assays ranged from 89 to 97%, specificity for CSF BDG was only 70%. No false-positive GM results from CSF were obtained. Sensitivity for diagnosing CNS aspergillosis and CNS candidiasis from serum is mediocre for all serological biomarkers. GM testing in CSF proved excellent performance. With a sensitivity of 100% but a specificity of only 70%, CSF BDG might be most useful when used in patients with a high pre-test probability.