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
Mycoses. 2022 May 4. doi: 10.1111/myc.13451. Online ahead of print.
BACKGROUND: The incidence of Aspergillus and Candida CNS infection, which are characterized 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.
PATIENTS, MATERIALS, METHODS: Serum (19) and cerebrospinal fluid (CSF; 10) samples of 19 patients, whose CNS specimens yielded growth of Aspergillus or Candida, were analyzed for different biomarkers for fungal infection, i.e., 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.
RESULTS: GM, 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 – 97 %, specificity for CSF BDG was only 70 %. No false positive GM results from CSF were obtained.
CONCLUSION: 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.