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

Background 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. Patients, materials and methods: 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. Results 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. 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.

Treatment of Fusarium Infection of the Central Nervous System: A Review of Past Cases to Guide Therapy for the Ongoing 2023 Outbreak in the United States and Mexico

“…While culture from CSF, CNS abscess formations or blood remains the diagnostic gold standard, fungal biomarker testing was reported in only 1/26 cases reviewed here. However, fungal biomarkers tested from serum and CSF, like galactomannan and β-D-glucan, can be positive in fusariosis [ 1 ] and aid in the diagnosis of this CNS invasive fungal infection that carries very high morbidity and mortality [ 15 ], as does panfungal PCR from CSF or tissue. Next generation sequencing from blood specimens, which has shown promise for other mold infections [ 16 ], may present an important diagnostic method in the future, allowing detection of the causative species.…”

Developments in Fungal Serology

“…Interestingly, despite the limited presence of BDG in the cell wall of Cryptococcus neoformans, the sensitivity of CSF BDG for the diagnosis of cryptococcal meningitis was 89% [55•]. A recent study demonstrated that the sensitivity of CSF BDG for the diagnosis of cerebral candidiasis and cerebral aspergillosis was 100%, albeit specificity was 70% [56].…”

Host-directed immunotherapy to fight infectious diseases

“…The management of CNS candidiasis is challenging. Iatrogenic CNS candidiasis is typically acute, occurring in the context of microbiologically-documented candidemia in neonates or adults, and associated with 90% mortality rate [79,80]. sCNSc is typically sub-acute, for example, manifesting with chronic meningitis and/or mass/abscesses; candidemia is not commonly identified in such patients [68,78].…”