Abstract

Purpose: Cerebral aspergillosis (CA) is a rare but often fatal, difficult-to-diagnose, opportunistic infection. The utility of metagenomic next-generation sequencing (mNGS) for diagnosis of CA is unclear. We evaluated the usefulness of mNGS of the cerebrospinal fluid (CSF) for the diagnosis of CA.Methods: This prospective study involved seven consecutive patients with confirmed CA in whom CSF mNGS was performed. Serum (1→3)-β-D-glucan and galactomannan levels were determined, and histopathological examination and mNGS of the CSF were conducted. CSF specimens from three non-infected patients were used as positive controls.Results: mNGS of the CSF was positive in six of the seven confirmed CA cases (85.71% sensitivity). In the cryptococcal meningitis group (control), mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity). The positive likelihood ratio, negative likelihood ratio, and Youden’s index of mNGS for CA in the CSF were 5.565, 0.169, and 0.7, respectively. Among the six mNGS-positive cases, more than two Aspergillus species were found in four (4/6, 66.67%). In the positive controls, the addition of one A. fumigatus spore yielded a standardised species-specific read number (SDSSRN) of 25.45 by mNGS; the detection rate would be 0.98 if SDSSRN was 2.Conclusion: mNGS facilitates the diagnosis of CA and may reduce the need for cerebral biopsy in patients with suspected CA.Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800020442.

Highlights

  • Cerebral aspergillosis (CA) is a rare and life-threatening opportunistic infection caused by Aspergillus species

  • We evaluated the usefulness of metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid (CSF) for the diagnosis of CA

  • In the cryptococcal meningitis group, mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity)

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Summary

Introduction

Cerebral aspergillosis (CA) is a rare and life-threatening opportunistic infection caused by Aspergillus species. This notorious complication of invasive aspergillosis, which accounts for 5–10% of all intracranial fungal pathologies (Ellenbogen et al, 2016), is associated with a >90% mortality rate (Walsh et al, 2008). The gold standard for diagnosing CA is histopathological evidence or a positive culture result for a biopsy or cerebrospinal fluid (CSF) specimen (Walsh et al, 2008) These methods are time-consuming, laborious, and have variable sensitivity and specificity (McCarthy and Walsh, 2017). Confirmation of CA is problematic, and the misdiagnosis rate is high (Wang et al, 2017)

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