ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Clinical Infectious Diseases
Metagenomic Next-generation Sequencing for Cryptococcal Meningitis Diagnosis: A Single-Center Experience
Provisionally accepted
- Second Hospital of Hebei Medical University, Shijiazhuang, China
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Purpose Cryptococcal meningitis (CM) is a devastating central nervous system infection with substantial mortality, particularly when diagnosis is delayed. This study aims to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) for CM detection in comparison with conventional tests. Methods We enrolled 23 consecutive patients with suspected CM at a tertiary center. All patients met a composite reference standard (CRS) based on CSF cryptococcal antigen (CrAg), CSF/sterile-site culture for Cryptococcus, or CNS histopathology; mNGS was excluded from the CRS. Primary outcomes were CRS-based sensitivity (computed only among CRS-positive patients who underwent each assay) and turnaround times (TATs); pairwise agreement metrics (PPA/NPA) between mNGS and conventional assays were estimated in co-tested subsets. Results mNGS identified Cryptococcus in 18/23 (78.3%) cases and detected viral co-pathogens (EBV/CMV/HIV-1) in 5 patients. CRS-based sensitivities were: CrAg LFA (CSF) 83.3% (5/6), Alcian blue 72.7% (16/22), India ink 50.0% (3/6), and CSF culture 66.7% (8/12). Pairwise agreement favored mNGS against culture and CrAg (e.g., PPA 100% vs culture 8/8] and vs CSF CrAg [5/5]), with limited NPA where denominators were small. Median (IQR) TATs were 0.5 (0.5–0.5) days for CrAg LFA, 1 (0.5– 1) day for India ink, 5 (3–8) days for first positive culture, and 2 (1–4) days for mNGS. Conclusion CSF mNGS complements CrAg, microscopy, and culture by increasing Cryptococcus detection and revealing mixed infections, with particular utility in atypical, pretreated, or complex hosts. Larger studies are warranted to validate clinical utility and define optimal integration with existing workflows.
Keywords: Cryptococcal meningitis, metagenomic next-generation sequencing, Fungal Infection, rapiddiagnostics, immunocompromised
Received: 10 May 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Zhao, Zhang, Fu and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lili Yu
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