Diagnostic Performance of Metagenomic Next-Generation Sequencing in Central Nervous System Cryptococcosis Using Cerebrospinal Fluid

使用脑脊液进行宏基因组下一代测序对中枢神经系统隐球菌病的诊断性能

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作者:Xuan Zhang, Yaqing Lin, Huixin Chen, Jianhua Hu, Hong Zhao, Meifang Yang, Dongsheng Han

Conclusion

mNGS is an effective tool for diagnosing CNS cryptococcosis using CSF; however, its sensitivity decreases considerably in patients who have been effectively treated with antifungal drugs.

Methods

From March 2021 to March 2023, 290 patients with suspected CNS infection were recruited from the First Affiliated Hospital, School of Medicine, Zhejiang University, and 74 patients were ultimately included in the study. Lastly, 22 patients with CNS cryptococcosis were included. Of these patients, 25 CSF samples were enrolled. The diagnostic performance of conventional assays [including India ink, cryptococcal antigen (CrAg) testing, and culture] and mNGS was evaluated for CNS cryptococcosis.

Purpose

Metagenomic next-generation sequencing (mNGS) has been widely used to diagnose infectious diseases. However, there are few studies on its diagnostic performance in the central nervous system (CNS) cryptococcosis. This study examined the diagnostic efficacy of mNGS in identifying Cryptococcus spp. in cerebrospinal fluid (CSF) samples. Patients and

Results

In the 25 samples collected, the coincidence rates of mNGS with India ink, CrAg, and culture were 64.0% (16/25), 80.0% (20/25), and 80.0% (20/25), respectively. Without antifungal drug exposure, the coincidence rates were increased to 66.7% (10/15), 100.0% (15/15), and 93.3% (14/15), respectively. The coincidence rates after antifungal therapy were all decreased to 60.0% (6/10), 50.0% (5/10), and 60.0% (6/10), respectively. Moreover, in the 25 samples, the sensitivity of mNGS reached 80.0%, and of India ink, CrAg testing, and culture were 68.0, 100.0, and 60.0%, respectively. The mNGS showed an excellent positive rate (100.0%) in the 15 samples collected without antifungal drug exposure, which was significantly higher than the antifungal drug-exposed group (n = 10) (50.0%) (P = 0.005). The reads of Cryptococcus spp. before antifungal therapy were significantly higher than after it (median, 25,915 vs 2, P = 0.008).

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