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Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections
Nature Medicine ( IF 58.7 ) Pub Date : 2024-11-12 , DOI: 10.1038/s41591-024-03275-1
Patrick Benoit, Noah Brazer, Mikael de Lorenzi-Tognon, Emily Kelly, Venice Servellita, Miriam Oseguera, Jenny Nguyen, Jack Tang, Charles Omura, Jessica Streithorst, Melissa Hillberg, Danielle Ingebrigtsen, Kelsey Zorn, Michael R. Wilson, Tim Blicharz, Amy P. Wong, Brian O’Donovan, Brad Murray, Steve Miller, Charles Y. Chiu

Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is an agnostic method for broad-based diagnosis of central nervous system (CNS) infections. Here we analyzed the 7-year performance of clinical CSF mNGS testing of 4,828 samples from June 2016 to April 2023 performed by the University of California, San Francisco (UCSF) clinical microbiology laboratory. Overall, mNGS testing detected 797 organisms from 697 (14.4%) of 4,828 samples, consisting of 363 (45.5%) DNA viruses, 211 (26.4%) RNA viruses, 132 (16.6%) bacteria, 68 (8.5%) fungi and 23 (2.9%) parasites. We also extracted clinical and laboratory metadata from a subset of the samples (n = 1,164) from 1,053 UCSF patients. Among the 220 infectious diagnoses in this subset, 48 (21.8%) were identified by mNGS alone. The sensitivity, specificity and accuracy of mNGS testing for CNS infections were 63.1%, 99.6% and 92.9%, respectively. mNGS testing exhibited higher sensitivity (63.1%) than indirect serologic testing (28.8%) and direct detection testing from both CSF (45.9%) and non-CSF (15.0%) samples (P < 0.001 for all three comparisons). When only considering diagnoses made by CSF direct detection testing, the sensitivity of mNGS testing increased to 86%. These results justify the routine use of diagnostic mNGS testing for hospitalized patients with suspected CNS infection.



中文翻译:


用于诊断中枢神经系统感染的临床宏基因组下一代测序测试的 7 年表现



脑脊液 (CSF) 的宏基因组下一代测序 (mNGS) 是一种与中枢神经系统 (CNS) 感染基础诊断的不可知方法。在这里,我们分析了加州大学旧金山分校 (UCSF) 临床微生物学实验室从 2016 年 6 月到 2023 年 4 月对 4,828 个样本进行的 7 年临床 CSF mNGS 检测的性能。总体而言,mNGS 检测从 4,828 个样本中的 697 个 (14.4%) 中检测到 797 个生物体,包括 363 种 (45.5%) DNA 病毒、211 种 (26.4%) RNA 病毒、132 种 (16.6%) 细菌、68 种 (8.5%) 真菌和 23 种 (2.9%) 寄生虫。我们还从 1,053 名 UCSF 患者的样本子集 (n = 1,164) 中提取了临床和实验室元数据。在该子集的 220 例感染诊断中,48 例 (21.8%) 仅通过 mNGS 鉴定。mNGS 检测 CNS 感染的敏感性、特异性和准确性分别为 63.1% 、 99.6% 和 92.9%。mNGS 检测的敏感性 (63.1%) 高于间接血清学检测 (28.8%) 和来自 CSF (45.9%) 和非 CSF (15.0%) 样本的直接检测 (P < 0.001所有三个比较)。当仅考虑通过 CSF 直接检测检测做出的诊断时,mNGS 检测的敏感性增加到 86%。这些结果证明了对疑似 CNS 感染的住院患者常规使用诊断性 mNGS 检测是合理的。

更新日期:2024-11-12
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