Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients
Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients
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DOI：
10.3389/fcimb.2020.00088
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发表时间：
2020-03-05
影响因子：
5.7
通讯作者：
Yu, Sheng-Yuan
中科院分区：
文献类型：
--
作者：
Xing, Xiao-Wei;Zhang, Jia-Tang;Yu, Sheng-Yuan
目的：我们评估新一代宏基因组测序（mNGS）在感染性脑炎和脑膜炎诊断中的作用。方法：这是一项前瞻性多中心研究。对病毒性脑炎和/或脑膜炎、结核性脑膜炎、细菌性脑膜炎、真菌性脑膜炎和非中枢神经系统（CNS）感染患者的脑脊液样本进行mNGS检测。结果：2016年11月至2019年5月，共纳入感染性和非感染性中枢神经系统疾病患者213例；明确中枢神经系统感染的mngs阳性检出率为57.0%。当物种特异性读数(SSRN) >= 2时，mNGS诊断病毒性脑炎和/或脑膜炎的效果最佳（曲线下面积[AUC] = 0.659, 95%可信区间[CI] = 0.566-0.751）；阳性率为42.6%。当属特异性读数>= 1时，mNGS诊断结核性脑膜炎（明确或可能）的性能最佳（AUC=0.619, 95% CI=0.516-0.721）；阳性率为27.3%。SSRNs >= 5或10时，诊断细菌性脑膜炎的效果最佳（AUC=0.846, 95% CI = 0.711-0.981）；灵敏度为73.3%。mNGS（在SSRN >= 2时）对隐球菌性脑膜炎和脑曲霉病的诊断敏感性分别为76.92和80%。结论：脑脊液mNGS能有效鉴别感染性中枢神经系统疾病病原。mNGS应与常规微生物检测结合使用。
Purpose: We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis.Methods: This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS.Results: In total, 213 patients with infectious and non-infectious CNS diseases were finally enrolled from November 2016 to May 2019; the mNGS-positive detection rate of definite CNS infections was 57.0%. At a species-specific read number (SSRN) >= 2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] = 0.659, 95% confidence interval [CI] = 0.566-0.751); the positivity rate was 42.6%. At a genus-specific read number >= 1, mNGS performance in the diagnosis of tuberculous meningitis (definite or probable) was optimal (AUC=0.619, 95% CI=0.516-0.721); the positivity rate was 27.3%. At SSRNs >= 5 or 10, the diagnostic performance was optimal for definite bacterial meningitis (AUC=0.846, 95% CI = 0.711-0.981); the sensitivity was 73.3%. The sensitivities of mNGS (at SSRN >= 2) in the diagnosis of cryptococcal meningitis and cerebral aspergillosis were 76.92 and 80%, respectively.Conclusion: mNGS of cerebrospinal fluid effectively identifies pathogens causing infectious CNS diseases. mNGS should be used in conjunction with conventional microbiological testing.