Wilson M R, Zimmermann L L, Crawford E D, Sample H A, Soni P R, Baker A N, Khan L M, DeRisi J L
Department of Biochemistry and Biophysics, University of California, San Francisco, CA.
Howard Hughes Medical Institute, Chevy Chase, MD.
Am J Transplant. 2017 Mar;17(3):803-808. doi: 10.1111/ajt.14058. Epub 2016 Oct 21.
Solid organ transplant patients are vulnerable to suffering neurologic complications from a wide array of viral infections and can be sentinels in the population who are first to get serious complications from emerging infections like the recent waves of arboviruses, including West Nile virus, Chikungunya virus, Zika virus, and Dengue virus. The diverse and rapidly changing landscape of possible causes of viral encephalitis poses great challenges for traditional candidate-based infectious disease diagnostics that already fail to identify a causative pathogen in approximately 50% of encephalitis cases. We present the case of a 14-year-old girl on immunosuppression for a renal transplant who presented with acute meningoencephalitis. Traditional diagnostics failed to identify an etiology. RNA extracted from her cerebrospinal fluid was subjected to unbiased metagenomic deep sequencing, enhanced with the use of a Cas9-based technique for host depletion. This analysis identified West Nile virus (WNV). Convalescent serum serologies subsequently confirmed WNV seroconversion. These results support a clear clinical role for metagenomic deep sequencing in the setting of suspected viral encephalitis, especially in the context of the high-risk transplant patient population.
实体器官移植患者容易因多种病毒感染而出现神经系统并发症，并且可能成为人群中的哨兵，率先从西尼罗河病毒、基孔肯雅病毒、寨卡病毒和登革热病毒等新发感染中出现严重并发症。病毒性脑炎的潜在病因多样且迅速变化，这给传统的基于候选病原体的传染病诊断带来了巨大挑战，在大约50%的脑炎病例中，传统诊断方法已无法确定致病病原体。我们报告了一例14岁接受肾移植免疫抑制治疗的女孩，她出现了急性脑膜脑炎。传统诊断未能确定病因。从她的脑脊液中提取的RNA进行了无偏倚的宏基因组深度测序，并使用基于Cas9的宿主耗竭技术进行了增强。该分析确定了西尼罗河病毒（WNV）。恢复期血清学检测随后证实了WNV血清转化。这些结果支持了宏基因组深度测序在疑似病毒性脑炎情况下的明确临床作用，特别是在高风险移植患者群体中。
