Clinical and Molecular Virology Unit, University Hospital and EA-4684 Cardiovir SFR-CAP Santé, Faculty of Medicine, Reims, France.
J Clin Microbiol. 2014 Jan;52(1):212-7. doi: 10.1128/JCM.02270-13. Epub 2013 Nov 6.
Viruses are the leading cause of central nervous system (CNS) infections, ahead of bacteria, parasites, and fungal agents. A rapid and comprehensive virologic diagnostic testing method is needed to improve the therapeutic management of hospitalized pediatric or adult patients. In this study, we assessed the clinical performance of PCR amplification coupled with electrospray ionization-time of flight mass spectrometry analysis (PCR-MS) for the diagnosis of viral CNS infections. Three hundred twenty-seven cerebrospinal fluid (CSF) samples prospectively tested by routine PCR assays between 2004 and 2012 in two university hospital centers (Toulouse and Reims, France) were retrospectively analyzed by PCR-MS analysis using primers targeted to adenovirus, human herpesviruses 1 to 8 (HHV-1 to -8), polyomaviruses BK and JC, parvovirus B19, and enteroviruses (EV). PCR-MS detected single or multiple virus infections in 190 (83%) of the 229 samples that tested positive by routine PCR analysis and in 10 (10.2%) of the 98 samples that tested negative. The PCR-MS results correlated well with herpes simplex virus 1 (HSV-1), varicella-zoster virus (VZV), and EV detection by routine PCR assays (kappa values [95% confidence intervals], 0.80 [0.69 to 0.92], 0.85 [0.71 to 0.98], and 0.84 [0.78 to 0.90], respectively), whereas a weak correlation was observed with Epstein-Barr virus (EBV) (0.34 [0.10 to 0.58]). Twenty-six coinfections and 16 instances of uncommon neurotropic viruses (HHV-7 [n = 13], parvovirus B19 [n = 2], and adenovirus [n = 1]) were identified by the PCR-MS analysis, whereas only 4 coinfections had been prospectively evidenced using routine PCR assays (P < 0.01). In conclusion, our results demonstrated that PCR-MS analysis is a valuable tool to identify common neurotropic viruses in CSF (with, however, limitations that were identified regarding EBV and EV detection) and may be of major interest in better understanding the clinical impact of multiple or neglected viral neurological infections.
病毒是导致中枢神经系统（CNS）感染的主要原因，超过了细菌、寄生虫和真菌病原体。需要一种快速而全面的病毒学诊断检测方法，以改善住院儿科或成年患者的治疗管理。在这项研究中，我们评估了聚合酶链反应扩增结合电喷雾电离-飞行时间质谱分析（PCR-MS）在诊断病毒性 CNS 感染中的临床性能。2004 年至 2012 年期间，在法国图卢兹和兰斯的两个大学医院中心，通过常规 PCR 检测了 327 份脑脊液（CSF）样本，通过使用针对腺病毒、人类疱疹病毒 1 至 8（HHV-1 至-8）、BK 和 JC 多瘤病毒、细小病毒 B19 和肠道病毒（EV）的引物进行 PCR-MS 分析，对这些样本进行了回顾性分析。PCR-MS 在 190 份（83%）常规 PCR 分析阳性的样本和 98 份（10.2%）常规 PCR 分析阴性的样本中检测到单一或多种病毒感染。PCR-MS 结果与单纯疱疹病毒 1（HSV-1）、水痘-带状疱疹病毒（VZV）和 EV 的常规 PCR 检测结果相关性良好（kappa 值[95%置信区间]，0.80[0.69 至 0.92]、0.85[0.71 至 0.98]和 0.84[0.78 至 0.90]），而与 EBV 的相关性较弱（0.34[0.10 至 0.58]）。通过 PCR-MS 分析鉴定了 26 种合并感染和 16 种罕见的神经嗜性病毒（HHV-7[n=13]、细小病毒 B19[n=2]和腺病毒[n=1]），而仅通过常规 PCR 检测到 4 种合并感染（P<0.01）。总之，我们的结果表明，PCR-MS 分析是一种有价值的工具，可用于鉴定 CSF 中的常见神经嗜性病毒（然而，在 EBV 和 EV 检测方面存在局限性），对于更好地了解多种或被忽视的病毒性神经感染的临床影响可能具有重要意义。
