[Clinical experience and next-generation sequencing analysis of encephalitis caused by pseudorabies virus].

[Clinical experience and next-generation sequencing analysis of encephalitis caused by pseudorabies virus].
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DOI:
10.3760/cma.j.issn.0376-2491.2018.15.006
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发表时间:
2018-04-17
影响因子:
--
通讯作者:
Guan, H Z
Guan, H Z
中科院分区:
其他
文献类型:
--
作者:
Zhao, W L;Wu, Y H;Guan, H Z

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目的:检测中国不明原因脑炎患者中包括伪狂犬病病毒在内的潜在病原体,并描述新的脑炎实体。方法:纳入北京协和医院脑炎项目中临床疑似感染性脑炎患者进行病原体鉴定的多中心研究。对2016年至2017年入组的不明原因脑炎患者进行脑脊液(CSF)二代测序(NGS)。对诊断为PRV脑炎的患者进行研究,以描述这一新实体。结果:4例患者(男3例,男1例,年龄38~54岁)在猪肉生产、销售过程中存在职业性接触生猪园的情况,至少1例在猪肉切割过程中受伤,其中2例经脑脊液NGS确诊,3例血清血清学分析抗PRV抗体阳性,均在1~4 d内出现急性发热、抽搐、意识丧失、呼吸衰竭等症状,病情迅速恶化,甚至病情迅速恶化。全部患者入ICU,3例需要机械通气。2例患者同时出现双侧视网膜炎。神经影像显示边缘系统、基底节、中脑等灰质对称性病变,无明显出血。腰穿提示颅内压升高,脑脊液淋巴细胞增多[(6-64)*10(6)/L]。阿昔洛韦联合静脉注射治疗无效。免疫球蛋白和类固醇。末次随访时4例患者的改良Rankin评分分别为3、5、5和6(死亡)。结论:PRV可能是导致重症脑炎的原因之一,疑似伪狂犬病脑炎(PRE)患者需及时进行PRV DNA检测。职业暴露患者双侧边缘系统、基底神经节、丘脑和中脑受累的重症脑炎提示新出现的传染性脑炎。
Objective: To detect potential pathogens including pseudorabies virus in patients with encephalitis of unknown etiology in China and describe novel encephalitic entities. Methods: Patients with clinically suspected infectious encephalitis were enrolled in a multicenter study to identify the pathogens in PUMCH Encephalitis Program.Next-generation sequencing(NGS) of cerebrospinal fluid (CSF) was used in patients with encephalitis of unknown etiology enrolled from 2016 to 2017.The patients diagnosed as PRV encephalitis were studied to describe this novel entity. Results: The four patients(3 male, 1 male, 38-54 years old) had occupational exposure to raw park when working in the production or marketing of pork and at least one got injured during pork-cutting.Two of them were confirmed with NGS of CSF, and anti-PRV antibodies were positive in 3 patients whose serum was available for serological analysis.They all presented with an acute onset of fever, convulsion, loss of consciousness and respiratory failure within 1 to 4 days and rapidly deteriorated even on extensive treatment.All the patients needed ICU admission and 3 needed mechanical ventilation.Two patients also had bilateral retinitis.Neuroimaging revealed symmetric gray matter lesions including limbic system, basal ganglia and midbrain without obvious hemorrhage.Lumbar puncture revealed elevated intracranial pressure and lymphocytic pleocytosis [(6-64)*10(6)/L] of CSF.The patients failed to response to the treatment of acyclovir combined with intravenous immunoglobulin and steroids.Modified Rankin Score was 3, 5, 5 and 6 (died) for the 4 patients respectively on last follow-up. Conclusions: PRV could be a cause of severe encephalitis.The patients with suspected pseudorabies encephalitis (PRE) need to be tested for PRV DNA timely.Severe encephalitis with bilateral involvement of limbic system, basal ganglion, thalamus and midbrain in patient with occupational exposure indicate this emerging infectious encephalitis.