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首例致命性脑炎在西欧由欧洲蝙蝠狂犬病病毒 1 型引起。

First Case of Lethal Encephalitis in Western Europe Due to European Bat Lyssavirus Type 1.

机构信息

Pathogen Discovery Laboratory, Institut Pasteur, Paris, France.

The OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Institut Pasteur, Paris, France.

出版信息

Clin Infect Dis. 2022 Feb 11;74(3):461-466. doi: 10.1093/cid/ciab443.

DOI:10.1093/cid/ciab443
PMID:33991184
Abstract

BACKGROUND

Inaccurate diagnosis of encephalitis is a major issue as immunosuppressive treatments can be deleterious in case of viral infection. The European bat lyssavirus type 1 (EBLV-1), a virus related to rabies virus, is endemic in European bats. No human case has yet been reported in Western Europe. A 59-year-old patient without specific past medical history died from encephalitis. A colony of bats lived in an outbuilding of his house. No diagnosis was made using standard procedures.

METHODS

We used a next generation sequencing (NGS) based transcriptomic protocol to search for pathogens in autopsy samples (meninges and brain frontal lobe). Results were confirmed by polymerase chain reaction (PCR) and by antibody testing in serum. Immunochemistry was used to characterize inflammatory cells and viral antigens in brain lesions. Cells and mice were inoculated with brain extracts for virus isolation.

RESULTS

The patient's brain lesions were severe and diffuse in white and gray matter. Perivascular inflammatory infiltrates were abundant and rich in plasma cells. NGS identified European bat lyssavirus type 1a in brain, which was confirmed by PCR. A high titer of neutralizing antibodies was found in serum. No viral antigen was detected, and the virus could not be isolated by cell culture or by mouse inoculation.

CONCLUSIONS

The patient died from European bat lyssavirus type 1a infection. NGS was key to identifying this unexpected viral etiology in an epidemiological context that did not suggest rabies. People exposed to bats should be strongly advised to be vaccinated with rabies vaccines, which are effective against EBLV-1.

摘要

背景

脑炎的误诊是一个主要问题,因为免疫抑制治疗在病毒感染的情况下可能是有害的。欧洲蝙蝠 1 型 lyssavirus(EBLV-1)是一种与狂犬病病毒相关的病毒,在欧洲蝙蝠中流行。在西欧还没有报告过人类病例。一名 59 岁的患者没有特定的既往病史,死于脑炎。一个蝙蝠聚居地生活在他房子的附属建筑里。标准程序没有做出诊断。

方法

我们使用基于下一代测序(NGS)的转录组学方案在尸检样本(脑膜和大脑额叶)中搜索病原体。结果通过聚合酶链反应(PCR)和血清中的抗体检测得到证实。免疫化学用于在脑病变中表征炎症细胞和病毒抗原。细胞和小鼠接种脑提取物以进行病毒分离。

结果

患者的脑部病变在白质和灰质中严重且弥漫。血管周围炎症浸润丰富,富含浆细胞。NGS 在大脑中鉴定出欧洲蝙蝠 1 型 lyssavirus 1a,PCR 证实了这一点。血清中发现了高滴度的中和抗体。未检测到病毒抗原,细胞培养或小鼠接种均未能分离出病毒。

结论

患者死于欧洲蝙蝠 1 型 lyssavirus 1a 感染。NGS 是在没有提示狂犬病的流行病学背景下识别这种意外病毒病因的关键。接触过蝙蝠的人应强烈建议接种狂犬病疫苗,该疫苗对 EBLV-1 有效。

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