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Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999-2019: an epidemiological investigation.
The Lancet Infectious Diseases ( IF 36.4 ) Pub Date : 2020-01-07 , DOI: 10.1016/s1473-3099(19)30546-8
Hans Helmut Niller 1 , Klemens Angstwurm 2 , Dennis Rubbenstroth 3 , Kore Schlottau 4 , Arnt Ebinger 4 , Sebastian Giese 5 , Silke Wunderlich 6 , Bernhard Banas 7 , Leonie F Forth 4 , Donata Hoffmann 4 , Dirk Höper 4 , Martin Schwemmle 5 , Dennis Tappe 8 , Jonas Schmidt-Chanasit 9 , Daniel Nobach 10 , Christiane Herden 10 , Christoph Brochhausen 11 , Natalia Velez-Char 11 , Andreas Mamilos 11 , Kirsten Utpatel 11 , Matthias Evert 11 , Saida Zoubaa 12 , Markus J Riemenschneider 12 , Viktoria Ruf 13 , Jochen Herms 13 , Georg Rieder 14 , Mario Errath 14 , Kaspar Matiasek 15 , Jürgen Schlegel 16 , Friederike Liesche-Starnecker 16 , Bernhard Neumann 2 , Kornelius Fuchs 2 , Ralf A Linker 2 , Bernd Salzberger 17 , Tobias Freilinger 18 , Lisa Gartner 19 , Jürgen J Wenzel 1 , Udo Reischl 1 , Wolfgang Jilg 1 , André Gessner 1 , Jonathan Jantsch 1 , Martin Beer 4 , Barbara Schmidt 1
Affiliation  

BACKGROUND In 2018-19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report the occurrence of BoDV-1-associated encephalitis in cases submitted to the Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany, and provide a detailed description of newly identified cases of BoDV-1-induced encephalitis. METHODS All brain tissues from 56 encephalitis cases from Bavaria, Germany, of putative viral origin (1999-2019), which had been submitted for virological testing upon request of the attending clinician and stored for stepwise diagnostic procedure, were systematically screened for BoDV-1 RNA. Two additional BoDV-1-positive cases were contributed by other diagnostic centres. Positive results were confirmed by deep sequencing, antigen detection, and determination of BoDV-1-reactive antibodies in serum and cerebrospinal fluid. Clinical and epidemiological data from infected patients were collected and analysed. FINDINGS BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analysed encephalitis cases and the first human BoDV-1 isolate was obtained from an unequivocally confirmed human BoDV-1 infection from the endemic area. Six of the eight BoDV-1-positive patients had no record of immunosuppression before the onset of fatal disease, whereas two were immunocompromised after solid organ transplantation. Typical initial symptoms were headache, fever, and confusion, followed by various neurological signs, deep coma, and severe brainstem involvement. Seven of nine patients with fatal encephalitis of unclear cause were BoDV-1 positive within one diagnostic centre. BoDV-1 sequence information and epidemiological analyses indicated independent spillover transmissions most likely from the local wild animal reservoir. INTERPRETATION BoDV-1 infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spillover infections in horses and sheep. BoDV-1 infection can result in fatal encephalitis in immunocompromised and apparently healthy people. Consequently, all severe encephalitis cases of unclear cause should be tested for bornaviruses especially in endemic regions. FUNDING German Federal Ministry of Education and Research.

中文翻译:

导致致命人类脑炎的博尔纳病病毒1的人畜共患性外溢感染,1999-2019年:一项流行病学调查。

背景技术在2018-19年度,德国有5例重度至致命性脑炎人类患者中报告了伯纳病病毒1(BoDV-1),它是马,绵羊和其他家养哺乳动物中伯纳氏病的病原体。但是,仍然缺乏有关病例发生率,临床过程以及详细的流行病学分析的信息。我们报告了提交给德国雷根斯堡雷根斯堡大学医院临床微生物学和卫生学研究所的病例中BoDV-1相关性脑炎的发生,并对新发现的BoDV-1引起的脑炎病例进行了详细描述。方法:来自德国巴伐利亚州的56例脑炎病例的所有脑组织,其推定病毒来源(1999-2019年),对BoDV-1 RNA进行了系统筛选,根据主治医生的要求将其提交进行病毒学测试并保存以用于逐步诊断程序。其他诊断中心还贡献了另外两个BoDV-1阳性病例。通过深度测序,抗原检测以及血清和脑脊液中BoDV-1反应性抗体的测定,证实了阳性结果。收集并分析了来自感染患者的临床和流行病学数据。研究结果在八例新近分析的脑炎病例中检测到BoDV-1 RNA和天花病毒反应性抗体,并且从流行区明确证实的人BoDV-1感染中获得了第一批人BoDV-1分离株。在8例BoDV-1阳性患者中,有6例在致命疾病发作之前没有免疫抑制的记录,实体器官移植后有两个免疫受损。典型的初始症状是头痛,发烧和精神错乱,其次是各种神经系统症状,深度昏迷和严重的脑干受累。在一个诊断中心内,九名原因不明的致命性脑炎患者中有七名BoDV-1阳性。BoDV-1序列信息和流行病学分析表明,最有可能来自当地野生动物库的独立溢出传播。解释BoDV-1感染在地方病地区被认为是潜在的致命人畜共患病,据报道在马和羊中有溢出感染。BoDV-1感染可导致免疫力低下和显然健康的人致命的脑炎。所以,应检查所有原因不明的严重脑炎病例的病毒,尤其是在流行地区。资助德国联邦教育和研究部。
更新日期:2020-01-07
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