PDF(Pubmed)
Abstract：
BACKGROUND: The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans.
RESULTS: A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor.
CONCLUSIONS: Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation.
RESULTS: A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor.
CONCLUSIONS: Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation.
摘要：
背景：博尔纳病病毒（BoDV-1）是一种新兴的人畜共患病毒，可在人类中引起严重且大部分致命的脑炎。
结果：在同一村庄发现了一组致命的BoDV-1脑炎病例，相隔三年，影响了两个孩子。虽然第一例在病程中被诊断为晚期，在第二种情况下，通过提高意识，实现了非常早期的诊断和治疗尝试。治疗早在疾病的第12天开始。抗病毒治疗包括favipirravir和利巴韦林，and,在生物信息学建模之后，还有Remdesivir.由于这种疾病是免疫病理学介导的，强化抗炎治疗.在最初令人印象深刻的临床改善之后，当然也是致命的,虽然明显延长。通过qPCR检测泪液和唾液中的病毒RNA，对卫生保健专业人员构成可能的传播风险。验尸后在嗅神经和边缘系统中发现了最高的病毒载量，可能反映了BoDV-1的入口。两名患者的全外显子组测序均未提示潜在的免疫缺陷。在两种情况下都通过下一代测序获得了属于同一簇的完整病毒基因组。序列不相同，表明自然水库中的病毒多样性。通过结构化访谈未发现特定的传播事件或常见的感染源。患者彼此相距750米，位于定居点的边缘，最近显示的相关风险因素。
结论：我们的报告强调了迫切需要有效的治疗策略，提高意识和早期诊断。关于风险因素的知识差距，传输事件，量身定制的预防方法变得显而易见。该病例群是否反映地方性或地理热点，需要进一步调查。
结果：在同一村庄发现了一组致命的BoDV-1脑炎病例，相隔三年，影响了两个孩子。
结论：我们的报告强调了迫切需要有效的治疗策略，
