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浣熊狂犬病病毒变异株通过实体器官移植传播。

Raccoon rabies virus variant transmission through solid organ transplantation.

机构信息

Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

出版信息

JAMA. 2013 Jul 24;310(4):398-407. doi: 10.1001/jama.2013.7986.

Abstract

IMPORTANCE

The rabies virus causes a fatal encephalitis and can be transmitted through tissue or organ transplantation. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation.

OBJECTIVES

To investigate whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients from the same donor.

DESIGN

Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients. Viral ribonucleic acid was extracted from tissues and amplified for nucleoprotein gene sequencing for phylogenetic comparisons.

MAIN OUTCOMES AND MEASURES

Determination of whether the donor died from undiagnosed rabies and whether other organ recipients developed rabies.

RESULTS

In retrospect, the donor's clinical presentation (which began with vomiting and upper extremity paresthesias and progressed to fever, seizures, dysphagia, autonomic dysfunction, and brain death) was consistent with rabies. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor. The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9% identical across the entire N gene (1349/1350 nucleotides), thus confirming organ transplantation as the route of transmission. The 3 other organ recipients remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis (range, 0.3-40.8 IU/mL).

CONCLUSIONS AND RELEVANCE

Unlike the 2 previous clusters of rabies virus transmission through solid organ transplantation, there was a long incubation period in the recipient who developed rabies, and survival of 3 other recipients without pretransplant rabies vaccination. Rabies should be considered in patients with acute progressive encephalitis of unexplained etiology, especially for potential organ donors. A standard evaluation of potential donors who meet screening criteria for infectious encephalitis should be considered, and risks and benefits for recipients of organs from these donors should be evaluated.

摘要

重要性

狂犬病病毒可引起致命性脑炎,可通过组织或器官移植传播。2013 年 2 月,一名肾移植受者在移植后 18 个月死于狂犬病,此前未报告有接触过可能患有狂犬病的动物。

目的

调查器官移植是否为肾移植受者接触狂犬病病毒的来源,并评估同一供体的其他器官移植受者是否存在狂犬病。

设计

回顾性分析器官供者和所有移植受者的病历。对供者和受者的血清、脑脊液和组织等可利用标本进行狂犬病病毒特异性结合抗体、狂犬病病毒中和抗体和狂犬病病毒抗原的实验室检测。从组织中提取病毒核糖核酸进行核蛋白基因测序进行系统发生比较。

主要结果和措施

确定供者是否死于未确诊的狂犬病,以及其他器官受者是否发生狂犬病。

结果

回顾性分析,供者的临床表现(始于呕吐和上肢感觉异常,进展为发热、癫痫、吞咽困难、自主神经功能障碍和脑死亡)与狂犬病一致。在存档的供者尸检脑组织中检测到狂犬病病毒抗原。感染供者和已故肾移植受者的狂犬病病毒与浣熊狂犬病病毒变异株一致,整个 N 基因(1349/1350 个核苷酸)超过 99.9%相同,因此证实器官移植是传播途径。其他 3 名器官受者仍无症状,在完成暴露后预防后血清中检测到狂犬病病毒中和抗体(范围 0.3-40.8 IU/mL)。

结论和相关性

与前 2 例通过实体器官移植传播的狂犬病病毒聚集不同,发生狂犬病的受者潜伏期较长,另外 3 名受者在没有移植前狂犬病疫苗接种的情况下存活。对于病因不明的急性进行性脑炎患者,应考虑狂犬病。应考虑对符合传染性脑炎筛查标准的潜在供者进行标准评估,并评估这些供者器官的受者的风险和获益。

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