Hemorrhagic Fever Caused by a Novel Bunyavirus in China: Pathogenesis and Correlates of Fatal Outcome
Hemorrhagic Fever Caused by a Novel Bunyavirus in China: Pathogenesis and Correlates of Fatal Outcome
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DOI：
10.1093/cid/cir804
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发表时间：
2012-02-15
影响因子：
11.8
通讯作者：
Xu, Jianguo
中科院分区：
文献类型：
--
作者：
Zhang, Yong-Zhen;He, Yong-Wen;Xu, Jianguo
背景。由一种新型布尼亚病毒——淮阳山病毒（HYSV，也称为发热伴血小板减少病毒[SFTSV]和发热、血小板减少和白细胞减少综合征[FTLS]）引起的出血热样疾病最近在中国被报道。本研究纳入2010年4月至2010年10月在协和医院或中南医院收治的经实验室确诊的HYSV感染患者。收集临床和常规实验室资料，并尽可能采集血液、咽拭子、尿液或粪便。实时逆转录聚合酶链反应定量检测病毒RNA。检测血液中一系列细胞因子、趋化因子和急性期蛋白的水平。共纳入49例HYSV出血热患者；死亡8例（16.3%）。致命的结果与入院时血液中高病毒RNA载量，以及较高的血清肝转氨酶水平，更明显的凝血障碍（活化的部分凝血活酶时间，凝血酶时间），以及较高水平的急性期蛋白（磷脂酶A，纤维蛋白原，hepcidin），细胞因子（白细胞介素[IL]-6， IL-10，干扰素-c）和趋化因子（IL-8，单核细胞趋化蛋白1，巨噬细胞炎症蛋白1b）有关。这些宿主参数的水平与病毒RNA水平相关。血液病毒RNA水平在发病后3-4周内逐渐下降，伴随症状缓解和实验室异常。病毒RNA也可在相当比例患者的喉咙、尿液和粪便样本中检测到，包括所有死亡病例。病毒复制和宿主免疫反应在HYSV感染患者的严重程度和临床结果中起重要作用。
Background. Hemorrhagic fever-like illness caused by a novel Bunyavirus, Huaiyangshan virus (HYSV, also known as Severe Fever with Thrombocytopenia virus [SFTSV] and Fever, Thrombocytopenia and Leukopenia Syndrome [FTLS]), has recently been described in China.Methods. Patients with laboratory-confirmed HYSV infection who were admitted to Union Hospital or Zhongnan Hospital between April 2010 and October 2010 were included in this study. Clinical and routine laboratory data were collected and blood, throat swab, urine, or feces were obtained when possible. Viral RNA was quantified by real-time reverse-transcriptase polymerase chain reaction. Blood levels of a range of cytokines, chemokines, and acute phase proteins were assayed.Results. A total of 49 patients with hemorrhagic fever caused by HYSV were included; 8 (16.3%) patients died. A fatal outcome was associated with high viral RNA load in blood at admission, as well as higher serum liver transaminase levels, more pronounced coagulation disturbances (activated partial thromboplastin time, thrombin time), and higher levels of acute phase proteins (phospholipase A, fibrinogen, hepcidin), cytokines (interleukin [IL]-6, IL-10, interferon-c), and chemokines (IL-8, monocyte chemotactic protein 1, macrophage inflammatory protein 1b). The levels of these host parameters correlated with viral RNA levels. Blood viral RNA levels gradually declined over 3-4 weeks after illness onset, accompanied by resolution of symptoms and laboratory abnormalities. Viral RNA was also detectable in throat, urine, and fecal specimens of a substantial proportion of patients, including all fatal cases assayed.Conclusions. Viral replication and host immune responses play an important role in determining the severity and clinical outcome in patients with infection by HYSV.