Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China

Xue‐jie Yu(Chinese Center For Disease Control and Prevention), Mi-Fang Liang(National Institute for Viral Disease Control and Prevention), Shou-Yin Zhang(National Institute for Communicable Disease Control and Prevention), Yan Liu(Anhui Provincial Center for Disease Control and Prevention), Jiandong Li(National Institute for Viral Disease Control and Prevention), Yu-Lan Sun(National Institute for Viral Disease Control and Prevention), Lihong Zhang(The University of Texas Medical Branch at Galveston), Quan-Fu Zhang(National Institute for Viral Disease Control and Prevention), Vsevolod L. Popov(The University of Texas Medical Branch at Galveston), Chuan Li(National Institute for Viral Disease Control and Prevention), Jing Qu(National Institute for Viral Disease Control and Prevention), Qun Li, Yan-Ping Zhang(Hubei Provincial Women and Children's Hospital), Rong Hai(National Institute for Communicable Disease Control and Prevention), Wei Wu(National Institute for Viral Disease Control and Prevention), Qin Wang(National Institute for Viral Disease Control and Prevention), Fa-Xian Zhan, Wang Xian-jun(Shandong Center for Disease Control and Prevention), Biao Kan(National Institute for Communicable Disease Control and Prevention), Shi-Wen Wang(National Institute for Viral Disease Control and Prevention), Kang-Lin Wan(National Institute for Communicable Disease Control and Prevention), Huai-Qi Jing(National Institute for Communicable Disease Control and Prevention), Jin-Xin Lu(National Institute for Communicable Disease Control and Prevention), Wen-Wu Yin, Hang Zhou, Xu-Hua Guan, Jia-Fa Liu, Zhen-Qiang Bi(Shandong Center for Disease Control and Prevention), Guo-Hua Liu(Henan Provincial Center for Disease Control and Prevention), Jun Ren(Anhui Provincial Center for Disease Control and Prevention), Hua Wang, Zhuo Zhao(Shenyang Center for Disease Control and Prevention), Jing-Dong Song(National Institute for Viral Disease Control and Prevention), Jin-Rong He(National Institute for Communicable Disease Control and Prevention), Wan Tao(National Institute for Viral Disease Control and Prevention), Jing-Shan Zhang, Xiu-Ping Fu(National Institute for Communicable Disease Control and Prevention), Li-Na Sun(National Institute for Viral Disease Control and Prevention), Xiao-Ping Dong, Zi‐Jian Feng, Wei-Zhong Yang, Tao Hong(National Institute for Viral Disease Control and Prevention), Yu Zhang(Hubei Provincial Women and Children's Hospital), David H. Walker(The University of Texas Medical Branch at Galveston), Yu Wang, De-Xin Li(National Institute for Viral Disease Control and Prevention)
New England Journal of Medicine
March 16, 2011
Cited by 1,924Open Access
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Abstract

BACKGROUND: Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing. METHODS: We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples. RESULTS: We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness. CONCLUSIONS: A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).


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