Fever with thrombocytopenia associated with a novel bunyavirus in China

Xue Jie Yu, Mi Fang Liang, Shou Yin Zhang, Yan Liu, Jian Dong Li, Yu Lan Sun, Lihong Zhang, Quan Fu Zhang, Vsevolod Popov, Chuan Li, Jing Qu, Qun Li, Yan Ping Zhang, Rong Hai, Wei Wu, Qin Wang, Fa Xian Zhan, Xian Jun Wang, Biao Kan, Shi Wen Wang & 26 others Kang Lin Wan, Huai Qi Jing, Jin Xin Lu, Wen Wu Yin, Hang Zhou, Xu Hua Guan, Jia Fa Liu, Zhen Qiang Bi, Guo Hua Liu, Jun Ren, Hua Wang, Zhuo Zhao, Jing Dong Song, Jin Rong He, Tao Wan, Jing Shan Zhang, Xiu Ping Fu, Li Na Sun, Xiao Ping Dong, Zi Jian Feng, Wei Zhong Yang, Tao Hong, Yu Zhang, David Walker, Yu Wang, De Xin Li

Research output: Contribution to journalArticle

616 Citations (Scopus)

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-chainreaction 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.)

Original languageEnglish (US)
Pages (from-to)1523-1532
Number of pages10
JournalNew England Journal of Medicine
Volume364
Issue number16
DOIs
StatePublished - Apr 21 2011
Externally publishedYes

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Orthobunyavirus
Thrombocytopenia
China
Fever
Phlebovirus
Viruses
Viral RNA
Bunyaviridae
Anaplasma phagocytophilum
RNA Sequence Analysis
Antibodies
Leukopenia
DNA-Directed RNA Polymerases
Indirect Fluorescent Antibody Technique
Serum
Virion
Nucleic Acids
Communicable Diseases
Electron Microscopy
Cell Culture Techniques

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yu, X. J., Liang, M. F., Zhang, S. Y., Liu, Y., Li, J. D., Sun, Y. L., ... Li, D. X. (2011). Fever with thrombocytopenia associated with a novel bunyavirus in China. New England Journal of Medicine, 364(16), 1523-1532. https://doi.org/10.1056/NEJMoa1010095

Fever with thrombocytopenia associated with a novel bunyavirus in China. / Yu, Xue Jie; Liang, Mi Fang; Zhang, Shou Yin; Liu, Yan; Li, Jian Dong; Sun, Yu Lan; Zhang, Lihong; Zhang, Quan Fu; Popov, Vsevolod; Li, Chuan; Qu, Jing; Li, Qun; Zhang, Yan Ping; Hai, Rong; Wu, Wei; Wang, Qin; Zhan, Fa Xian; Wang, Xian Jun; Kan, Biao; Wang, Shi Wen; Wan, Kang Lin; Jing, Huai Qi; Lu, Jin Xin; Yin, Wen Wu; Zhou, Hang; Guan, Xu Hua; Liu, Jia Fa; Bi, Zhen Qiang; Liu, Guo Hua; Ren, Jun; Wang, Hua; Zhao, Zhuo; Song, Jing Dong; He, Jin Rong; Wan, Tao; Zhang, Jing Shan; Fu, Xiu Ping; Sun, Li Na; Dong, Xiao Ping; Feng, Zi Jian; Yang, Wei Zhong; Hong, Tao; Zhang, Yu; Walker, David; Wang, Yu; Li, De Xin.

In: New England Journal of Medicine, Vol. 364, No. 16, 21.04.2011, p. 1523-1532.

Research output: Contribution to journalArticle

Yu, XJ, Liang, MF, Zhang, SY, Liu, Y, Li, JD, Sun, YL, Zhang, L, Zhang, QF, Popov, V, Li, C, Qu, J, Li, Q, Zhang, YP, Hai, R, Wu, W, Wang, Q, Zhan, FX, Wang, XJ, Kan, B, Wang, SW, Wan, KL, Jing, HQ, Lu, JX, Yin, WW, Zhou, H, Guan, XH, Liu, JF, Bi, ZQ, Liu, GH, Ren, J, Wang, H, Zhao, Z, Song, JD, He, JR, Wan, T, Zhang, JS, Fu, XP, Sun, LN, Dong, XP, Feng, ZJ, Yang, WZ, Hong, T, Zhang, Y, Walker, D, Wang, Y & Li, DX 2011, 'Fever with thrombocytopenia associated with a novel bunyavirus in China', New England Journal of Medicine, vol. 364, no. 16, pp. 1523-1532. https://doi.org/10.1056/NEJMoa1010095
Yu, Xue Jie ; Liang, Mi Fang ; Zhang, Shou Yin ; Liu, Yan ; Li, Jian Dong ; Sun, Yu Lan ; Zhang, Lihong ; Zhang, Quan Fu ; Popov, Vsevolod ; Li, Chuan ; Qu, Jing ; Li, Qun ; Zhang, Yan Ping ; Hai, Rong ; Wu, Wei ; Wang, Qin ; Zhan, Fa Xian ; Wang, Xian Jun ; Kan, Biao ; Wang, Shi Wen ; Wan, Kang Lin ; Jing, Huai Qi ; Lu, Jin Xin ; Yin, Wen Wu ; Zhou, Hang ; Guan, Xu Hua ; Liu, Jia Fa ; Bi, Zhen Qiang ; Liu, Guo Hua ; Ren, Jun ; Wang, Hua ; Zhao, Zhuo ; Song, Jing Dong ; He, Jin Rong ; Wan, Tao ; Zhang, Jing Shan ; Fu, Xiu Ping ; Sun, Li Na ; Dong, Xiao Ping ; Feng, Zi Jian ; Yang, Wei Zhong ; Hong, Tao ; Zhang, Yu ; Walker, David ; Wang, Yu ; Li, De Xin. / Fever with thrombocytopenia associated with a novel bunyavirus in China. In: New England Journal of Medicine. 2011 ; Vol. 364, No. 16. pp. 1523-1532.
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title = "Fever with thrombocytopenia associated with a novel bunyavirus in China",
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-chainreaction 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.)",
author = "Yu, {Xue Jie} and Liang, {Mi Fang} and Zhang, {Shou Yin} and Yan Liu and Li, {Jian Dong} and Sun, {Yu Lan} and Lihong Zhang and Zhang, {Quan Fu} and Vsevolod Popov and Chuan Li and Jing Qu and Qun Li and Zhang, {Yan Ping} and Rong Hai and Wei Wu and Qin Wang and Zhan, {Fa Xian} and Wang, {Xian Jun} and Biao Kan and Wang, {Shi Wen} and Wan, {Kang Lin} and Jing, {Huai Qi} and Lu, {Jin Xin} and Yin, {Wen Wu} and Hang Zhou and Guan, {Xu Hua} and Liu, {Jia Fa} and Bi, {Zhen Qiang} and Liu, {Guo Hua} and Jun Ren and Hua Wang and Zhuo Zhao and Song, {Jing Dong} and He, {Jin Rong} and Tao Wan and Zhang, {Jing Shan} and Fu, {Xiu Ping} and Sun, {Li Na} and Dong, {Xiao Ping} and Feng, {Zi Jian} and Yang, {Wei Zhong} and Tao Hong and Yu Zhang and David Walker and Yu Wang and Li, {De Xin}",
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T1 - Fever with thrombocytopenia associated with a novel bunyavirus in China

AU - Yu, Xue Jie

AU - Liang, Mi Fang

AU - Zhang, Shou Yin

AU - Liu, Yan

AU - Li, Jian Dong

AU - Sun, Yu Lan

AU - Zhang, Lihong

AU - Zhang, Quan Fu

AU - Popov, Vsevolod

AU - Li, Chuan

AU - Qu, Jing

AU - Li, Qun

AU - Zhang, Yan Ping

AU - Hai, Rong

AU - Wu, Wei

AU - Wang, Qin

AU - Zhan, Fa Xian

AU - Wang, Xian Jun

AU - Kan, Biao

AU - Wang, Shi Wen

AU - Wan, Kang Lin

AU - Jing, Huai Qi

AU - Lu, Jin Xin

AU - Yin, Wen Wu

AU - Zhou, Hang

AU - Guan, Xu Hua

AU - Liu, Jia Fa

AU - Bi, Zhen Qiang

AU - Liu, Guo Hua

AU - Ren, Jun

AU - Wang, Hua

AU - Zhao, Zhuo

AU - Song, Jing Dong

AU - He, Jin Rong

AU - Wan, Tao

AU - Zhang, Jing Shan

AU - Fu, Xiu Ping

AU - Sun, Li Na

AU - Dong, Xiao Ping

AU - Feng, Zi Jian

AU - Yang, Wei Zhong

AU - Hong, Tao

AU - Zhang, Yu

AU - Walker, David

AU - Wang, Yu

AU - Li, De Xin

PY - 2011/4/21

Y1 - 2011/4/21

N2 - 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-chainreaction 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.)

AB - 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-chainreaction 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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