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 L. 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 WangKang 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 H. Walker, Yu Wang, De Xin Li

Research output: Contribution to journalArticle

701 Scopus citations

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

ASJC Scopus subject areas

  • Medicine(all)

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    Yu, X. J., Liang, M. F., Zhang, S. Y., Liu, Y., Li, J. D., Sun, Y. L., Zhang, L., Zhang, Q. F., Popov, V. L., Li, C., Qu, J., Li, Q., Zhang, Y. P., Hai, R., Wu, W., Wang, Q., Zhan, F. X., Wang, X. J., Kan, B., ... 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