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-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.)

Genetic characterization of Bhanja virus and Palma virus, two tick-borne phleboviruses

“…In 2009, a severe fever with thrombocytopenia syndrome was described in China and SFTSV was subsequently isolated from blood of patients that had been bitten by ticks [3,27]. Complete genome analysis revealed it to be a Phlebovirus, which was then also detected in the tick Haemaphysalis longicornis [3,27].…”

“…Complete genome analysis revealed it to be a Phlebovirus, which was then also detected in the tick Haemaphysalis longicornis [3,27]. Person-to-Person transmission was described to people caring for infected patients [2,11,19].…”

The Pathogenesis of Severe Fever with Thrombocytopenia Syndrome Virus Infection in Alpha/Beta Interferon Knockout Mice: Insights into the Pathologic Mechanisms of a New Viral Hemorrhagic Fever

“…S evere fever with thrombocytopenia syndrome (SFTS) is a newly recognized viral hemorrhagic fever that has emerged in rural areas of China and more recently in Japan and Korea (1)(2)(3). SFTS is caused by SFTS virus (SFTSV), a new phlebovirus of the family Bunyaviridae.…”

“…The major clinical manifestations and laboratory abnormalities of SFTS are fever, gastrointestinal symptoms, thrombocytopenia, leukopenia, and elevated serum hepatic enzymes. Patients with severe cases of SFTSV hemorrhagic fever usually die of multiorgan failure (1). The disease was first recognized in cases of nosocomial transmission, which were caused by contact with infectious blood of patients (5,6).…”

Antiviral responses of arthropod vectors: an update on recent advances

“…Viruses with RNA genomes have a high mutation rate [31] and can be associated with a broad host range and high zoonotic potential. It is not surprising that highly pathogenic arboviruses such as chikungunya virus (CHIKV) [19,95], severe fever with thrombocytopenia syndrome virus (SFTSV) [132], Heartland virus [79,100] and possibly a new dengue virus (DENV) serotype [90], among others, have emerged or re-emerged over the past decade. CHIKV shows the impact of adaptation to arthropod vectors on arbovirus spread.…”