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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Fever with thrombocytopenia associated with a novel bunyavirus in China.

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.).

Fever with thrombocytopenia associated with a novel bunyavirus in China

Summary: Hantaviruses are enzootic viruses that maintain persistent infections in their rodent hosts without apparent disease symptoms. The spillover of these viruses to humans can lead to one of two serious illnesses, hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and natural history of these viruses following an increase in the number of outbreaks in the Americas. In this review, current concepts regarding the ecology of and disease associated with these serious human pathogens are presented. Priorities for future research suggest an integration of the ecology and evolution of these and other host-virus ecosystems through modeling and hypothesis-driven research with the risk of emergence, host switching/spillover, and disease transmission to humans.

A Global Perspective on Hantavirus Ecology, Epidemiology, and Disease

Rodents are the most abundant and diversified order of living mammals in the world. Already since the Middle Ages we know that they can contribute to human disease, as black rats were associated with distribution of plague. However, also in modern times rodents form a threat for public health. In this review article a large number of pathogens that are directly or indirectly transmitted by rodents are described. Moreover, a simplified rodent disease model is discussed.

Rodent-borne diseases and their risks for public health

ObjectiveTo develop consensus-based recommendations for measures to be taken
by medical and public health professionals if hemorrhagic fever viruses (HFVs)
are used as biological weapons against a civilian populationParticipantsThe Working Group on Civilian Biodefense included 26 representatives
from academic medical centers, public health, military services, governmental
agencies, and other emergency management institutionsEvidenceMEDLINE was searched from January 1966 to January 2002 Retrieved references,
relevant material published prior to 1966, and additional sources identified
by participants were reviewedConsensus ProcessThree formal drafts of the statement that synthesized information obtained
in the evidence-gathering process were reviewed by the working group Each
draft incorporated comments and judgments of the members All members approved
the final draftConclusionsWeapons disseminating a number of HFVs could cause an outbreak of an
undifferentiated febrile illness 2 to 21 days later, associated with clinical
manifestations that could include rash, hemorrhagic diathesis, and shock
The mode of transmission and clinical course would vary depending on the specific
pathogen Diagnosis may be delayed given clinicians' unfamiliarity with these
diseases, heterogeneous clinical presentation within an infected cohort, and
lack of widely available diagnostic tests Initiation of ribavirin therapy
in the early phases of illness may be useful in treatment of some of these
viruses, although extensive experience is lacking There are no licensed vaccines
to treat the diseases caused by HFVs

https://jamanetwork.com/journals/jama/articlepdf/194908/JST20006.pdf

Hemorrhagic Fever Viruses as Biological Weapons: Medical and Public Health Management

Hantaviruses chronically infect rodents without apparent disease, but when they are spread by aerosolized excreta to humans, two major clinical syndromes result: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Both diseases appear to be immunopathologic, and inflammatory mediators are important in causing the clinical manifestations. In HPS, T cells act on heavily infected pulmonary endothelium, and it is suspected that gamma interferon and tumor necrosis factor are major agents of a reversible increase in vascular permeability that leads to severe, noncardiogenic pulmonary edema. HFRS has prominent systemic manifestations. The retroperitoneum is a major site of vascular leak and the kidneys suffer tubular necrosis. Both syndromes are accompanied by myocardial depression and hypotension or shock. HFRS is primarily a Eurasian disease, whereas HPS appears to be confined to the Americas; these geographic distinctions correlate with the phylogenies of the rodent hosts and the viruses that coevolved with them.

Gary L. Simpson

Papers

Spectrum of hantavirus infection: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome.