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      Epidemiology, clinical characteristics, and treatment of severe fever with thrombocytopenia syndrome

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          Abstract

          Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by a novel phlebovirus (SFTS virus, SFTSV) in the family Phenuiviridae of the order Bunyavirales. The disease causes a wide spectrum of clinical signs and symptoms, ranging from mild febrile disease accompanied by thrombocytopenia and/or leukocytopenia to hemorrhagic fever, encephalitis, multiple organ failure, and death. SFTS was first identified in China and was subsequently reported in South Korea and Japan. The case-fatality rate ranges from 2.7% to 45.7%. Older age has been consistently shown to be the most important predictor of adverse disease outcomes. Older age exacerbates disease mainly through dysregulation of host immune cells and uncontrolled inflammatory responses. Tick-to-human transmission is the primary route of human infection with SFTSV, and Haemaphysalis longicornis is the primary tick vector of SFTSV. Despite its high case-fatality rate, vaccines and antiviral therapies for SFTS are not currently available. The therapeutic efficacies of several antiviral agents against SFTSV are currently being evaluated. Ribavirin was initially identified as a potential antiviral therapy for SFTS but was subsequently found to inefficiently improve disease outcomes, especially among patients with high viral loads. Favipiravir (T705) decreased both time to clinical improvement and mortality when administered early in patients with low viral loads. Anti-inflammatory agents including corticosteroids have been proposed to play therapeutic roles. However, the efficacy of other therapeutic modalities, such as convalescent plasma, is not yet clear.

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          Fever with thrombocytopenia associated with a novel bunyavirus in China.

          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. 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. 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. 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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            Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

            The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro–endocrine–immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.
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              The First Identification and Retrospective Study of Severe Fever With Thrombocytopenia Syndrome in Japan

              Abstract Background.  Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic in central and northeastern China. This article describes the first identified patient with SFTS and a retrospective study on SFTS in Japan. Methods.  Virologic and pathologic examinations were performed on the patient's samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification and/or the detection of anti-SFTSV immunoglobulin G antibody in sera. Physicians were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS. Results.  A female patient who died in 2012 received a diagnosis of SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged ≥50 years and lived in western Japan. Six cases were fatal. The ratio of males to females was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all of the Japanese SFTSV isolates formed a genotype independent to those from China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis. Conclusions.  SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.
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                Author and article information

                Contributors
                Journal
                Infect Med (Beijing)
                Infect Med (Beijing)
                Infectious Medicine
                Elsevier
                2097-0684
                2772-431X
                01 January 2022
                March 2022
                01 January 2022
                : 1
                : 1
                : 40-49
                Affiliations
                [0001]State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China
                Author notes
                [#]

                These authors have contributed equally to this work.

                Article
                S2772-431X(21)00001-0
                10.1016/j.imj.2021.10.001
                10699716
                38074982
                05866195-880e-4993-9eaa-9bc3bb64472e
                © 2021 The Author(s). Published by Elsevier Ltd on behalf of Tsinghua University Press.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 5 September 2021
                : 25 October 2021
                : 25 October 2021
                Categories
                Review

                sfts,epidemiology,transmission,risk factors,treatment
                sfts, epidemiology, transmission, risk factors, treatment

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