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Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-born disease and its animal-to-human transmission has come to attention recently. During our sero-survey of SFTS virus (SFTSV) among veterinary professionals in 2018, a veterinarian and his assistant working in an animal hospital were tested positive by enzyme-linked immunosorbent assay (ELISA). An additional survey implied a cluster of SFTS cases in which four more people, a family who brought two sick dogs to the animal hospital in 2003, were involved. This study aimed at assessing the possibility of animal-to-human transmission of SFTSV in this cluster., Methods: Retrospective interviews were performed with the owner family of the dogs and their clinical records were obtained from each hospital. SFTSV-IgG were tested by ELISA and virus neutralization test using the sera collected from them in 2018., Results: The interviews revealed that a total of six people, the two veterinary professionals and the owner family who took care of the sick dogs, suffered from SFTS-like symptoms in the same period of time in 2003. All patients did not have tick bite before the onset and all suspected causative agents were excluded by laboratory tests. The serological tests in this study revealed the four owner family members were all positive for SFTSV antibodies., Conclusions: Considering the extremely low seroprevalence of SFTSV antibodies among inhabitants of the region, the existence of SFTSV antibodies in all these six people presents a possibility that they were involved in an SFTS outbreak originated in the sick dogs in 2003., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Toscana virus is an arbovirus transmitted by sand flies within the Mediterranean area where it can cause febrile illness and neuroinvasive infections during the seasonal circulation period of the vector. Although it is an important cause of meningitis and encephalitis, it remains a neglected virus with limited published data, as demonstrated by <250 peer-reviewed articles since the 1970s., Objective: The last review article on Toscana virus was published in 2012. The aim was to compile peer-reviewed articles to provide an updated review highlighting recent findings to complement previous review articles., Sources: PubMed database was searched using the 'Toscana virus' keyword from 2010 to present. A total of 152 articles were retrieved and identified studies were assessed for novel information on virus genetics, and geographic and medical aspects compared with existing knowledge reported in previous review articles., Content: Studies addressing medical, veterinary and entomological aspects have provided evidence that Toscana virus is present in North Africa, in the Balkan Peninsula, and in most of the Mediterranean islands. Besides the two previously recognized genetic lineages, a novel evolutionary lineage has been identified in the Balkan Peninsula. Co-circulation of two genetic lineages has been demonstrated in France, in Turkey and in Croatia. In addition to meningitis and meningo-encephalitis, which have been reported for 40 years, various neuroinvasive forms have been recently reported such as Guillain-Barré syndrome, hydrocephalus, myositis, fasciitis, polymyeloradiculopathy, deafness and facial paralysis., Implication: Because it is endemic in countries bordering the Mediterranean, physicians should include Toscana virus in the differential diagnosis of patients presenting with febrile illness and/or neurological manifestations., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a novel bunyavirus. The mechanism underlying disease progression remains unknown, and effective treatment strategy for SFTS is yet to be completely established, making its increasing incidence and subsequent mortality a great concern. Here, we present the autopsy case of a patient with rapidly progressed, fatal SFTS infection. Her viral titer and serum cytokines levels were measured daily and compared with the values of a survivor of the infection. Our findings elucidate the clinical features and pathophysiology of SFTS., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This study reports the etiological identification, clinical diagnosis, and the results of the local epidemiological surveillance of the first case of severe fever with thrombocytopenia syndrome virus (SFTSV) infection in 2014 in Hunan Province, China. The infected patient was isolated and closely monitored. The virus is a member of the Bunyaviridae sandfly family and is characterized by real-time PCR, electron microscopy, immunofluorescence, and whole-genome sequencing. We also detected IgG and IgM antibodies against SFTSV among the local human population and domestic animals in a serological surveillance. Prevalence of SFTSV-specific antibodies was monitored in the local population for two years after the identification of the first SFTS case. Approximately 5% (4/77) of the people who had direct contact with the patient were seropositive, which is significantly higher than the seropositivity of the general local population [1.57% (44/2800), P < 0.05]. Furthermore, the percentage of the general population who were seropositive was higher in 2015 than in 2014 (χ2 = 7.481, P = 0.006). The epidemiological investigation found that the SFTSV is epidemic in goats, cattle, and chickens in Hunan Province. The risk of infection of domestic animals can be minimized by feeding in pens rather than allowing foraging., (Copyright © 2018. Published by Elsevier GmbH.)

We report on a patient with severe fever with thrombocytopenia syndrome who fully recovered. Imaging with 2-deoxy-2-fluoro-glucose positron emission tomography showed hypermetabolism in regional lymph nodes and the spleen. Histopathological findings of affected lymph nodes showed subacute necrotizing lymphadenitis and the presence of virus-infected cells., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Oropouche virus is the aetiological agent of Oropouche fever, a zoonotic disease mainly transmitted by midges of the species Culicoides paraensis. Although the virus was discovered in 1955, more attention has been given recently to both the virus and the disease due to outbreaks of Oropouche fever in different areas of Brazil and Peru. Serological studies in human and wild mammals have also found Oropouche virus in Argentina, Bolivia, Colombia, and Ecuador. Several mammals act as reservoirs of the disease, although the sylvatic cycle of Oropouche virus remains to be assessed properly. Oropouche fever lacks key symptoms to be differentiated from other arboviral febrile illnesses from the Americas. Sporadic cases of aseptic meningitis have also been described with good prognosis. Habitat loss can increase the likelihood of Oropouche virus emergence in the short-term in South America., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to dynamically investigate laboratory parameters and peripheral blood lymphocyte subsets in severe fever with thrombocytopenia syndrome (SFTS) patients at different stages, to evaluate the significance of these changes in the infection process and its influence on prognosis., Methods: Case-control study was used in the research. Sixty-nine confirmed thrombocytopenia syndrome virus(SFTSV) infected patients were enrolled. They were divided into two groups, recovery group and poor prognosis group, according to the clinical prognosis of the diseases. The laboratory parameters were measured by matched fully-automatic detector. The dynamic lymphocyte subsets of each group were tested by flow cytometry. Independent-group Student's t-test, Bonferroni test and Nemenyi test were used to compare the mean value of every group., Results: The clinical manifestations typically became worse on about the 7th day. Most of them had multi organ dysfunction, and part of them had hemophagocytic lymphohistiocytosis histiocytosis (HLH). The characteristic laboratory findings in the early stage were the drop of platelets (PLT), while the increase of alanine aminotransferase (ALT), aspartate amino transferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH). SFTSV viral loads reached the highest on Days 7-10 after onset of fever in SFTS patients. CD3+, CD3+CD4+ T cell counts were significantly reduced in poor prognosis group, more so on Days 7-10 after onset of fever. CD3-CD19+ (B cell) counts in SFTS patients were significantly higher than that of healthy controls. 11 days after illness onset, symptoms were improved, accompanied by resolution of laboratory abnormalities., Conclusions: These results indicated that SFTS had an acute onset and self-limited course. It was a systemic infection. The host immune response caused tissues and organs injury. The improvement of symptoms and laboratory tests was consistent with the elimination of the virus and recover of immune response. Further investigation should be done in order to reveal the mechanisms of SFTSV pathogenesis and guide the clinical treatment., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Korea and Japan caused by a novel bunyavirus, SFTS virus (SFTSV). Although central nervous system manifestations are common in SFTS patients, the pathogenesis has not been elucidated; and there are few reports of myocardial dysfunction. Here we report an elderly Japanese patient with reversible myocardial dysfunction and encephalopathy. A previously healthy 65-year-old male engaged in forestry got a tick bite and developed fever and fatigue in 3 days. Three days after onset, he presented to a local hospital where the diagnosis of SFTS with hemophagocytotic syndrome was made. The blood test showed leukopenia and thrombocytopenia as well as elevated levels of alanine aminotransferase and aspartate aminotransferase. Marked hemophagocytosis was found on bone marrow smear. Peripheral blood was positive for SFTSV gene by reverse-transcription polymerase chain reaction. On day 7, the patient was transferred to our hospital. We observed disturbance of consciousness, Kernig sign and myoclonus to face and limbs. Decreased blood flow of whole cerebral cortex was detected by single photon emission computed tomography (SPECT). Chest X-ray revealed cardiomegaly and electrocardiography (ECG) showed abnormal T waves. These data suggested acute encephalopathy and myocardial dysfunction. We treated him with corticosteroid and blood transfusion, which resulted in the complete recovery of the above abnormal symptoms and laboratory data including the findings in SPECT and ECG in about a month. This case demonstrated transient myocardial dysfunction and encephalopathy can occur in addition to typical clinical manifestation of SFTS., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is a newly discovered emerging infectious disease that has recently become epidemic in Asia. The causative agent of SFTS is a novel phlebovirus in the family Bunyaviridae, designated SFTS virus (SFTSV). SFTS clinically presents with high fever, thrombocytopenia, leukocytopenia, gastrointestinal disorders, and multi-organ dysfunction, with a high viral load and a high case-fatality rate. In human infection, SFTSV targets microphages, replicates in the spleen of infected mice, and causes thrombocytopenia and a cytokine storm. The tick disseminates virus to humans and animals, forming a special transmission model in nature. Person-to-person transmission though direct contact with patient blood has been frequently reported. Measurements of viral RNA and antibodies have been established for diagnosis, but vaccines and specific therapeutics are not available so far., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Two typical symptoms of severe fever with thrombocytopenia syndrome (SFTS) are fever and thrombocytopenia. Here we report a laboratory confirmed SFTS case with no fever during the entire hospitalization period, in Daishan County, Zhejiang Province, China. A 77-year-old woman was admitted to hospital with symptoms including nausea, retching, and anorexia. Laboratory tests revealed thrombocytopenia, leukopenia, and liver and brain damage. The case was later confirmed as a novel bunyavirus infection. Epidemiological investigations revealed that she had no history of tick bites or skin damage, and no known exposure to persons with a similar illness in the area prior to illness onset. The patient was hospitalized for 15 days, and during the whole admission period, she did not experience any fever. The patient recovered and was discharged., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Toscana virus (TOSV) represents a frequent cause of viral meningitis in the Mediterranean Basin that remains neglected in neighbouring countries. We report a documented TOSV meningitis case in a traveller returning from Tuscany to Switzerland. While routine serological and PCR assays could not discriminate between TOSV and Sandfly fever Naples virus infection, a high-throughput sequencing performed directly on the cerebrospinal fluid specimen and analysed with the ezVIR pipeline provided an unequivocal viral diagnostic. TOSV could be unequivocally considered as the aetiological agent, proving the potential of ezVIR to improve standard diagnostics in cases of infection with uncommon or emerging viruses., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

An emerging infectious disease, severe fever with thrombocytopenia syndrome (SFTS), was identified to be associated with a novel SFTS virus (SFTSV). Transmission of the disease among humans has been described, but clinical impact factors and transmission mechanisms still need further study. An outbreak of person-to-person transmission of SFTS in a cluster of nine patients that occurred in an SFTS endemic area, Penglai County, Shandong province, China, was investigated. We found that the onset date of all eight secondary SFTS patients ranged from 7 to 13 days after exposure to the corpse of the index patient, and clinical incubation time was mostly focused on 9-10 days (n = 6). The two dead patients, including the index patient and one secondary infected patient, presented unusually high levels of viral load (6 × 10(8-9) copies/mL), low levels of platelets count (<55 × 10(9)/L), and significant increase of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase values in the second week, and died on day 10 or 11 after disease onset. Genetic sequencing revealed 100% homology among virus strains isolated from the index patient and five secondary patients. Risk factors assessment of the person-to-person transmission revealed that the major exposure factor was blood contact without personal protection equipment. Information from this study provided solid references of SFTS incubation time, clinical and laboratory parameters related to SFTS severity and outcome, and biosafety issues for preventing person-to-person transmission or nosocomial infection of SFTSV., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The wide epidemic and high case fatality rate have made severe fever with thrombocytopenia syndrome (SFTS) a significant public health problem. The diagnosis and discrimination of SFTS virus (SFTSV) infection at an early stage of the disease is important for treatment choice. A prospective study was performed in an SFTS reference hospital during 2011-2013. Suspected SFTS patients were recruited and prospectively observed. Comparison between SFTSV-positive and -negative patients was made to identify the parameters that were related to positive detection by discriminant and classification tree analysis. A total of 538 SFTSV-positive and 396 negative patients were recruited and observed. Multiple logistic regression models demonstrated the significant parameters associated with positive detection, including decreased platelet counts and elevated aspartate aminotransferase (AST) level during the first stage (1∼4 days), decreased white blood cell and platelet counts, elevated creatine kinase (CK) and AST levels during the second stage (5∼7 days), and older age, decreased consciousness and elevated CK and AST during the third stage (8-11 days). The classification trees disclosed that the significant predictors for positive SFTSV detection were AST >50.6 U/L and AST/alanine transaminase (ALT) >1.3 at the first stage, CK >257 U/L or 57.7 U/L < CK ≤98.5 U/L with AST/ALT >1.6 at the second stage, as well as CK >630.7 U/L or 114.3 U/L < CK ≤630.7 U/L with decreased consciousness at the third stage. In making the clinically probable diagnosis of SFTS, the supplementation of AST and CK evaluations might remarkably improve the diagnostic capacity of routine laboratory tests, while the leukopenia is of limited use., (Copyright © 2014. Published by Elsevier Ltd.)

The cases of two patients (a husband and wife) with thrombocytopenia syndrome (SFTS) are reported herein. Both patients had a history of recent tick bite and displayed typical clinical SFTS symptoms including fever, thrombocytopenia, and leukopenia. The diagnosis was laboratory-confirmed by the provincial Center for Disease Control and Prevention (CDC). The husband died while the wife survived. SFTS virus was eventually identified in ticks collected from the couple., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

SFTS virus (SFTSV) is a novel bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease that occurred in China in recent years, with an average case fatality rate of 10-12%. Intervention in the early clinical stage is the most effective measure to reduce the mortality rate of disease. To elucidate the natural course of and immune mechanisms associated with the pathogenesis of SFTSV, 59 laboratory-confirmed SFTS patients in the acute phase, who were hospitalized between October 2010 and September 2011, were enrolled in this study, and the patients sera were dynamically collected and tested for SFTSV viral RNA load, 34 cytokines or chemokines and other related laboratory parameters. All clinical diagnostic factors in the acute phase of SFTS were evaluated and assessed. The study showed that the severity of the disease in 11 (18.6%) patients was associated with abdominal pain (p 0.007; OR = 21.95; 95% CI, 2.32-208.11) and gingival bleeding (p 0.001; OR=122.11; 95% CI, 6.41-2328). The IP-10, TNF-α, IL-6, IL-10, granzyme B and HSP70 levels were higher over the 7-8 days in severe cases, accompanied by altered AST, CK and LDH levels. HSP70 (p 0.012; OR=8.29; 95% CI, 1.58-43.40) was independently correlated with the severity of the early acute phase of SFTSV infection. The severity of SFTS can be predicted based on the presence of symptoms such as abdominal pain and gingival bleeding and on the level of HSP70 in the acute phase of the disease., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Background: Patients have been identified with hemorrhagic fever (HF) caused by Huaiyangshan virus (HYSV) infection since 2009. This study aimed to investigate the characteristics of clinical symptoms, laboratory examinations, epidemiological factors, and therapeutic responses in patients with Huaiyangshan hemorrhagic fever (HYSHF)., Methods: A total of 57 patients with a suspected HF were admitted to the Department of Infectious Diseases, the Affiliated Union Hospital of Tongji Medical College between June 2009 and October 2010. A potential infection with HYSV was determined by indirect immunofluorescent assay and reverse-transcription (RT)-PCR. The clinical symptoms, epidemiological characteristics, laboratory examinations, and therapeutic responses of these patients were evaluated., Results: Forty-eight out of 57 patients were diagnosed with HYSHF. They displayed diverse clinical symptoms, such as an acute febrile flu-like illness, and progressed to proteinuria, hemorrhagic manifestations, and encephalopathy. Some patients exhibited progressive leukopenia, thrombocytopenia, liver and kidney dysfunction, and systemic cell injury. Following symptom-specific treatment, 35 patients recovered completely and 13 patients died from severe complications, including central nervous system manifestations., Conclusions: Patients with HYSHF displayed diverse clinical symptoms and laboratory findings. Such patients should be treated immediately and closely monitored to prevent severe complications., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A large-scale epidemic of Akabane virus (AKAV) encephalomyelitis in cattle aged 4-72 months occurred in the southern part of Korea from late summer to late autumn in 2010. Affected cattle exhibited neurological signs including locomotor ataxia, astasia, tremor and hypersensitivity. Samples of brain (n = 116), spinal cord (n = 116) and whole blood (n = 205) were submitted to the National Veterinary Research and Quarantine Service for diagnosis. Microscopical analysis of the brains and spinal cords revealed the presence of non-suppurative encephalomyelitis in 99 of 116 brains and/or spinal cords (85%). The brains and spinal cords were evaluated by reverse transcriptase polymerase chain reaction and AKAV antigens were detected by immunohistochemistry using rabbit antiserum against AKAV strain OBE-1. Fifteen AKAVs were isolated from the brain and spinal cord samples. Antibodies against AKAV in a virus neutralization test were detected in 188 of 205 serum samples (91.7%). This is the first report of a large-scale outbreak of bovine epidemic encephalomyelitis caused by AKAV infection in Korea., (Copyright © 2012 Elsevier Ltd. All rights reserved.)