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Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic disease with a high mortality rate for humans and cats. The clinical course and prognosis of SFTS in dogs remains unclear. In the present study, we investigated the clinical and epidemiological characteristics of SFTS virus (SFTSV) infection in dogs. All evaluated dogs exhibited an acute course and symptoms including fever (57.1%), anorexia (57.1%), depression (42.9%), and vomiting (35.7%). Thrombocytopenia was present in 45.5% of dogs, while jaundice was not observed. C-reactive protein, alanine transaminase, and alkaline phosphatase were elevated in some cases. Viral clearance occurred within 6 to 26 days. Phylogenetic analysis revealed that the SFTSV sequences were consistent with viruses circulating in the Republic of Korea. As dogs often live in close contact with humans, awareness of the clinical and epidemiological features of SFTS in dogs is crucial. Further large-scale studies are necessary to investigate SFTSV infection in dogs.

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that are usually localized in the mesothelium of soft tissues. Although SFTs of pleural origin are common, SFTs arising in the small intestine are extremely rare, and there are few reports of laparoscopic resection of these tumors. A 74-year-old woman presented to her local physician with intermittent pain in the lower abdomen. Computed tomography showed a 25 mm mass in the ileum with extramural protrusion and small intestine capsule endoscopy showed a submucosal tumor-like elevation covered by normal mucosa. The diagnosis was ileal tumor, which was removed by laparoscopic partial resection of the small intestine. Macroscopically, the tumor was found to be a substantial mass within subplasmalemmal fatty tissue that had no continuity with the muscular layer. Histological analysis showed proliferation of homogeneous spindle-shaped cells against a background of fibrous stroma. Immunostaining was positive for STAT6 and negative for KIT, Dog1, and S100, and SFT was diagnosed. The tumor was low risk according to Demicco's risk classification. In conclusion, a less invasive laparoscopic procedure is preferable if the tumor can be resected completely without applying excessive external force that results in seeding of tumor cells in the abdominal cavity.

Seasonal activity of ticks, including disease vectors of fatal severe fever with thrombocytopenia syndrome (SFTS) virus, was monitored using CO

Background The transmission and fatal risk of severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease first discovered in China in 2009, still needed further quantification. This research aimed to analyze the SFTS clusters and assess the transmission and mortality risk for SFTS. Methods Both epidemiological investigation and case reports regarding SFTS clusters in China during 2011–2021 were obtained from the Public Health Emergency Information Management System of the Chinese Center for Disease Control and Prevention Information System. The transmission risk was evaluated by using the secondary attack rate (SAR) and relative risk (RR). Mortality risk factors were analyzed using a logistic regression model. Results There were 35 SFTS clusters during 2011–2021 involving 118 patients with a fatality rate of 22.0%. The number of clusters annually increased seasonally from April to September. The clusters mainly occurred in Anhui (16 clusters) and Shandong provinces (8 clusters). The SAR through contact with blood or bloody fluids was much higher than that through contact with non-bloody fluids (50.6% vs 3.0%; χ2 = 210.97, P RR of 16.61 [95% confidence interval (CI): 10.23–26.97]. There was a statistically significant difference in the SAR between exposure to the blood of a deceased person during burial preparation and exposure to the living patients’ blood (66.7% vs 34.5%; χ2 = 6.40, P RR of 1.93 (95% CI: 1.11–3.37). The mortality risk factors were a long interval from onset to diagnosis [odds ratio (OR) = 1.385), 95% CI: 1.083–1.772, P = 0.009) and advanced age (OR: 1.095, 95% CI: 1.031–1.163, P = 0.01). Conclusions The SFTS clusters showed a high mortality rate and resulted in a high SAR. Contact with a bleeding corpse was associated with a higher infection risk, compared with contacting the blood from living patients. It is important to promote early detection and appropriate case management of patients with SFTS, as well as improved handling of their corpses, to prevent further transmission and mortality. Graphical abstract

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne phlebovirus with a high fatality rate of 12–30%, which has an expanding endemic and caused thousands of infections every year. Central nervous system (CNS) manifestations are an important risk factor of SFTS outcome death. Further understanding of the process of how SFTSV invades the brain is critical for developing effective anti-SFTS encephalitis therapeutics. We obeserved changes of viral load in the brain at different time points after intraperitoneal infection of SFTSV in newborn C57/BL6 mice. The virus invaded the brain at 3 h post-infection (hpi). Notably, the viral load increased exponentially after 24 hpi. In addition, it was found that in addition to macrophages, SFTSV infected neurons and replicated in the brain. These findings provide insights into the CNS manifestations of severe SFTS, which may lead to drug development and encephalitis therapeutics.

Background Severe fever with thrombocytopenia syndrome (SFTS), one kind of tick-borne acute infectious disease, is caused by a novel bunyavirus. The relationship between meteorological factors and infectious diseases is a hot topic of current research. Liaoning Province has reported a high incidence of SFTS in recent years. However, the epidemiological characteristics of SFTS and its relationship with meteorological factors in the province remain largely unexplored. Methods Data on reported SFTS cases were collected from 2011 to 2019. Epidemiological characteristics of SFTS were analyzed. Spearman’s correlation test and generalized linear models (GLM) were used to identify the relationship between meteorological factors and the number of SFTS cases. Results From 2011 to 2019, the incidence showed an overall upward trend in Liaoning Province, with the highest incidence in 2019 (0.35/100,000). The incidence was slightly higher in males (55.9%, 438/783), and there were more SFTS patients in the 60–69 age group (31.29%, 245/783). Dalian City and Dandong City had the largest number of cases of SFTS (87.99%, 689/783). The median duration from the date of illness onset to the date of diagnosis was 8 days [interquartile range (IQR): 4–13 days]. Spearman correlation analysis and GLM showed that the number of SFTS cases was positively correlated with monthly average rainfall (rs = 0.750, P β = 0.285, P rs = 0.683, P β = 0.096, P rs = 0.822, P β = 0.154, P rs = 0.810, P β = 0.134, P rs = −0.728, P β = −0.145, P rs = −0.272, P β = −1.048, P Conclusion The annual incidence of SFTS increased year on year in Liaoning Province. Incidence of SFTS was affected by several meteorological factors, including monthly average air pressure, monthly average temperature, and monthly average wind speed. Graphical Abstract

Background Hemangiopericytomas (HPCs) are uncommon soft tissue tumors. HPCs that grow in the cranial base are rare. Therefore, skull-base surgeons tend to overlook this disease. This study aimed to increase the awareness of HPCs by summarizing case data from our institution and related publications. We also aimed to contribute to the number of reported cases for future systematic reviews of HPCs. Methods This study included all patients who underwent surgery for HPC/solitary fibrous tumor (SFT) between August 2015 and August 2019. All surgeries were performed at Xiangya Hospital Central South University. We analyzed clinical characteristics, surgical highlights, treatment modalities, and outcomes. Results We included six patients, aged 32–64 years. Lesions were located in the parapharyngeal space in three patients, pterygopalatine fossa in two, and saddle area in one. All patients underwent nasal endoscopic endonasal surgery. In five patients, tumors involved the internal carotid artery (ICA). The exposure and protection of the ICA during surgery are challenging but critical to complete tumor removal. The 3-year overall survival(OS) rate was 66.7%. Conclusions HPC/SFTs are rare tumors of the cranial base that are prone to recurrence. Cranial base HPC/SFTs are often closely associated with the ICA. To our knowledge, this case series reports the largest number of cases of HPCs associated with the ICA. We believe that there is a strong relationship between patient prognosis and whether the tumor encircles the ICA and whether the tumor is completely resected. To confirm this suggestion, more cases are needed for further analysis.

An emerging infectious disease first identified in central China in 2009, severe fever with thrombocytopenia syndrome (SFTS) was found to be caused by a novel phlebovirus. Since SFTSV was first identified, epidemics have occurred in several East Asian countries. With the escalating incidence of SFTS and the rapid, worldwide spread of SFTSV vector, it is clear this virus has pandemic potential and presents an impending global public health threat. In this review, we concisely summarize the latest findings regarding SFTSV, including vector and virus transmission, genotype diversity and epidemiology, probable pathogenic mechanism, and clinical presentation of human SFTS. Ticks most likely transmit SFTSV to animals including humans; however, human-to-human transmission has been reported. The majority of arbovirus transmission cycle includes vertebrate hosts, and potential reservoirs include a variety of both domestic and wild animals. Reports of the seroprevalence of SFTSV in both wild and domestic animals raises the probability that domestic animals act as amplifying hosts for the virus. Major clinical manifestation of human SFTS infection is high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and a high case-fatality rate. Several animal models were developed to further understand the pathogenesis of the virus and aid in the discovery of therapeutics and preventive measures., Virology: An emerging tick-borne disease Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne infectious disease caused by a novel phlebovirus, is a growing global health concern. The main symptoms are high fever, low platelet and white blood cell levels, and gastrointestinal problems. The disease was first identified in China in 2009, and several SFTS epidemics have occurred in East Asia, with mortality rates of between 6 and 27 per cent. Researchers in South Korea led by Young Ki Choi at Chungbuk National University, Cheongju, review the latest research into SFTS virus and disease, including transmission, genetic diversity, epidemiology, pathology and clinical features, and pandemic potential. Animal models are helping researchers understand the virus and disease and develop treatments and vaccines.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the SFTS virus (SFTSV) of family Phenuiviridae. Since the virus was first identified in 2009, it has been rapidly spread in many Asian countries including Myanmar, Korea, Japan, and central China. In this study, we investigated the epidemiological characteristics of SFTS patients in Hefei from 2011 to 2018. In addition, we conducted a serological survey of SFTSV-specific antibody among healthy residents of five counties. We performed a retrospective observational study of SFTS cases reported to Hefei Center for Disease Control and Prevention (CDC) during Jan 2011 to Dec 2018. Almost every patient completed a structure questionnaire including clinical examination, course of disease, and history of epidemiology. A total of 754 serum specimens were collected and tested for IgG antibody with double-antigen sandwich ELISA method. Of 257 cases reported during that period, 33 died, with a case fatality rate of 13.0%. We found no significant difference between 30 non-survivors and 198 survivors except for age. The overall rate of seropositivity for SFTSV antibodies among healthy residents were 20.16%. We demonstrated that living in hilly areas, direct contact with domestic livestock and knowledge of tick-borne disease were significantly associated with positive serology result. SFTSV infection was prevalent among farming-related populations. Our study identified a relatively high seroprevalence of SFTSV-specific antibody in healthy residents, which provided the basis for asymptomatic SFTSV infections. More attention should be given to susceptible population and prevent SFTSV outbreak in high-endemic areas.

Severe fever with thrombocytopenia syndrome (SFTS) is being reported annually in South Korea since its first detection there in 2010. The causal agent is a negative-strand RNA virus 80–100 nm in diameter. It causes fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and neural symptoms. The mortality rate of SFTS was 32.6% among 172 cases reported from 2012 to 2015 in South Korea. Thus, is necessary to develop an effective diagnostic method that selectively identifies the isolates circulating in South Korea. The real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay is a simple, rapid, and sensitive approach for molecular diagnosis. Here, we designed novel primers for this assay and found that the technique had very high specificity, sensitivity, and efficiency. This real-time RT-LAMP approach using the novel primers developed herein can be applied for early diagnosis of SFTSV strains in South Korea to reduce the mortality rate of SFTS.

Encephalitis is an infrequent manifestation in the various spectrums caused by severe fever with thrombocytopenia syndrome virus (SFTSV) infection. There are few data about the possible pathogenic mechanisms of SFTSV-associated encephalitis. Here, two SFTSV-infected patients with onset of encephalitis were enrolled. The whole genome of two SFTSV strains isolated from cerebrospinal fluid (CSF) was deeply sequenced by next-generation sequencing (NGS) and phylogenetic analysis was conducted. The specific mutations of M fragment were P98L and T665S respectively. The three-dimensional structure of glycoprotein Gn which was encoded by M fragment, an important virulence factor of SFTSV, was constructed by SWISS-MODEL. There was no significant variation in glycoprotein Gn of the two isolates comparing to other strains without encephalitis. Phylogenetic trees based on the complete sequences of M segment showed the two strains were highly identical to other local strains without encephalitis. Our study demonstrates that the virulence factors of SFTSV with encephalitis are not different from those without encephalitis. SFTSV itself is a neurotropic virus.

Background Severe fever and thrombocytopenia syndrome (SFTS) is an acute illness with a high mortality (16.2–29.1%). Unfortunately, there is no specific cure or vaccine for SFTS. Methods In this open-label study, two patients with SFTS were treated with favipiravir, a new antiviral drug. Results Patients had a sustainable virologic, immunologic and symptomatic recovery. Conclusions Favipiravir may be a prosiming drug for the treatment of SFTS. Electronic supplementary material The online version of this article (10.1007/s15010-019-01364-9) contains supplementary material, which is available to authorized users.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease in China, Japan, and Korea. This study aimed to estimate the monthly SFTS occurrence and the monthly number of SFTS cases in the geographical area in Korea using epidemiological data including demographic, geographic, and meteorological factors. Important features were chosen through univariate feature selection. Two models using machine learning methods were analyzed: the classification model in machine learning (CMML) and regression model in machine learning (RMML). We developed a novel model incorporating the CMML results into RMML, defined as modified-RMML. Feature importance was computed to assess the contribution of estimating the number of SFTS cases using modified-RMML. Aspect to the accuracy of the novel model, the performance of modified-RMML was improved by reducing the MSE for the test data as 12.6–52.2%, compared to the RMML using five machine learning methods. During the period of increasing the SFTS cases from May to October, the modified-RMML could give more accurate estimation. Computing the feature importance, it is clearly observed that climate factors such as average maximum temperature, precipitation as well as mountain visitors, and the estimation of SFTS occurrence obtained from CMML had high Gini importance. The novel model incorporating CMML and RMML models improves the accuracy of the estimation of SFTS cases. Using the model, climate factors, including temperature, relative humidity, and mountain visitors play important roles in transmitting SFTS in Korea. Our findings highlighted that the guidelines for mountain visitors to prevent SFTS transmissions should be addressed. Moreover, it provides important insights for establishing control interventions that predict early identification of SFTS cases.

Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic disease caused by the SFTS virus (SFTSV). SFTS can be considered a life-threatening notifiable infectious disease. The unavailability of specific therapeutics encourages the investigation of potential efficacy of existing drugs against this infection. Drug repurposing was done by performing virtual screening of already established drug molecules followed by 100 ns molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area–based binding-energy calculation by targeting the SFTS L protein. On the basis of binding energy and protein–ligand interactions, top 10 promising hits were identified, showing stable binding with SFTS L protein. Further 100 ns atomistic MD simulation refined the hits from top 10 to top 4 with docking-based binding energy lesser than −8.0 kcal/mol toward the SFTS L protein and engaged in π–π interactions with pivotal amino acid residues. Various parameters and binding affinity of top 4 ligands towards L protein was computed. Ligand zaltoprofen exhibited best binding energy −220.095 kJ/mol. The present work is the first in silico study to assess bromfenac, cinchophen, elliptinium, and zaltoprofen; four promising hits against SFTS. Nonetheless, further proper biological evaluation is necessary to determine their efficacy against SFTS.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease caused by a new type of SFTS virus (SFTSV). Here, a longitudinal sampling study is conducted to explore the differences in transcript levels after SFTSV infection, and to characterize the transcriptomic and epigenetic profiles of hospitalized patients. The results reveal significant changes in the mRNA expression of certain genes from onset to recovery. Moreover, m6A-seq reveals that certain genes related with immune regulation may be regulated by m6A. Besides the routine tests such as platelet counts, serum ALT and AST levels testing, distinct changes in myocardial enzymes, coagulation function, and inflammation are well correlated with the clinical data and sequencing data, suggesting that clinical practitioners should monitor the above indicators to track disease progression and guide personalized treatment. In this study, the transcript changes and RNA modification may lend a fresh perspective to our understanding of the SFTSV and play a significant role in the discovery of drugs for effective treatment of this disease., Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by tick-borne SFTS virus. Here, Wang et al. characterize transcriptomic and epigenetic changes in infected patients and correlate them with clinical parameters to improve the understanding of disease progression.

Background We report a mononucleosis-like illnesses case due to co-infection with severe fever with thrombocytopenia syndrome virus (SFTSV) and spotted fever group rickettsia (SFGR), which to the best of our knowledge, has never been reported . Case presentation A 64-year-old male with an 11-day history of fever, sore throat, malaise, nausea, and non-pruritic rash was admitted to our emergency department. Prior to admission, he was bitten by ticks. Laboratory tests revealed a white blood cell count of 24,460 cells/μL with 25% atypical lymphocytes and 20% mononucleosis, thrombocytopenia. Test results were positive for SFTSV RNA, SFTSV-specific IgM antibody, and SFGR-specific IgM antibody. He was diagnosed with mononucleosis-like illnesses due to co-infection with SFTSV and SFGR. After administration of doxycycline, he recovered completely. Conclusions The clinical presentation may be atypical in co-infection with SFTSV and SFGR. This finding highlighted the importance of considering SFGR infection, as well as a SFSTV and SFGR co-infection for the differential diagnosis of patients bitten by ticks in SFTSV-endemic areas.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne emerging infectious disease caused by the SFTS virus (SFTSV) and is a threat to public health due to its high fatality rate. However, details on tick-to-human transmission of SFTSV are limited. In this study, we determined the whole-genome sequence of a South Korean SFTSV strain (CUK-JJ01), compared it to those of other recent human SFTSV isolates, and identified the genetic variations and relationships among the SFTSV strains. The genome of CUK-JJ01 was consistent with the genome of other members of the genus Phlebovirus, including the large (L), medium (M), and small (S) segments of 6368, 3378, and 1744 nucleotides, respectively. Based on amino acid sequences of the M and S segments, which are used to distinguish the six SFTSV genotypes, CUK-JJ01 was classified as genotype B. Segment analysis revealed that the L, M, and S segments were 97.49%, 97.18%, and 97.94% similar to those of KAJNH2/2013/Korea, ZJZHSH-FDE/2012/China, and KADGH/2013/Korea, respectively. Currently, only few studies on SFTSV have been conducted in Korean population and most were limited to serological analysis. Although the present study has limitations in terms of number of sample analyzed, the findings may serve as basis to understand the transmission and spread of SFTSV, as well as for the development of diagnostic and detection methods for viral recombinants by comparing the whole genome sequence of SFTSV isolates from South Korea and that of foreign isolates.

Ticks are the most important vectors of human diseases after mosquitoes. Emergency physicians throughout the USA can be expected to encounter Lyme disease, Rocky Mountain spotted fever, ehrlichiosis, and other disorders based upon geographic location. The number of identifiable disorders transmitted by these arthropods has increased in recent years. Severe fever with thrombocytopenia syndrome has only been described within the past decade, and the new millennium has seen over 10 new species of rickettsial disease discovered. Ticks transmit more pathogenic species than any other group of blood-feeding arthropods. This review provides an update on the diagnosis and management of the diseases most likely to be encountered in clinical practice.

Many pathogens causing hemorrhagic fevers of medical and veterinary importance have been identified and isolated from rodents in the Republic of Korea (ROK). We investigated the occurrence of emerging viruses causing hemorrhagic fevers, such as hemorrhagic fever with renal syndrome (HFRS), severe fever with thrombocytopenia syndrome (SFTS), and flaviviruses, from wild rodents. Striped field mice, Apodemus agrarius (n = 39), were captured during 2014–2015 in the south-west of ROK. Using molecular methods, lung samples were evaluated for SFTS virus, hantavirus, and flavivirus, and seropositivity was evaluated in the blood. A high positive rate of hantavirus (46.2%) was detected in A. agrarius lungs by reverse transcription-nested polymerase chain reaction (RT-N-PCR). The monthly occurrence of hantavirus was 16.7% in October, 86.7% in November, and 25% in August of the following year (p

Background Severe fever thrombocytopenia syndrome virus (SFTSV) is the causative agent of severe fever thrombocytopenia syndrome (SFTS). SFTS is an emerging infectious disease, characterized by high fever, gastrointestinal symptoms, leukopenia, thrombocytopenia, and a high mortality rate. Until now, little importance has been given to the association of SFTS with leukocytosis and bacterial co-infection. Case presentation A 51-year old man visited our hospital with fever and low blood pressure. He was a farmer by occupation and often worked outdoors. He had a Foley catheter inserted due to severe BPH. Laboratory tests revealed thrombocytopenia, elevated liver function, and elevated CRP levels. He had marked leukocytosis, proteinuria, hematuria, and conjunctival hemorrhage. Initially, we thought that the patient was suffering from hemorrhagic fever with renal syndrome (HFRS). However, we confirmed SFTS through PCR and increasing antibody titer. However, his blood culture also indicated E. coli infection. Conclusion SFTS displays characteristics of fever, thrombocytopenia, elevated liver function, and leukocytopenia. We described a case of SFTS with leukocytosis due to coinfection with E. coli. Since patients with SFTS usually have leukocytopenia, SFTS patients with leukocytosis are necessarily evaluated for other causes of leukocytosis. Here, we report the first case of an SFTS with concurrent E. coli bacteremia.

Background At present, viral diseases become major concern for the world. SARS-CoV2 and SFTS viruses are deadly in nature, and there is a need for developing best treatments for them. Modern in silico approaches were found to be very handy in determining putative drug molecules. In this study, we analyze interaction of beta-sesquiphellandrene (compound belongs to ginger) with spike protein (Sp) and membrane glycoprotein polyprotein (MPp). Results Our molecular docking and simulation study reveals the perfect binding pocket of Sp and MPp holding beta-sesquiphellandrene (bS). Binding energies for MPp-bS and Sp-bS were found to be − 9.5 kcal/mol and − 10.3 kcal/mol respectively. RMSD and RMSF values for docked complexes were found to be in selectable range, i.e., 1 to 3 Å and 1 to 8 Å respectively. Modern computational tools were used here to make this investigation fast and effective. Further, ADME analysis reveals the therapeutic validations for beta-sesquiphellandrene to act as a useful pharmacoactive compound. Beta-sesquiphellandrene provides not only inhibitory effect on spike protein of SARS-CoV2 but also similar inhibitory effects on membrane glycoprotein polyprotein complex of SFTS virus, which hampers the pathological initiation of the diseases caused by both the viruses, i.e., COVID-19 and severe fever with thrombocytopenia syndrome. Conclusion This method of computational analysis was found to be rapid and effective, and opens new doors in the domain of in silico drug discovery. Beta-sesquiphellandrene can be used as effective medicine to control these harmful pathogens after wet lab validations.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease, which causes high fever, thrombocytopenia, and death in humans and animals in East Asian countries. The pathogenicity of SFTS virus (SFTSV) remains unclear. We intraperitoneally infected three groups of mice: wild-type (WT), mice treated with blocking anti-type I interferon (IFN)-α receptor antibody (IFNAR Ab), and IFNAR knockout (IFNAR−/−) mice, with four doses of SFTSV (KH1, 5 × 105 to 5 × 102 FAID50). The WT mice survived all SFTSV infective doses. The IFNAR Ab mice died within 7 days post-infection (dpi) with all doses of SFTSV except that the mice were infected with 5 × 102 FAID50 SFTSV. The IFNAR−/− mice died after infection with all doses of SFTSV within four dpi. No SFTSV infection caused hyperthermia in any mice, whereas all the dead mice showed hypothermia and weight loss. In the WT mice, SFTSV RNA was detected in the eyes, oral swabs, urine, and feces at 5 dpi. Similar patterns were observed in the IFNAR Ab and IFNAR−/− mice after 3 dpi, but not in feces. The IFNAR Ab mice showed viral shedding until 7 dpi. The SFTSV RNA loads were higher in organs of the IFNAR−/− mice compared to the other groups. Histopathologically, coagulation necrosis and mononuclear inflammatory cell infiltration in the liver and white pulp atrophy in the spleen were seen as the main lesions in the IFN signaling lacking mice. Immunohistochemically, SFTSV antigens were mainly detected in the marginal zone of the white pulp of the spleen in all groups of mice, but more viral antigens were observed in the spleen of the IFNAR−/− mice. Collectively, the IFN signaling-deficient mice were highly susceptible to SFTSV and more viral burden could be demonstrated in various excreta and organs of the mice when IFN signaling was inhibited.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that commonly has a lethal course caused by the tick-borne Huaiyangshan banyang virus [former SFTS virus (SFTSV)]. The viral load in various body fluids in SFTS patients and the best infection control measure for SFTS patients have not been fully established. CASE PRESENTATION: A 79-year-old man was bitten by a tick while working in the bamboo grove in Nagasaki Prefecture in the southwest part of Japan. Due to the occurrence of impaired consciousness, he was referred to Nagasaki University Hospital for treatment. The serum sample tested positive for SFTSV-RNA in the genome amplification assay, and he was diagnosed with SFTS. Furthermore, SFTSV-RNA was detected from the tick that had bitten the patient. He was treated with multimodal therapy, including platelet transfusion, antimicrobials, antifungals, steroids, and continuous hemodiafiltration. His respiration was assisted with mechanical ventilation. On day 5, taking the day on which he was hospitalized as day 0, serum SFTSV-RNA levels reached a peak and then decreased. However, the cerebrospinal fluid collected on day 13 was positive for SFTSV-RNA. In addition, although serum SFTSV-RNA levels decreased below the detectable level on day 16, he was diagnosed with pneumonia with computed tomography. SFTSV-RNA was detected in the bronchoalveolar lavage fluid on day 21. By day 31, he recovered consciousness completely. The pneumonia improved by day 51, but SFTSV-RNA in the sputum remained positive for approximately 4 months after disease onset. Strict countermeasures against droplet/contact infection were continuously conducted. CONCLUSIONS: Even when SFTSV genome levels become undetectable in the serum of SFTS patients in the convalescent phase, the virus genome remains in body fluids and tissues. It may be possible that body fluids such as respiratory excretions become a source of infection to others; thus, careful infection control management is needed., BMC infectious diseases, 20(1), art.no.281; 2020

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV). Hubei Province is a major epidemic area for SFTS in China. In this study, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and serological testing (IgM) were used simultaneously for laboratory detection of SFTS; however, testing results showed poor consistency between these two methods. Further analysis revealed that time post-onset was the main factor leading to inconsistent results. Thus, qRT-PCR is unable to detect all SFTS cases, and serological testing is essential. Here, 15 strains of SFTSV were successfully isolated from serum samples of acute SFTSV infection and their complete genomes were sequenced and submitted to GenBank. Phylogenetic analysis showed that the 15 SFTS virus strains clustered into four independent genotypes (A, B, D, and E), demonstrating that at least four genotypes of SFTSV have been co-circulating in Hubei Province. Furthermore, four strains of our isolates (HB2014-31, HB2014-35, HB2014-36, and HB2014-37) clustered in genotype E, which was the predominant genotype in Japan and South Korea. In this study, we identified multiple co-prevalent genotypes and confirmed the existence of genotype E viruses circulating in the Dabie Mountains of Hubei, central China. We concluded that SFTSV strains from Hubei exhibit most of the genetic diversity found in China.

Background Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection that has recently emerged. This infectious disease is due to the transfer of SFTS virus (SFTSV) from the infected blood of animals to humans. Approximately 30% of patients who are infected with SFTS die from multiorgan failure associated with severe infection, systemic inflammatory response syndrome, or disseminated intravascular coagulation. We treated an elderly Japanese couple (husband and wife) who had genetically identical SFTSV infections and who both developed severe rhabdomyolysis. Case presentation An 80-year-old man presented to the clinic with a fever; his 74-year-old wife presented with a fever 9 days later. Their laboratory results at diagnosis showed severe rhabdomyolysis with significantly elevated creatinine kinase (detected levels: husband, 9546 U/L; wife, 15,933 U/L). The creatinine kinase isozyme was 100% MM type in both patients. In both the husband and wife, SFTSV was identified with real-time polymerase chain reaction analysis. The detected SFTSVs in both the husband and wife were identical according to the genome sequence analysis. The husband’s bone marrow indicated macrophage activation syndrome, but he responded to supportive therapy. He was discharged after being hospitalized for 32 days. The wife was admitted to our hospital in critical condition 2 days after SFTS symptom onset. She died of multiorgan failure 8 days after onset, despite being cared for in an intensive care unit. Both of the patients presented with rhabdomyolysis following SFTS symptom onset. The patients’ clinical outcomes were different from each other; i.e., the husband survived, and the wife died. Conclusions SFTSV infection-associated rhabdomyolysis has been reported in one patient, and simultaneous onset in two related patients has not been described previously. Our findings suggest that similar biological responses occurred, but they resulted in different clinical outcomes in the patients infected by the identical SFTSV isolates. Notably, a patient’s clinical outcome depends on their own immune response. We suggest that one component of viral rhabdomyolysis involves immune-mediated responses. Severe immunological responses may adversely affect the treatment outcome, as demonstrated by the wife’s clinical course. Our findings demonstrate that a patient’s immune response contributes to their prognosis following SFTSV infection.

A growing number of bunyaviruses are known to cause viral hemorrhagic fever (VHF), a severe febrile illness which can progress to hypovolemic shock and multi-organ failure and is characterized by hematologic abnormalities and vascular leak. At present, there are no approved vaccines or antiviral therapies to effectively prevent or treat VHF caused by pathogenic bunyaviruses. Advances in the modeling of bunyaviral infections have facilitated efforts towards the development of novel post-exposure prophylactic and therapeutic countermeasures, several of which may some day be approved for human use. Here, we review recent progress in animal models of severe bunyaviral infections essential to this mission, as well as promising antivirals and biologicals that are at various stages of the development process.

Background Severe fever with thrombocytopenia syndrome (SFTS) is a novel emerging viral infectious disease. We explored the percentage, origins and functional roles of low density neutrophils (LDNs), one of the neutrophils subsets, in SFTS. Methods The LDNs and normal density neutrophils (NDNs) from blood of SFTS and normal volunteers which were collected separately. The percentage, origins and the phagocytic capability of SFTS viral (SFTSV) of LDNs were investigated by flow cytometry and real time PCR. The capacity of LDNs to secrete cytokines and to damage endothelial cells was assessed by ELISA and flow cytometry. Results We observed that the proportion of LDNs increased dramatically compared with the healthy donors and became the dominant circulating neutrophil population in SFTS patients. Interestingly, the NDNs from the normal donors could switch to LDNs under the SFTS environment. Moreover, SFTSV load in LDNs was significantly higher than that of NDNs in the severe SFTS patients. In addition, the LDNs secreted much higher levels of pro-inflammatory cytokines than NDNs in SFTS and could induce endothelial cell injury. Conclusion The NDNs can be converted to LDNs. This conversion mechanism could become the source of LDNs. The LDNs in severe SFTS patient could engulf more SFTSV and exhibit pro-inflammation functions. Trial registration The Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (IORG No: IORG0003571) gave a final APPROVAL for the study.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV). Although SFTS originated in China, it is an emerging infectious disease with prevalence confirmed in Japan, Korea, and Vietnam. The full-length genomes of 51 Korean SFTSV isolates from 2013 to 2016 were sequenced, and the sequences were deposited into a public database (GenBank) and analyzed to elucidate the phylogeny and evolution of the virus. Although most of the Korean SFTSV isolates were closely related to previously reported Japanese isolates, some were closely related to previously reported Chinese isolates. We identified one Korean strain that appears to have resulted from multiple inter-lineage reassortments. Several nucleotide and amino acid variations specific to the Korean isolates were identified. Future studies should focus on how these variations affect virus pathogenicity and evolution.

s Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS bunyavirus (SFTSV), a tick borne bunyavirus. However, Immunohistochemistry of SFTS patients are not well studied. Methods We obtained multiple of tissues from a fatal case with SFTS, including blood, lungs, kidneys, heart, and spleen. The blood samples were used to isolate the causative agent for detection of viral RNA and further expression of recombinant viral protein as primary antibody. Immunohistochemistry of the heart, lungs, spleen and kidneys was used to characterize the viral antigen in tissue sections. Results A 79-year-old man, together with his wife, was admitted because of fever. Both patients were diagnosed with SFTS by the positive SFTSV RNA in the blood. The gentleman died of multiple organ failure 8 days after hospitalization. However, his wife recovered and was discharged. Immunohistochemistry indicated that SFTSV antigens were present in all studied organs including the heart, kidney, lung and spleen, of which the spleen presented with the highest amount of SFTSV antigens. The kidney was next while the heart and lungs showed lower amount of SFTSV antigens. Conclusions SFTSV can direct infect multiple organs, resulting in multiple organ failure and ultimately in an unfavorable outcome. Electronic supplementary material The online version of this article (10.1186/s12985-018-1006-7) contains supplementary material, which is available to authorized users.

Severe fever with thrombocytopenia syndrome (SFTS) as an emerging infection disease results in high morbidity and mortality in China. In this study, the circulating levels of 36 inflammatory mediators in 33 SFTS patients on days 3–7, 8–12 and 13–20 post-illness were measured by a multiplex Luminex® system dynamically. Among the patients, 15 severe patients recovered, 11 severe patients died within three weeks. We found IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, eotaxin, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β and fractalkine were significantly upregulated in SFTS patients. Elevated IL-15 and eotaxin in SFTS patients were reported firstly. The highest levels of pro-inflammatory and anti-inflammatory cytokines coexisted in fatal patients during the first week. Inflammatory mediators remained high levels when death occurred in fatal patients, they were recovered within three weeks in nonfatal patients. Our results showed the occurrence of inflammatory storm in SFTS patients were associated with the severity of SFTS. RANTES and PDGF were down regulated and remained significantly lower levels in fatal patients throughout the course of disease, the concentrations of RANTES and PDGF were remarkably positively correlated with the platelet count. Our results demonstrated that dysregulated inflammatory response was associated with disease pathogenesis and mortality in SFTS patients.

Severe fever with thrombocytopenia syndrome (SFTS) is emerging and the number of SFTS cases increased year by year in China. In order to explore the epidemiology trend, we analyzed the changing epidemiological characteristics of SFTS cases in different years and compare characteristics in different provinces. From 2011 to 2016, a total of 5360 laboratory-confirmed SFTS cases were reported and annual case numbers increased year by year. Most SFTS cases occurred in individuals aged between 40 years and 80 years (91.57%), but age distributions of SFTS cases in different years were significantly different and the median ages increased slightly year by year. The numbers of affected counties from 2011 to 2016 increased sharply from 98 to 167. Of note, the seasonal distributions of SFTS cases in different provinces were significantly different (Fisher = 712.157, P = 0.000) and provinces in south regions showed earlier epidemic peak and longer epidemics durations. The median time from illness onset to confirmation of different years was significantly different (χ2 = 896.088, P = 0.000) and it peaked in 2014. Furthermore, case fatality rate was associated with province, year, and age of SFTS cases. These results may be helpful for authorities to better preventive strategy and improve interventions against SFTS.

Background Severe fever with thrombocytopenia syndrome (SFTS) was first reported in China in 2011. Human-to-human transmission of the virus occurred occasionally in family clusters. However, pneumonia as an onset syndrome was not common in most SFTS cases. Our aim is to report a family cluster of SFTS with clinical manifestation of pneumonia in Shanghai. Methods Epidemiologic investigations were conducted when a family cluster of severe fever with thrombocytopenia syndrome virus (SFTSV) infection was identified in Shanghai in June 2016. Samples were collected from two secondary cases and two close contacts with fever. SFTSV was detected by Real-Time reverse transcription polymerase chain reaction (RT-PCR). Results There were two confirmed STFS cases and one potential index case. The potential index case became ill on 21 May and died on 31 May. Case A had onset from 4 to 23 June and case B from 8 June to 25 June. All the three cases experienced pneumonia at the early stage of SFTSV infection. Three (3) out of thirty two (32) close contacts had symptoms of fever or cough but were detected STFSV negative by real-time RT-PCR. According to epidemiologic investigations, the potential index case had outdoor activities on a nearby hill. A tick bite could have been the reason for the SFTSV infection in the potential index case as ticks were found both in grassland or shrubs on the hill and also found on mice caught in her house. Both cases A and B had provided bedside care for the potential index case without any protection and had contacted with blood and other body fluids. Conclusion It was a family cluster of SFTSV infection imported from Jiangsu province located in the east of China. We suggested to become alert to atypical SFTSV infected cases.

Background Severe fever with thrombocytopenia syndrome (SFTS) caused by SFTS virus (SFTSV) usually have a high fatality. At present no effective therapy or vaccine are available, so early diagnosis of SFTS is crucial to prevent and control SFTSV infection. This study aimed to establish a national reference for these diagnostic kits of SFTSV genome and make the diagnosis of the disease effective. Methods Six SFTSV strains isolated from different regions, and five relative viruses with similar clinical manifestations were selected as positive and negative references and assessed using real time quantitative PCR (q-PCR) using specific primers and probe and two commercial kits. The stability of the references was also assessed at 37 °C, room temperature or -70 °C for 8 days, 14 days or 8 months respectively, or following several cycles of freezing-thawing. Collaborative calibration of the references was performed by three labs. Results The references indicated good accuracy and specificity. The lowest detection limit was 102 U/mL. The accuracy was coefficient of variation less than 5%. The references were highly stable at high temperatures and after long storing and freezing-thawing treatment. Conclusions We successfully established a national reference with good accuracy, high specificity, sensitivity and stability, which can be applied for quality control of commercial SFTSV diagnostic kits, thus preventing and controlling SFTS. Trial registration The references have been finished and it was retrospectively registered in the following article. Electronic supplementary material The online version of this article (doi:10.1186/s12985-017-0682-z) contains supplementary material, which is available to authorized users.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia, which is caused by a novel bunyavirus-SFTSV. Many studies have reported the clinical characters of SFTS patients, but the reports were not consistent and a systematic summary of clinical manifestations and laboratory parameters are not available. Method A comprehensive literature research of Web of Science, PubMed, Wan Fang Data, and Chinese National Knowledge Infrastructure databases was conducted on articles which have described the clinical characters of SFTS patients. Data from selected studies were pooled by using STATA VERSION 12.0 software. Result Nine articles comprising 844 laboratory-confirmed SFTSV cases were included in this meta-analysis. The pooled case fatality rate was 16% (95% CI: 0.13–0.19). The major clinical characters of patients with SFTSV infection were fever, thrombocytopenia, leucopenia, gastrointestinal symptoms, and central nervous system manifestations. The risk factors for severe disease included bleeding tendency, central nervous system manifestations, elevated serum enzymes, and high viral load. Although there is no specific antiviral therapy for SFTSV infection, symptomatic treatment and supportive therapy including intensive monitoring is the most essential part of case management. Conclusion The major clinical characters of patients with SFTSV infection were fever, thrombocytopenia, leucopenia and gastrointestinal symptoms, and central nervous system manifestations. The risk factors for severity and fatality among SFTS patients included: old age, CNS manifestations, bleeding tendency, elevated serum enzymes, and high vial load.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV) with a high fatality rate. But the immunofunction was still unclear. The objective of our study was to assess the immunofunction in SFTS patients. Immunofunction test with flow cytometry which contains CD3+, CD4+ and CD8+ T lymphocytes, B cells and NK cells would be used for detecting serum samples collected from 34 SFTS cases and 20 healthy donors. We found that CD3+ and CD4+ T lymphocytes were significantly diminished in SFTS compared to normal control. In contrast, the percentage of NK cells was elevated. Further analysis revealed that the number of CD3+ and CD4+ T lymphocytes showed that there was a more robust pattern of depression in acute phase and severe SFTS infection compared to the patients in recovery phase and mild SFTS infection. But NK cells were significantly increased in acute phase and severe SFTS. They reverted to the near normal levels in convalescent phase. Additionally, the levels of CD3+ and CD4+ T lymphocytes progressively decreased in death group when compared with the survival group, but the level of B cells was higher. The damages of immune system were obvious, and the immune dysfunction might be partly responsible for disease progression of patients with SFTSV infection.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in rural areas of China and is caused by a new bunyavirus, SFTSV, named after the disease. The transmission vectors and animal hosts of SFTSV are unclear. Ticks are the most likely transmission vectors and domestic animals, including goats, dogs, and cattle, are potential amplifying hosts of SFTSV. The clinical symptoms of SFTS are nonspecific, but major symptoms include fever, gastrointestinal symptoms, myalgia, dizziness, joint pain, chills, and regional lymphadenopathy. The most common abnormalities in laboratory test results are thrombocytopenia (95%), leukocytopenia (86%), and elevated levels of serum alanine aminotransferase, aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. The fatality rate for SFTS is 12% on average, and the annual incidence of the disease is approximately five per 100000 of the rural population.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that was first reported in China in 2011. It is caused by SFTS virus (SFTSV) which is a member of the Phlebovirus genus in the Bunyaviridae family. SFTSV has been classified as a BSL3 pathogen. There is a need to develop safe and affordable serodiagnostic methods for proper clinical management of infected patients. Methods: The full length nucleocapsid (N) gene of SFTSV Yamaguchi strain was amplified by RT-PCR and cloned to an expression vector pQE30. The recombinant (r) SFTSV-N protein was expressed by using Escherichia coli (E. coli) expression system and purified under native conditions. rSFTSV-N protein based indirect IgG and IgM enzyme linked immunosorbent assay (ELISA) systems were established to detect specific human IgG and IgM antibodies, respectively. One hundred fifteen serum samples from clinically suspected-SFTS patients were used to evaluate the newly established systems and the results were compared with the total antibody detecting sandwich ELISA system. Results: The native form of recombinant (r) SFTSV-N protein was expressed and purified. Application of the rSFTSV-N protein based indirect IgG ELISA to the 115 serum samples showed results that perfectly matched those of the total antibody sandwich ELISA with a sensitivity and specificity of 100 %. The rSFTSV-N protein based indirect IgM ELISA missed 8 positive samples that were detected by the total antibody sandwich ELISA. The sensitivity and specificity of rSFTSV-N-IgM capture ELISA were 90.59 and 100 %, respectively. Conclusions: The rSFTSV-N protein is highly immunoreactive and a good target for use as an assay antigen in laboratory diagnosis. Its preparation is simpler in comparison with that used for the total antibody sandwich system. Our rSFTSV-N protein-based IgG and IgM ELISA systems have the advantage of distinguishing two types of antibodies and require small volume of serum sample only. They are safe to use for diagnosis of SFTS virus infection and especially fit in large-scale epidemiological investigations., Virology Journal, 12, 117; 2015

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus (SFTSV) in China. Humans of all ages living in endemic areas have high risk of acquiring SFTS. Most clinical data so far have been from adults and no clinical study was available from children yet. The present study identified four SFTSV infected children through hospital based surveillance. A prospective observational study was performed to obtain their clinical and laboratory characteristics. Case presentation The patients’ age ranged from 4–15 years old and two were male. On hospitalization, fever, malaise and gastrointestinal syndromes were the most commonly presenting symptoms. Hemorrhagic symptoms or neurological manifestation was not recorded in any of the four pediatric patients. Hematological abnormalities at admission into hospital included leucopenia (4 cases), thrombocytopenia (1 case) and bicytopenia (1 case). The abnormal parameters included elevated aminotransferase (1 case), alanine transaminase (2 case), and lactate dehydrogenase (3 case). Laboratory parameters indicative of renal damage was not observed during the hospitalization. All the patients recovered well without sequelae being observed. Conclusion Compared with adults, pediatric patients with SFTSV infection seem to have less vague subjective complaints and less aggressive clinical course. Thrombocytopenia is suggested to be used less rigorously in recognizing SFTSV infection in pediatric patients, especially at early phase of disease.