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Severe fever with thrombocytopenia syndrome (SFTS) is a new infectious disease caused by bunyavirus, and the critically cases conform to the definition of sepsis. In order to compare the differences between SFTS sepsis and non-SFTS sepsis, a retrospective analysis was performed. Thirty-seven SFTS sepsis and 96 non-SFTS sepsis patients were enrolled. The clinical characteristics, laboratory results were compared between the two groups and independent prognostic risk of mortality were investigated respectively. Compared with non-SFTS sepsis, SFTS cases had lower white blood cell, neutrophil and platelet counts, prolonged activated partial thromboplastin time and decreased fibrinogen, slightly elevated inflammatory indicators. Interleukin-6 (IL-6), and acute physiology and chronic health evaluation Ⅱ (APACHE II) score were independent prognostic risk factors in non-SFTS sepsis. The mortality risk of STFS sepsis was related to the viral clearance. There was no difference in viral load between SFTS survivors and non-survivors on admission. However, the differences were significant on 5th, 7th, 10th, and 14th day, and all SFTS non-survivors died within 14 days. Viral clearance rate on 7th day was an independent risk factor for mortality in SFTS sepsis. The mortality risk of STFS sepsis was related to the viral clearance rate. • SFTS cases had lower leukocyte, neutrophil, platelet, coagulation disorder, elevated inflammatory indicators. • Interleukin-6, and APACHE II score were independent prognostic risk factors in non-SFTS sepsis. • Viral clearance rate (7th) was an independent risk factor for mortality in SFTS sepsis. [ABSTRACT FROM AUTHOR]

• The function of NK cells in peripheral blood of SFTS patients was impaired. • The expression of Siglec-9 in circulating NK cells of SFTS patients was decreased. • Expression of Siglec-9 on NK cells was negatively correlated with DBV viral load. • The decrease of Siglec-9+NK cells may cause NK cell dysfunction in SFTS patients. To investigate the changes and mechanism of Siglec-9 on NK cells in peripheral blood of patients with severe fever with thrombocytopenia syndrome (SFTS). First, we used single-cell RNA sequencing to analyze the frequency of NK cells in Peripheral Blood Mononuclear Cells (PBMCs) of SFTS patients and healthy controls (HCs), as well as the differences in the genes on NK cells. Secondly, we analyzed the expression of Siglec-9 and other receptors on NK cells by flow cytometry. Thirdly, we analyzed the correlation between Siglec-9 on NK cells and DBV viral load in plasma. Compared with HCs, the frequency of NK cells in peripheral blood of SFTS patients was significantly decreased, and the activating receptors on NK cells were reduced. The expression of Siglec-9 on NK cells and the frequency of Siglec-9+NK cells decreased significantly in SFTS patients. The expression of Siglec-9 on CD16+CD56dim NK cells was negatively correlated with DBV viral load. In addition, Siglec-9+NK cells expressed higher levels of activating receptors and exhibited stronger effector functions than Siglec-9−NK cells. The decreased expression of Siglec-9 on NK cells predicts NK cell dysfunction in SFTS patients, suggesting that Siglec-9 may be a potential marker for functional NK cell subsets in SFTS patients. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome is a hemorrhagic fever caused by a tick-borne infection. The causative agent, Dabie bandavirus , is also called the severe fever with thrombocytopenia syndrome virus (SFTSV). Ogawa et al. (2022) reported that levodopa, an antiparkinsonian drug with an o -dihydroxybenzene backbone, which is important for anti-SFTSV activity, inhibited SFTSV infection. Levodopa is metabolized by dopa decarboxylase (DDC) and catechol- O -methyltransferase (COMT) in vivo. We evaluated the anti-SFTSV efficacy of two DDC inhibitors, benserazide hydrochloride and carbidopa, and two COMT inhibitors, entacapone and nitecapone, which also have an o -dihydroxybenzene backbone. Only DDC inhibitors inhibited SFTSV infection with pretreatment of the virus (half-maximal inhibitory concentration [IC 50 ]: 9.0–23.6 μM), whereas all the drugs inhibited SFTSV infection when infected cells were treated (IC 50 : 21.3–94.2 μM). Levodopa combined with carbidopa and/or entacapone inhibited SFTSV infection in both conditions: pretreatment of the virus (IC 50 : 2.9–5.8 μM) and treatment of infected cells (IC 50 : 10.7–15.4 μM). The IC 50 of levodopa in the above-mentioned study for pretreatment of the virus and treatment of infected cells were 4.5 and 21.4 μM, respectively. This suggests that a synergistic effect was observed, especially for treatment of infected cells, although the effect is unclear for pretreatment of the virus. This study demonstrates the anti-SFTSV efficacy of levodopa-metabolizing enzyme inhibitors in vitro. These drugs may increase the time for which the levodopa concentration is maintained in vivo. The combination of levodopa and levodopa-metabolizing enzyme inhibitors might be a candidate for drug repurposing. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is frequently associated with neurological injury, but there are currently few relevant studies. The goal of this study was to look at the risk factors for SFTA-associated encephalopathy (SFTSAE) and the short- and long-term prognosis of such patients. We retrospectively studied 145 patients with SFTS who were treated at our hospital between May 2019 and November 2021. Clinical characteristics were collected, and patients were divided into two groups based on whether there was neurological injury during the disease: SFTSAE group and non-SFTSAE group. Univariate analysis was used to compare the differences in clinical data and outcomes between two groups, and multivariate Logistic regression analysis was used to reveal the independent risk factors for SFTSAE, and the predictive efficacy was assessed using the receiver operating characteristic (ROC) curve. Furthermore, survivors of SFTSAE were contacted by phone 6 months after discharge to assess the case fatality rate and quality of life. The prevalence of SFTSAE was 22.7% (33/145). Bleeding symptoms, D-dimer level and blood amylase level were all independent risk factors for SFTSAE (P < 0.05). The combined AUC of these three factors was 0.969. Patients with SFTSAE had a 45.4% in-hospital mortality rate, and survivors had a largely normal quality of life after discharge. Patients with SFTSAE frequently have multiple organ dysfunction, a high mortality rate, and a favorable long-term prognosis for survivors. Clinical manifestations of bleeding symptoms, elevated serum amylase, and elevated D-dimer were all independent risk factors for SFTSAE. [ABSTRACT FROM AUTHOR]

• Efficacy of glucocorticoid therapy in patients with severe fever with thrombocytopenia syndrome depends on the severity of the disease. • Glucocorticoid treatment increased fatality in patients with mild disease. • Increased fatality was only observed in patients ≤65 years, male, and early admission. • Low-moderate glucocorticoids reduced fatality in critically ill patients. To determine whether glucocorticoids can improve clinical outcomes of severe fever with thrombocytopenia syndrome (SFTS) patients, and how to identify patients who may benefit from the treatment. A retrospective study was performed to include patients with confirmed SFTS from designated hospitals. The effect of glucocorticoids in reducing case fatality rate (CFR) and improving clinical recovery was evaluated by multivariate logistic regression models. A total of 2478 eligible patients were analyzed, of whom 331 received glucocorticoids. An integrated parameter (L-index) based on Log 10 (lactate dehydrogenase*blood urea nitrogen/lymphocyte count) was constructed to discriminate disease severity. In patients with L-index >3.823 indicating severe SFTS, significantly reduced CFR was observed in patients receiving low-moderate glucocorticoid doses with ≤60 mg daily methylprednisolone or equivalent (odds ratio [OR] 0.46, 95% confidence interval [CI], 0.23-0.88), but not in patients receiving high doses. In patients with L-index ≤3.823 indicating mild SFTS, glucocorticoid treatment was significantly associated with increased CFR (OR 3.34, 95% CI, 1.35-9.51), and mainly attributable to high-dose glucocorticoids (OR 2.83, 95% CI, 1.72-4.96). Disaggregated data analysis revealed a significant effect only in patients ≤65 years old, male, and early admission within 7 days after onset, but not in their counterparts. Glucocorticoids are not recommended for mild patients defined by L-index <3.823; however, patients with severe SFTS may benefit from low-moderate doses of glucocorticoids. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. Early identification of patients who may advance to critical stages is crucial. This investigation aimed to establish models to predict SFTS before it reaches the critical illness stage. Between January 2016 and September 2022, 278 cases have been included in this study. There were 87 demographic and systemic chosen variables. For selecting the predictive variables from the cohort, the LASSO was utilized, and for identifying independent predictors, multivariate logistic regression was performed. Based on these factors, a nomogram was established for critical illness. Concordance index values, decision curve analysis and the area under the curve (AUC) were also examined. Multivariate logistic regression demonstrated the most important differentiating factors as;> 65 years old (P < 0.001, OR 3.388, 95 % CI 1.767–6.696), elevated serum PT (P = 0.011, OR 6.641, 95 % CI 1.584–31.934), elevated serum TT (P = 0.005, OR 3.384, 95 % CI 1.503–8.491), and elevated serum bicarbonate (P = 0.014, OR 0.242, 95 % CI 0.070–0.707). The C-index of the nomogram was 0.812 (95 % CI: 0.754–0.869), representing good discrimination. The model also showed excellent calibration. The AUC of the nomogram established based on four factors, as mentioned earlier, was 0.806. Furthermore, the model had the excellent net benefit, as revealed by the decision curve analysis. An accurate risk score system built on manifestations noted in patients with SFTS upon admission to hospital, might be advantageous in managing SFTS. [ABSTRACT FROM AUTHOR]

• Ocular route is suggested as a highly possible mode for severe fever with thrombocytopenia syndrome (SFTS) virus transmission. • Greater exposure to blood from patients with SFTS may result in poor prognosis. • Excretions from patients with SFTS without bleeding may confer lower transmission risk. Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease with high mortality, was first reported in 2009 in China and subsequently endemic to South Korea, Japan, Vietnam, and Myanmar. This disease is transmitted predominantly by tick bites and potentially human-to-human. Personal protective equipments (PPEs) have been recommended to prevent SFTS human-to-human transmission, whereas the specific use of PPEs and the effect on viral transmission have rarely been reported. This report identified a family cluster of six patients with SFTS virus (SFTSV) infection. All five secondary patients had been wearing gloves and masks when exposed to the blood of the index patient, but none of them wore goggles or face shields for eye protection. Ocular route was suggested as a highly possible mode for SFTSV transmission through epidemiological, serological, and phylogenetic analysis. Eye protection should be stressed for clinicians when exposed to blood or bloody secretions. [ABSTRACT FROM AUTHOR]

Severe Fever with Thrombocytopenia Syndrome (SFTS) is a tick-borne disease caused by the SFTS virus (SFTSV) which has the potential to become a pandemic and is currently a major public health concern. We present the case of a 74-year-old female from an urban area of Chongqing, with leukocytopenia, thrombocytopenia, organ function, inflammatory, blood coagulation, and immune abnormalities. SFTSV infection was confirmed through molecular detection and metagenomic next-generation sequencing (mNGS) analysis, indicating a diagnosis of SFTS due to the patient's history of tick bites. The patient received symptomatic and supportive therapy, including antibiotics, antiviral treatment, and antifungal therapy, and finally discharged from the hospital on day 18. This study highlights the need for increased awareness, early diagnosis, and prompt treatment for tick-borne SFTS. It also provides a comprehensive understanding of the disease's characteristics, pathogenesis, detection methods, and available treatments. [ABSTRACT FROM AUTHOR]

• For the first time, established a predictive model to anticipate the cytokine storms in the acute phase of SFTS patients. • By visualizing the predictive model through a nomogram, it becomes more convenient and user-friendly. • The predictive capacity of the model was evaluated based on the outcomes of 48 cytokines in the validation cohort. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients. [ABSTRACT FROM AUTHOR]

• Corticosteroid therapy for severe fever with thrombocytopenia syndrome is controversial • The study showed that steroid treatment had no influence on fatality in patients • Corticosteroid therapy increased secondary infection rate in patients with severe fever with thrombocytopenia syndrome • Cox regression and propensity score matching provided strong evidence To evaluate the effect and safety of corticosteroid (CS) treatment in patients with severe fever with thrombocytopenia syndrome (SFTS). Patients with and without CS were retrospectively compared by Cox regression and 1:1 propensity score matching analysis to evaluate the effects of CS on mortality and secondary infections in patients with SFTS. A total of 467 patients with SFTS were enrolled in the cohort study, there were 52 fatal cases and 415 nonfatal cases, the overall fatality rate was 11.1%. The mortality was observed in 36/144 (25%) and 16/323 (5%) patients in the CS-treated and non-CS-treated groups, respectively (P < 0.001). Multi variate Cox regression analysis showed that the difference was not statistically significant for CS treatment in fatality (P > 0.05, aHR 0.767, 95% CI 0.360-1.634). Difference in survival time between the CS-treated and non-CS-treated groups after propensity score matching had no statistical significance (Log-rank test P = 0.390), whereas there was a significant difference in secondary infections between the CS-treated and non-CS-treated groups (P = 0.007). Although the CS treatment had no impact on fatality in patients with SFTS, it increased the risk of secondary infections. Administration of CS in patients with SFTS should be carefully considered and evaluated the balance between therapeutic efficacy and adverse effects. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

In August 2020, 17 healthcare workers (HCWs) were simultaneously diagnosed with severe fever with thrombocytopenia syndrome (SFTS) at a university hospital in Daegu, Republic of Korea. An epidemiologic investigation using questionnaires was conducted for all suspected HCWs who had viral infection symptoms or who had the possibility of exposure to the index patient. A total of 17 HCWs infected with the SFTS virus (SFTSV) (28.8%) were identified among the 59 HCWs who had contact with the patient. Operating a bag valve mask during cardiopulmonary resuscitation (CPR) (OR 7.50, 95% CI 1.75–41.07), cardiac massage during CPR (OR 12.00, 95% CI 1.76–241.94), exposure to the patient's body fluids (OR 7.43, 95% CI 1.91–34.69), and shorter individual hospital work experience periods (OR 6.79, 95% CI 1.70–32.10) were significantly associated with SFTS infection in the univariate analysis. However, exposure to body fluids was found to be the only statistically significant risk factor when multivariate analysis was conducted (OR 6.27. 95% CI 1.23–42.81, p = 0.036). This finding illustrates the importance of wearing appropriate personal protective equipment in treatment areas and when conducting any medical procedures, including CPR for patients with SFTS, and any procedure that involves potential exposure to body fluids. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate. How the glucose level might affect the clinical outcome remains obscure. A multicenter study was performed in 2 hospitals from 2011 to 2021. Patients with SFTS and acute hyperglycemia (admission fasting plasma glucose [FPG] ≥7 mmol/L), postadmission hyperglycemia (admission FPG <7 mmol/L but FPG ≥7 mmol/L after admission), and euglycemia (FPG <7 mmol/L throughout hospitalization) were compared for their clinical progress and outcomes. A total of 3225 patients were included in this study, 37.9% of whom developed acute hyperglycemia and 7.6% postadmission hyperglycemia. The presence of acute hyperglycemia, with or without known diabetes, was associated with increased risk of death (odds ratio [OR]: 1.63; 95% confidence interval [CI]: 1.29-2.05) compared with euglycemia. This effect, however, was only determined in female patients (OR: 2.15; 95% CI: 1.54-2.93). Insulin treatment of patients with SFTS and acute hyperglycemia without previous diabetes was associated with significantly increased mortality (OR: 1.58; 95% CI: 1.16-2.16). Acute hyperglycemia can act as a strong predictor of SFTS-related death in female patients. Insulin treatment of hyperglycemia in patients with SFTS without pre-existing diabetes has adverse effects. [ABSTRACT FROM AUTHOR]

Person-to-person transmission of severe fever with thrombocytopenia syndrome virus (SFTSV) is a new threat to human health. Here we report an outbreak of nosocomial person-to-person transmission of SFTS. Among eight persons with face-to-face contact distance ≤50 cm and/or exposure time ≥30 min to the index patient, six became infected. Only one of the 17 persons with exposure distance ≥50 cm and exposure time ≤30 min became infected (75% vs 6.25%, P < 0.001). Epidemiological investigation revealed high viral load, bloody secretions and bleeding, exposure time, and distance as the key factors in person-to-person transmission. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever. Patients mainly develop fever, thrombocytopenia, and leukopenia. A high case fatality rate of 16.2–47% has been reported. Vaccines and antivirals that are effective against SFTS virus (SFTSV) are not yet available in clinical practice. We previously showed that o -dihydroxybenzene is the important chemical core structure for anti-SFTSV activity. In this study, we evaluated the anti-SFTSV efficacy of 3-Hydroxy-L-tyrosine (L-DOPA), a treatment for Parkinson's disease and its enantiomer, 3-hydroxy-D-tyrosine (D-DOPA), both of which have an o -dihydroxybenzene backbone. SFTSV was preincubated with L- or D-DOPA and then inhibition of viral infection as well as viral attachment to host cells were evaluated by viral quantification. Both L- and D-DOPA inhibited SFTSV infection in a dose-dependent manner, mainly by blocking viral attachment to host cells. The half-maximal inhibitory concentration (IC 50) of L-DOPA was 4.46–5.09 μM. IC 50 of D-DOPA was 4.23–6.72 μM. IC 50 of L-DOPA is very close to its maximum blood concentration after oral administration as a therapy for Parkinson's disease. D-DOPA, which IC 50 was almost the same as that of L-DOPA, might not cause side effect. Thus, our present study demonstrated that L- and D-DOPA are potentially useful candidates for anti-SFTSV drugs. [ABSTRACT FROM AUTHOR]

• The rising incidence of SFTS poses a risk to public health • SFTS has a high fatality rate and there are currently no effective treatments • Administration of single dose tocilizumab in a patient with SFTS improved symptoms • Tocilizumab can be used to treat non-fatal SFTS We report the administration of an anti-interleukin (IL)-6 antibody in a case of severe fever with thrombocytopenia syndrome (SFTS) with an increase in IL-6. On the day of admission, SFTS viral load and IL-6 concentration were 93 831 copies/ml and 5.4 pg/ml, respectively, and tocilizumab was administered. SFTS viral load decreased to 17 821.1 copies/ml on the 3rd day of admission, while IL-6 levels increased to 104.9 pg/ml; SFTS viral load and IL-6 levels had decreased to 2876.4 copies/ml and 48.2 pg/ml on 7th day of admission, respectively. The patient fully recovered no tocilizumab adverse events. [ABSTRACT FROM AUTHOR]

• Invasive pulmonary aspergillosis (IPA) is a frequent complication in patients with severe fever with thrombocytopenia syndrome (SFTS). • This study identified wheezing as an independent predictor of IPA in SFTS patients. • It is not clear whether prophylactic anti- Aspergillus therapy should be administered to SFTS patients. Invasive pulmonary aspergillosis (IPA) usually occurs in immunocompromised hosts. It has recently been reported that patients with severe fever with thrombocytopenia syndrome (SFTS) can also develop IPA. The aim of this study was to determine the incidence of IPA in SFTS patients and to investigate the relevant clinical, imaging, and laboratory characteristics. A retrospective review was conducted of all patients with SFTS admitted to Nanjing Drum Tower Hospital, a tertiary hospital in Nanjing City, China, between January 2016 and December 2019. The patients were divided into two groups according to whether they had IPA: the IPA group and the non-IPA group. Data on clinical manifestations, laboratory findings, imaging characteristics, treatments, and outcomes were collected and analysed. A total of 91 SFTS patients were included, of whom 29 (31.9%) developed IPA. In-hospital mortality (22.0%) was higher in the IPA group than in the non-IPA group. Univariate logistic regression showed that diabetes, cough, wheezing, amylase level, vasopressor use, encephalopathy, and intensive care unit transfer were risk factors for the development of IPA. Multivariate logistic regression analysis identified wheezing as an independent predictor of IPA in SFTS patients. SFTS combined with IPA is associated with high morbidity and mortality. It is necessary to strengthen screening for fungal infections after admission in SFTS patients. However, whether early antifungal prophylaxis should be administered needs further investigation. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerged tick-borne viral zoonosis and widely prevalent in China, Japan and South Korea. Most reported SFTS cases have been identified in mountainous and hilly areas, with a few in island areas. In this study, we conducted a systematic investigation about natural infection of SFTS virus (SFTSV) among humans, animals and ticks in a coastal endemic prefecture, containing island, plains and mountain settings, in Zhejiang Province, Southeastern China. From July 2020 to June 2021, 1117 participants completed a survey with questionnaire interview and serum testing. Meanwhile, 862 serum samples of domestic animals, 275 spleen tissue samples of wild animals and 829 ticks representing five species (predominantly Haemaphysalis longicornis and Rhipicephalus sanguineus sensu lato) were collected. The seroprevalence of anti-SFTSV total antibody and IgM antibody among the participants was 4.8 % (54/1117) and 0.6 % (7/1117), respectively. Multivariate logistic regression analysis indicated that living in the island area (OR=2.66; 95 %CI: 1.04–6.80; P = 0.041) was significantly associated with seropositivity of total antibody to SFTSV. Furthermore, a higher seroprevalence was observed in domestic animals (36.1 %), while the SFTSV-RNA infection rate was 0.4 % in wild animals and the minimum infection rate (MIR) was 0.8 % for all tick species combined. The only tick species infected with SFTSV was H. longicornis. The prevalence of SFTSV infection in the island area, manifested by anti-SFTSV total antibody (P = 0.012) and IgM antibody (P = 0.004) among humans, anti-SFTSV total antibody (P <0.001) among domestic animals, and SFTSV-RNA among ticks (P = 0.022), was significantly higher than that in the mountainous area and the plain area. Furthermore, phylogenetic analysis showed that SFTSV sequences obtained from ticks in the island area were clustered with reported strains in Japan and South Korea. These results suggest that islands in the study area might be an important natural focus of SFTSV. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever caused by SFTS virus (SFTSV). The mortality rate of SFTS is pretty high, but no vaccines and antiviral drugs are currently available. The antiviral effects of six green tea-related polyphenols, including four catechins and two flavonols, on SFTSV were evaluated to identify natural antiviral compounds. Pretreatment with all polyphenols inhibited SFTSV infection in a concentration-dependent manner. The half-maximal inhibitory concentrations of (−)-epigallocatechin gallate (EGCg) and (−)-epigallocatechin (EGC) were 1.7–1.9 and 11–39 μM, respectively. The selectivity indices of EGCg and EGC were larger than those of the other polyphenols. Furthermore, pretreatment with EGCg and EGC dose-dependently decreased viral attachment to the host cells. Additionally, the treatment of infected cells with EGCg and EGC inhibited infection more significantly at a lower multiplicity of infection (MOI) than at a higher MOI, and this effect was less effective than that of pretreatment. Pyrogallol, a trihydroxybenzene that is the structural backbone of both EGCg and EGC, also inhibited SFTSV infection, as did gallic acid. Our study revealed that green tea-related polyphenols, especially EGCg and EGC, are useful as candidate anti-SFTSV drugs. Furthermore, the structural basis of their antiviral activity was identified, which should enable investigations of more active drugs in the future. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS), a novel tick-borne disease caused by SFTS virus (SFTSV), has been reported in China, Japan, South Korea, and Vietnam since 2009. SFTSV infection can cause multiple organ damage, including acute pancreatitis (AP). We summarize the clinical features, treatment and outcome of AP associated with SFTSV. We retrospectively review the clinical manifestations, laboratory tests, treatment, and outcome of AP associated with SFTSV infection from January 2009 to December 2018 in Liaoning Province, China. A total of 418 SFTS patients were reviewed. Fifteen (3.6%) of 418 met the criteria for AP associated with SFTSV infection. The first reported symptom for all SFTS-AP patients was fever. All the SFTS-AP patients presented with thrombocytopenia, and 13 (86.7%) of them presented with leukopenia on admission. Thirteen (86.7%) of 15 SFTS-AP patients were severe SFTS patients, and 9 (60.0%) patients were diagnosed with multiple organ dysfunction syndrome. One SFTS-AP patient died of multiple organ failure. Six (40%) of 15 SFTS-AP patients were not confirmed with SFTSV infection when AP was diagnosed, and the median delay between SFTSV infection and AP diagnosis was 5 days (range, 2–7 days). AP is not a frequent complication of SFTS, and is more frequently seen in severe SFTS patients. Most patients with SFTS-AP have mild or moderate disease, and can recover with conservative management; however, severe SFTS-AP can be fatal. In SFTS endemic areas, clinicians should be alert to the possibility of SFTS when AP patients with tick exposure, thrombocytopenia, and leukopenia have a fever before abdominal pain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Objectives Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by the SFTS virus (SFTSV) and has a high fatality rate. SFTSV-specific antibody profiles among patients with different clinical outcomes are yet to be described. The nucleocapsid protein (NP) is the most immunogenic viral antigen of the SFTSV. This study, therefore, sought to determine NP-specific antibody responses among SFTS patients with different disease progressions. Methods In the present study, 43 patients with confirmed SFTS were enrolled in our cohort, and 9 of them deceased. The clinical presentations and key laboratory parameters associated with SFTS fatality were also recorded. Serum samples from each patient were collected every 2 days during their hospitalization. NP-specific IgM and IgG responses as well as Gn or Gc-specific IgM responses were examined by enzyme-linked immunosorbent assay (ELISA), whereas, the dynamic viral loads of SFTSV RNA were quantified via real-time reverse transcription polymerase chain reaction (RT-PCR). Results First, 77% of patients generated positive NP-specific IgM antibody responses within two weeks since illness onset, defined as 'N-specific IgM-positive patients', while the rest of the patients were termed as 'N-specific IgM-delayed patients'. Only 17% of the patients generated NP-specific IgG responses. The absence of NP-specific humoral responses was strongly associated with a high risk of fatality and severity of SFTS. IgM-positive patients had significantly lower levels of viral loads, less disturbed coagulopathy, and hepatic and cardiac damage compared to IgM-delayed patients. Moreover, compared to severe or fatal SFTS patients, mild SFTS patients had significantly higher magnitudes of NP-specific IgM responses, but not NP-specific IgG, Gn-specific IgM, or Gc-specific IgM responses. The abundance of NP-specific IgM responses negatively correlated with viral loads, coagulation disturbances, and hepatic injuries among SFTS patients. Conclusions Our data highlight distinct humoral profiles of NP-specific IgM responses among SFTS patients with different disease progressions and clinical outcomes. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) caused by SFTS virus (SFTSV), a novel phlebovirus, was reported to be endemic to central and northeastern PR China and was also to be endemic to South Korea and western Japan. SFTS is an emerging viral infection, which should be categorized as a viral hemorrhagic fever disease as Crimean-Congo hemorrhagic fever (CCHF) is caused by CCHF virus. SFTS is a tick-borne viral infection. SFTSV is maintained between several species of ticks and wild and domestic animals in nature. Patients with SFTS show symptoms of fever, general fatigue, and gastrointestinal symptoms such as bloody diarrhea. The severely ill SFTS patients usually show gastrointestinal hemorrhage and deteriorated consciousness. The case fatality rate of SFTS ranges from 5 to 40%. Pathological studies on SFTS have revealed that the mechanisms behind the high case fatality rate are virus infection-related hemophagocytic syndrome associated with cytokine storm, coagulopathy due to disseminated intravascular coagulation causing bleeding tendency, and multi-organ failure. Favipiravir was reported to show efficacy in the prevention and treatment of SFTSV infections in an animal model. A clinical study to evaluate the efficacy of favipiravir in the treatment of SFTS patients has been initiated in Japan. SFTSV is circulating in nature in PR China, Korea, and Japan, indicating that we cannot escape from the risk being infected with SFTSV. The development of specific therapy and preventive measures is a pressing issue requiring resolution to reduce the morbidity and mortality of SFTS patients. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) was first identified as an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) in China and has also been found to be endemic to Japan and South Korea, indicating that SFTS is of great concern in East Asia. The aim of the present study was to determine the seroprevalence of SFTSV antibodies in humans and animals in SFTS-endemic regions of Japan. One of 694 (0.14%) healthy persons over 50 years of age and 20 of 107 (18.7%) wild and domestic animals in Ehime prefecture of western Japan were determined to be seropositive for SFTSV antibodies by virus neutralization test and ELISA, respectively. The seropositive person, a healthy 74-year-old woman, was a resident of the southwest part of Ehime prefecture engaged in citriculture and field work. This woman's sample exhibited neutralizing activity against SFTSV although she had neither a clear experience with tick bites nor SFTS-like clinical illness. These findings indicate that most people living in the endemic regions are not infected with SFTSV and suggest that most of the SFTS patients reported so far do not reflect the tip of an iceberg of people infected with SFTSV, but at the same time, that SFTSV infection does not always induce severe SFTS-associated symptoms. These findings also suggested that SFTSV has been maintained in nature within animal species and ticks. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease caused by the SFTS virus (SFTSV) of the family Bunyaviridae . Since the virus was first isolated in 2009, it has become widespread in China, with an increasing number of cases year on year. Although the disease has been researched extensively in past years, there are still no effective measures to suppress the epidemic situation. This article reports a pilot study of comprehensive measures, including health education and risk communication, weed removal, livestock management, and tick control, to prevent this emerging disease in an endemic region of China. The density of ticks decreased dramatically month by month after acaricides were sprayed in the areas surrounding recreational and agricultural settings. The number of SFTS cases and villages involved declined in the years after the integrated measures were applied. Comprehensive measures, especially community-based tick control, may be a promising means of preventing SFTS in endemic regions. [ABSTRACT FROM AUTHOR]

Objective To determine the clinical features of confirmed cases of severe fever with thrombocytopenia syndrome (SFTS) and to explore the early warning indicators of death from SFTS. Methods A retrospective case–control study was performed at a single medical institution in Yantai. A total of 20 SFTS patients who died (death group) during January 2014 to December 2015 and another 40 age- and sex-matched SFTS patients who survived (survivor group) were identified from the case records. The differences in demographic characteristics, clinical signs and symptoms, and laboratory parameters in the early stage of disease were compared between the two groups. Conditional logistic regression was used to identify the independent risk factors for mortality in SFTS patients. Results Univariate logistic regression analysis showed that a disturbance of consciousness, pulse–temperature deficit, neurological signs, hemorrhagic manifestations, pulmonary infection, decreased lymphocyte percentage, high lactate dehydrogenase and creatine kinase levels, increased serum creatinine, blood urea nitrogen, and C-reactive protein (CRP), hyponatremia, and prolonged activated partial thromboplastin time (APPT) and prothrombin time were associated with mortality. On multivariate logistic regression analysis, the independent predictors of death were neurological signs (odds ratio (OR) 31.247, 95% confidence interval (CI) 4.813–202.853), hemorrhagic manifestations (OR 20.251, 95% CI 2.056–199.443), disturbance of consciousness (OR 15.359, 95% CI 2.139–110.268), hyponatremia (OR 5.280, 95% CI 1.235–22.575), increased CRP (OR 2.641, 95% CI 1.090–6.396), increased serum creatinine (OR 6.776, 95% CI 1.047–43.840), and prolonged APTT (OR 6.018, 95% CI 1.450–24.975). Conclusions Neurological signs, hemorrhagic manifestations, disturbance of consciousness, hyponatremia, prolonged APTT, and increased CRP and serum creatinine are risk factors for death in SFTS. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) causes tick-borne hemorrhagic fever in East Asia. The disease is characterized by high morbidity and mortality. Here, we evaluated the effects of caffeic acid (CA), a coffee-related organic acid with antiviral effects, against SFTSV infection. CA dose-dependently inhibited SFTSV infection in permissive human hepatoma Huh7.5.1–8 cells when SFTSV was added into the culture medium with CA. However, quinic acid (QA), another coffee-related organic acid, did not inhibit SFTSV infection. The 50% inhibitory concentration (IC 50 ) of CA against SFTSV was 0.048 mM, whereas its 50% cytotoxic concentration was 7.6 mM. The selectivity index (SI) was 158. Pre-incubation of SFTSV with CA for 4 h resulted in a greater inhibition of SFTSV infection (IC 50 = 0.019 mM; SI = 400). The pre-incubation substantially decreased viral attachment to the cells. CA treatment of the SFTSV-infected cells also inhibited the infection, albeit less effectively. CA activity after cell infection with SFTSV was more pronounced at a low multiplicity of infection (MOI) of 0.01 per cell (IC 50 = 0.18 mM) than at a high MOI of 1 per cell (IC 50 > 1 mM). Thus, CA inhibited virus spread by acting directly on the virus rather than on the infected cells. In conclusion, CA acted on SFTSV and inhibited viral infection and spread, mainly by inhibiting the binding of SFTSV to the cells. We therefore demonstrated CA to be a potential anti-SFTSV drug for preventing and treating SFTS. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is emerging and some studies reported that SFTS incidence was associated with meteorological factors, while no report on SFTS forecast models was reported up to date. In this study, we constructed and compared three forecast models using autoregressive integrated moving average (ARIMA) model, negative binomial regression model (NBM), and quasi-Poisson generalized additive model (GAM). The dataset from 2011 to 2015 were used for model construction and the dataset in 2016 were used for external validity assessment. All the three models fitted the SFTS cases reasonably well during the training process and forecast process, while the NBM model forecasted better than other two models. Moreover, we demonstrated that temperature and relative humidity played key roles in explaining the temporal dynamics of SFTS occurrence. Our study contributes to better understanding of SFTS dynamics and provides predictive tools for the control and prevention of SFTS. [ABSTRACT FROM AUTHOR]

Introduction Severe fever with thrombocytopenia syndrome (SFTS) has been prevalent in parts of Asia during recent years. However, SFTS with invasive pulmonary aspergillosis (IPA) is rare, and it is important to understand its clinical features. Materials and methods Total four cases of SFTS with IPA are reviewed and detailing the disease progression, treatment options, and prognosis were summarized and analyzed. Results The patients with SFTS-associated IPA first presented with fever, gastrointestinal symptoms, thrombocytopenia, leukopenia, and multiple organ failure. After 1–2 weeks, the patients developed mild polypnea and wheezing rales, and quickly developed dyspnea and respiratory failure. Tracheal intubation was usually performed, but did not relieve the intractable airway spasm and pulmonary ventilation failure. Bronchoscopy confirmed that the antifungal treatment was ineffective and the aspergillosis had worsened. All patients died of type 2 respiratory failure caused by continued airway obstruction and spasticity. Conclusions Given the high mortality rate in this series, there is a need for increased awareness of SFTS-associated IPA. Additional examinations should be performed in these cases, and early-stage antifungal treatment with organ support may be helpful. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). Clinical symptoms of SFTS often involve encephalopathy and other central neurological symptoms, particularly in seriously ill patients; however, pathogenesis of encephalopathy by SFTSV is largely unknown. Herein, we present case reports of three patients with SFTS, complicated by encephalopathy, admitted to Tokushima University hospital: one patient was a 63-year-old man, while the other two were 83- and 86-year-old women. All of them developed disturbance of consciousness around the 7th day post onset of fever. After methylprednisolone pulse therapy of 500 mg/day, all of them recovered without any neurological sequelae. SFTSV genome was not detected in the cerebrospinal fluid of 2 out of the 3 patients that were available for examination. In these patients, disturbance of consciousness seemed to be an indirect effect of the cytokine storm triggered by SFTSV infection. We propose that short-term glucocorticoid therapy might be beneficial in the treatment of encephalopathy during early phase of SFTSV infection. [ABSTRACT FROM AUTHOR]

Objective Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. T cell deficiency has recently been described, but the changes in T cell functionality during acute SFTS virus (SFTSV) infection and the mechanisms leading to T lymphocyte death remain largely unknown. This study was conducted to evaluate T cell functionality and the expression of apoptotic/proliferation and activation/inhibition markers during acute SFTSV infection. Methods Twenty-eight surviving SFTS patients were sequentially sampled during their entire hospital stay. SFTSV RNA copies were investigated using real-time RT-PCR. The expression levels of apoptotic markers (annexin V and CD95) and proliferation and activation markers (Ki-67, HLA-DR, and CD25) and the expression levels of programmed cell death-1 (PD-1), interferon gamma (IFN-γ), and granzyme B in T cells were evaluated by flow cytometry for the SFTS patients. Results In parallel with T cell depletion, higher annexin V and CD95 expression was observed in SFTS patients. Additionally, the expression levels of Ki-67, HLA-DR, CD25, and PD-1 and the levels of IFN-γ and granzyme B in T lymphocytes were markedly increased in the SFTS patients. Conclusions T cell proliferation, activation, and functional enhancement were apparent despite the observation of T cell apoptosis, suggesting that these processes are involved in the complex protective response to SFTSV infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is emerging and the number of SFTS cases have increased year by year in China. However, spatiotemporal patterns and trends of SFTS are less clear up to date. In order to explore spatiotemporal patterns and predict SFTS incidences, we analyzed temporal trends of SFTS using autoregressive integrated moving average (ARIMA) model, spatial patterns, and spatiotemporal clusters of SFTS cases at the county level based on SFTS data in China during 2011–2016. We determined the optimal time series model was ARIMA (2, 0, 1) × (0, 0, 1) 12 which fitted the SFTS cases reasonably well during the training process and forecast process. In the spatial clustering analysis, the global autocorrelation suggested that SFTS cases were not of random distribution. Local spatial autocorrelation analysis of SFTS identified foci mainly concentrated in Hubei Province, Henan Province, Anhui Province, Shandong Province, Liaoning Province, and Zhejiang Province. A most likely cluster including 21 counties in Henan Province and Hubei Province was observed in the central region of China from April 2015 to August 2016. Our results will provide a sound evidence base for future prevention and control programs of SFTS such as allocation of the health resources, surveillance in high-risk regions, health education, improvement of diagnosis and so on. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS), a severe infectious disease caused by novel bunyavirus, SFTS virus (SFTSV), is endemic to China, Korea, and Japan. Most SFTS patients show abnormalities in consciousness. Pathological findings in the central nervous system (CNS) of SFTS patients are not reported. A 53-year-old Japanese man was admitted to Uwajima City Hospital with an 8-day history of fever and diarrhea. Laboratory tests revealed leukopenia, thrombocytopenia, and liver enzyme elevation. He was diagnosed as having severe fever with thrombocytopenia syndrome (SFTS) following detection of the SFTSV genome in his blood. Bone marrow aspiration revealed hemophagocytic lymphohistiocytosis. He suffered progressive CNS disturbance and died on day 13 from onset of first symptoms. The SFTSV genome load in blood and levels of certain cytokines increased over the disease course. Necrotizing lymphadenitis with systemic lymphoid tissues positive for nucleocapsid protein (NP) of SFTSV was revealed by immunohistochemical (IHC) analysis. SFTSV-NP-positive immunoblasts were detected in all organs examined, including the CNS, and in the vascular lumina of each organ. Parenchymal cells of all organs examined were negative for SFTSV-NP on IHC analysis. Microscopic examination of the pons showed focal neuronal cell degeneration with hemosiderin-laden macrophages around extended microvessels with perivascular inflammatory cell infiltration and intravascular fibrin deposition. Autopsy confirmed this patient with SFTS was positive for systemic hemophagocytic lymphohistiocytosis including in the CNS. This patient's neurological abnormalities may have been caused by both functional and organic abnormalities. These novel findings provide important insights into the pathophysiology of SFTS. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the seroprevalence of antibodies against severe fever with thrombocytopenia syndrome virus (SFTSV) in shelter dogs in the Republic of Korea (ROK) using an indirect immunofluorescence assay and virus neutralization test. Sera were collected from 426 dogs in 12 animal shelters throughout the ROK from March 2016 to November 2016. Overall, 59 of 426 (13.9%) samples were seropositive for antibodies against SFTSV. A significant difference was observed in accordance with the sampling region ( p < 0.001), but not according to the sex ( p = 0.279) or breed ( p = 0.729) of the dogs. The seroprevalence of SFTSV showed an inversely proportional trend to the latitude of the sampling regions: the highest rate was observed in the southern region followed by the Jeju-do region. This is the first report on the nationwide prevalence of antibodies against SFTSV in companion dogs in animal shelters throughout the ROK. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome is a tick-borne infectious disease. The present study investigated the prevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in shelter dogs and cats in the Republic of Korea (ROK). Blood samples were collected from 426 dogs and 215 cats in animal shelters throughout the ROK in 2016. Of the tested samples, one (0.2%) dog and one (0.5%) cat were positive for SFTSV. Phylogenetic analysis of the sequences obtained in the present study showed that the viruses belonged to the J3 clade, which is considered the dominant clade in the ROK. This study reports the first molecular detection of SFTSV in shelter dogs and cats in the ROK. [ABSTRACT FROM AUTHOR]

Background Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease caused by a novel bunyavirus, was discovered in rural areas of Central China in 2009. Methods A case-control study based on hospital data was applied to detect the potential risk sources for SFTS in SFTS-endemic counties in Hubei Province. Cases were defined as hospitalized SFTSV confirmed patients. Controls were randomly selected from non-SFTSV patients in the same hospital ward within 2 weeks of inclusion of the cases, and they were matched by age (+/− 5 years) and gender according to 1:2 matching condition. Results 68 cases and 136 controls participated in this study. In multivariate analysis, “Contact with cattle tick” was the major risk source (Conditional Logistic Regression OR-MH = 8.62, 95% CI = 1.79-41.51), outdoor activities and working in weeds or hillside fields could increase risk of cattle tick contact and SFTS infection (Conditional Logistic Regression OR-MH = 8.82, 95% CI = 1.69-46.05, P value = 0.01). Conclusion Our results suggested cattle might be dominant hosts in SFTS-endemic regions in Hubei Province, which provided clues to transmission mechanism of “vectors, host animals, and humans”, thus more effectively preventing and controlling the disease. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). The aim of this study was to clarify whether SFTS is potentially mis-diagnosed as rickettsioses, including spotted fever, typhus fever, and scrub typhus, which are also tick-borne disease. A total of 464 serum samples collected from 222 patients with clinically suspected rickettsiosis between 1999 and 2012 were tested for antibodies against the SFTSV. Of the 464 serum samples, one was positive for antibodies against the virus in an enzyme-linked immunosorbent assay and indirect immunofluorescence assay. The patient of SFTSV antibody-positive sample (15 days after disease onset) was positive for SFTSV genome in the acute phase sample (3 days after disease onset) as determined via reverse transcription-quantitative polymerase chain reaction. This patient, who was a resident of the Yamaguchi prefecture in Western Japan, was in his 40s when he showed symptoms in 2011. As the result, 1 of 222 patients, who was clinically suspected of rickettsiosis, was retrospectively diagnosed with SFTS. In this case, both the C-reactive protein and white blood cell count levels were lower than the ranges of these parameters for patients diagnosed with rickettsiosis. Therefore, SFTS should be considered in the differential diagnosis for rickettsiosis in Japan. [ABSTRACT FROM AUTHOR]

Summary Objectives Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus in which host immune system suppression is thought to be crucial in the development of disease. This study was designed to study the frequencies and activation status of dendritic cells (DCs) at different stages of SFTS and their association with disease severity. Methods All confirmed SFTS patients ( N = 115) were recruited from the Wuhan Union Hospital in 2015; routine laboratory parameters were collected. The frequencies, phenotypes, and subsets of circulating DCs, including myeloid and plasmacytoid dendritic cells (mDCs and pDCs), were analyzed by flow cytometry. Serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) were detected by ELISA. The laboratory parameters and other clinical events related to mortality were assessed by multivariate logistic regression analysis and receiver operating characteristic (ROC) curves. Results The frequency of circulating mDCs, especially from day 9 after disease onset, could serve as a valuable prognostic biomarker for the outcome in SFTS patients (area under the curve = 0.929, p < 0.0001). In addition, persistent down-regulation of the co-stimulatory molecules CD80/CD86 on the mDCs was observed during the disease process. Moreover, levels of mDCs were inversely correlated with the production of IL-6, IL-10, and TNF-α and with viral load at admission. Conclusions The present results indicate that DCs might be functionally impaired in SFTS. A decreased level of circulating mDCs was closely correlated with the severity of SFTS. [ABSTRACT FROM AUTHOR]

• Japanese badgers displayed 68% seropositivity of antibodies against SFTSV. • Japanese raccoon dogs showed 23% seropositivity of antibodies against SFTSV. • A total of 3% of the Japanese badgers presented with the viral RNA. • The SFTSV could be shared among these mammals and humans and companion animals. Severe fever with thrombocytopenia syndrome (SFTS) is a fatal emerging tick-borne zoonotic disease caused by the SFTS virus (SFTSV). SFTSV infection in humans and companion animals is a matter of concern in endemic areas. Various wild animals are involved in the transmission cycle of SFTSV with vector ticks. Because the home range of medium-sized wild mammals commonly overlaps with humans' living spheres, this study aimed to reveal the endemicity of SFTSV in such mammals. This study investigated the prevalence of antibodies against SFTSV and viral RNA in medium-sized wild mammals in Miyazaki Prefecture, Japan where human cases have been most frequently reported in Japan and performed a phylogenetic analysis to compare the detected SFTSV with those previously reported. Forty-three of 63 (68%) Japanese badgers (Meles anakuma) and 12 of 53 (23%) Japanese raccoon dogs (Nyctereutes procyonoides viverrinus) had antibodies against SFTSV. Japanese marten (n = 1), weasels (n = 4), and Japanese red fox (n = 1) were negative. Two of 63 (3%) badgers tested positive for SFTSV RNA, whereas the other species were negative. Phylogenetic analysis of the partial nucleotide sequence of SFTSV revealed that viral RNA detected from badgers exhibited 99.8% to 100% similarity to SFTSV, as previously reported in humans, cat, and ticks in the study area. This study demonstrated high seropositivity of antibodies in medium-sized wild mammals and suggested that SFTSV could be shared among these mammals, humans, and companion animals in endemic areas. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV), a novel phlebovirus belonging to the family Bunyaviridae, was reported in China for the first time in 2009. We observed two cases where the SFTSV was isolated for the first time in Nagasaki, Japan, in 2005. Two males in their 60s, a farmer and a hunter, respectively, living in Nagasaki developed SFTS during the same period. The patients developed similar clinical symptoms and signs, such as fever, loss of consciousness, and multiple organ dysfunction. The farmer died and the hunter survived. A retrospective diagnosis of SFTS was made in 2013, and genetic analysis revealed that the patients were infected with different SFTSV strains. Retrospective analysis of cytokine production in non-fatal case revealed interleukin (IL)-6, IL-8 and interferon-γ level of acute phase was low and could be potential prognostic factors. As there are no epidemiological studies of positive rate of SFTSV antibody in people living in endemic areas in Japan, a field study was performed. Volunteers at high risk for tick bites, such as hunters, farmers, and soldiers, were recruited in 6 regions, including the areas where the SFTS cases occurred. Three hundred and twenty six volunteers in Nagasaki prefecture were examined and none of these tested positive for the SFTSV antibody. Our data indicates that the risk for SFTSV infection is not high in Nagasaki prefecture. Further collection of blood samples from endemic areas is warranted for the prevention of SFTSV infection. [ABSTRACT FROM AUTHOR]

Background Severe fever with thrombocytopenia syndrome (SFTS), caused by novel bunyavirus (SFTSV) is a potentially fatal disease that was first identified in China. Person to person transmission through contact with blood or body fluids was considered as an important infection route. Objectives The study is designed to investigate the longitudinal viral loads following SFTSV infection and to identify factors affecting viral shedding in SFTS patients. Methods A prospective, observational study was performed on 208 laboratory-confirmed SFTSV infected patients in Xinyang, Henan Province. Sequential serum samples were collected on admission and during the hospitalization for quantification of SFTSV RNA by real-time RT-PCR. Results The viral RNA was undetectable in 55.6% of the patients on admission into the hospital, becoming detectable in most cases until three days and attained maximum level on six days after disease onset. This was followed by an obvious decrease thereafter, but maintained detectable for over 20 days. Viral load was independently predictable of severe disease outcome throughout the hospitalization. Viral load of >10 7 copies/mL was predictable of fatal outcome. The serum levels of PLT, WBC, LDH, AST and CK were significantly associated with viral loads level. Conclusions The diagnosis of SFTSV infection based on PCR test should be performed at least three days after disease onset. Peaking viral loads were attained around six days after disease, posing a highest risk of human-to-human transmission. [ABSTRACT FROM AUTHOR]

Abstracts Background Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne, novel bunyavirus-caused emerging infectious disease. It becomes a threat to public health due to its high fatality rate. Objective To clarify the epidemiological characteristics of SFTS and natural host(s) of SFTS-causing virus (SFTSV) in East China. Study design Serum antibody against SFTSV in 496 healthy villagers was examined by ELISA. SFTSV in acute sera of SFTS cases and lung tissues of house and field mouse/rats were identified using quantitative RT-PCR, cell culture, and sequencing. Results A total of 22 laboratory-confirmed SFTS cases were diagnosed between 2012 and 2014, of which 5 (22.7%) reported a history of tick-bites. The seroprevalance of SFTSV antibody was 10.5% in healthy villagers. SFTSV genomic RNAs were identified in 2 of 8 Apodemus agrarius but not in Rattus norvegicus ( n = 40) and Rattus losea ( n = 4). The 3 segments of SFTSV from 11 SFTS cases and 2 A. agrarius were successfully sequenced. Phylogenetic analyses indicated that at least 3 different SFTSV strains (inland-type, Ningbo-native-type, and their reassortant-type) were present in Ningbo. The 3 segments of the 2 SFTSV isolates from A. agrarius shared great sequence homologies to those isolated from the patients living in nearby villages. Conclusion The present study indicated that A. agrarius might be a natural host of SFTSV in East China. [ABSTRACT FROM AUTHOR]

Severe Fever with Thrombocytopenia Syndrome (SFTS) is associated with high mortality rate, for which antiviral therapy with ribavirin was recommended. Based on our previous study, no visible effect of ribavirin therapy in improving clinical outcome was observed. Here we have accumulated the sample size to 634, and by performing prospective observation on the clinical progress and laboratory parameters, we found a significantly higher incidence of anemia and hyperamylasemia in patients who received ribavirin therapy in comparison with those who received no therapy. Generalized estimating equation model disclosed a significant effect on hemoglobin reduction and blood amylase augmentation from ribavirin administration. The occurrence of anemia and hyperamylasemia was associated with SFTS patients receiving ribavirin therapy, which might be adverse event of this drug administration. The recommendation of ribavirin for treating SFTS should be applied with caution. [ABSTRACT FROM AUTHOR]

Background The immunological responses of patients with severe fever with thrombocytopenia syndrome (SFTS) remain largely unknown. We aim to study the magnitude and sustainability of host immune responses and their correlation with clinical, virological and hematological parameters. Methods A longitudinal cohort study was performed in a SFTS reference hospital. The sequential immunological evaluation was determined for SFTSV infected patients, including anti-SFTSV IgM, IgG antibodies and the lymphocyte subsets. Results Altogether 298 laboratory-confirmed SFTS cases were analyzed, from whom 55 patients were followed after convalescence. SFTSV specific IgM antibody could be detected at medium of 9 days, surged to peak levels by 4 weeks, and remained persistent until 6 months after disease onset. SFTSV specific IgG antibody could be detected at medium of 6 weeks; surged to peak levels by 6 months, and remained positive in most of the patients even at 3 years after infection. SFTS patients experienced obvious T cell, B cell and NK cells loss during the first week of infection, which was rapidly restored to normal levels. A significantly lower level of humoral immunity was identified concurrently from severe disease, especially in acute phase of the infection. These abnormalities can be used as a potential indicator in the prediction of an adverse clinical outcome. Conclusions Information gained from this study have clinical significance in enhancing our understanding of SFTS immunological characteristics and the disease pathogenesis. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia with case fatality up to 50%. SFTS is caused by SFTSV, a tick borne bunyavirus. In endemic area in China 1%–3% population was infected with SFTSV, but age is critical risk factor for hospitalization and death of SFTS patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]