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Background Severe fever with thrombocytopenia syndrome (SFTS) virus was first isolated in China in 2009 and has since spread to several Asian countries. SFTS is closely related to environmental factors that accelerate vector growth. We evaluated the associations of SFTS and deforestation with environmental variables. Methods For this observational study, we generated multiple Poisson models using national SFTS outbreak data (2013–2018) and official environmental data for Korea. We included established risk factors as variables. Deforestation was used as the main variable. All variables were analyzed according to their spatial characteristics using the R-INLA package. Results SFTS cases increased over time and peaked in 2017, at 272, followed by a decrease in 2018. Disease mapping showed a high incidence of SFTS nationwide, with particular risks in Gangwon and Gyeonggi Provinces in the north, and Jeju in the south of South Korea. Deforestation was significantly associated with a higher risk of SFTS in the final model (relative risk, 1.751 [95% confidence interval, 1.125–2.743]). Conclusions SFTS outbreaks are associated with deforestation. Therefore, deforestation in Gyeonggi, Gangwon, and Jeju provinces of South Korea needs to be considered in vector-control strategies and active surveillance of SFTS occurrence. [ABSTRACT FROM AUTHOR]

Since the identification of severe fever with thrombocytopenia syndrome virus (SFTSV) in 2010, there has been an increase in reported cases in China and other Asian countries. Cardiac abnormalities are highly prevalent in SFTS patients. We searched 5 Chinese and international databases for published SFTS articles and extracted patient characteristics, cardiac complications, electrocardiography findings, and imaging findings. Twenty-seven studies were identified, covering 1938 patients and 621 cardiac abnormalities. Arrhythmia was the most prevalent, reported in 24 studies and 525 cases, with a prevalence of 27.09%. The 2 major types of arrhythmias were bradycardia and atrial fibrillation. Heart failure was the second most prevalent abnormality, with 77 cases. Changes in the ST segment and T wave were the most common. Valve regurgitation, reduced ejection fraction, and pericardial effusion were also documented. We recommend that physicians pay close attention to newly onset arrhythmia and structural heart disease in SFTS patients. [ABSTRACT FROM AUTHOR]

Background Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) are the 2 most common tick-borne infectious diseases in Korea. Every year, an increasing number of cases are reported, which is a public health concern. Therefore, we aimed to investigate the prevalence of SFTS–scrub typhus coinfection in patients with SFTS. Methods Clinical samples were collected from 129 patients with SFTS. One-step reverse-transcription polymerase chain reaction (PCR) was performed to identify the SFTS virus (SFTSV), and real-time PCR followed by nested PCR was performed to detect the Orientia tsutsugamushi gene for scrub typhus. Phylogenetic analysis was conducted to confirm the evolutionary relationships among different species. Results Among 129 SFTS cases, 2 patients with SFTSV were positive for O. tsutsugamushi with a prevalence of coinfection of 1.6% (95% confidence interval,.001–.06). Phylogenetic analysis confirmed these as O. tsutsugamushi strain Boryong. Conclusions Our study found that 1.6% of patients were coinfected with SFTS and scrub typhus infection. We believe that this information will add a new dimension to clinical diagnosis, which should be considered for better public health management. Further research is needed to better understand the ecological transmission dynamics and geographical distribution of SFTSV and O. tsutsugamushi in endemic countries. [ABSTRACT FROM AUTHOR]

Background Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening infectious disease for which no effective treatment strategy has been established. Although corticosteroids (CSs) are widely administered to patients with SFTS, their efficacy remains uncertain. This study aimed to assess the impact of CS therapy on the in-hospital mortality of patients with SFTS. Methods In this nationwide observational study using the Japanese Diagnosis Procedure Combination database, patients hospitalized for SFTS from April 2013 to March 2021 were reviewed. We compared patients who were treated with CSs to those who were treated without them after propensity score matching to adjust for their background, disease severity, and combination therapy. Results We included 494 patients with SFTS, and 144 pairs of them were analyzed after propensity score matching. No significant difference in the 30-day mortality (19% vs 15%, P =.272) and the number of survival days (log-rank test, P =.392) was found between the CS treatment group and the non-CS treatment group. However, in subgroup analyses, the CS treatment group tended to have better survival among patients with impaired consciousness on admission and/or shock status within 7 days after admission. Conclusions CS therapy does not seem effective for all patients with SFTS; however, the impact might be altered by disease severity assessed by the consciousness level and shock status. A large-scale interventional study is required to determine its efficacy, especially for critically ill patients with SFTS. [ABSTRACT FROM AUTHOR]

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever in China, Korea, and Japan. Japanese spotted fever (JSF), which belongs to spotted fever group rickettsioses, is also endemic to Western Japan. Patients with SFTS and those with JSF display many of the same clinical manifestations. Sudden fever, rash, tick bite, and neurological and gastrointestinal symptoms may be seen in both infections, but the frequency and severity of each disease have not been compared and studied. Because laboratory confirmation of pathogens takes time, it is important to predict diagnosis of SFTS vs JSF based on the features of the clinical characteristics at the initial presentation, particularly in primary care settings. Methods We conducted a case series review at 4 medical facilities in Miyazaki, Japan. Based on the medical records, clinical and laboratory characteristics were compared between patients with SFTS and those with JSF. Results Eighty-one patients were enrolled in this study, including 41 with SFTS and 40 with JSF. The absence of rash (P  < .001), leukopenia (P  < .001), and normal C-reactive protein (CRP) levels (P  < .001) were the variables distinguishing SFTS from JSF. Normal CRP levels (≤1.0 mg/dL) had a 95% sensitivity (84%–99%) and 97% specificity (87%–100%) for SFTS, with a positive likelihood ratio of 37.1 (5.35–257). Conclusions Normal serum CRP levels were shown to differentiate SFTS from JSF with a very high probability. [ABSTRACT FROM AUTHOR]

Background: The extensive geographical distribution and high mortality rate of severe fever with thrombocytopenia syndrome (SFTS) have made it an important threat to public health. Neutrophil extracellular traps (NETs) can be activated by a variety of pathogens and are associated with thrombocytopenia in viral infections. We aimed to identify NET production and its predictive value for disease progression and prognosis in patients with SFTS. Methods: A prospective study was performed with a multicenter cohort of patients with SFTS (n = 112) to quantify serum NET levels. Three markers of NETs-namely, cell-free DNA (cfDNA), myeloperoxidase-DNA complexes, and lactoferrin-DNA complexes-were measured with PicoGreen double-stranded DNA assays and enzyme-linked immunosorbent assays. Receiver operating characteristic curves and multivariate regression analyses were performed to calculate the predictive value of cfDNA levels. Results: SFTS was characterized by pronounced NET formation. The serum levels of NETs changed dynamically during disease progression, with an inverse pattern of the trends of platelet and neutrophil levels. High cfDNA levels were strongly associated with multiple pathological processes, including coagulopathy, myocardial damage, liver dysfunction, and the development of encephalopathy. A high level of cfDNA (>711.7 ng/mL) at the time of the initial diagnosis predicted severe illness in patients with SFTS (odds ratio, 8.285 [95% confidence interval, 2.049-33.503]; P = .003). Conclusions: This study has a high degree of clinical impact for identification of cfDNA as a useful predictive biomarker of clinical outcomes of SFTS. [ABSTRACT FROM AUTHOR]

Sixteen of 45 patients with severe fever with thrombocytopenia (36%) were admitted to an intensive care unit; 9 (56%) developed invasive pulmonary aspergillosis (IPA) within a median of 8 days (range, 2–11). Mortality was higher in the IPA vs non-IPA patients and in those without vs with antifungal therapy. [ABSTRACT FROM AUTHOR]

Atypical lymphocytes in the peripheral blood in patients with severe fever with thrombocytopenia syndrome (SFTS) have not been well examined. In this study, we analyzed counts and characteristics of atypical lymphocytes in 7 patients with SFTS. Atypical lymphocytes resembled plasma cells morphologically and appeared in the peripheral blood of all patients 4-8 days after onset of disease. Among these lymphocytes flow cytometry showed a CD19+CD38+CD138-/+ phenotype, and immunohistochemical staining revealed a CD79a+CD38+CD138-/+CD27+ phenotype. From our observations, atypical lymphocytes transiently that appeared in the peripheral blood during the acute phase of SFTS were considered to be plasmablasts. [ABSTRACT FROM AUTHOR]

We developed a scoring system to differentiate severe fever with thrombocytopenia syndrome (SFTS) in 21 patients with SFTS and 91 with scrub typhus; it provided 100% sensitivity and 97% specificity (score > 1). Criteria included altered mental status, leukopenia, prolonged activated partial thromboplastin time, and normal C-reactive protein (1-point each). [ABSTRACT FROM AUTHOR]

We have shown that human alveolar lining fluid (ALF) contains homeostatic hydrolases capable of altering the Mycobacterium tuberculosis cell wall and subsequently its interaction with human macrophages. Neutrophils are also an integral part of the host immune response to M. tuberculosis infection. Here we show that the human lung mucosa influences M. tuberculosis interaction with neutrophils, enhancing the intracellular killing of ALFexposed M. tuberculosis and up-regulating the expression of tumor necrosis factor and interleukin 8. In contrast, ALF-exposed M. tuberculosis does not induce neutrophil apoptosis or necrosis, degranulation, or release of extracellular traps, and it decreases the oxidative response. These results suggest an important role for the human alveolar mucosa: increasing the innate capacity of the neutrophil to recognize and kill M. tuberculosis by favoring the use of intracellular mechanisms, while at the same time limiting neutrophil extracellular inflammatory responses to minimize their associated tissue damage. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne acute infectious disease caused by the SFTS virus (SFTSV). SFTS has been reported in China, South Korea, and Japan as a novel Bunyavirus. Although several molecular epidemiology and phylogenetic studies have been performed, the information obtained was limited, because the analyses included no or only a small number of SFTSV strains from Japan. Methods: The nucleotide sequences of 75 SFTSV samples in Japan were newly determined directly from the patients' serum samples. In addition, the sequences of 7 strains isolated in vitro were determined and compared with those in the patients' serum samples. More than 90 strains that were identified in China, 1 strain in South Korea, and 50 strains in Japan were phylogenetically analyzed. Results: The viruses were clustered into 2 clades, which were consistent with the geographic distribution. Three strains identified in Japan were clustered in the Chinese clade, and 4 strains identified in China and 26 in South Korea were clustered in the Japanese clade. Conclusions: Two clades of SFTSV may have evolved separately over time. On rare occasions, the viruses were transmitted overseas to the region in which viruses of the other clade were prevalent. [ABSTRACT FROM AUTHOR]

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

This study identifies clinical indicators that were associated with STFS fatal outcome. However, it finds no evidence to support effectiveness for use of ribavirin in the treatment of individuals with SFTS.Background. The wide distribution and high case-fatality ratio of severe fever with thrombocytopenia syndrome (SFTS) have made it a significant public health problem. This study was designed to identify the predictors of fatal outcomes and to evaluate the effectiveness of antiviral therapy in treating SFTS virus (SFTSV)–infected patients.Methods. A cross-sectional study was performed in a general hospital located in Xinyang city, whereas the largest number of patients with SFTS in China were treated during 2011–2012. The primary outcome for the treatment effect analysis was death. Other outcomes included sequential platelet levels and viral loads observed throughout the hospitalization and the interval between the initiation of ribavirin therapy and the return of the platelet count to a normal level.Results. A total of 311 SFTSV-infected patients were included in the study. The most frequent clinical presentations were fever, weakness, myalgia, and gastrointestinal symptoms. Each patient had thrombocytopenia, leukopenia, or both. The case-fatality ratio (CFR) was 17.4% (95% confidence interval [CI], 13.1%–21.6%). Older age (odds ratio [OR], 1.061; 95% CI, 1.023–1.099; P = .001), decreased level of consciousness (OR, 5.397; 95% CI, 2.660–10.948; P < .001), and elevated levels of lactate dehydrogenase (>1200 U/L; OR, 2.620; 95% CI, 1.073–6.399; P = .035) and creatine kinase (>800 U/L; OR, 2.328; 95% CI, 1.129–4.800; P = .022) were significantly associated with fatal outcome. The CFRs were similar between patients who received ribavirin and those who did not. Ribavirin treatment showed no significant effect on either platelet counts or viral loads during hospitalization of patients with fatal or nonfatal cases.Conclusions. These findings can improve knowledge about the characteristics of patients with fatal outcomes and the use of antiviral drug for SFTS. [ABSTRACT FROM PUBLISHER]

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease often accompanied by immune catastrophic course and subsequent fatal outcome. More than 90% of patients with SFTS had leukopenia and about one-third of those need the admission of intensive care unit (ICU) during the hospital course. So, there has been growing concern about the complications such as invasive pulmonary aspergillosis (IPA) in critical SFTS patients. We thus investigate the incidence and clinical characteristics of IPA in patients with SFTS. Methods All patients who were confirmed as SFTS in a tertiary care hospital, Seoul, South Korea, between January 2013 and October 2018 were enrolled. The modified AspICU algorithm was used to identify cases of putative invasive pulmonary aspergillosis (PIPA) and discriminate these invasive diseases from colonization. Results Of the 45 PCR-confirmed SFTS patients, 16 (36%) received ICU care. Of these 16 patients, 9 (56%) developed PIPA during hospitalization. The median duration from admission to the first evidence of PIPA was 8 days (range, 2–11 days). None of the PIPA cases met the revised EORTC/MSG criterion. Septic shock and corticosteroid administration preceded more frequently in PIPA group than non-PIPA group (100% vs. 19%, P < 0.0001 and 67% vs. 14%, P = 0.003, respectively). Patients complicated by PIPA showed significantly higher mortality than non-PIPA patients (44% vs. 8%, P = 0.048 by log-rank test). Mortality was lower in patients with PIPA who received antifungal treatment (17% [1/6]) than in those with PIPA who did not (100% [3/3]) (log-rank test, P = 0.002). Conclusion More than half of patients with SFTS in ICU were complicated by IPA during early hospital course. Cautious scrutiny for IPA in patients with SFTS followed by early appropriate antifungal therapy for IPA is needed. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background SFTS and scrub typhus have similar clinical features and difficult to differentiate. Thus, a study to develop a scoring system to differentiate between two diseases in a clinical setting before the confirmation of laboratory results was reported by Kim et al. However, the statistical power could be low because of low numbers of cases (21 SFTS, 91 scrub typhus), our study analyzed by increasing the number of cases to overcome these limitations. Methods We retrospectively collected data from 183 SFTS and 178 scrub typhus patients who visited the 21 hospitals in South Korea between October, 2013 and November, 2017. The study protocol was approved by the IRB of each institution. SFTS was diagnosed through detection of SFTS viral RNA using RT–PCR. Scrub typhus was diagnosed either detection of 56-kDa antigen of O. tsutsugamushi using nested PCR or ≥ 4 fold rise in IgM or IgG titer using indirect IFA. Statistical analyses were performed by using SPSS and Medcalc. Results To differentiate SFTS from scrub typhus, we applied the scoring system proposed by Kim et al. After multivariable logistic regression, altered mental status, leukopenia, prolonged aPTT, and normal CRP(≤ 1.0 mg/dL) were significantly associated with SFTS compared with scrub typhus. Each variable was scored by 1 point, with a total score of 0–4 points, the optimal cutoff value was > 1 for the ROC curve. A score > 1 had 92% sensitivity, 96% specificity for diagnosis of SFTS, with a ROC AUC of 0.974. Because the sensitivity was less than 95%, we changed the normal CRP criteria to ≤ 3.0 mg/dL. The modified scoring system had 97% sensitivity, 96% specificity for diagnosis of SFTS, with an AUC of 0.983, and it showed a statistically higher accuracy than original scoring system (P = 0.0487). In this study, four factors for predicting SFTS were newly developed: leukopenia, prolonged aPTT, normal CRP (≤3.0 mg/dL), and elevated CK (>1,000 IU/L). Our study scoring system had 97% sensitivity, 98% specificity for diagnosis of SFTS, with an AUC of 0.992, and it showed a statistically higher accuracy than original scoring system (P = 0.0308). Conclusion In conclusion, we can easily differentiate SFTS from scrub typhus by using our scoring system of leukopenia, prolonged aPTT, normal CRP, and elevated CK in the endemic area. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

An effective differentiation between severe fever with thrombocytopenia syndrome and hemorrhagic fever with renal syndrome was attained by a model considering patients' age, mouse/tick contact, presence of blush, low back pain, diarrhea, enlarged lymph nodes, and white blood cell count. [ABSTRACT FROM AUTHOR]

Background Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne emerging infectious disease caused by SFTS virus (SFTSV). Mortality of SFTS estimated to be 21.8% in South Korea, and this disease is difficult differential diagnosis. Here, we analyzed clinical characteristics between SFTS positive group (SPG) and negative group (SNG) in a primary clinical setting. Methods In this prospective observational study, data were collected on patients with SFTS test performed at the single teaching hospital, in South Korea, between April 2013 and December 2018. The association between each demographic, climatic, clinical, and laboratory variable was assessed. All SFTS was confirmed at the KCDC by detecting the M segment gene of SFTSV RNA using reverse transcription-polymerase chain reaction (RT–PCR), and were confirmed at our laboratory by S segment gene of SFTSV RNA using RT–PCR about patient's family member and those with close contact. Results Of the 199 patients in the study periods, 61 (31%) were SPG and 138 (69%) were SNG. Mean age was 55.1 ± 20.3 years, and 103 (52%) patients were male. In SPG, the comorbidity score and history of tick bite were significantly higher compared with SNG. SPG and SNG were prevalent in summer and autumn, respectively (60.7% vs. 45.7%, P < 0.05). SPG was associated with mean outdoor temperature, humidity and rainfall compared with SNG (22.9°Cvs. 18.9 ℃; 78.8% vs. 70.6%; 12.6 mm vs. 8.5 mm, all P < 0.01). Dizziness, poor oral intake, nausea, and diarrhea were common in SPG. In laboratory findings, white blood cell counts, absolute neutrophil count, and C-reactive protein were significantly lower in SPG. Lymphocyte fraction, activated partial thromboplastin time, and creatinine phosphokinase were significantly higher in SPG. Case fatality of the SPG and SNG were 9.8% and 1.0%, respectively. In multivariate analysis, mean outdoor temperature, humidity, dizziness, and low CRP were predictive factors in SPG. Conclusion Early prediction of SFTS diagnosis is important because this emerging zoonotic disease was a high fatality in endemic areas. When a physician wants to do SFTS test, they would consider according to this predictive variable for differentiating SFTS in primary care settings. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumors (SFT) are uncommon fibroblastic mesenchymal neoplasms that display a wide range of histologic behaviors. These tumors, which are estimated to account for 2% of all soft tissue neoplasms, typically follow a benign clinical course. However, it is estimated that 10–30% of SFTs are malignant and demonstrate aggressive behavior with local recurrence and metastasis up to several years after surgical resection. We report a case of SFT arising from the stomach, which is an exceptionally rare finding and has been reported only six times in the literature. Our case was complicated by diagnostic dilemma with GIST, highlighting the challenges of diagnosing and characterizing SFTs. Additionally, this tumor was associated with dedifferentiation into undifferentiated pleomorphic sarcoma. To our knowledge, there are no documented cases of a malignant SFT arising from the stomach to demonstrate dedifferentiation into an undifferentiated pleomorphic sarcoma. [ABSTRACT FROM AUTHOR]