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Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high fatality rate. This disease has become increasingly prevalent in recent years in Jiangsu province, with a noticeable rise in its incidence. Notably, fatal cases have also been increasing. Our study aimed to analyze the epidemiological characteristics and risk factors associated with the fatal cases of SFTS in Jiangsu province from 2011 to September 2022., Methods: A retrospective study was performed among 698 SFTS cases during 2011-2022 in Jiangsu Province, China. Cox regression analyses were used to determine the dependent and independent risk factors that affected patient survival time. ArcGIS 10.7 was used for the visualization of the geographical distribution of the deaths from SFTS., Results: There were 698 SFTS cases reported, with an increasing incidence, over the 12-year period. Among these cases, 43 deaths were reported. Fatal cases of SFTS were reported in 12 district counties from 2011 to 2022. Notably, most of the deaths occurred in Lishui county of Nanjing City. The median age of those who died was 69 years, with age ranges from 50 to 83 years. Multivariable Cox regression analysis showed that older age (>70) and living in Lishui county were risk factors for death from SFTS in Jiangsu province. Therefore, older adults aged over 70 years and residing in Lishui county were the high-risk group for SFTS mortality., Discussion: Over the past 12 years, we have observed a consistent rise in the incidence of SFTS, accompanied by a relatively high case fatality rate, making it a critical public health issue. Therefore, it is urgently necessary to study the impact of meteorological factors on SFTS epidemics and devise prevention and control strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liang, Xie, Li, Zhang, Wang, Qin, Bao and Hu.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, which is caused by severe fever with thrombocytopenia syndrome virus (SFTSV) with high fatality. Recently, the incidence of SFTS increased obviously in Jiangsu Province. However, the systematic and complete analysis of spatiotemporal patterns and clusters coupled with epidemiological characteristics of SFTS have not been reported so far., Methods: Data on SFTS cases were collected during 2011-2021. The changing epidemiological characteristics of SFTS were analyzed by adopting descriptive statistical methods. GeoDa 1.18 was applied for spatial autocorrelation analysis, and SaTScan 10.0 was used to identify spatio-temporal clustering of cases. The results were visualized in ArcMap., Results: The annual incidence of SFTS increased in Jiangsu Province from 2011 to 2021. Most cases (72.4%) occurred during May and August with the obvious peak months. Elderly farmers accounted for most cases, among which both males and females were susceptible. The spatial autocorrelation and spatio-temporal clustering analysis indicated that the distribution of SFTS was not random but clustered in space and time. The most likely cluster was observed in the western region of Jiangsu Province and covered one county (Xuyi county) (Relative risk = 8.18, Log likelihood ratio = 122.645, P < 0.001) located in southwestern Jiangsu Province from January 1, 2017 to December 31, 2021. The Secondary cluster also covered one county (Lishui county) (Relative risk = 7.70, Log likelihood ratio = 94.938, P < 0.001) from January 1, 2017 to December 31, 2021., Conclusions: The annual number of SFTS cases showed an increasing tendency in Jiangsu Province from 2011 to 2021. Our study elucidated regions with SFTS clusters by means of ArcGIS in combination with spatial analysis. The results demonstrated solid evidences for the orientation of limited sanitary resources, surveillance in high-risk regions and early warning of epidemic seasons in future prevention and control of SFTS in Jiangsu Province., (© 2023. The Author(s).)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging natural focus, tick-borne disease caused by a novel bunyavirus named SFTS virus (SFTSV). The main purpose of this study was to analyze the environmental risk factors and geographic distribution of SFTS natural foci in Jiangsu Province. A retrospective space-time analysis by SaTScan software was used to detect clusters at the town level. The maximum entropy modeling method was applied to construct the ecological niche model and analyze the environmental risk factors, and then to draw the predicted risk map. The performance of the model was assessed using the area under the curve (AUC) and known occurrence locations. During the years 2010-2016, a total of 140 laboratory-confirmed indigenous SFTS cases occurred in Jiangsu Province, with 66 occurrence locations. The reported number of SFTS cases increased year by year and SFTS cases occurred from April to October with a peak between May and August each year. Three clusters detected by space-time scan statistical analysis were connected together and shared the similar ecological environmental characteristic of hilly landscape. Fifteen environmental variables with different percent contribution can influence the ecological niche model in different degrees, whereas slope (suitable range: 0.1-4) and maximum temperature of warmest month (suitable range: 32.8-34.2°C) as the key environmental factors contributed 46.1% and 23.2%, respectively. The model had high accuracy on prediction with the averaged training AUC of 0.926. Within a predicted risk map, potential areas at high risk and 10 previously unidentified endemic regions were recognized. The distribution of SFTS natural foci was under the influence of multidimensional environmental factors. Slope and maximum temperature of warmest month were the key environmental risk factors. These results provide a valuable basis for the selection of prevention and control strategies, and the identification of potential risk areas.

Background: A cluster of eleven patients, including eight family members and three healthcare workers with fever and thrombocytopenia occurred in Yixing County, Jiangsu Province, China, from October to November 1996. However, the initial investigation failed to identify its etiology. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS bunyavirus (SFTSV), which was first discovered in 2009. The discovery of novel SFTSV resulted in our consideration to test SFTSV on the remaining samples of this cluster in September 2010., Methodology/principal Findings: We retrospectively analyzed the epidemiological and clinical data of this cluster. The first case, one 55-year-old man with fulminant hemorrhagic diseases, died on October 14, 1996. His younger brother (the second case) developed similar hemorrhagic diseases after nursing him and then died on November 3. From November 4 to November 15, nine other patients, including six family members and three medical staffs, developed fever and thrombocytopenia after exposure to the second case. The sera of six patients were collected on November 24, 1996. IgM antibodies against SFTSV were detected in all of the six patients' sera using enzyme-linked immunosorbent assay (ELISA), while IgG antibodies were detected in one patient's serum using an indirect immunofluorescence assay (IFA). We also found that IgG antibodies against SFTSV were still detected in four surviving patients' sera 14 years after illness onset., Conclusions and Significance: The mysterious pathogen of the cluster in 1996 was proved to be SFTSV on the basis of its epidemiological data, clinical data and serological results. It suggests that SFTSV has been circulating in China for more than 10 years before being identified in 2009, and SFTSV IgG antibodies can persist for up to 14 years., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To identify specific clinical and epidemiological parameters for clinical diagnosis of SFTSV infection with relatively higher accuracy., Methods: 231 suspected cases of SFTS were reported by various medical institutions from 2011 to 2013 in Jiangsu Province, China. They were followed with SFTSV diagnosis tests and interview-administered questionnaires about demographic characteristics, clinical symptoms and epidemiological exposure factors. Univariate and multivariable logistic regression analysis were used to examine the diagnostic value of these parameters., Results: SFTSV infection occurred only from April to October annually and usually in hilly areas of specific regions. Three prediction models of SFTSV infection were constructed. Model 3 with clinical and epidemiological parameters combined the benefits of both Model 1and Model 2, which was optimal and had an overall accuracy of 80.2%. Independent indicators for clinical diagnosis of SFTSV infection in Model 3 were as follows: lymphadenopathy (P = 0.01), leucopenia (P<0.01), age >50 years (P = 0.01), tick bites (P<0.01), raising domestic animals in the residential areas (P<0.01) and farming (P = 0.03)., Conclusions: Our results show that using a combination of clinical and epidemiological parameters may be a feasible strategy to provide preliminary fast diagnosis as differentiating SFTSV infection from SFTS-like diseases, thus reducing the risk of misdiagnosis.

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by a novel bunyavirus, is an emerging infectious disease in China. In 2011, this new virus was designated as severe fever with thrombocytopenia syndrome virus (SFTSV). The aim of the present study was to determine the seroprevalence and risk factors of SFTSV infection. The investigation was conducted among the general population in Jiangsu Province, China in 2011. A total of 2,510 serum samples were collected. Testing by enzyme-linked immunosorbent assay was conducted to determine the seroprevalence of SFTSV infection. Result showed that the overall seroprevalence of SFTSV infection was 0.44% (11 of 2,510) in seven counties in Jiangsu Province. Multiple variable logistic regression analysis showed that raising goats, farming, and grazing were risk factors for SFTSV infection. Raising goats, farming, and grazing might be important risk factors for virus exposure, and appropriate health education could be useful in preventing infections.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus that causes a hemorrhagic fever known as the severe fever with thrombocytopenia syndrome (SFTS). Inflammasomes are a molecular platform that are assembled to process pro-caspase 1 and subsequently promote secretion of interleukin (IL)-1β/IL-18 for proinflammatory responses induced upon infection. We hypothesize that inflammasome activation and pyroptosis induced in SFTS results in elevated levels of IL-1β/IL-18 responsible for high fever and hemorrhage in the host, characteristic of SFTS. Here we report that IL-1β secretion was elevated in SFTS patients and infected mice and IL-1β levels appeared to be reversibly associated to disease severity and viral load in patients' blood. Increased caspase-1 activation, IL-1β/IL-18 secretion, cell death, and processing of gasdermin D were detected, indicating that pyroptosis was induced in SFTSV-infected human peripheral blood monocytes (PBMCs). To characterize the mechanism of pyroptosis induction, we knocked down several NOD-like receptors (NLRs) with respective shRNAs in PBMCs and showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome was critical for processing pro-caspase-1 and pro-IL-1β. Our data with specific inhibitors for NLRP3 and caspase-1 further showed that activation of the NLRP3 inflammasome was key to caspase-1 activation and IL-1β secretion which may be inhibitory to viral replication in PBMCs infected with SFTSV. The findings in this study suggest that the activation of the NLPR3 inflammasome and pyroptosis, leading to IL-1β/IL-18 secretion during the SFTSV infection, could play important roles in viral pathogenesis and host protection. Pyroptosis as part of innate immunity might be essential in proinflammatory responses and pathogenicty in humans infected with this novel phlebovirus. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) was listed as one of the most severe infectious disease by world health organization in 2017. It can mostly be transmitted by tick bite, while human-to-human transmission has occurred on multiple occasions. This study aimed to explore the epidemiological and clinical characteristics and make risk analysis of SFTS human-to-human transmission. Methods: Descriptive and spatial methods were employed to illustrate the epidemiological and clinical characteristics of SFTS human-to-human transmission. The risk of SFTS human-to-human transmission was accessed through secondary attack rate (SAR) and basic reproductive number (R0). Logistic regression analysis was used to identify the associated risk factors. Results: A total of 27 clusters of SFTS human-to-human transmission were reported in China and South Korea during 1996–2019. It mainly occurred among elder people in May, June and October in central and eastern China. The secondary cases developed milder clinical manifestation and better outcome than the index cases. The incubation period was 10.0 days (IQR:8.0–12.0), SAR was 1.72%-55.00%, and the average R0 to be 0.13 (95%CI:0.11–0.16). Being blood relatives of the index case, direct blood/bloody secretion contact and bloody droplet contact had more risk of infection (OR = 6.35(95%CI:3.26–12.37), 38.01 (95%CI,19.73–73.23), 2.27 (95%CI,1.01–5.19)). Conclusions: SFTS human-to-human transmission in China and South Korea during 1996–2019 had obvious spatio-temporal distinction. Ongoing assessment of this transmission risk is crucial for public health authorities though it continues to be low now. Author summary: This study is first to explore the epidemiological and clinical characteristics of SFTS human-to-human transmission. We found SFTS human-to-human transmission had obvious characteristic temporal and spatial distinction, which mainly occurred among elder people in May, June and October in the central and eastern China. The secondary cases developed milder clinical manifestation and better outcome than the index cases. The incubation period was 10.0 days (IQR:8.0–12.0). The risk of SFTS human-to-human transmission continues to be low, with the secondary attack rate (SAR) among humans was 1.72%-55.00% and basic reproductive number (R0) to be 0.13 (95%CI:0.11–0.16). Being blood relatives of the index case, direct blood/bloody secretion contact and bloody droplet contact had more risk of acquiring infection. [ABSTRACT FROM AUTHOR]

Background Severe fever with thrombocytopenia syndrome (SFTS) is a typical tick-borne, natural focal disease. The natural foci of SFTS were considered to exist in hilly and mountainous areas before 2015. A cluster of 3 patients exposed to a patient with a fulminant disease consistent with SFTS occurred from July to August 2015 in Dongtai County, which is characterized by alluvial plains; this prompted investigation. Methods The epidemiological, clinical, and laboratory features of 4 patients in the cluster were analyzed. Serum samples from the indigenous healthy population and native domesticated animals were collected to conduct laboratory tests, along with small wild animals and ticks. Results In 3 secondary case patients, high fever, thrombocytopenia and leukopenia developed within 8–13 days after contact with blood or bloody secretions from the index patient; SFTS was then diagnosed by means of reverse-transcription polymerase chain reaction. Genomic sequencing and analysis of S and L segments of 2 viral strains isolated from 2 secondary case patients showed that they shared 99.8%–99.9% homology in nucleotide sequence. The seroprevalences among indigenous healthy population, native livestock, native poultry, and small wild animals was 0.74%, 17.54%, 6.67%, and 1.12%, respectively. Three questing ticks, 61 feeding ticks, and 178 small wild animals were collected in August 2015. Survey on tick density and seasonal fluctuation in 2016 showed that ticks were active from March to October. All ticks were identified as Haemaphysalis longicornis. Severe fever with thrombocytopenia bunyavirus (SFTSV)–specific RNA was detected in the ticks collected in 2016, and the minimum SFTSV infection rate in these ticks was 0.54% (1 of 185).Wild mammals and ticks collected in August 2015 tested negative for SFTSV-specific RNA. Conclusions Aside from hilly or mountainous area, a coastal plain was identified as the natural foci of SFTSV in Dongtai County, China. The involvement of migration in the evolution of SFTSV might lead to a transregional transmission event of SFTSV. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a tick-borne phlebovirus in family Bunyaviridae. Studies have found that humans, domestic and wildlife animals can be infected by SFTSV. However, the viral ecology, circulation, and transmission remain largely unknown. Methodology/Principal Findings: Sixty seven human SFTS cases were reported and confirmed by virus isolation or immunofluorescence assay between 2011 and 2014. In 2013–2014 we collected 9,984 ticks from either vegetation or small wild mammals in the endemic area in Jiangsu, China, and detected SFTSV-RNA by real-time RT-PCR in both questing and feeding Haemaphysalis longicornis and H. flava. Viral RNA was identified in larvae of H. longicornis prior to a first blood meal, which has never been confirmed previously in nature. SFTSV-RNA and antibodies were also detected by RT-PCR and ELISA, respectively, in wild mammals including Erinaceus europaeus and Sorex araneus. A live SFTSV was isolated from Erinaceus europaeus captured during the off tick-feeding season and with a high SFTSV antibody titer. Furthermore, SFTSV antibodies were detected in the migratory birds Anser cygnoides and Streptopelia chinensis using ELISA. Conclusions/Significance: The detection of SFTSV-RNA in non-engorged larvae indicated that vertical transmission of SFTSV in H. longicornis might occur in nature, which suggests that H. longicornis is a putative reservoir host of SFTSV. Small wild mammals such as Erinaceus europaeus and Sorex araneus could be infected by SFTSV and may serve as natural amplifying hosts. Our data unveiled that wild birds could be infected with SFTSV or carry SFTSV-infected ticks and thus might contribute to the long-distance spread of SFTSV via migratory flyways. These findings provide novel insights for understanding SFTSV ecology, reservoir hosts, and transmission in nature and will help develop new measures in preventing its rapid spread both regionally and globally. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and evaluate a two-tube multiplex real-time RT-PCR assay for the detection and identification of four viral hemorrhagic fever (VHF) pathogens, severe fever with thrombocytopenia syndrome virus (SFTSV), Hantaan virus (HTNV), Seoul virus (SEOV), and dengue virus (DENV), from human clinical samples. The two-tube multiplex real-time RT-PCR assay we developed has a sensitivity of 10 copies/μL for each of the targets, and the performance was linear within the range of at least 10 transcript copies. Moreover, we evaluated the specificity of the assay using other virus RNA as template, and found no cross-reactivity. This new assay is able to detect SFTSV, HTNV, SEOV and DENV in two reactions and brings a cost of 40 % compared to separate reactions. Evaluation of this assay with clinical serum samples from laboratory-confirmed patients and healthy donors showed 100 % clinical diagnostic sensitivity and over 99 % specificity. The assay was applied for scanning 346 clinical samples collected from patients admitted to the hospital with suspected VHF and compared with virus isolation and immunofluorescence assay (IFA). The assay indentified 59 SFTSV-, 12 HTNV-, 11 SEOV- and 9 DENV-positive samples and showed higher sensitivity. This assay thus provides a reliable and cost-effective screening tool for early clinical diagnosis of SFTSV, HTNV, SEOV and DENV in the acute phase. [ABSTRACT FROM AUTHOR]

Highlights: [•] SFTS virus seroprevalence among farmers was higher than in general population. [•] SFTS virus readily infects humans with farming-related exposures. [•] SFTS virus circulates widely in animal species of Jiangsu Province. [Copyright &y& Elsevier]