Difference in hematocrit and plasma albumin levels as an early biomarker of severity and prognosis in patients with severe fever and thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a widespread infectious disease with high mortality. Hence, identifying valuable biomarkers for detecting the early changes in SFTS is crucial. In this study, we investigated the relationship between the difference in hematocrit (HCT) and serum albumin (ALB) levels (HCT-ALB) and the prognosis of patients with SFTS virus infection. After excluding the patients who did not meet the SFTS diagnostic criteria, those with SFTS from the First Affiliated Hospital of Wannan Medical College were divided into a fatal and Nonfatal group based on their disease prognosis. A dynamic analysis of the daily laboratory data was conducted for 14 days following SFTS onset. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of HCT-ALB. Another sample of patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University was utilized to verify the study conclusions. A total of 158 patients with SFTS were included. Among them, 126 patients were categorized in the Nonfatal group and 32 in the fatal group, leading to a mortality rate of 20.25% (32/158). Univariate analysis of the laboratory test findings and ROC curve analysis showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), HCT-ALB, and lactate dehydrogenase (LDH) had a relatively better ability to discriminate the disease condition of the patients with SFTS. Moreover, HCT-ALB served as a predictor of SFTS prognosis. Additionally, an area under the ROC curve (AUC) of 0.777 and a critical HCT-ALB value of 4.75 on day 7 were associated with a sensitivity of 83.3% and a specificity of 73.9%. On day 8 (AUC = 0.882), the critical value of HCT-ALB was 9.25, while the sensitivity was 100% and specificity was 76.5%. Further verification based on the data of 91 patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University demonstrated a mortality rate of 51% (24/47) among those with HCT-ALB values >4.75 on day 7 of the disease course, highlighting the potential of the HCT-ALB value of >4.75 for predicting SFTS prognosis. High HCT-ALB values are closely related to the mortality of patients with SFTS. HCT-ALB is a sensitive and independent predictor of early disease in patients with SFTS.

Acute kidney injury as a prognostic marker in severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne illness with a notable morality risk that is becoming increasingly prevalent in East Asia (14-36%). Increasing evidence indicates a more direct role of the SFTS virus in renal impairment. However, few studies have explored the risk factors for and clinical outcomes of AKI in patients with SFTS. Therefore, in this study, we aimed to investigate risk factors and outcomes associated with AKI in patients with SFTS. In this retrospective cohort study, we included the data of 53 patients who were diagnosed with SFTS virus infection at Kangwon National University Hospital between 2016 and 2020. We incorporated laboratory data and medical information including comorbidities, complications, and mortality. Baseline characteristics, clinical features, laboratory parameters, and mortality rates of the non-AKI and AKI groups were compared. Patient survival of non-AKI and AKI groups were compared using the Kaplan-Meier method. To identify the population with poor prognosis, Cox regression analysis was used to identify the independent risk factors for in-hospital mortality in patients with SFTS. Of the 53 individuals, 29 (54.7%) were male, with an average age of 66.5 years. Nine patients (15.1%) died of SFTS. Twenty-seven (50.9%) patients exhibited AKI; the average time interval from fever onset to AKI occurrence was 3.6 days. Notably, 24 (88.9%) patients developed AKI within the first week of fever onset. Patients in the AKI group exhibited a significantly higher prevalence of diabetes and were older than those in the non-AKI group. The mortality rate was notably higher (29.6%) in the AKI group than in the non-AKI group (3.8%). Within the AKI cohort, advanced stages (stages 2 and 3) showed a 50% mortality rate, which was significantly higher than the 17.6% mortality rate in patients with stage 1 AKI. Additionally, Kaplan-Meier curves revealed lower survival rates among patients with AKI than among those without AKI (P = 0.017). Cox regression analysis identified leukopenia and elevated serum creatinine levels as significant risk factors for mortality. AKI is a common complication associated with SFTS. Moreover, the mortality rate was significantly higher in the patients who developed AKI than in those who did not. Our findings underscore the pivotal role of AKI as a prognostic marker of disease severity in patients with SFTS.

Procalcitonin levels in severe fever with thrombocytopenia syndrome patients: a retrospective investigation in Anhui, China.

INTRODUCTION: This work aim to evaluate the association of procalcitonin (PCT) levels with disease severity and prognosis in severe fever with thrombocytopenia syndrome (SFTS) patients. METHODOLOGY: The medical records of 158 confirmed SFTS patients at two hospitals were reviewed. The patients were divided into survival group and nonsurvival group according to outcomes. Additionally, to assess mortality rates at different PCT levels, patients were divided into two groups, PCT < 0.25 ng/mL and PCT ≥ 0.25 ng/mL. RESULTS: Among the 158 confirmed SFTS patients, 26 died; the case fatality rate was 16.46%. PCT data were available for 132 of these patients; 66 were in the PCT < 0.25 ng/mL group, and 66 were in the PCT ≥ 0.25 ng/mL group. The SFTS patients had abnormal results on routine blood tests, indicating varying degrees of thrombocytopenia and leukopenia, and most patients presented with multiple organ dysfunction. The PCT level of the nonsurvival group was significantly higher than that of the survival group (p < 0.01). Additionally, the mortality of the PCT ≥ 0.25 ng/mL group was significantly higher than that of the PCT < 0.25 ng/mL group (p < 0.01); mortality increased sharply ( ≥ 25%) when the PCT level exceeded 0.1 ng/mL. CONCLUSIONS: PCT levels in SFTS patients are closely related to the severity and prognosis of their illness. The serum PCT level is a promising predictor of mortality and severity in SFTS patients when considered in combination with clinical data and other laboratory tests.

Clinical and etiological characteristics of severe hemorrhagic fever caused by coinfection of hantaan orthohantavirus and severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) and hemorrhagic fever with renal syndrome (HFRS) usually have different infection routes, and coinfection is relatively rare. This study examines the clinical and etiological characteristics of coinfection by these two pathogens to provide important references for clinical diagnosis and treatment. Blood samples from 22 clinically diagnosed patients with HFRS were collected for molecular detection of HFRS and common tick and mouse borne diseases. Inoculate the blood of six severe and critically patients into cells to isolate and proliferate potential viruses, and retest the cell culture to determine the pathogen. In addition, complete data were collected from these 22 HFRS and concurrent SFTS patients, and white blood cells (WBCs), platelet (PLT), blood urea nitrogen (BUN), creatinine (Cr) and other data were compared and analyzed. A total of 31 febrile patients, including 22 HFRS patients and 9 SFTS patients, were collected from September 2021 to October 2022. Among these HFRS patients, 11 were severe or critical. Severe and critical HFRS patients were characterized by rodent exposure history, pharyngeal and conjunctival hyperemia, abnormal WBC and PLT counts, and elevated BUN and Cr values. Virus isolation and molecular detection on blood samples from 6 patients showed that three of the six severe patients were positive for hantaan virus (HTNV), and two of the three HTNV positives were also positive for SFTS bunyavirus (SFTSV). The two coinfected patients exhibited different clinical and laboratory characteristics compared to those infected by either virus alone. Coinfection of HTNV and SFTSV leads to severe and complex hemorrhagic fever. Laboratory characteristics, such as the indicators of WBC, PLT, BUN, and Cr, may differ between HFRS and SFTS. These findings have implications and provide references for the diagnosis and treatment of coinfected cases.

Spatial and Temporal Analysis of Severe Fever with Thrombocytopenia Syndrome in Anhui Province from 2011 to 2023.

OBJECTIVE: To analyze the spatial autocorrelation and spatiotemporal clustering characteristics of severe fever with thrombocytopenia syndrome(SFTS) in Anhui Province from 2011 to 2023. METHODS: Data of SFTS in Anhui Province from 2011 to 2023 were collected. Spatial autocorrelation analysis was conducted using GeoDa software, while spatiotemporal scanning was performed using SaTScan 10.0.1 software to identify significant spatiotemporal clusters of SFTS. RESULTS: From 2011 to 2023, 5720 SFTS cases were reported in Anhui Province, with an average annual incidence rate of 0.7131/100,000. The incidence of SFTS in Anhui Province reached its peak mainly from April to May, with a small peak in October. The spatial autocorrelation results showed that from 2011 to 2023, there was a spatial positive correlation(P < 0.05) in the incidence of SFTS in all counties and districts of Anhui Province. Local autocorrelation high-high clustering areas are mainly located in the south of the Huaihe River. The spatiotemporal scanning results show three main clusters of SFTS in recent years: the first cluster located in the lower reaches of the Yangtze River, the eastern region of Anhui Province; the second cluster primarily focused on the region of the Dabie Mountain range, while the third cluster primarily focused on the region of the Huang Mountain range. CONCLUSIONS: The incidence of SFTS in Anhui Province in 2011-2023 was spatially clustered.

Construction and validation of a dynamic nomogram using Lasso-logistic regression for predicting the severity of severe fever with thrombocytopenia syndrome patients at admission.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression. METHODS: All eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model's performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance. RESULTS: 299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017-1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003-1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175-2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005-1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035-26.858; P < 0.001) and hemorrhage symptoms (OR, 3.414; 95% CI, 1.096-10.974; P = 0.035). The AUC-ROC, C-index, calibration plots, and DCA demonstrated the robust performance of the nomogram in predicting severity at admission, and Kaplan-Meier survival analysis indicated its utility in predicting 28-day mortality among SFTS patients. The dynamic nomogram is accessible at https://sfts.shinyapps.io/SFTS_severity_nomogram/ . CONCLUSION: This study provided a practical and readily applicable tool for the early identification of high-risk SFTS patients, enabling the timely initiation of intensified treatments and protocol adjustments to mitigate disease progression.

A nomogram and heat map based on LASSO-Cox regression for predicting the risk of early-stage severe fever with thrombocytopenia syndrome patients developing into critical illness at 7-day and 14-day.

Severe fever with thrombocytopenia syndrome (SFTS) represents an emerging infectious disease characterized by a substantial mortality risk. Early identification of patients is crucial for effective risk assessment and timely interventions. In the present study, least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was conducted to identify key risk factors associated with progression to critical illness at 7-day and 14-day. A nomogram was constructed and subsequently assessed for its predictive accuracy through evaluation and validation processes. The risk stratification of patients was performed using X-tile software. The performance of this risk stratification system was assessed using the Kaplan-Meier method. Additionally, a heat map was generated to visualize the results of these analyses. A total of 262 SFTS patients were included in this study, and four predictive factors were included in the nomogram, namely viral copies, aspartate aminotransferase (AST) level, C-reactive protein (CRP), and neurological symptoms. The AUCs for 7-day and 14-day were 0.802 [95% confidence interval (CI): 0.707-0.897] and 0.859 (95% CI: 0.794-0.925), respectively. The nomogram demonstrated good discrimination among low, moderate, and high-risk groups. The heat map effectively illustrated the relationships between risk groups and predictive factors, providing valuable insights with high predictive and practical significance.

Molecular mechanism and structure-guided humanization of a broadly neutralizing antibody against SFTSV.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), with a high mortality rate of up to 30%. The envelope glycoproteins of SFTSV, glycoprotein N (Gn) and glycoprotein C (Gc), facilitate the recognition of host receptors and the process of membrane fusion, allowing the virus to enter host cells. We previously reported a monoclonal antibody, mAb 40C10, capable of neutralizing different genotypes of SFTSV and SFTSV-related viruses. However, the specific neutralization mechanism is poorly understood. In this study, we elucidated the high-resolution structure of the SFTSV Gn head domain in complex with mAb 40C10, confirming that the binding epitope in the domain I region of SFTSV Gn, and it represented that a novel binding epitope of SFTSV Gn was identified. Through in-depth structural and sequence analyses, we found that the binding sites of mAb 40C10 are relatively conserved among different genotypes of SFTSV and SFTSV-related Heartland virus and Guertu virus, elucidating the molecular mechanism underlying the broad-spectrum neutralizing activity of mAb 40C10. Furthermore, we humanized of mAb 40C10, which is originally of murine origin, to reduce its immunogenicity. The resulting nine humanized antibodies maintained potent affinity and neutralizing activity. One of the humanized antibodies exhibited neutralizing activity at picomolar IC50 values and demonstrated effective therapeutic and protective effects in a mouse infection model. These findings provide a novel target for the future development of SFTSV vaccines or drugs and establish a foundation for the research and development of antibody therapeutics for clinical applications.

Establishment and validation of a clinical risk scoring model to predict fatal risk in SFTS hospitalized patients.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases. METHODS: From January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance. RESULTS: The multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452-4.360), elevated serum PT (p < 0.001, OR = 1.383, 95% CI 1.143-1.673), high viral load (p < 0. 001, OR = 1.496, 95% CI 1.290-1.735) and high level of serum urea (> 8.0 µmol/L) (p < 0.001, OR = 4.433, 95% CI 1.888-10.409). The AUC of the nomogram based on these four factors was 0.813 (95% CI, 0.758-0.868). The bootstrap resampling internal validation model performed well, and decision curve analysis indicated a high net benefit. CONCLUSIONS: The nomogram based on age, elevated PT, high serum urea level, and high viral load can be used to help early identification of SFTS patients at risk of fatality.

Recent research advances in the development of Dabie Banda virus vaccines.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral hemorrhagic fever caused by Dabie Banda virus (DBV). The virus was first discovered in eastern China in 2009 and is now considered an infectious disease with a mortality rate ranging from 6.3% to 30%. The best strategy for controlling SFTS is to develop effective vaccines. However, no approved vaccines are currently available to prevent this disease, despite the number of extensive and in-depth studies conducted on DBV in the past few years. This review focuses on the structure of DBV and the induced host immune responses which are the fundamental factors in vaccine development, and thoroughly summarizes the current research progress on DBV vaccines. The developing DBV vaccines include protein subunit vaccines, live attenuated vaccines, recombinant virus vector vaccines, and DNA vaccines. At present, almost all candidate vaccines for DBV are in the laboratory development or preclinical stages. There remain challenges in successfully developing clinically approved DBV vaccines.

Early predictors of Epstein-Barr virus infection in patients with severe fever with thrombocytopenia syndrome.

BACKGROUND: Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients. METHODS: In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups. We compared the demographic characteristics, clinical manifestations and signs, laboratory tests and prognosis, and explored the risk factors of EBV infection by receiver operating characteristic (ROC) curve and logistic regression. RESULTS: A total of 120 hospitalized SFTS patients with EBV-DNA testing were enrolled in this study. Patients with EBV infection had statistically significant higher mortality rate (32.0% vs. 11.43%, P = 0.005). Compared with the non-infected group, the EBV-infected group had higher levels of C-reactive protein (CRP), creatine-kinase (CK), fasting blood glucose (FBG), blood urea nitrogen (BUN), D-dimer, and CD56+ cell counts, lower levels of immunoglobulin G (IgG), IgM, complement 3 (C3), and C4. The proportion of patients with age ≥ 60 years and ferritin > 1500.0 ng/ml in the EBV-infected group was significantly higher than that in the non-infected group. The results of ROC analysis showed that the cut-off values of CRP, IgG, C3, C4, and CD56+ cell counts to predict EBV infection were 13.2 mg/l, 12.5 g/l, 1.1 g/l, 0.6 g/l, 0.3 g/l, and 94.0 cells/µl. Multivariable logistic analysis showed that age ≥ 60 years old, CRP > 13.2 mg/l, BUN > 5.4 mmol/l, ferritin > 1500.0 ng/ml, IgG < 12.5 g/l, IgM < 1.1 g/l, C4 < 0.3 g/l, and CD56+ cell counts > 94.0 cells/µl were the independent risk factors of EBV infection in SFTS patients. CONCLUSIONS: SFTS combined with EBV infection is associated with high morbidity and mortality. It is necessary to strengthen screening for EBV infection and its early predictive markers after admission in SFTS patients.

Antiviral Activity of Selective Estrogen Receptor Modulators against Severe Fever with Thrombocytopenia Syndrome Virus In Vitro and In Vivo.

Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection.

A broadly protective antibody targeting glycoprotein Gn inhibits severe fever with thrombocytopenia syndrome virus infection.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection.

Analysis of early warning indicators of death in patients with severe fever with thrombocytopenia syndrome.

BACKGROUND: Since its discovery, severe fever with thrombocytopenia syndrome (SFTS) has been characterized by rapid progression and poor prognosis, and no specific treatment is available. The aim of this study was to investigate the early warning indicators of mortality in SFTS patients. METHODS: This is a retrospective cross-sectional study. The study subjects were patients who were admitted to the hospital with a confirmed diagnosis of SFTS from January 2023 to October 2023, and their clinical symptoms and signs at the time of admission, as well as the laboratory indexes of the first blood collection after admission were collected, grouped according to the prognosis, and statistically analyzed. RESULTS: A total of 141 patients were collected, of which 27 patients died and 114 patients were in the survival group. Through statistical analysis, patients with combined hemorrhagic manifestations, disturbance of consciousness, lymphopenia, elevated lipase, and prolonged thrombin time on admission were independent risk factors for patients' death. By plotting the working characteristic curve of the subjects, as well as calculating the area under the curve, the results showed that the AUC of lymphopenia count was 0.670, 95% CI (0.563-0.776), P = 0.006; the AUC of elevated serum lipase index was 0.789, 95% CI (0.699-0.878), p < 0.001; the AUC of prolonged thrombin time was 0.749, 95% CI (0.645-0.854), p < 0.001. CONCLUSION: Patients with hemorrhagic manifestations, disturbance of consciousness, lymphocyte reduction, elevated serum lipase, and prolonged thrombin time on admission are more worthy of the clinician's attention, and require early and effective interventions to avoid further disease progression.

The use of glucocorticoid in severe fever with thrombocytopenia syndrome: a retrospective cohort study.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is prevalent in East Asia. However, the use of glucocorticoids (GCs) in the treatment of SFTS remains controversial. Methods: In this retrospective cohort study, we collected the data from patients with SFTS at Wuhan Union Hospital to evaluate the effect of GC therapy. Mortality and secondary infections were compared as outcomes. After searching public databases, we also included articles that examined GC use in patients with SFTS for meta-analysis. Results: Patients treated with GC had higher fatality rates (21.1% vs. 11.9%, respectively; P=0.006) and a longer length of stay (10.6 ± 5.1 vs. 9.5 ± 4.2, respectively; P=0.033). In cohorts adjusted using propensity score matching and inverse probability of treatment weighting, no significant differences in fatality rates and length of stay were observed. A meta-analysis of 4243 SFTS patient revealed that those treated with GCs had significantly higher mortality (OR=3.46, 95% CI =2.12-5.64, P<0.00001) and secondary infection rate (OR=1.97, 95% CI=1.45-2.67, P<0.0001). Discussion: GC should be used cautiously when treating SFTS. No significant differences were identified in terms of mortality and secondary infection rates between patients with SFTS treated with or without GC.

Comparison of epidemiological characteristics between hemorrhagic fever with renal syndrome patients and severe fever with thrombocytopenia syndrome patients.

Hemorrhagic fever with renal syndrome (HFRS) and severe fever with thrombocytopenia syndrome (SFTS) are both endemic in rural areas and some characteristics are similar between HFRS and SFTS, which usually lead to misdiagnosis. In this study, we summarized and compared some characteristics of HFRS and SFTS which will provide scientific information for differential diagnosis. From 2011 to 2022, a total of 4336 HFRS cases and 737 SFTS cases were reported in Zhejiang Province. Compared to SFTS, there was a higher proportion of males among HFRS cases (72.46% [3142/4336] vs. 50.88% [375/737], p = 0.000). The median age of all 4336 HFRS cases was 49 (39, 59), while the median age of SFTS cases was 66 (57, 74). In addition, the involved counties of HFRS were more than SFTS, but the number of counties affected by SFTS increased from 2011 to 2022. The majority of SFTS cases occurred in summer (from May to July), but besides summer, HFRS cases also showed a peak in winter. Finally, our results showed that the case fatality rate of SFTS was significantly higher than that of HFRS. Although there were some similarities between HFRS and SFTS, our study found several differences between them, such as gender distribution, age distribution, and seasonal distribution, which will provide scientific information for differential diagnosis of HFRS and SFTS. Further studies should be carried out to explore the mechanism of these differences.

Factors Associated With the Spatial Distribution of Severe Fever With Thrombocytopenia Syndrome in Zhejiang Province, China: Risk Analysis Based on Maximum Entropy.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was first identified in mainland China in 2009 and has been reported in Zhejiang Province, China, since 2011. However, few studies have focused on the association between ticks, host animals, and SFTS. Objective: In this study, we analyzed the influence of meteorological and environmental factors as well as the influence of ticks and host animals on SFTS. This can serve as a foundational basis for the development of strategic policies aimed at the prevention and control of SFTS. Methods: Data on SFTS incidence, tick density, cattle density, and meteorological and environmental factors were collected and analyzed using a maximum entropy-based model. Results: As of December 2019, 463 laboratory-confirmed SFTS cases were reported in Zhejiang Province. We found that the density of ticks, precipitation in the wettest month, average temperature, elevation, and the normalized difference vegetation index were significantly associated with SFTS spatial distribution. The niche model fitted accurately with good performance in predicting the potential risk areas of SFTS (the average test area under the receiver operating characteristic curve for the replicate runs was 0.803 and the SD was 0.013). The risk of SFTS occurrence increased with an increase in tick density, and the response curve indicated that the risk was greater than 0.5 when tick density exceeded 1.4. The risk of SFTS occurrence decreased with increased precipitation in the wettest month, and the risk was less than 0.5 when precipitation exceeded 224.4 mm. The relationship between elevation and SFTS occurrence showed a reverse V shape, and the risk peaked at approximately 400 m. Conclusions: Tick density, precipitation, and elevation were dominant influencing factors for SFTS, and comprehensive intervention measures should be adjusted according to these factors to reduce SFTS incidence in Zhejiang Province.