Predictive risk score model for severe fever with thrombocytopenia syndrome mortality based on qSOFA and SIRS scoring system.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a severe systemic virus infectious disease usually having multi-organ dysfunction which resembles sepsis. METHODS: Data of 321 patients with laboratory-confirmed SFTS from May 2013 to July 2017 were retrospectively analyzed. Demographic and clinical characteristics, calculated quick sequential organ failure assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria for survivors and nonsurvivors were compared. Independent risk factors associated with in-hospital mortality were obtained using multivariable logistic regression analysis. Risk score models containing different risk factors for mortality in stratified patients were established whose predictive values were evaluated using the area under ROC curve (AUC). RESULTS: Of 321 patients, 87 died (27.1%). Age (p < 0.001) and percentage numbers of patients with qSOFA≥2 and SIRS≥2 (p < 0.0001) were profoundly greater in nonsurvivors than in survivors. Age, qSOFA score, SIRS score and aspartate aminotransferase (AST) were independent risk factors for mortality for all patients. qSOFA score was the only common risk factor in all patients, those age ≥ 60 years and those enrolled in the intensive care unit (ICU). A risk score model containing all these risk factors (Model1) has high predictive value for in-hospital mortality in these three groups with AUCs (95% CI): 0.919 (0.883-0.946), 0.929 (0.862-0.944) and 0.815 (0.710-0.894), respectively. A model only including age and qSOFA also has high predictive value for mortality in these groups with AUCs (95% CI): 0.872 (0.830-0.906), 0.885(0.801-0.900) and 0.865 (0.767-0.932), respectively. CONCLUSIONS: Risk models containing qSOFA have high predictive validity for SFTS mortality.

Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne banyangvirus and is associated with high fatality. Despite increasing incidence of SFTS and serious public health concerns in East Asia, the pathogenesis of lethal SFTS virus (SFTSV) infection in humans is not fully understood. Numbers of postmortem examinations to determine target cells of the viral infection have so far been limited. Here we showed that B cells differentiating into plasmablasts and macrophages in secondary lymphoid organs were targets for SFTSV at the end stage of lethal infection, and the majority of SFTSV-infected cells were B cell-lineage lymphocytes. In affected individuals, B cell-lineage lymphocytes with SFTSV infection were widely distributed in both lymphoid and nonlymphoid organs, and infiltration of these cells into the capillaries of the organs could be observed occasionally. Moreover, a human plasmablastic lymphoma cell line, PBL-1, was susceptible to SFTSV propagation and had a similar immunophenotype to that of target cells of SFTSV in fatal SFTS. PBL-1 can therefore provide a potential in vitro model for human SFTSV infection. These results extend our understanding of the pathogenesis of human lethal SFTSV infection and can facilitate the development of SFTSV countermeasures.

Preexisting chronic conditions for fatal outcome among SFTS patients: An observational Cohort Study.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus SFTSV. Currently our knowledge of the host-related factors that influence the pathogenesis of disease is inadequate to allow prediction of fatal outcome. Here we conducted a prospective study of the largest database on the SFTS patients, to identify the presence of comorbidities in SFTS, and estimate their effect on the fatal outcome. Among 2096 patients eligible for inclusion, we identified nine kinds of comorbidities, from which hyperlipidemia (12.2%; 95% CI: 10.8%-13.6%), hypertension (11.0%; 95% CI: 9.6%-12.3%), chronic viral hepatitis (CVH) (9.3%; 95% CI: 8.1%-10.5%), and diabetes mellitus (DM) (6.8%; 95% CI: 5.7%-7.9%) were prevalent. Higher risk of death was found in patients with DM (adjusted OR = 2.304; 95% CI: 1.520-3.492; P<0.001), CVH (adjusted OR = 1.551; 95% CI: 1.053-2.285; P = 0.026) and chronic obstructive pulmonary diseases (COPD) (adjusted OR = 2.170; 95% CI: 1.215-3.872; P = 0.009) after adjusting for age, sex, delay from disease onset to admission and treatment regimens. When analyzing the comorbidities separately, we found that the high serum glucose could augment diseases severity. Compared to the group with max glucose < 7.0 mmol/L, patients with glucose between 7.0-11.1 mmol/L and glucose ≥11.1 mmol/L conferred higher death risk, with the adjusted OR to be 1.467 (95% CI: 1.081-1.989; P = 0.014) and 3.443 (95% CI: 2.427-4.884; P<0.001). Insulin therapy could effectively reduce the risk of severe outcome in DM patients with the adjusted OR 0.146 (95% CI: 0.058-0.365; P<0.001). For CVH patients, severe damage of liver and prolongation of blood coagulation time, as well as high prevalence of bleeding phenotype were observed. These data supported the provocative hypothesis that treating SFTS related complications can attain potentially beneficial effects on SFTS.

Analysis of clinical features and early warning indicators of death from severe fever with thrombocytopenia syndrome.

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.

Correlations between clinical features and death in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging high-fatality infectious disease caused by a novel phlebovirus belonging to the Bunyaviridae family. Thus, the independent predictors of death in this disease must be identified to improve the survival of affected patients.A total of 25 hospitalized patients with SFTS virus infection were enrolled in our study, and their medical records and laboratory data were reviewed. The risk factors for death were examined by binary logistic regression.The patient age was significantly higher in the deceased cases than in those who recovered (P = .020). Moreover, the occurrence of shock, respiratory failure, hemorrhagic manifestations, kidney dysfunction, and arrhythmia was significantly more common in the deceased cases than in the recovered cases (P = .016, P = .004, P = .005, P = .002, P = .038). Univariate binary logistic regression showed that shock, arrhythmia, and hemorrhage, as well as PCT, serum creatinine (Scr), and blood urea nitrogen (BUN) elevations, were the risk factors for death (odds ratio, OR 28.5, P = .015; OR 13.5, P = .027; OR 36, P = .008; OR 28.5, P = .015; OR 36, P = .008; and OR 76.0, P = .004). However, the BUN increase was the only independent risk factor for death indicated by multivariate logistic regression (OR 76.0, P = .004).SFTS presents with a high fatality rate. When patients with SFTS manifest shock, arrhythmia, hemorrhage, PCT increase, and Scr and BUN elevations, especially BUN > 8.2 µmol/L, health care providers should be alerted and must administer early intervention to prevent the progress to death.

Severe Fever with Thrombocytopenia Syndrome in South Korea, 2013-2015.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea. METHODS/PRINCIPAL FINDINGS: SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed. CONCLUSIONS: SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS.

Meta-analysis of the clinical and laboratory parameters of SFTS patients in China.

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

Genetic Susceptibility Is One of the Determinants for Severe Fever with Thrombocytopenia Syndrome Virus Infection and Fatal Outcome: An Epidemiological Investigation.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China and case-fatality rate of SFTS is very high (approximately 10%). However, genetic susceptibility for SFTS virus (SFTSV) infection and fatal outcome of SFTSV infection in humans are unclear. In this study, we investigated the clinical, laboratory and epidemiological features of SFTS in a cluster of three sisters who died of SFTSV infection between late April and mid-May 2014. Before disease onset, two of the sisters (Case A and case B) had common exposure history for ticks by working together in a field to pick tea leaves from April 8 to April 12. The third sister (Case C) did not live or work together with case A and B, but had ticks in her living environment. SFTSV RNA sequences were amplified from three cases were not identical, suggesting that the three sisters were most likely infected with SFTSV through tick bite rather than through person-to-person transmission of SFTSV. The sequence of SFTSV from case C was identical to SFTSV sequences from 3 groups of ticks collected around the residential area of case C. Seroprevalence of SFTSV IgG antibody among healthy population in the area where the patients resided was 4.05% (3/74). The majority of SFTSV infections were mild cases and all three sisters died of SFTSV infection suggested that they were highly susceptible to SFTSV. Our findings indicated that genetic susceptibility was a risk factor for SFTSV infection and fatal outcome.

Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome.

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.

Close correlation between development of MODS during the initial 72 h of hospitalization and hospital mortality in severe fever with thrombocytopenia syndrome.

An emerging infectious disease was identified as severe fever with thrombocytopenia syndrome (SFTS) in central China since late March 2009. We found the patients with SFTS had severe clinical symptoms, and progressed rapidly to multiple organ dysfunction syndrome (MODS) with high fatality rate of 25%-30%. The aim of this study was to assess the significance of risk factors predicting the development of MODS and death in SFTS patients. Consecutive SFTS admissions between May 2009 and September 2011 were analyzed for parameters of organ function during hospitalization using Marshall scoring system for MODS, and platelet counts were recorded on admission and at 24, 48, 72 h and one week after admission. We investigated the kinetics of organ failures and analyzed the association between age, platelet count and development of MODS or death. A total of 92 SFTS patients were enrolled in this study. Among them, 32 patients with dysfunction of over 4 organs were identified, 45% of them died within 72 h, 72% died within 5 days, and 76% died within 7 days after admission. We also found cumulative Marshall score was significantly higher in death patients (11.76±2.05) than in survival patients (4.22±1.98) (P<0.001). In addition, SFTS patients had older age and lower platelet counts in MODS and death groups. Furthermore, we also observed that there was a close correlation between platelet count on admission and Marshall score (P<0.001). High Marshall score, advanced age and lower platelet counts were the main risk factors for the development of MODS, and those factors could predict mortality in SFTS patients, suggesting prompt treatment and close monitoring of severe complications, especially MODS, are of great importance in saving patients' lives.

[Epidemic situation and surveillance on SFTS in China, 2011-2012].

OBJECTIVE: To analyze the data of surveillance on severe fever with thrombocytopenia syndrome (SFTS), from 2011 to 2012 in China. METHODS: Descriptive methods were conducted to analyze the surveillance data from 2011 to 2012 which were collected from the internet-based National Notifiable Disease Reporting System. RESULTS: From 2011 to 2012, a total of 1229 SFTS cases and 107 deaths were reported in China with the average annual incidence rate of 0. 046/100 000 and case fatality rate of 8.7%. Compared to 2011, morbidity of 2012 has increased by 23.5% and mortality has decreased by 32%. 16 provinces reported SFTS cases. More cases occurred in spring and summer seasons,with the peak in May to July, during this period, 69% of the total cases were reported. The ages of the patients ranged from 1 to 85 years, 44.2% of total case was 55 to 70 years old, there were no differences in sex. Of all the cases 86. 8% was farmer. CONCLUSION: Severe fever with thrombocytopenia syndrome in widely distributed in China, especially in the central and eastern regions, the incidence has obvious seasonal. Surveillance and immigration quarantine should be strengthened.

The S segment of Punta Toro virus (Bunyaviridae, Phlebovirus) is a major determinant of lethality in the Syrian hamster and codes for a type I interferon antagonist.

Two strains of Punta Toro virus (PTV), isolated from febrile humans in Panama, cause a differential pathogenesis in Syrian hamsters, which could be a useful model for understanding the virulence characteristics and differential outcomes in other phleboviral infections such as Rift Valley fever virus. Genetic reassortants produced between the lethal Adames (A/A/A) and nonlethal Balliet (B/B/B) strains were used in this study to investigate viral genetic determinants for pathogenesis and lethality in the hamster model. The S segment was revealed to be a critical genome segment, determining lethality with log(10) 50% lethal doses for each PTV genotype as follows (L/M/S convention): A/A/A, <0.7; B/A/A, <0.7; A/B/A, 1.5; B/B/A, 2.2; B/A/B, 4.7; A/B/B, >4.7; A/A/B, >4.7; B/B/B, >4.7. In addition, the Adames strain inhibits the induction of alpha/beta interferon (IFN-alpha/beta) in vivo and in vitro and inhibits the activation of the IFN-beta promoter. Expression of the PTV Adames NSs protein, encoded by the S RNA segment, inhibited the virus-mediated induction of an IFN-beta promoter-driven reporter gene, suggesting that PTV NSs functions as a type I IFN antagonist. Taken together, these data indicate a mechanism of pathogenesis in which the suppression of the type I IFN response early during PTV infection leads to early and uncontrolled viral replication and, ultimately, hamster death. This study contributes to our understanding of Phlebovirus pathogenesis and identifies potential targets for immune modulation to increase host survival.