Study On The Epidemiological And Clinical Features Of Severe Fever With Thrombocytopenia Syndrome

Background Severe fever with thrombocytopenia syndrome?SFTS?is an emerging hemorrhagic fever caused by a novel bunyavirus virus?SFTSV?,which was first discovered and reported in China^[1].Subsequently,Japan and South Korea also reported the first confirmed SFTS patients worldwide in 2012 and 2013 respectively^[2-4].The United Arab Emirates reported the first case of SFTS earlier in 2011^[5].Early in the emergence of SFTS cases,the case fatality rate reported by South Korea was even as high as 50%^[2-4].The average case fatality rate of SFTS in China is 12%,but the number of new SFTS cases is increasing year by year.Since 2010,SFTS has been included in disease surveillance system by the Ministry of Health of the People's Republic of China and the monitoring data are recorded by health-care providers and submitted to local Center for Disease Control and Prevention?CDC?^[6].These reports provide valuable insight into the general demographic information,but do not reflect the clinical characterization.Especially the fatal cases might be underreported nationwide,making the death risk analysis less reliable than estimation from the clinical data.10In this report we processed the largest cohort study of SFTS patients from 2011 to 2017 to provide complete SFTS epidemiology and clinical features^[7].Objective To analyze the epidemiological characteristics of fever with thrombocytopenia syndrome?SFTS?cases in different years and explore its prevalence trends.Provides a complete description of the clinical features of fever with thrombocytopenia syndrome?SFTS?.Method This was a prospective observational study performed at the PLA154 hospital,Xinyang city,Henan Province,China,located at the center of Dabie mountain,which has been proved to be the originating region and hot spot of the SFTS epidemic.In this report,we made an observational study on the largest cohort of SFTS patients from2011 to 2017 by analyzing the association between the epidemiological features,clinical features,laboratory indicators,and viral load of SFTS and death outcomes determined at follow-up visits.We used the case definition for SFTS patient recruitment developed by the Ministry of Health of the People's Republic of China.The confirmed cases that included in the analysis were suspected patients who had at least one of the laboratory-diagnosed criteria:detection of SFTSV RNA;seroconversion or?4-fold increase of IgG antibody titers between two serum samples collected at acute and convalescent phases;isolation of SFTSV.Result From 2011 to 2017,a survey was performed in a military hospital?Hospital154?in Xinyang administrative district of Henan Province.A total of 3562 hospitalized patients of suspected SFTS were tested,and 2096 cases?58.9%?were laboratory confirmed to be infected with SFTSV.Their mean?SD?age at inclusion was 61.4±12.2years old,and 59.1%of the confirmed patients were female.The mean?SD?age of the patients gradually increased,from 57.4±13.0 years old in 2011 to 62.6±12.2 years old in 2017?p<0.0001?,while the sex proportion did not differ among the studied years.The spatial distribution of the patients expanded from Xinyang to the surrounding cities,with the number of inflicted townships increased from 77 in 2011 to 194 in 2017.In addition,the epidemic focus inside Xinyang gradually spread from south to north part of the city.Beyond Xinyang,the epidemic areas spread to the city of Nanyang and Suizhou obviously.In our study,the case fatality rate?CFR?was 16.2%,which was significantly higher than that recorded from disease surveillance system of China.The epidemiological and clinical parameters that significantly associated with higher CFR included elder age,longer hospital admission delay,presence of diarrhea or dyspnea,and development of hemorrhagic or neurological manifestations.We disclosed diarrhea,dyspnea,hemorrhagic signs,and neurological symptoms to be important predictors of fatal outcome,among which neurological symptom was the most critical death predictor,while most neurological symptom usually occurred at late phase of disease?symptom onset time lasts more than 6 days?.Only pre-treatment data were used to analyze clinical features in this study.At early phase of illness?from day 3 to day 6 after symptom onset?,lactate dehydrogenase?LDH?,aspartate aminotransferase?AST?,blood urea nitrogen?BUN?,and neutrophil percentage?NEU%?were significantly higher in fatal patients than that in survivors at each evaluated time point,indicating the potential usage of the 4 laboratory indicators to predict death at early SFTSV illness phase.Its combination with age and neurological symptoms composed a clinical scoring system.Receiver operating characteristic?ROC?analysis showed a total score>8 had a good power to predict death.Moreover,the viremia level measured at all phases of illness was related to CFR.The viral load was found to be a strong predictor of fatal outcome,with the CFR increased remarkably to 52.7%in those with super high viremia??10⁸?from 4.4%in those with low viremia?<10⁶?.Conclusion The age of onset of SFTS is gradually increasing;male,advanced age,delayed from onset to admission?>6 days?and high viral load on admission are risk factors for the death of fever with thrombocytopenia syndrome;The spatial distribution of SFTS in Xinyang continues to expand,with the tendency to spread from the south to the north and from the east and west to the center.This study revealed that diarrhea,dyspnea,signs of bleeding,and neurological symptoms are important predictors of fatal outcome,with nervous system symptoms being the most critical.But most neurological symptoms usually occur at late phase in the disease,therefore the other three manifestations?hemorrhagic symptoms,dyspnea,and diarrhea?can supplement the predictors of death.We also established a clinical scoring system based on four routine laboratory testing parameters?LDH,AST,BUN,and NEU%?as well as age and neurological symptoms.It has been clinically proven to have good results in predicting the outcome of death in the early stages of SFTS.