| Background: Severe fever with thrombocytopenia syndrome(SFTS)is a new infectious disease infected by the novel bunya virus(SFTSV)through the blood,tick-to-human transmission is the primary route by which people are infected with SFTSV.In May 2010,Professor Yu of the National Center for Disease Control and Prevention isolated a new virus from the patient’s serum,which was identified as a novel phlebovirus(SFTS virus,SFTSV)in the family Phenuiviridae of the order Bunyavirales.SFTS is a new tick-borne disease,which has been widely spread in East Asia in recent years and first appeared in China in 2009.South Korea and Japan both reported their first cases in 2013.According to retrospective case investigation,South Korea can be traced back to 2010.The main epidemic regions of SFTS are concentrated in China,Japan,South Korea.Recently,retrospective cases have been reported in Vietnam,where RNA and antibodies to SFTSV have been detected in ruminants and ticks in Taiwan.In China,SFTS is mainly distributed in Henan,Anhui,Hubei,Liaoning,Shandong,Zhejiang and Jiangsu provinces.The whole country of South Korea is an epidemic area,while Japan is mainly distributed in the southern region,especially in the coastal areas.Among the hospitalized patients,the mortality rate of SFTS is between 12% and 50%.This phenomenon has caused panic in the domestic society and has become a serious public health safety problem in our country and even the whole world.According to the information obtained from the portals of relevant disease prevention and control departments in China,Japan,South Korea and literature survey of SFTS cases,we could know that as of December 31,2018,a total of 13,259 SFTS cases(including lab-confirmed cases and clinical cases)had been reported.The provincial administrative regions affected by SFTS in China,Japan and South Korea are 25,23 and 17 respectively.The distribution of cases in China was highly spatially clustered,among which 215 counties in Henan,Shandong,Hubei and Anhui provinces had reported a total of 6,658 confirmed cases,accounting for 86.23% of the confirmed cases in China.The reported cases(including lab-confirmed cases and clinical cases)in Japan and South Korea were 396 and 866 respectively.The environmental risk factors for the occurrence of SFTS were the middle and low altitude mountainous areas and hilly areas with warm and humid climate and rich vegetation.The time of onset of SFTS had obvious seasonality,the number of infected cases increases rapidly in March every year,the peak is from May to July,and then the cases could continue to appear until November.In terms of time,the time distribution of SFTS was consistent with the active time of ticks,which was the same as other tick-borne natural foci diseases.Studies had confirmed that Haemaphysalis longicornis was the main transmission vector of SFTSV.As an emerging infectious disease,although some investigations had been made on the epidemiological,etiological and clinical characteristics of SFTS domestic and overseas,there are still some shortcomings,such as regional limitations,time span is not large enough,few types of research factors are included,the spatiotemporal distribution of epidemiological features need further improvement,and the regional differences of related eco-environmental factors are still lack of detailed research.Therefore,the comprehensive use of space epidemiology and other multidisciplinary theories,methods and technical means to carry out relevant research on the cases and main transmission vectors of SFTS in key epidemic areas of emerging infectious diseases is conducive to a sustainable grasp of the temporal and spatial epidemic characteristics,related environmental factors and potential risk areas of the disease in the world,and is of great significance for the global implementation of prevention and control strategies guided by classification and adapting measures to local conditions.Objectives and Contents:(1)Obtain the information of lab-confirmed cases of SFTS in China from 2010 to 2018 and build a case database,establish a database of eco-environmental factors in China,combined with modern spatial information technology,further understand and improve the spatiotemporal distribution characteristics and epidemic trends of SFTS,identify the hot areas where the disease has spread in China in the past eight years,clarify the associated landscape structure characteristics,and quantitatively evaluate the risk of SFTS spread in mainland China.The purpose of this study is not only to fill the knowledge gaps in the epidemiology and ecology of SFTS,but also to provide a method for risk assessment of SFTS transmission,which can be used as a basis for disease surveillance planning and improvement.(2)Aiming at H.longicornis,an important transmission vector of SFTS,the global spatial database of H.longicornis was constructed,and the suitable living areas of H.longicornis were analyzed and predicted by using the maximum entropy niche model,which provides data support for selecting the key surveillance areas of H.longicornis,and provides the basis of vector spatial distribution for the prevention and control of infectious diseases with H.longicornis as the main vector.(3)Obtain the global SFTS reported case information(including lab-confirmed cases and clinical cases)from 2010 to 2018 and construct the case database,establish the global eco-environmental factors database,and clarify the temporal and spatial distribution characteristics and epidemic trend of global SFTS.Establish a global SFTS transmission risk boosted regression tree model(Boosted regression tree,BRT),to explore the main risk factors affecting the transmission of SFTS around the world,so as to provide information basis for targeted prevention and control of SFTS around the world.Methods:(1)The data of lab-confirmed cases of SFTS infectious diseases from 2010 to 2018 were collected and sorted out to establish the Chinese SFTS case database,and the data was spatialized through spatial correlation.The spatial trend surface statistics method was used to determine the spatiotemporal two-dimensional high-incidence areas and dynamic trends of SFTS in China in the past nine years,based on which the epidemiological characteristics of SFTS in key epidemic areas in China were analyzed.Collect data such as population,economic and environmental factors to establish a database of ecological and environmental factors,and appropriate variables were selected to construct statistical models and landscape models,such as Joinpoint regression model and Cox proportional hazard regression model in survival analysis,to quantitatively evaluate the environmental risk factors that may be related to the spread of SFTS.The generalized boosted regression tree(GBRT)model is used to further analyze the impact of climate,landcover and other environmental factors on the sudden occurrence and persistent epidemic of SFTS in China in the past nine years,and build a SFTS disease risk prediction map in mainland China.(2)By consulting relevant literature and collecting data from professional websites,a more comprehensive global comprehensive database of H.longicornis including the recorded location and occurrence time was formed,and the global ecological and climatic environment data were collected.The resolution of the data layer was unified to 0.1 °× 0.1 °(about 11 km × 11 km near the equator),and converted to ASC II format.The ecological niche model(ENM)of H.longicornis was constructed in Max Ent environment,the environmental factors affecting the survival of H.longicornis were analyzed,and the suitable living areas of H.longicornis in the world were predicted.(3)The global SFTS reported case information(including lab-confirmed cases and clinical cases)from 2010 to 2018 was collected,and the global SFTS case database was constructed.It was spatially associated with the global digital map through the administrative division code,and the spatiotemporal distribution characteristics of SFTS in the world were analyzed by using the principle of spatial analysis.Taking the counties where SFTS cases(including lab-confirmed cases and clinical cases)were reported in China from January 2010 to December 2018 as the positive point,and the counties where no SFTS cases(including lab-confirmed cases and clinical cases)were reported in the same period as negative points,combined with the data of altitude,eco-climate,landcover,migratory birds,population density,livestock density,mammal richness and other environmental factors.The BRT model at county-level in China is established by using R language(version 3.6.1;R Core Team 2019),and extrapolated globally to quantitatively evaluate the risk factors that affect the global transmission of SFTS,and draw the global SFTS transmission risk prediction map according to the probability value of the transmission risk output of the model.(4)The software and programming environments involved in this study mainly include Microsoft office 2019,Arc GIS 10.3,STATA 14.0,SPSS Statistics 23,Maxent 3.3.3,R language 3.6.1.Results:(1)From 2010-2018,7,721 laboratory-confirmed SFTS cases were reported in China,with a case fatality rate(CFR)of 10.5%.The average annual incidence increased >20 times and endemic region expanded from 27 to 1,574 townships,with median age of SFTS patients increased from 56 to 64 years.Four geographical clusters that were located surrounding the Changbai Mountain area,the Jiaodong Peninsula,the Taishan Mountain area and the Huaiyangshan Mountain area were identified,showing disparity in epidemiological features and diffusion patterns.Diffusion and persistence of the disease were both driven by elevation,high coverages of woods,crops and shrub,and the vicinity of habitats of migratory birds,but had different meteorological drivers.Resident 60 years old in rural areas,especially areas with crop fields and tea farms,were at increased risk to SFTS.The spatial distribution of GBRT model-predicted incidences largely matched that of the observed incidences in the endemic regions,with extra ecologically suitable high-risk areas predicted,mostly in the vicinity of the observed high-incidence areas where no cases have been reported yet.(2)The ecological niche model was established to evaluate the suitability of the global environment of H.longicornis.The results showed that the average area under the curve(AUC)was 0.967,indicating that the model had excellent predictive power.Ten predictors were identified contributing to the global distribution for H.longicornis with relative contribution ≥1%,which are the precipitation of warmest quarter,annual mean temperature,density of population,density of livestock,mammalian richness,herbaceous vegetation of closed to open type,mean diurnal range of temperature,rainfed croplands,elevation and broadleaved deciduous forest of closed type.The potential habitat suitable for this vector tick were significantly wider than the already reported areas,mainly distributed in the eastern and central China,the southeast Russia that bordered China and North Korea,the whole country of North Korea,South Korea and Japan,the eastern coastal areas of Australia,the southwestern coastal and northern regions of New Zealand and several Oceania countries/regions.It is notable that a range of areas in the eastern and central USA were also highly suitable for the breeding of H.longicornis,significantly wider than the already reported areas.In addition,the southeastern and southwestern coastal areas of South America,southern Europe,the southeastern coastal areas of Africa and Madagascar,and the northern area of western Asia also showed a high environmentally suitability for H.longicornis tick.(3)The estimated AUC of the BRT model established by using the distribution of reported SFTS cases in China to predict the risk region of global SFTS is 0.9705,indicating that the model has excellent performance in predicting the risk probability of global human SFTS cases.Among the significant contributors,elevation had the highest RC of about 17.3%,with a negative effect on the SFTS presence,for example,a higher risk of the disease presence was seen in regions where the average elevation was less than 1000 m.Higher risk of SFTS presence was positively associated with the model-predicted probability of H.longicornis occurrence,with RC as high as 11.8%.Two temperature-related factors contributed to the risk of SFTS presence with quadratic effect,for example,a higher risk was related to the annual mean temperature between 5℃ and 15℃ and the mean diurnal range between 8℃ and 11℃.Two precipitation-related factors were positively associated with higher risk of SFTS presence,including precipitation in the warmest quarter and driest month.The richness of mammals was positively related to the risk of SFTS presence in regions hosting <20 mammals species,while negatively related to the SFTS risk in regions hosting ≥20 mammals species.The risk of SFTS presence had a quadratic effect with the percentage coverage of water bodies.The predictive map for occurrence of SFTS was created,demonstrating the highest-risk areas located in the east-central China,most parts of the Korean peninsula and southern Japan,additionally at the coastal areas in northern and limited region in the southern New Zealand.The model-predicted risk probability of SFTS presence was further validated by using the reported data in three SFTS-affected countries,Japan,South Korea and Vietnam.The results showed effective for discriminating the actual affected and unaffected areas(P<0.001),with a median predictive value of 0.74(IQR: 0.54?0.86)for affected counties and 0.04(IQR: 0.03?0.05)for unaffected counties.Conclusion: This study effectively integrates modern spatial information technology and more mature mathematical modeling theories and methods,and carries out the research on the spatiotemporal distribution and transmission risk prediction of SFTS and its main vector.The results show that:(1)Based on the information of national SFTS epidemic situation,the epidemiological characteristics of human SFTS cases in China were described in detail,four geographical clusters were identified,the relationship between different environmental factors and the spread and persistent epidemic of the disease was revealed,and more high-risk areas suitable for SFTS transmission in China were predicted,which provided a scientific basis for delineating key prevention and control areas and formulating prevention and control strategies more effectively.(2)Temperature,precipitation,human and livestock activities are important driving factors affecting the survival and reproduction of H.longicornis.In addition to the known distribution areas of H.longicornis,we also predicted additional suitable areas of H.longicornis.They span two continents,North America and Oceania,so different countries and regions around the world need to make corresponding monitoring plans according to local conditions.(3)Among the important risk factors for human infection with SFTS,elevation,temperature,precipitation,distribution probability of H.longicornis,mammal richness and percentage of water bodies play a particularly prominent role.The generated global risk prediction map establishes the priority of SFTS transmission risk in different regions,which provides data support for local public health departments to strengthen surveillance of H.longicornis and SFTSV infection.It is helpful to detect the disease vector and epidemic situation early and carry out prevention and control in time. |
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