| Background: Severe fever with thrombocytopenia(SFTS)is a new tick-borne infectious disease caused by fever with thrombocytopenia syndrome virus(SFTSV,also known as neobunya virus).The virus belongs to the order Bunyavirales,Phenuiviridae,and Banyangvirus.The virus particles are spherical with a diameter of 80-100 nm,and the outer layer is a lipid bilayer of 5-7 nm,which encloses the gene of the virus.SFTSV consists of large(L,6,368 bp),medium(M,3,378 bp),and small(S,1,744 bp)single-stranded negative-stranded RNA fragments.The L fragment encodes an RNA-dependent RNA polymerase composed of 2048 amino acids.The M segment encodes a membrane protein precursor containing 1073 amino acids,after a series of transformations,the virus envelope glycoprotein(Gn and Gc)is formed.The S segment is an ambiguous RNA with two reading frames in opposite directions,encode nucleoprotein and non-structural protein respectively.SFTS was first discovered and reported in China in 2009,and then successively discovered in South Korea,Japan,Vietnam and other Asian countries.The United States also discovered Heartland virus,which was familiar with SFTSV in 2012.The clinical manifestations of SFTS patients were mostly mild symptoms,include fever,gastrointestinal symptoms,thrombocytopenia,and leukopenia.However,5%-30% of patients have severe or even life-threatening symptoms.Current epidemiological studies had shown that SFTS was a zoonotic disease,and its main source of infection was infected animals,such as goats,dogs,cattle and small wild mammals.The main route of transmission was through tick bites.And it could also be spread through aerosols,direct contact with patients or their body fluids,and there had been reports of sexual transmission.The main transmission medium of SFTS was Haemaphysalis longhorned ticks,and there were also reports that the pathogen had been isolated from other ticks such as Rhipicephalus miniatures.Therefore,the occurrence of SFTS was closely related to the activity of ticks,and had obvious epidemiological characteristics.The onset time was generally from March to November,and the peak period of incidence in China was from May to July.The peak periods of incidence in Japan and South Korea were from May to August and April to August,respectively.The areas were mainly concentrated in areas with abundant rainfall and more woods and shrubs.In mountainous and hilly areas,the patients were mainly middle-aged and elderly people over 50 years old engaged in agricultural activities.As a new infectious disease,SFTS was currently limited in the distribution of cases and the number wa relatively small.Researches on the disease were relatively insufficient.The research direction mainly focused on epidemiology,etiology,diagnostics and clinical treatment,but lacked pathogenic mechanisms.The epidemiological studies of the disease mostly used cross-sectional survey methods,and lacked of observational research.The research contents mainly focused on the epidemiological characteristics analysis of past cases,and investigated the seropositive rate of the general population and its influencing factors.According to the general rule of the epidemic of infectious diseases,the cases discovered and reported account for only a small part of pathogen exposure,and there were often a large proportion of subclinical infections in healthy people.However,there was currently a lack of research specifically targeting this part of the population.The researches of this part of the population might help public health practitioners understand the true and status of SFTSV infection,so as to formulate and adopt more accurate prevention and control measures.Therefore,it was necessary to carry out a cohort seroepidemiological survey of subclinical infections to grasp the real situation of SFTSV infection in the population,and to observe and study the dynamic changes of antibodies,so as to determine the protective effect of antibodies and whether there are secondary infections.In addition,SFTS was also a natural foci disease.The occurrence and spread of the disease were greatly affected by the local natural environment.This required us to use geographic epidemiology to determine the high-risk areas of the disease.In the past,there were few researches on SFTS-related geographic environment influencing factors,and limited by the accuracy of the map,the research scale was relatively large,mostly at the level of township and above.Therefore,it was necessary to deal with infected persons on a more precise scale,such as households.Research on the geographical and environmental factors in order to determine the surrounding environment of high-risk families,guide the local people to carry out corresponding environmental remediation,and provide reference opinions for health and epidemic prevention personnel to formulate corresponding prevention and control measures.Objectives:(1)To understand the epidemiological characteristics of patients in the endemic areas;(2)To investigate the background value of SFTSV subclinical infection in healthy people in SFTS endemic areas,explore the risk factors of SFTSV subclinical infection,study the dynamic change process and law of antibodies in subclinical people in different SFTS epidemic periods,and then observe and judge Whether there is a secondary infection;(5)To grasp the natural environmental factors related to SFTSV infection.Method: Firstly,we collect all SFTS cases reported in Shangcheng County from January 1,2011 to December 31,2019,and analyze the distribution characteristics of cases in time,space,and population.And then use random sampling method to select 5villages in SFTS epidemic areas,and carry out seroepidemiological surveys on healthy people,fill out questionnaires,collect blood samples,and detect the titers of SFTSV-IgG antibody and neutralizing antibody.Follow up to establish a certain number of cohort populations,thereby establish a population serological database,sort out and analyze the background values of SFTS subclinical infections in healthy people,and analyze the related factors of subclinical infections,explore the ebb and flow of antibodies and dynamic changes,and then determine whether there is a possibility of secondary infection.Lastly,use spatial epidemiology methods,combined with "3R" technology,locate the home address of the surveyed person,and collect local confirmed case information,so as to identify infected and non-infected families,and extract data and information about the surrounding environment of the residence for analysis Geographical environmental factors related to SFTSV infection.Results:(1)1089 confirmed cases of SFTS in Shangcheng County from 2011 to2019 was collected in our study.The middle age of the patients was 64 years(IQR=53-71 years).With the increase of age,the ratio of cases increases(Spearman rank correlation analysis,r=0.989,P<0.001),the gender ratio was 1:1.53(male to female,430:659),and the occupation was mainly farmers(97.70%).There was a certain fluctuation in the number of cases in each year,and the peak incidence was from May to August(64.00%).The five townships with the highest average annual incidence rates were Wanggang Town(25.75 per 100,000 people),Fengdian Township(24.77 per100,000 people),Yuji Town(22.72 per 100,000 people),Wuhe Township(21.71 per100,000 people)and Fushan Township(21.40 per 100,000 people).The annual average incidences of SFTS in the central and southern regions of the county were significantly higher than that in the north,which basically consistented with the distribution of mountain forests.(2)The seroepidemiological investigation found that the seropositive rate of SFTSV-IgG antibody in the local healthy population in Shangcheng county was approximately 11.93%(70/587,95%CI: 9.42%-14.83%),and that of neutralizing antibody was 6.81%(40/587,95% CI: 4.91%–9.16%),and in the during-epidemic period,the seropositive were 13.43%,(47/350,95% CI: 10.04%–17.45%)and 7.71%(27/350,95%CI: 5.15%–11.03%),respectively,in the post-epidemic period were15.75%(80/508,95% CI: 12.69%–19.21%)and 9.84%(50/508,95%CI:7.39%–12.77%),respectively.The seropositive rates of the two antibodies were relatively stable during different periods of the epidemic(chi-square test,P value scores were 0.185 and 0.696,respectively),which were similar to that of the cohort population.The seropositive rates of IgG antibodies were 16.46%(27/164,95% CI:11.14%–23.04%),17.07%(28/164,95% CI: 11.65%–23.72%)and 18.9%(31/164),95% CI: 13.22%-25.74%),respectively,in the three periods,and that of neutralizing antibodies were 6.10%(10/164,95% CI: 2.96%-10.93%),10.37%(17/164,95% CI:6.16 %-16.08%)and 10.37%(17/164,95% CI: 6.16%-16.08%),respectively.To analysis of the relationship between 24 variables and IgG antibody test results found that age ≥ 70 years old(OR=2.440,95% CI: 1.334-4.461,P=0.004),exposure to cats in the past two weeks(OR=2.195,95% CI: 1.261-3.818,P=0.005)and recent work in tea gardens(OR=1.698,95% CI: 1.002-2.880,P=0.049)were risk factors for antibody positive.But for the neutralizing antibodies,only age ≥ 70 years old(OR=2.691,95%CI: 1.271-5.695,P=0.010)and exposure to cats in the past two weeks(OR=2.648,95%CI: 1.419-4.941,P= 0.002)left.The results of the dynamic of change to the anti-titer in the cohort population,the GMRTs of SFTSV-IgG antibody were 247.55(95% CI:57.12-1072.9)in the per-epidemic period,131.49(95% CI: 5.88-2941.75)in the mid-epidemic period,and 161.47(95% CI: 6.44-4048.40)in the post-epidemic.And that of neutralizing antibody were 173.47(95% CI: 14.13-2130),34.87(95% CI:0.2-6081.22)and 38.73(95% CI: 0.21-6991.47),respectively.The GMRTs of them didn’t changed with significant statistical difference.However,for the 10 participants with positive NAb before epidemic,three(30.00%)turned negative during epidemic,and none turned negative after epidemic.Among the 154 individuals who were negative for NAb before epidemic,10(6.49%)turned positive during epidemic,with two of them turned negative after epidemic,and another six(4.16%,6/144)turned positive after epidemic.In addition,this study also found that the results of the two detected methods are inconsistent.Among 197 SFTSV-IgG antibody positive samples,only 117(59.39%)neutralizing antibody test results are positive.The higher titer of IgG antibody titer,the higher seropositive rate of neutralizing antibody(chi-square trend test,P<0.001).(3)Collect environmental information of 175 SFTSV-infected families and 630non-infected families,and multi-factor analysis shows that pathogen exposure and distance to main roads(OR=0.998,95%CI: 0.997-0.999,P<0.001),The distance of cultivated land(OR=1.236,95%CI: 1.026-1.488,P=0.026),the distance of shrubland(OR=0.999,95%CI: 0.998-1.000,0.034)and the distance of impervious surface(OR=1.043,95%CI: 1.007-1.081,P=0.018).Clear and accurate image maps were obtained through remote sensing positioning.Conclusion:(1)Patients in SFTS endemic areas were mainly elderly farmers,and there were more women than men,and the peak incidence was from May to July.The average annual incidence rate of towns in the central and southern parts of the county were higher than that in the north,and was consistent with the distribution of forest land;(2)There was a relatively high subclinical infection rate in healthy people in SFTS endemic areas,and the subclinical infection rate and antibody level were basically stable in different epidemic periods of the disease.There were 3 neutralizing antibodies in the cohort that turned negative,indicating that the protective antibodies of subclinical infections were not persistent,and there was a possibility of secondary infection.Age,recent exposure to cats and tea garden work were related to subclinical infections.Some IgG antibody-positive individuals had negative neutralizing antibodies,suggesting that the antibodies obtained by some subclinical infections might not have a protective effect;(3)SFTSV infection was related to the four research variables of main roads,shrubland,arable land,and impervious surface near the residential area.The closer to the main road and shrubland,the farther away from the arable land and impervious surface,the more susceptible to infection.Innovation and significance: First of all,this study conducted a systematic study of patients and healthy people in SFTS endemic areas for the first time,and collected more detailed local SFTS case information,with a large time span and a full number of cases.Second,this study carried out a cohort seroepidemiological survey for subclinical infections for the first time,established a cohort with a larger sample size,and included the different epidemic periods of the disease into the analysis,and studied the positive rates and levels of antibodies in different epidemic periods.Thirdly,this study also fully considered the difference between the two antibody detection methods and the different sampling time of the investigation,and found that some IgG antibody-positive people do not have protective antibodies,and different detection methods and different sampling time risk factors might influence the results,suggesting that the detection method and sampling time should be carefully selected.At the same time,we also found that recent exposure to cats was associated with the positive rates of the two antibodies.This had been rarely reported in previous studies,suggesting that cats played an important role in the local SFTS epidemic.Finally,this study conducted a geographic epidemiological analysis with households as the survey object for the first time,combined with remote sensing maps,and obtained clear and accurate remote sensing images near the residence. |
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