| Background:Syphilis remained the third among class B national notifiable infectious diseases and one of the important public health concerns in China.Compared with traditional epidemiological research methods,spatio-temporal epidemiological research methods can provide a basis for accurate prevention and control of syphilis,but China has not yet conducted a study on the long-term spatio-temporal evolution pattern of syphilis by county and district.In addition,with the epidemic of syphilis,its disease spectrum has changed,and latent syphilis has become the major component,and early latent syphilis is highly infectious while late latent syphilis is non-infectious.The reported cases of latent syphilis in China do not distinguish between early and late stages,and the situation of infectious early latent syphilis is still unknown.Studying the longterm spatio-temporal evolution of syphilis at the county levels nationwide and investigating the early stage of latent syphilis infection become important tasks of syphilis prevention and control.Objectives:Through constructing a geographic information system(GIS)database of reported syphilis cases at county levels over years,and comprehensively applying methods such as time series,spatial global trends,spatial autocorrelation,spatiotemporal scanning analysis and spatial regression analysis to deeply understand the epidemic trend of syphilis in China,determine the clusters and hotspots,clarify the focus of syphilis prevention and control,and reveal its spatiotemporal distribution characteristics and evolution regulation,identify spatial distribution associated factors,providing a basis for precise prevention and control of syphilis,optimizing resource allocation,and improving syphilis prevention and control work.Through the investigation of the sexual behavior,recent medical history and the early infection marker TP-IgM antibody of patients infected with latent syphilis in different regions in China,assessing the proportion of early infection in latent syphilis.and the epidemiological significance in syphilis transmission was explored to provide a basis for scientific evaluation of the epidemic situation of syphilis.Method:The time series Joinpoint regression model was applied to analyze the temporal trends of the reported prevalence of syphilis,including primary and secondary syphilis(P&S syphilis),and latent syphilis.Pearson and Spearman correlation analysis was applied to initially explore the factors associated with different stages of change trends;GIS of reported syphilis cases in China from 2004 to 2021 was established by county and district database,on the basis of which,ArcGIS 10.5 software was applied to analyze the frequency distribution characteristics,spatial distribution characteristics and spatial aggregation areas of syphilis using spatial global trend and spatial autocorrelation research methods;SaTScan 10.02 software was applied to analyze the spatial and temporal aggregation areas of syphilis and their change characteristics using spatial and temporal scanning research methods;GeoDa 1.20 software was applied to fit Spatial error model and spatial lag model(reported prevalence of syphilis in 2019 and 2020 were selected)to analyze the factors(eg.population,economy and medical services)associated with the spatial distribution of syphilis.A cross-sectional survey was conducted on the sexual behavior characteristics and recent medical history of patients infected with latent syphilis in different regions of China,while serum specimens were collected to detect the early infection marker TP-IgM antibody,and the correlates were analyzed using Logistic regression model.Results:The results of time series Joinpoint regression analysis showed that the reported prevalence of all syphilis in China(excluding Hong Kong,Macao and Taiwan)increased from 7.12/100 000 in 2004 to 34.05/100 000 in 2021,with an average annual percent change of 9.46%(95%CI:8.03%—10.90%,P<0.001),divided into four periods:2004-2006,2006-2010,2010-2019 and 2019-2021,with an average annual increase of 35.24%、20.72%、3.08%,and-4.60%,respectively.Among which,the change trend of P&S syphilis can be divided into two periods:2004-2011 and 2011-2021,and the change trend of latent syphilis can also be divided into the same four periods as all syphilis.Pearson correlation analysis showed that there was a positive correlation between the number of reported syphilis cases and the number of syphilis screenings from 2013 to 2021(r=0.87,P<0.001),with negative correlation between P&S syphilis(r=-0.93,P<0.001)and positive correlation between latent syphilis(r=0.96,P<0.001);Spearman correlation analysis showed that the number of reported syphilis cases in China from 2020 to 2021 was negatively correlated with the number of novel coronavirus infections(rs=-0.54,P=0.006).The results of spatial global trend analysis indicated that from 2004 to 2021,syphilis in various counties were positively skewed,with the percentage of counties with syphilis reported greater than 90%each year.The whole distribution of syphilis from northwest to southeast appeared as "U" shaped.From 2004 to 2008,the prevalence of syphilis was mainly high in southeast,and the magnitude of the "U" shaped trend was gentle;from 2009 to 2019,the reported prevalence of syphilis increased in the northwest and southeast,and the magnitude of the "U" shaped trend gradually increased;from 2020 to 2021,the reported prevalence of syphilis in northwest and southeast both decreases in 2020-2021,and the magnitude of the "U" shaped trend decreases.Spatial autocorrelation analysis showed that syphilis was significant positive global spatial autocorrelation,with Moran’l range of 0.10-0.45,P<0.001,among which P&S syphilis,and latent syphilis were all significant positive global spatial autocorrelation,with Moran’l range of 0.06-0.45 and 0.1 1-0.41.both P<0.001.respectively.From 2004 to 2010,high-high clusters were mainly concentrated in the southeastern coastal provinces such as Jiangsu.Shanghai.Zhejiang.Fujian,and Guangdong;from 2004 to 2018,clusters in Inner Mongolia,Xinjiang,and Qinghai gradually increased,and gradually radiated to the Tibet and Gansu over time;from 2019 to 2020,the high-high clusters in Northwest China,East China and South China gradually increased and spread to the Southwest China,showing fusion phenomena:the fusion of high-high clusters decreases in 2021.Spatio-temporal scan analysis showed that there were 5 spatio-temporal aggregation areas for syphilis in China from 2004-2021.with the 4th and 5th aggregation areas involving a wide range.The 4th spatio-temporal aggregation area was in Southwest China during 2019-2021,involving 693 counties in 13 provinces,and the 5th spatiotemporal aggregation area was in South Central China during 2017-2021,involving 387 counties in 11 provinces.Among which,there are 4 spatio-temporal aggregation areas for P&S syphilis,and the 2nd and 3rd aggregation areas involve a wider range.The 2nd spatio-temporal aggregation area was in the Central and Eastern China during 2004-2010,involving 905 counties and districts in 14 provinces,the 3rd spatio-temporal aggregation area was mainly in Southwest and Northwest China in 2019,involving 659 counties and districts in 14 provinces;there were 5 spatio-temporal aggregation areas for latent syphilis,and the 3rd aggregation area was more widely involved,located in Southwest and Northwest China during 2019-2021,involving 872 counties and districts in 13 provinces(all P<0.001).The spatial regression analysis showed that the spatial error model fitted better than the spatial lag model.The results of the spatial error model analysis showed that the economic indicator GDP per capita was significantly associated with spatial distribution of syphilis,with the regression coefficient β=0.00013 in 2019,P<0.001,and the regression coefficient β=0.00016 in 2020,P<0.001.The results of a survey of 1311 cases of latent syphilis in 12 cities showed that the TP-IgM positivity rate was 41.50%,the proportion of early latent syphilis assessed by comprehensive behavior,recent medical history and TP-IgM test results was 67.89%.After standardizing,TP-IgM positivity rate and the proportion of early latent syphilis were 35.52%and 61.84%,respectively.The number of early latent syphilis was estimated to be 143 476(35.52%X 403 929)calculating with standardizd TP-IgM positive rate and cases of latent syphilis in 2021,which was 2 times more than the number of P&S syphilis in the same year.Analysis of the factors associated with the TPIgM positive rate showed that the RPR titer was closely related to it,and the rate of TPIgM positivity in the RPR titer>1:4 group was 5.6 times higher than that in the RPR titer≤1:4 group.The number of non-marital sexual partners in the last 2 years in early latent syphilis patients in this survey was at least 1 and at most 32,with a mean of 2 and a median of 1.Conclusions:The overall trend of syphilis in China from 2004-2021 is increasing,among which P&S syphilis,reflecting the new infection,showed an increased trend from 2004 to 2011 and a decreased trend from 2011 to 2021;influenced by the expansion of syphilis screening,the number of reported cases of latent syphilis is increasing;influenced by the prevalence of novel coronavirus infection,reported cases of syphilis fluctuated from 2020 to 2021,thus,the trend of syphilis epidemic should be judged by considering various factors.The spatial distribution pattern of syphilis epidemic in China generally showed high prevalence in Northwestern and Southeastern region,and low in the Central and Northeastern region;high-high clusters and hotspots are also distributed in the Northwestern and Southeastern region;spatio-temporal aggregation areas are mainly distributed in the Southwestern and Northwestern region;syphilis is highly prevalent in economically underdeveloped and developed regions,and resources should be optimized to strengthen precise prevention and control of syphilis in economically underdeveloped regions such as the Northwest and Southwest as well as economically developed regions such as the Southeast.At least 1/3 of the cases of latent syphilis are early latent syphilis,which is highly infectious and much more than the P&S syphilis.And there are multiple sexual partners among early latent syphilis patients.Early latent syphilis is a major source of syphilis infection with more important significance in the transmission of syphilis,and the identification and management of early latent syphilis should be strengthened to curb the further spread of syphilis. |
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