Analysis Of Epidemiological Characteristics Of HFMD And VP1 Gene Variation Of EV71 In Zhengzhou City

ObjectiveComprehensive analysis the epidemic characteristics and trend of hand-foot-mouth disease in Zhengzhou;Understanding the molecular evolution of enterovirus 71;master the basic data of HFMD cases;To investigate the epidemic situation background from the time and the molecular level.To clarify the epidemic regularity,key areas and high-risk groups of HFMD,Provide scientific basis for prevention and control of HFMD in Zhengzhou City.Methods1.Collecting the epidemic data of HFMD in Zhengzhou from 2009 to 2019,descriptive epidemiological study was conducted.We constructed a ARIMA time series model based on the incidence rate of HFMD from 2009 January to 2019December.The model was used to predict the incidence rate of HFMD in 2020.and compared with the actual incidence rate,The prediction effect of the model was tested.2.Collection the data of HFMD prevalence rate in Zhengzhou from 2010～2019,then match the data and electronic map,By using the software geoda 1.14.0 to analyze the global and local spatial autocorrelation,Explores the regional distribution characteristics of HFMD aggregation in Zhengzhou City;at the same time,combined with the software Sa TScan 9.6 to analyze the temporal spatial changes of HFMD hotspots in Zhengzhou city.3.Real time PCR was used to detect the nucleic acid of HFMD pathogenic samples collected in Zhengzhou from 2009 to 2019,and the positive samples were isolated and cultured.The VP1 gene of EV71 virus isolated in Zhengzhou from 2018to 2019 was amplified,cloned and sequenced.Bioedit 7.2.5,dnaman9.0,vector NTI suite 9.0 and other bioinformatics software were used to edit,correct and splice the sequences.Cluster X software was used to analyze the homology of the obtained sequences with HFMD vaccine strains and domestic reference strains,and phylogenetic tree was constructed to explore the genetic variation characteristics of VP1 gene of EV71 virus in Zhengzhou city.Results1.175102 cases of HFMD were reported in Zhengzhou during 2009～2019,the average annual incidence rate was 193.69/ten-thousand,and the ratio of male to female was about 1.51:1.Children under 5 years old accounted for 92.20%and infants under 3 years old accounted for 74.72%of the total cases.Scattered children accounted for 64.95%of the total of children,followed by 32.57%of children in kindergartens;2.According to the time series model parameters determined by HFMD incidence rate in Zhengzhou 2009～2019,the parameters of ARIMA（1,0,1）（2,1,0）₁₂,AIC=800.3,BIC=813.71;the average relative error of HFMD incidence rate and prediction value in 2020 is 17.14%,and the prediction effect is better.3.The spatial autocorrelation analysis of incidence rate of HFMD in Zhengzhou city in 2010～2019 showed that the spatial clustering of HFMD in Zhengzhou city was significant,except for 2014,which was statistically significant（Moran’s I>0,P<0.05）.The location of HFMD cluster I detected by local spatial autocorrelation and Sa TScan was relatively fixed,mainly including Jinshui District,Huiji district and Guancheng District,and the cluster time was concentrated from April to June every year;4.A total of 9125 HFMD samples were detected in Zhengzhou from 2009 to2019,and 6201 samples were enterovirus nucleic acid positive,with a positive rate of66.33%.In terms of etiological composition of HFMD in Zhengzhou,the positive rate of EV71 was the highest（2647cases,41.86%）,followed by other enteroviruses（2362cases,38.96%）.EV71 was the main enterovirus of HFMD epidemic in Zhengzhou from 2009 to 2014,with a constituent ratio of more than 55%;after 2015,the constituent ratio of other enteroviruses increased to more than 50%year by year,becoming the dominant pathogen of HFMD epidemic in Zhengzhou in recent years,while the positive rate of Cox A16 has been at a low level,with a constituent ratio of less than 25%in most years from 2009 to 2019.5.Eight new EV71 strains were found in Zhengzhou from 2018 to 2019.Compared with the vaccine strains,the nucleotide and amino acid sequence homology of VP1 region of the eight strains were 94%～96%and 99%～100%,respectively.The major antigenic epitopes of the eight strains had no amino acidmutation,and they were close to the D subtype epitopes in phylogenetic tree,and there were two evolutionary branches.Conclusions1.The HFMD population in Zhengzhou city is mainly 0-5 years old children,in which boys are more than girls,and most of the children in kindergartens and scattered children;the incidence of HFMD in different counties and districts is quite different,and the incidence areas are mainly in Jinshui District,Huiji District,Guancheng District and other densely populated urban areas,the peak of the disease was from April to June,The ARIMA product seasonal model can be used for short-term prediction of incidence rate of HFMD in Zhengzhou.The predicted trend is consistent with the actual situation;2.From 2009 to 2019,the etiological characteristics of HFMD in Zhengzhou City showed that the proportion of EV71 infection continued to decline,and the proportion of other enterovirus infection continued to rise,and gradually replaced EV71 and Cox A16 as the dominant pathogens.Further typing and detection of other enteroviruses should be strengthened in the future;3.The eight representative strains of EV71 virus isolated from HFMD in Zhengzhou City from 2018 to 2019 belong to subtype D.There are two transmission chains,which are far from the early strains in Henan Province.But it has high homology with domestic vaccine strains...