| Objectives:?1?To describe the epidemiology of hand,foot and mouth disease?HFMD?in the urban area of Xiangyang City from 2009 to 2017,and to compare the features of the population,spatial and temporal distribution of HFMD before and after the mass vaccination of enterovirus 71?EV-A71?vaccine.?2?Establishing the transmission dynamics models of HFMD in the urban area of Xiangyang City to assess the effect of mass vaccination of EV-A71 vaccine on the incidence of HFMD,and to compare the effect of EV-A71 vaccine with different vaccination strategies?pulse vaccination combined routine vaccination vs routine vaccination?on the reduction of EV-A71-associated HFMD cases in this region.?3?To analyze the feature of viral spectrum caused HFMD after EV-A71 vaccine introduction in the urban area of Xiangyang City,and to provide scientific evidence for the virological surveillance of HFMD.Methods:?1?The features of the population,spatial and temporal distribution of HFMD before and after EV-A71 vaccine introduction in the urban area of Xiangyang City.This study relied on the program"The intervention trial research of the effectiveness of enterovirus 71 vaccine in community",which was implemented in2016-2017 in the urban area of Xiangyang City.Pulse vaccination of EV-A71 vaccine has been implemented in children aged 0-71 months in September-October,2016 in the urban area of Xiangyang City,then turned to routine vaccination.The safety and effectiveness of EV-A71 vaccine were assessed by surveying the occurrence of HFMD in the target population.The data of EV-A71 vaccine inmmunization was collected from the Children Immunization Information Management System?CIIMS?of Hubei Province.Data of HFMD incidence was collected from Diseases Reporting Information System,and the numbers of cases infected with EV-A71,CV-A16 and other non-EV-A71 and non-CV-A16 enterovirus were collected from the virological surveillance of Hubei province.Descriptive epidemiology methods were used to analyze the epidemiologic features of HFMD during 2009-2017,and to compare the population,spatial and temporal distribution characteristics of HFMD and the proportion of enterovirus serotypes?including EV-A71,CV-A16 and other non-EV-A71and non-CV-A16 enterovirus?in different periods,i.e.,early HFMD report period?January,2009-December 2010?,pre-vaccination period?January,2011-September,2016?and vaccination period?October,2016-December,2017?.?2?Based on transmission dynamics models to assess the effect of mass vaccination of EV-A71 vaccine on HFMD incidence in this region,and the effect of EV-A71 vaccine on EV-A71-associated HFMD incidence under different vaccination strategies.Notifications of HFMD from January,2013-September,2016 collected from the the Diseases Reporting Information System and the data on enterovirus serotypes?EV-A71,CV-A16 and other non-EV-A71 and non-CV-A16 enterovirus?from the virological surveillance of Hubei province during the same period were used to construct time-series Susceptible-Infected-Recovered?TSIR?models.The TSIR models were applied to simulate the incidence of HFMD,EV-A71-associated HFMD and non-EV-A71-associated HFMD during January,2013-September,2016,and to estimate their transmission dynamics parameters,including seasonal transmission rate and basic reproductive number.We also predicted the incidence of HFMD from October,2016 to December,2017 without EV-A71 vaccine introduction.The predicted cases and observed cases were compared to evaluate the effect of EV-A71 vaccine on HFMD occurrence.In addition,we applied TSIR model to predict the EV-A71-associated HFMD incidence under different vaccination strategies?pulse vaccination combined routine vaccination vs routine vaccination?in September,2016-Decmber,2019.?3?The feature of viral spectrum caused HFMD in the first year following EV-A71vaccine introduction in the urban area of Xiangyang City.This study relied on two programs,ie.,"The intervention trial research of the effectiveness of enterovirus 71 vaccine in community"program and"The study of virological spectrum of HFMD and the effectiveness of natural infections with HFMD associated enterovirus in Xiangyang City"program.Nucleic acid detect kit for EV-A71and pan-enterovirus,and sequencing were applied to detect the enterovirus serotypes in the clinical samples collected from all HFMD cases in the first year following EV-A71vaccine introduction.We analyzed the features of viral spectrum of HFMD in the first year following EV-A71 vaccine introduction and compared the population characteristics,disease severity and enterovirus serotypes distribution between vaccinated and unvaccinated HFMD cases.Result:?1?Totally,54,627 children have received EV-A71 vaccine?102,126 doses?from September 10,2016 to December 30,2017,of which 47,499 children?86.95%?have received both two doses in this period.There are 40,244?73.67%?and 29,812?62.76%?children who received the first and second dose in September-October,2016,respectively.A total of 56,643 HFMD cases have been reported in the urban area of Xiangyang City,with 191 severe cases?including 20 deaths?from 2009 to 2017.During the period of 9 years,the HFMD incidence firstly increased and then decreased,with highest incidence in the year of 2011?473.83 per 100,000?.The incidence of 2017 decreased to179.06 per 100,000.The HFMD incidence of total and age-specific population were all smaller than the average level of 2009-2016.The severity rate in 2017?0.87 per100,000?was also smaller than the average level of the previous 8 years?0.98 per100,000?.No death has been reported in 2017.Compare to the pre-vaccination period?January,2011-September,2016?,the proportion of HFMD cases aged 3-5 years became larger?29.22%vs 25.73%,P<0.001?,while the proportion of cases younger than 1 year old turned to be smaller?10.19%vs13.12%,P<0.001?in vaccination period?October,2016-December,2017?.Semiannual peaks of HFMD were observed in April-June and October-December.The major perk has been found much higher than the second one in 2009-2016.But the first peak fell flat with the second one in 2017 with HFMD cases reported during these two peaks accounting for 31.83%and 32.28%of the whole year,respectively.The incidence of severe cases peaked in April-June,while the majority of death occurred in April-May.The result of virological surveillance indicated that the proportion of EV-A71 infection is smaller in vaccination period?6.54%?than that in pre-vaccination period?28.09%?in Xiangyang City.?2?The incidence of HFMD,EV-A7-associated HFMD and non-EV-A71-associated HFMD from the urban area of Xiangyang City in January,2013-September,2016 were used to fit TSIR models.The analysis indicated that the three models fitted successfully,with R2 of the models to be 0.83,0.91 and 0.80,respectively.Transmission rate estimated from models for HFMD,EV-A7-associated HFMD and non-EV-A71-associated HFMD were 5.35×10-5(IQR?Interquartile range?:4.74×10-5-6.06×10-5),5.56×10-5(IQR:5.01×10-5-6.18×10-5)and 4.22×10-5(IQR:3.83×10-5-4.63×10-5),respectively.And their basic reproductive numbers were 2.21?IQR:1.96-2.50?,2.93?IQR:2.64-3.26?,and 1.97?IQR:1.79-2.16?,respectively.The seasonal transmission rate and basic reproductive number reached to be smallest during winter vacation,summer vacation and National Days,and the seasonal transmission rate peaked at 10-16 weeks and 36-40weeks.There was about 1 month delay between HFMD cases and transmission rate peaks.As the result of predictive model demonstrated,compared to the predicted HFMD cases?10,238,IQR:8,246-12,524?without EV-A71 vaccine introduction,the number of observed HFMD cases?5,240?in vaccination period?October,2016-December,2017?decreased by 48.82%.The number of cases infected with EV-A71 predicted by the model was 2,213?IQR:2,065-2,361?,and the incidence of observed EV-A71 cases?127?reduced substantially.The number of non-EV-A71-associated HFMD cases?5,113?also decreased by 17.27%,compared to the predicted incidence without EV-A71 vaccine introduction?6,180,IQR:4,676-7,792?.Pulse vaccination combined routine vaccination can substantially reduce the incidence of cases infected with EV-A71.The number need to vaccinate?NNV?was higher than that of routine vaccination in the first year,but turned to be smaller in 3years when 10%children aged 0-71months can be vaccinated in pulse vaccination.?3?Clinical samples collected from HFMD cases in the first year following EV-A71 vaccine introduction?October,2016-September,2017?were detected for enterovirus serotypes.Eleven kinds of entervirus serotypes were detected from 3,208samples with sampling rate of 84.27%.CV-A6?1,257 cases,47.67%?and CV-A10?335cases,12.67%?were the most two prevalent serotypes,while the proportion of EV-A71decreased to 3.34%?88 cases?.The cases infected with CV-A6 peaked at March-April,2017,and formed a small peak in December,2016 and September,2017,respectively.Both cases infected with CV-A10 and CV-A5 peaked at April,but cases infected with CV-A2 peaked at June.In terms of EV-71 vaccination and HFMD incidence,1,118HFMD cases?29.37%?have received EV-A71 vaccine before HFMD onset.The time interval between disease onset and last vaccination was 4.32?IQR:1.94-6.17?months,and 38.68%cases experienced HFMD 28days-3months after EV-A71 vaccine immunization.The proportion of EV-A71 infection was smaller in vaccinated HFMD cases than that in unvaccinated cases?0.25%vs 4.68%,P<0.001?,but the proportion of CV-A6?51.25%?was larger than that in unvaccinated cases?46.11%,P=0.017?.The proportions of other enterovirus serotypes were similar between two groups in the whole year,but presented difference at different time-points.All 23 severe cases were classified into Phase II.Only 2 severe cases were infected with EV-A71,but neither receive EV-A71 vaccine before disease onset.Conclusions:?1?The incidence of HFMD has been decreased for each age group after the introduction of EV-A71 vaccine.The major peak of HFMD declined and fell flat with the second one.?2?Mass vaccination of EV-A71 vaccine can reduce EV-A71-associated HFMD cases substantially.Compared with the simple routine vaccination,pulse vaccination combined routine vaccination can reduce EV-A71-associated HFMD cases rapidly.Among different vaccination strategies,the NNV was smallest in 3 years when 10%children aged 0-71months can be vaccinated in pulse vaccination combined routine vaccination.?3?CV-A6 and CV-A10 were the predominant serotypes after EV-A71 vaccine introduction. |
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