Study On The Burden Of Hand,foot,and Mouth Disease And The Effectiveness Evaluation Of The EV-A71 Vaccination Program In Beijing

BackgroundHand,foot,and mouth disease(HFMD)has been the top-ranked notifiable disease in China since 2010.Children at the age of 5 years or below are especially susceptible.Severe and fatal cases have mainly been caused by enterovirus A71(EV-A71)infection.HFMD caused by EV-A71(EV-A71-HFMD)poses a particularly heavy threat on patients in China.However,the disease burden of HFMD has not been evaluated systematically and comprehensively yet.Getting vaccinated has been considered as one of the most effective measures to prevent HFMD.since there is no treatment for it.Three Chinese companies have licensed inactivated EV-A71 vaccines.all of which have demonstrated good safety and efficacy for preventing EV-A71-HFMD in phase III clinical trials.Beijing municipality began vaccinating children between 0.5 and 5 years with EV-A71 vaccine(voluntarily self-paid)in August 2016,and by the end of 2018,almost 30%children had received two-dose vaccines.However,the real-world performance of EV-A71 vaccinesand the impact of the vaccination program on the incidence and economic burden of HFMD have not been evaluated to date in Beijing.ObjectivesTo explore the epidemiological characteristics of HFMD and to estimate the actual number of infections and incidence of HFMD to evaluate its burden in Beijing comprehensively.To evaluate the post-licensure effectiveness of EV-A71 vaccines.based on which to evaluate the impact of the current vaccination program on the incidence and economic burden of HFMD in real world by establishing a mixed transmission dynamic model.MethodsBased on the surveillance data from the case surveillance and virological surveillance of HFMD in Beijing,as well as the parameter values of symptomatic rate,consultation rate,diagnosis rate and successful sampling rate.the actual number of infections and incidence rate of HFMD was estimated using the multiplier model.A retrospective and a prospective study were conducted to investigate the cost of each case of HFMD to estimate the economic burden of HFMD from 2011 to 2018 in Beijing.The test-negative case control study was conducted to evaluate the post-licensure effectiveness of EV-A71 vaccine.Based on the estimated number of infections,the number of vaccinations and the estimated VEs.a mixed transmission dynamic with age and seasonality structure was developed to evaluate the impact of the current vaccination program of EV-A71 vaccine on the incidence and economic burden of EV-A71-HFMD.Results1.There were an average of 32,761 HFMD cases reported in Beijing between 2011 and 2018,of which were mainly children at the age of 5 years or below-accounting for 87.68%of the total number of HFMD cases,with an incidence rate of 3.340%.During the eight years,a total of 261,005 mild cases.1,080 cases and 14 fatal cases were reported.EV-A71 infcetions accounted for 22.61%among mild cases,49.68%for severe cases and 100%for fatal cases.2.It was estimated that one reported confirmed HFMD cases actually represented 12.96 enterovirus infections,2.71 cases and 2.03 outpaitient and emergency visits.The average infection rate of enteroviruses was 27.74%per year,with an average incidence rate of 5.80%in Beijing between 2011 and 2018.The average cost for each case without medical attendance was 156.92 RMB(SD:175.80).Among those cases with medical attendance,the averaee cost for each mild case in 2018 was 2247.97 RMB(SD:2390.27),severe case 14,449.45 RMB(SD:9826.90),and fatal case 1.47 tol.70 million RMB.The total cost for HFMD was estitmated at 53-120 million per year.3.For mild HFMD cases,one-dose and two-dose VE estimates were 69.76%and 83.65%,respectively.The two-dose VE was 77.33%(95%CI:4.61%,94.61%)for the 6-35-month group and 86.81%(950%CI:44.59%,96.86%)for the 36-71-month group.4.Between August 2016 and December 2018,a total of 298.313 children at the age of 5 years or below had received two-dose vaccines,with an accumulative vaccination rate of 31.8%.Bv the end of December 2018.it was estimated that a total of 17.314(prevented fraction:57.69%)EV-A71 associated caseswere averted for the vaccination of EV-A71 vaccine,including 12,970 EV-A71 associated medically attended illness.It was estimated that about 30.11 million RMB were averted consequentlyConclusionsEnterovirus A71(EV-A71)is the main pathogenfor the severe and fatal cases of HFMD.The reported number of HFMD cases represents only a small fraction of the actual number of infections and cases.The economic cost for HFMD in Beijing is as much as 100 million RMB.EV-A71,vaccines are effective against EV-A71-HFMD for children under five.The current vaccination program of EV-A71 vaccines is effective to mitigate the incidence of EV-A71-HFMD.