The Safety Of EV71 Vaccine In Post-marketing Period Based On AEFI Information Surveillance System

Objectives:1.To analyze the vaccination situation of EV71 and the occurrence of AEFI after vaccination of EV71,and to evaluate the main types and distribution characteristics of AEFI for EV71 vaccine in a certain province.2.To analyze the occurrence of AEFI(Adverse Events Following Immunization)after the simultaneous administration of EV71 and the vaccines for children aged 6-12 months in the national immunization program.To compare the differences of AEFI after the separate inoculation of EV71 vaccine and the combined inoculation of EV71 vaccine and the national immunization program vaccine,in aim to provide scientific evidence for the development of vaccination program.Methods:1.The data of EV71 vaccination in a certain province was obtained from the Information Management System of Immunization Program,from August 1,2016 to July 31,2018.The AEFI data related to EV71 vaccine in a certain province was collected from AEFI Information Surveillance System of China Immunization Planning Information System,from August 1,2016 to July 31,2018.Descriptive epidemiological method was used to analyze the distribution characteristics of season,region,population and the vaccine types of EV71 vaccination,the distribution characteristics of season,region,population,vaccine types of EV71-related AEFI,as well as the type of EV71-related AEFI and the time interval of AEFI after vaccination.2.The information about vaccination history of children borned in a certain province was collected from August 1,2015 to January 31,2018 from the Information Surveillance System of Immunization Program.According to the date of vaccination registered by the system,the population was divided into three groups: the vaccination group of combining the EV71 vaccine and the vaccines recommended by the National Immunization Program for children aged 6-12 months,the separate vaccination group of EV71 vaccine and the separate vaccination group of vaccines recommended by the National Immunization Program for children aged 6-12 months.According to the vaccination data of the three groups and the corresponding vaccine-related AEFI data,the Poisson regression method was used to adjust gender,age,interval time of EV71 vaccine post-marketing,vaccination quarter and other factors of the vaccine recipients,to compare the differences in AEFI occurrence between single and combined vaccination.Results:1.The distribution characteristics of population vaccinated with EV71 vaccine:within two years after EV71 vaccine post-marketing in a certain province,836,934 people were inoculated with EV71 vaccine,and the ratio of male to female was1.14:1.00.The inoculation population was concentrated in the 6-36 months group.The cumulative EV71 vaccination rate in 14 regions of the province was the highest at22.43% and the lowest at 9.81%.There was a significant difference of the vaccination rate of EV71 in different cities(P<0.001).The peak of EV71 vaccination in the province was mostly from march to August,and the trough was from October to February.2.The distribution characteristics of AEFI related to EV71 vaccination in a certain province: the AEFI reporting incidence of EV71 vaccine was higher in males than in females(57.60/100,000 vs.51.77/100,000),with a ratio of 1.11:1.00.The AEFI rate was highest in the 6-24 month group,ranging from 56.07 per 100,000 to 59.45 per 100,000.There was no difference in AEFI reporting incidence among different gender and age groups.The highest incidence of AEFI in each region was134.28/100,000 and the lowest was 13.88/100,000.There was a significant difference in AEFI reporting incidence in 14 cities(P<0.001).There were two distinct seasonal peaks in the AEFI reporting incidence of EV71 vaccine,mainly in the second and third quarters.The EV71vaccine-related AEFI was mainly based on general reactions,followed by local reactions,with the AEFI reporting incidence 84.24/100,000 and 9.92/100,000,respectively,and the couplings were less.In general reactions,fever,crying and loss of appetite were the main causes.The AEFI reporting incidence was 16.73/100,000 to84.24/100,000.Most abnormal reaction was allergic,and the AEFI reporting incidence was 9.20/100,000.The EV71-related AEFI was mainly happened within 1 day after inoculation.3.The combination of EV71 vaccine and NIP vaccine in children aged 6-12months: the EV71 vaccine for children aged 6-12 months was combined with the national immunization plan vaccine to inoculate 31,410 person-times.The combination of EV71 and group A meningococcal polysaccharide vaccine was the main inoculation,and the combined inoculation was 13,723 person-times,accounting for 43.69% of all combined vaccination cases.4.The occurrence of AEFI in combination with EV71 vaccine and NIP vaccine for children aged 6-12 months: with adjustment for gender,age,EV71 vaccine marketing interval and vaccination quarter,it was found that the risk of AEFI increased by 3.29 times when EV71+MR(Measles and rubella combined attenuated live vaccine)were combined administered,compared with EV71 vaccine administered alone(RR=4.29,95%CI: 2.21-7.86).The risk of AEFI was increased by1.96 times(RR=2.96,95%CI: 1.48-5.33)in the EV71+JEV-L(Japanese encephalitis attenuated live vaccine)combination vaccination compared with EV71 vaccined alone.Compared with JEV-L alone,the risk of AEFI was reduced by 44.00% when EV71+JEV-L was co-vaccinated(RR=0.44,95%CI: 0.24-0.73).There were no differences in the risk of AEFI between EV71 vaccine and Hep B(Hepatitis b vaccine),EV71 vaccine and JEV-I(Japanese encephalitis inactivated vaccine),EV71 vaccine and MPV-A(Group A meningococcal polysaccharide vaccine)combined vaccine and vaccine separatly(P>0.05).Conclusions:Within two years after EV71 vaccine post-marketing in a province,the high risk quarters of AEFI for EV71 vaccine are the second and the third quarters.The AEFI incidence in males is higher than in females,and the age of AEFI is concentrated at6-24 months old.The EV71-related AEFI was mainly based on general reactions.The combined vaccination of EV71 vaccine with MR or JEV-L vaccine could increase the risk of AEFI in children aged 6-12 months,compared with the single vaccination of EV71 vaccine.No evidence has been found for increased AEFI risk after combination of EV71 with JEV-I,Hep B,and MPV-A.