Evaluation Of Influenza Vaccine Effectiveness In China

Background:Influenza viruses,one of the common pathogens that cause acute respiratory infections,are prone to mutating due to lack RNA-correcting enzymes during replication,causing heavy disease burden.WHO monitors the situation of influenza epidemics according to the Global Influenza Surveillance and Response System(GISRS),predicts the most likely epidemic influenza virus strains for the next influenza season,and recommends updated influenza vaccine components in the northern and southern hemispheres every year.So,vaccination annually is an effective way to prevent influenza virus infection.While influenza vaccine is not included in the National Immunization Program(NIP),most residents who want to get vaccination need to pay by themselves.As a result,the overall influenza vaccination rate in China has been maintained at a low level.As more and more studies shed light on the burden of flu disease in China,some regions have started to implement free vaccination policies for primary and middle school students and elderly people aged 60 and above,significantly increasing the vaccination rate in these population.However,one of the obstacles to the implementation of policies to promote influenza vaccination in most areas of China is the lack of high-quality evaluation data on influenza vaccine effectiveness(VE)and the failure to provide necessary research support for government decision-making.Based on this,we need to systematically review the previous published scientific literature on the evaluation of influenza vaccine effect in China,and plan to continue to carry out research on the evaluation of influenza vaccine effectiveness in China.Objectives:A systematic review of the influenza vaccine effectiveness in China’s mainland was conducted.We conducted a multicenter study to evaluate the influenza vaccine effectiveness in the 2019-2020 influenza season,and to evaluate the feasibility of integrating the evaluation study on the influenza vaccine effectiveness into routine influenza surveillance work.All of these were to provide basic data for promoting the formulation of influenza vaccination policy in China.Methods:1.We used the key words "influenza","influenza vaccination","vaccine effectiveness",and "China" as search terms to locate published articles.We searched the Wanfang Database,China National Knowledge Infrastructure(CNKI),China Biology Medicine(CBM),and VIP journal database for Chinese language studies;we searched PubMed and Web of Science for English language studies.The search was done on October 1,2019.Additional relevant articles from the reference sections were also reviewed.The articles that met the requirements were screened according to the inclusion and exclusion criteria,and then the data were extracted and sorted in Excel 2016 software.The quality of the included studies was evaluated using the Newcastle-Ottawa Scale(NOS),which is suitable for case-control studies.Meta-analysis was performed using RevMan 5.3 software.According to the results of heterogeneity test,fixed effect model(P>0.05 and I2<50%)or random effect model(P≤0.05 or I2>50%)was selected to evaluate the influenza vaccine effectiveness.Subgroup analysis was conducted to explore the influenza vaccine effectiveness in different age groups.2.A test negative design(TND)was used to evaluate the influenza vaccine effectiveness in 2019～2020 influenza season.Beijing,Suzhou,Xinxiang and Nanshan District of Shenzhen were selected as our research sites,and eligible subjects were recruited from the previously selected sentinel hospitals for influenza surveillance or community hospitals with cooperation intention.After the onset of local influenza epidemics,patients with acute respiratory infections(ARI)aged 6 to 18 years and 60 years and older who met the local influenza vaccination policy were included.A questionnaire survey was conducted by qualified nurses,they collected demographic information,health status and morbidity information,and influenza vaccination information with informed consent.Respiratory tract samples were collected and sent to the local influenza network laboratories.After receiving the samples,the laboratory technician performed real-time RT-PCR for detection and identification of influenza viruses.According to the laboratory results,those with positive nucleic acid of influenza virus were classified as the case group,and those with negative nucleic acid of influenza virus were classified as the control group.The vaccination status of patients was checked again in the electronic information database of vaccination in those four cities,and the Odds Ratio(OR)of influenza vaccination rate between the case group and the control group was calculated.Multivariate logistic regression model was used to estimate the influenza vaccine effectiveness in those four cities during the 2019-2020 influenza season,and stratified analysis was used to calculate the influenza vaccine effectiveness in different age groups,health states and vaccination states.Results:1.As of October 1,2019,there were a total of 21 influenza vaccine effectiveness studies evolved in Beijing,Guangzhou,Suzhou and Zhejiang met the requirements of the evaluation.The study period included 2010～2011 season to 2017～2018 seasons.The results of Meta-analysis showed that influenza vaccination had a moderate effectiveness against influenza,and the overall influenza VE was 36%(95%CI:26%-46%),indicating that the current influenza vaccine in China had a moderate protective effect against influenza.Subgroup analysis showed that influenza vaccine effectiveness of 2 doses(VE=57%,95%CI:50%～64%)was higher than that of only 1 dose(VE=45%,95%CI:18%～64%)for children aged 6 months to 3 years who received influenza vaccine for the first time.The influenza vaccine effectiveness in children aged 6 months to 8 years(VE=47%,95%CI:40%～55%)was higher than that in the elderly population aged 60 years or above(VE=18%,95%CI:0～33%).The influenza vaccine effectiveness was 21%(95%CI:-11%～44%)for patients requiring hospitalization and 13%(95%CI:-10%～32%)for patients with mild symptoms in the outpatient and emergency department.2.During the 2019～2020 influenza season,as of January 31,2020,a total of 2,305 influenza-like illness(ILI)patients were included in four study sites of China,including 1244 students aged 6-18 years old(53.97%),and 1061 eldly aged more than 60(46.03%).The positive rate of primary and secondary school students aged 6-18 years(793/1244)was significantly higher than that of the elderly aged 60 years or above(289/1061)(x2=306.42,P<0.001).With further identification of influenza virus types,we found that the positive samples were dominated by A(H3N2)subtype and B-Victoria lineage,and no B-Yamagata lineage virus were detected in influenza-like cases’ samples.Among the subjects in this study,261 people were vaccinated with influenza vaccine,meaning that the overall composition ratio of influenza vaccination was 11.32%in those four cities,and most of them were vaccinated with trivalent inactivated influenza vaccine,accounting for 66.28%.Except for Nanshan District in Shenzhen,all the other three sites finished vaccination work before November.Multivariate logistic regression showed that the overall influenza VE after adjusted was 42.73%(95%CI:21.47%～58.23%),and stratified analysis showed that the adjusted influenza VE in primary and secondary school students aged 6-18 years was 52.73%(95%CI:12.56%～74.45%),while in the elderly aged 60 and above,the influenza VE was relatively low(37.04%,95%CI:9.43%～56.23%).The adjusted influenza VE in subjects with underlying disease was 48.38%(95%CI:8.21%～70.97%).Conclusions:Systematic review results shown that influenza vaccines marketed in China’s mainland had a moderate effectiveness.Two doses of influenza vaccine should be suggested to children aged 6 months to 3 years when they first got influenza vaccination.However,the standard-dose dose influenza vaccine did not show obvious protective effect for the elderly population aged 60 years and above,Therefore,a high-dose influenza vaccine suitable for the elderly population should be developed and produced in the future in China.2.The evaluation of the mid-term influenza vaccine effectiveness in four regions in China showed a good effectiveness during the 2019～2020 influenza season,with influenza VE reaching 42.73%(95%CI:21.47%～58.23%),the influenza VE in primary and secondary school students aged 6-18 years was better than that in elderly people aged 60 years or above,and the risk of infection in people with underlying diseases was reduced by 48.38%(95%CI:8.2 1%～70.97%)after influenza vaccination.3.To monitor the effectiveness of influenza vaccine after the replacement of vaccine strains,studies on the evaluation of influenza VE can be incorporated into the routine surveillance of influenza.