Effectiveness Of Seasonal Influenza Vaccine In Children Aged6to59Months

BackgroundSeasonal influenza and seasonal influenza vaccine:seasonal influenza is a contagious respiratory illness caused by influenza viruses, which leads to more than250000deaths worldwide each year. Children are susceptible to influenza viruses, about40%preschool children and30%school child infected by influenza each year in China. Serious outcomes of influenza infection can result in serious complications or even death, especially those with certain health conditions. Guangzhou is located in south China with a subtropical monsoon climate, viral influenza strains that persist in this region could potentially serve as year-round reservoirs of global genetic diversity. The World Health Organization (WHO) contends that annual vaccination prior to the influenza epidemic peak is currently the principal strategy for preventing influenza. Influenza vaccines have to be reformulated annually based on the global surveillance of circulating viral strains. Since2010-2011, the A (H1N1) pdm09strain has added in the seasonal influenza vaccine. The replacement of composition of influenza vaccines each year, the increased annual supply and demand of influenza vaccines, makes it necessary to monitor and assess the vaccines for years. Postmarketing vaccines have been assessed the safety and validity by preclinical study and phase Ⅰ, Ⅱ, Ⅲ clinical trials. However, these studies are not possible to assess epidemiological effect, immune persistence and the aspect of health economics.Related research at home and abroad:several foreign studied have estimated the influenza vaccine effectiveness (VE) among children, however, their conclusions are inconsistent. Most of the postmarketing studies of influenza vaccine in China are serological studies, which the observation times are short. Also, these studies are not possible to assess epidemiological effect, immune persistence. The rest of the postmarketing studies of influenza vaccine in China are prospective observational studies. These studies estimated the protection against influenza-like illness (ILI), cold or respiratory illness by following the target population (people over three years old) for about six months. However, except influenza virus, respiratory syncytial virus, nasal virus, parainfluenza virus can also cause the above symptoms, so it was difficult to distinguish influenza cases from others based on their clinical symptoms. In conclusion, the influenza vaccine effectiveness is not completely assessed, and further postmarketing studies among children are needed to provide the scientific basis for decisions regarding influenza vaccination for children. We aimed to estimate the effectiveness of seasonal influenza vaccine for children age6-59months during influenza epidemic period of2010-13seasons.Methods We conducted a l:1or1:2matched case-control study among children aged6-59months. Cases and controls were matched by birth date (±7days), gender, and outpatient services of vaccination. The influenza cases from surveillance sites in Guangzhou were laboratory confirmed during the study periods. The healthy controls without ILI symptoms were confirmed by researchers from Guangzhou center for disease control and prevention by phone during the study period, and were randomly selected from the Children’s Expanded Programmed Immunization (EPI) Administrative Computerized System. The influenza epidemic periods were defined by the surveillance of circulating viral strains each year. The information of influenza cases and healthy controls were obtained from the surveillance system and the Children’s Expanded Programmed Immunization (EPI) Administrative Computerized System, respectively. And their influenza vaccination records for cases and controls were collected from the Children’s EPI Administrative Computerized System. Odds ratios (OR) were estimated by conditional logistic regression, and adjusted by household register, vaccination age and vaccination status for last year. And VEs were1minus ORs. We estimated VEs for3years, different age groups, vaccination status, genders, influenza viruses, influenza epidemic periods, vaccination for two years or the study year and VE by time since vaccination.ResultsOnset of influenza:In2010-2011,2011-2012and2012-2013, there were417,1710and2809reported laboratory confirmed influenza cases aged6-59months in Guangzhou,4936in total. The influenza season peaked form February to July in2010-2013. In the influenza season, there were315,1604and1717reported laboratory confirmed influenza cases aged6-59months in Guangzhou,3636in total(influenza season group), accounting for73.7%(3636/4936) of all influenza cases in2010-13. We included2782laboratory confirmed influenza cases aged6-59in3influenza seasons (included group), accounting for76.5%(2782/3636) of cases in2010-2013influenza season. There were205,1046and1531cases in2010-2011,2011-2012and2012-2013, respectively. The age of onset of cases was30.2±15.3months (mean±standard deviation), cases mainly were local children and male, and lived in Haizhu(20.2%), Baiyun(18.3%), and Yuexiu(15.7%). There were23.5%(854/3636) of cases missing vaccination records or loss to follow-up. There was no difference in gender between included group and the influenza season group, with the exception of onset age (30.2±15.3months and32.18±16.0months) and location. We matched410,2092and1531healthy controls for2010-2011,2011-2012and2012-2013, respectively. Cases subjects were similar to healthy controls with respect to vaccination age, gender and location, and with the exception of household register. However, the household register of cases and healthy controls were mainly local. The constituent ratios of influenza vaccination of cases in different year, age group, vaccination status were statistically lower than the controls, except in2010-2011. The constituent ratios of partial vaccination were statistically lower than full vaccination in children aged6-35months. We analyzed the vaccination information for2782sets of subjects in3influenza seasons in Guangzhou, China.Vaccine effectiveness (Vaccine effectiveness, VE):we found that the VE for2010-2013seasons was64.2%(95%Confidence interval(CI),56.7-70.5%), for2010-2011,2011-2012and2012-2013seasons for children6-59months were72.4%(95%CI,52.0-84.2%),52.9%(95%CI,42.1-61.7%),61.6%(95%CI,49.0-71.1%), respectively.The VE for children aged6-35and36-59months were64.1%(95%CI.54.9-71.5%) and75.4%(95%CI,60.2-84.8%), respectively.Full vaccination provided more protection than partial vaccination among children aged6-35(67.3%(95%CI,58.3-74.4%) vs.53.9%(95%CI,37.3-66.2%).The VE for boys and girls were63.2%(95%CI,53.3-71.0%) and66.8%(95%CI,54.9-75.5%), with borderline statistical significance (x2=0.326,F=0.568).The VE for influenza virus A, B were63.0%(95%CI,53.6-70.4%) and69.9%(95%CI,51.2-81.4%), respectively, and for A(H1N1)pdmO9was54.7%(95%CI,15.7-75.7%).The VE ofearlier influenza season(67.4%(95%CI,57.9-74.8%)) was statistically higher than late influenza season (60.3%(95%CI,46.8-70.3%), x2=47.793, P<0.001). The VE were found to be similarly between vaccination for two years (65.3%(95%CI,57.8-71.5%)) and vaccination for the study year [70.1%(95%CI,60.5-77.3%)](Wald=1.193, P=0.275).The VE decreased gradually from67.4%(95%CI,54.8-76.4%) in1-2months after vaccination to17.6%[95%CI,(-95.6)-65.3%] in11-12months after vaccination.Conclusions This post-licensing study of VE found moderate protection against influenza for vaccinated children aged6to59months. Full vaccination provides more protection than partial protection. There was no difference in protection of influenza vaccination for boys and girls. We found moderate protection against influenza A and B. Vaccination in last year provides no protection for the study year. Seasonal influenza vaccine is found moderate protection against A(H1N1)pdm09. Annual, full and timely vaccination prior to the influenza epidemic peak should be encouraged for children.