| Objectives1. Varicella vaccine has been used in China for13years, yet the incidence of varicella remains high. This study employed a case-control design to analyze the effectiveness of varicella vaccine during outbreaks in schools and kindergartens, including the vaccine effectiveness at different time points after varicella vaccination and the vaccine efficacy against moderate and severe varicella, after controlling for potential confounding variables.2. Implications for immunization strategies adjustments and the refinement of schedules are discussed.Subjects and Methods1. Study design:A1:1matched case-control design was employed.2. Sample volume: N=41.21,42pairs are needed.3. Cases:Outbreak cases in schools and kindergartens notified through the reporting system during January1to June30,2011were recruited into the study. 4. Controls:For each case, one control, matched for sex, household register (local/nonlocal), class and age (within an interval of±1month if the case was3years of age or younger, and within an interval of±3months if the case was4years of age or older) who had close contact with the case but never had varicella (at least up to21days after illness onset of the case) was selected.5. Evaluation indicator:Vaccine efficacy (VE) was used as the evaluation indicator. VE means out of every100people, the number of people being protected by the vaccine. The equation for calculating VE is:VE=(ARU-ARV)/ARU×100%Where ARU is the attack rate in the unvaccinated group and ARV is the attack rate in the vaccinated group. When the vaccination rate in a population is unknown, case-control studies from which relative risk (RR) can be estimated can be used to calculate VE. When the probability of the disease is low, the odds ratio (OR) approximates the true RR. Therefore, VE=(1-OR)×100%6. Method of investigation:A team of trained professionals conducted investigation with standardized forms. Varicella cases notified through the reporting system were investigated. For those confirmed to be outbreak cases, matched controls were selected, using1:1matching. Controls were sought from the outbreak affected classes and had never had varicella for up to21days after the outbreak was ended (or after illness onset of the case). The investigators were blinded to children’s immunization history when selecting the controls.The children’s immunization history was retrieved from the immunization record book kept by the guardians or from the computer system. Vaccination against varicella at least1month before the outbreak was considered valid. Children with unknown history of varicella vaccination were excluded from the study.The subjects were stratified into two age groups:2-8years and9-15years. A 1:1matched case-control study was employed to assess whether varicella vaccine provides protection against the disease.7. Statistical method:Data were analyzed with Microsoft Excel2003and SPSS11.5.1:1matched case-control study OR=c/b, χ2=(b-c-1)2/(b+c), OR95%CI=OR(1±1.96/sqrt(X^2)) vaccine efficacy=(1-OR)×100%Study Results1. Basic information1.1InvestigationOf the476varicella cases notified through the reporting system during January1to June30,2011,236were outbreak cases. Using1:1matching,236controls were selected. The controls were sought from the outbreak affected classes and had never had varicella until21days after the outbreak was ended (or after illness onset of the case).The varicella outbreaks occurred in45settings, including11kindergartens (3public kindergartens and8private kindergartens),29primary schools and5middle schools (23public schools and11private schools).The usual control measures were implemented in the outbreak settings, but postexposure vaccination had not been given.1.2The general disease situationThe attack rate ranged from4.26%to27.78%.The number of cases and controls were both236. The number of cases and controls aged2-8years were both127, and the number of cases and controls aged9-15years were both109. There was no statistically significant difference between the average age of subjects in the case group (8.58±2.63years) and the control group (8.67±2.65years)(F=0.142, P=0.707). The male to female ratios were both1:0.53in the case group and in the control group. Cases and controls were matched for age, sex, household register, and environmental exposure.1.3Varicella immunizationAbout45.67%of the cases aged2-8years and70.64%of the cases aged9-15years had been vaccinated against varicella. The difference was statistically significant (χ2=11.699, P=0.001). About81.54%of the controls aged2-8years and78.30%of the controls aged9-15years had received varicella vaccines. The difference was not statistically significant (χ2=0.384, P=0.536).Of the135cases who had been vaccinated against varicella, the time interval between vaccination and onset of disease was7.29±2.40years. The time interval was5.02±1.57years for the2-to-8-year-old cases who had been vaccinated and9.00±1.19years for the9-to-15-year-old cases who had been vaccinated.2. Efficacy of varicella vaccine2.1Case-control study (1:1matched)The OR for the age group of2-8years was0.083(95%CI:0.037-0.189), and the efficacy was91.7%(95%CI:.81.1%,96.3%). The result was statistically significant. The OR for the age group of9-15years was0.47(95%Ci:0.200-1.1211), not statistically significantly different.2.2Vaccine efficacy against severe varicellaDue to the small number of varicella cases with50or more skin lesions, all cases were included into the analysis. About27.27%(24/88) of the varicella cases with50or more skin lesions and59.28%(230/388) of the varicella cases with less than50skin lesions had been vaccinated. After adjusting for age, χ2M～H=27.721, P <0.001, OR was0.258(95%CI:0.154-0.431).Conclusion1. Overall, the varicella vaccine offers good protection (80%) when the outbreak occurred in schools and kindergartens.2. The varicella vaccine offers good protection against severe varicella. Therefore, increasing varicella vaccination coverage is essential for the prevention and control of the disease.3. The overall varicella immunization rate in the study subjects reached70%. However, one dose of varicella vaccine, even with70%varicella vaccination coverage rate, does not prevent school outbreaks and breakthrough cases.4. According to the present immunization schedule, children receive1dose of varicella vaccine at the age of1-2years. The protection provided by the vaccine seems to vanish in6-7years. Vaccinated individuals are likely to have breakthrough varicella when they reach their middle or senior years in primary school or junior high school age. A second dose of varicella vaccine will be important for the outbreak control.5. Further studies on varicella vaccine efficacy and confounding factors such as age when the vaccine is given, primary vaccine failure and risk exposure are warranted. Based on the research findings, the ideal timing of the second dose of varicella vaccine will be recommended and varicella vaccination strategies will be adjusted. |
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