Study On Effectiveness Of Live Attenuated S₇₉ Mumps Vaccine In Pupulation

BACKGROUND & OBJECTIVEMumps virus infection,a potentially serious viral infection of childhood and early adulthood,may lead to meningitis(15%of all mumps patients),sensorineural deafness(5 per 100,000),pancreatitis(4%),orchitis(20-30%of postpubertal men with mumps),and spontaneous abortion(25%,usually in the first trimester of pregnancy).Experience from mumps elimination in western countries showed that vaccination with mumps vaccine is the key for mumps control.The burden of disease and cost of mumps virus infection led to the development of a specific vaccine in China.This live attenuated S₇₉ mumps vaccine was derived from the Jeryl-Lynn strain(isolated in 1979) after 3 successive passages in primary chick embryo cell culture.Since 1990,several large domestic manufacturers of biological products (Shanghai,Beijing,and Lanzhou Institute of Biological Products,China) have been licensed to produce S₇₉ strain mumps vaccine,and Chinese children have been immunized with over 1 000 000 000 doses.However,little data is available on the vaccine's safety and efficacy.Emphasizing the best and latest studies,evidence-based medicine(EBM) can get the quantitative results based on relevant literatures.Evidence-based vaccinology (EBV) has been developed and till now no literature on EBV was found in domestic.Prelicensing studies normally evaluate protection under the optimal conditions of clinical trials.However,the real contribution of a vaccine is better estimated by its performance when used in practice.Efficacy figures from clinical trials cannot easily be converted to vaccine VE because,during routine practice,not all susceptible children will be immunized before exposure or receive a full immunization program. In addition,the spectrum of vaccine recipients in practice typically expands beyond the healthy,highly responsive groups usually selected for efficacy trials.So,from a public health perspective,the impact of vaccination on practical outcome should be analyzed.Classification and regression tree analysis was a non-parameter model used for multi-variables analysis,especially while independent variables were correlated.With no special requirement for variables category,the model has been in widely use in western countries.Partâ… Systematic review on S₇₉ mumps vaccine seroconversion studiesMethods of fuzzy mathematical meta analysis and case series analysis on S₇₉ mumps vaccine seroconversion studies were used to evaluate immunogenicity in population.Methodsi.With mumps and vaccine included in MeSH,database of MEDLINE,CBM, CHKD(1994-2008) and dometic articles of vaccine conferences during past 10 years were retrieved.ii.Literatures including controls were performed by fuzzy mathematical meta analysis.Relative effect(M) was calculated by different effect(L) in vaccine groups and control groups.iii.Literatures with no controls were performed by case series analysis.Studies that were carried out in 2 months since vaccination and specific test was used for mumps antibody detection were enrolled.Resultsi.13 studies of which 2 included controls and 11 included no controls were analyzed after evlavation from 182 articles. ii.Two studies were analysed by fuzzy mathematical meta analysis.The final Relative effect(M) was calculated as followed, M_V=L'_ZV/L'_ZC=l.92/1.63=1.18Vaccine group had a 18%more protection after 3 years since vaccination than controls.iii.11 literatures distributed in 10 domestic areas during 1992-2007 were included in case series analysis.Seroconversion ranged 54.3%-86.4%during 2 months since vaccination,of which serocnversion with sample size over 100 ranged 76.2%-84.2%in Shandong,Jiaxing,Tongxiang and Hangzhou.3 studies were in the first month with 54.3%-79.4%,and 8 were in the second month with 66.2%-86.4%.5 studies were among those aged less than 24 months old with seroconversion 54.3%-86.4%,and 6 studies were among those aged 2-13 years old with seroconversion 66.2%-84.4%.SummaryTwo methods were used to evaluate the studies on S79 mumps seroconversion. Children with different birth years had similar immunogenicity to the vaccine and protective effect was seen after 3 years since vaccination.Partâ…¡Effectiveness of live attenuated S₇₉ mumps vaccine against clinical mumps:a matched case-control studyMumps is a great threat to children in Guangzhou,one of the largest and most prosperous cities in China,where 5171 and 7934 mumps cases(incidence rate, 70.36/100 000 and 105.53/100 000,respectively) were reported in 2004 and 2005. The S₇₉ vaccine has been used in children since 1995 in Guangzhou and vaccination has been voluntary.Thus data was available for us to assess the VE of this vaccine, and we accordingly carried out a case-control study. Methodsi.Cases were selected during Sep 2006 to Mar 2007 from the China Information System for Disease Control and Prevention,which is a physician-based system for reporting all suspected mumps cases.ii.Controls were confirmed to be children without symptoms of mumps(i.e.,no acute onset of unilateral or bilateral tender swelling of the parotid or salivary gland). And confirmation was obtained by telephone or face-to-face interview with the child's parent or guardian.Controls were matched to cases by gender,age,and community or village of residence.For each case,three potential controls were randomly selected from the list generated by the Childrens' EPI Administrative Computerized System.Of the three potential controls,the one with a birth date closest to that of the case was interviewed first.The closeness of the date of birth to that of the case determined the order of the three interviews.iii.Only children(8 months to 12 years old) whose information was found in the Childrens' Expanded Programmed Immunization(EPI) Administrative Computerized System were enrolled.Basic information and S₇₉ mumps vaccine vaccination information were obtained for both cases and controls.iv.VE was calculated as one minus the adjusted matched odds ratio(OR)×100%,where the OR was the odds of cases developing in the vaccinated group compared with the odds of cases developing in the unvaccinated group.Cox survival regression was used to calculate the ORs and 95%confidence intervals(CIs)Resultsi.We identified 469 children with mumps in Guangzhou in 2006,with age 8.57±3.10 years old and gender ratio 1.97:1.Age,gender,and place of residence were identical for each pair.ii.Among 938 study participants,638 had not been vaccinated,300 had received 1 valid dose,and one child received 2 doses.There were twice as many vaccinated controls as vaccinated cases(43.9%versus 20.0%).iii.Overall the VE of the S₇₉ mumps vaccine against clinical mumps in children was 86.2%.It was a bit lower for one dose(86.0%,95%CI 77.2%-91.5%)(Table 2) and was not statistically valid for two doses because the sample was too small(98.5%, 95%CI,0%-100%).iv.As for analysis VE of 1 dose of vaccine,there was altoghter 147 distants,accounting for 31.4%of 468 pairs.VE could not be calculated for those aged 0,1,2,3,11,and 12 years because of small sample size.For those aged between 4 and 10 years,the seven 95%CIs for the VE of one dose overlapped,and similar VE points could be seen.No difference in VE was found for those aged 0-5 years(87.9%,95%CI65.8%-95.7%) and those aged over 6 years(64.6%, 95%CI73.0%-91.2%).SummaryThis post-licensing study of the VE of the live attenuated S₇₉ mumps vaccine found that 1 versus 0 doses was effective in preventing mumps and similar VEs were seen among those with different brith years.Partâ…¢Evaluation of Live Attenuated S₇₉ Mumps Vaccine Effectiveness in Mumps Outbreaks:a Matched Case-control StudyAn assessment of the public health role of the S₇₉ vaccine under the real-world conditions of clinical practice is now needed and we accordingly carried out a study among mumps outbreaks cases.Methodsi.Our case definition included those with clinical diagnose from mumps outbreaks in schools in Guangzhou in 2006 with outbreak defined as at least onset of three cases within one week in one school. ii.Controls were matched to cases by gender,age,and community or village of residence.Controls were confirmed to be children without symptoms of mumps(i.e., no acute onset of unilateral or bilateral tender swelling of the parotid or salivary gland).Confirmation was obtained by telephone or face-to-face interview with the child's parent or guardian.Resultsi.194 mumps cases in 49 outbreaks between grade 1 and grade 5 were finally enrolled in our study.ii.Age,gender,and place of residence were identical for each pair.Among 388 study participants,201 had been vaccinated with valid S₇₉ mumps vaccine,22 were vaccinated with 2 doses.iii.As for 1 dose of S₇₉ mumps vaccine,there were altoghther 55 distants and VE was 80.4%(95%CI,60.0%-90.4%).Statistical difference was not found between those aged less than 10 years old and those aged over 10 years old(95%CI 47.2%-93.7%and 45.4%-92.1%,respectively).For 2 doses of S₇₉ mumps vaccine, there were altoghther 22 distants and VE was 90.0%(95%CI,57.2%-97.7%).SumarryThis post-licensing study of the VE of the live attenuated S₇₉ mumps vaccine found that 1(versus 0) doses was effective in preventing mumps outbreaks.Partâ…£Study on the vaccine effectiveness of different time of vaccination and different time since vaccinationUsing 1:1 paired case control studies,we get VE of 1 dose of S₇₉ mumps vaccine in the community 86.0%(95%CI,77.2%-91.5%) and 80.4%(95%CI, 60.0%-90.4%) in outbreaks.Further analysis is done by combining the databases. MethodsTotal VE,VE of different age of vaccination and different time since vaccination of 1 dose of S₇₉ mumps vaccine were calculated by combining main variables mentioned in Partâ…¡and Partâ…¢.Resultsi.Among 640 enrollees,165 cases were vaccinated with S₇₉ mumps vaccine (25.8%percent vaccinated) and 313 controls were vaccinated(48.9%percent vaccinated).Overall VE of 1 dose of S₇₉ mumps vaccine was(95%CI,67.5%-94.9%), with pairs of case vaccinated control unvaccinated 27 and pairs of case unvaccinated control vaccinated 175.ii.VE for those with vaccination time of 8-11 months old was 78.4%(95%CI, 58.6%-88.8%),those with vaccination time of 12-23 months old was 86.1%(95%CI, 73.8%-92.6%) and those with vaccination time of≥24 months old was 87.2%(95%CI, 67.5%-94.9%).No statistical diffrence was found because three 95%CIs overlaped.iii.VE since vaccination was 98.5%(95%CI,0%-100%)(in the 1^st year),98.5% (95%CI,0%-100%)(in the 2^nd year),85.7%(95%CI,0%-98.2%)(in the 3^rd year),66.7%(95%CI,8.3%-87.9%)(in the 4^th year),90.0%(95%CI,67.2%-96.9%) (in the 5^th year),76.9%(95%CI,19.0%-93.4%)(in the 6^th year),93.3%(95%CI, 72.1%-98.4%)(in the 7^th year),77.8%(95%CI,34.3%-92.5%)(in the 8^th year),92.9% (95%CI,70.0%-98.3%)(in the 9^th year) and 60.0%(95%CI,0%-100%)(in the following≥10 years).Stastical difference was found in the 4^th,5^th,6^th,7^th,8^th,and 9^th year,with narrower CIs in the 5^th,7^th and 9^th year.iv.VE differenc was not found among those in the first 3 years 94.7%(95%CI, 60.7%-99.3%) and in the following years 83.3%(95%CI,74.5%-89.1%) since vaccination.There was no statistical difference between VEs among those in the first 4 years 82.4%(95%CI,58.0%-92.6%) and in the following years 85.2% (95%CI,76.3%-90.7%) since vaccination.v.For those with vaccination time of 8-11 months old,VE of in the first 3 years since vaccination was 98.5%(95%CI,0%-100%) and VE of in the following yearssince vaccination was 76.7%(95%CI,53.7%-88.3%).For those with vaccination time of 12-23 months old,VE of in the first 3 years since vaccination was 98.5%75.0%(95%CI,0%-97.2%) and VE of in the following yearssince vaccination was 86.7%(95%CI,74.2%-93.1%).For those with vaccination time of≥24 months old,VE of in the first 3 years since vaccination was(95%CI,0%-100%) and VE of in the following yearssince vaccination was 84.4%(95%CI,59.9%-93.9%).SummaryVE of 1 dose of S₇₉ mumups vaccine was 84.6%(95%CI,76.9%-89.7%) and statistical difference was not found among those at different year of vaccination.VE waning was not found.1 versus 0 doses of vaccine was effective in preventing mumps and keeps protection after protection is got.Partâ…¤Study on training mode of inoculation practitioners and Classification tree analysis on influencing factors of achievementsTo increase inoculation practitioners' service level and to control mumps by using vaccines,we established a training system in Guangzhou.Classification and regression tree model was used to determine the main factors influencing achiements.MethodsAll inoculation practitioners in Guangzhou were requied to take the 4 days' course in batch and 1 day's examination.Endermic injection was checked by 10 points as to practitioners' circulation and knowledge test was carried out with examination questions database.Analysis was performed by CART 5.0.Resultsi.Of all 23 classes from 2003 to 2005,the average score was 61.0±12.1 (ranged 18.5-90.5),with valid rate 83.2%(ranged 66.7%-93.1%) ii.1824 inoculation practitioners' achievements were analyzed by Classification and regression tree model and there were altogether 23 internal nodes and 24 teminal nodes in the model.iii.Predictive factors weighted over 10 score was age(100),working years in profession(45.84),whether middle techincal post(20.72),whether master degree or higher(16.93),whether junior diploma(13.99) and whether primary technical post (11.93),respectively.SummaryScore stabled a relative level and our training system was effective.Those who aged over 42.5 or worked for less years in inoculation field should be aimed at in particular.ConclusionsBy using fuzzy mathematical meta analysis and case series analysis on S79 mumps vaccine seroconversion studies,we discovered that Children with different birth years had similar immunogenicity to the vaccine and protective effect was seen after 3 years since vaccination.By using 1:1 paired case control studies conducted in communities and outbreaks in school,we revealed that 1 dose of S₇₉ mumps vaccine was effective in preventing clinical mumps.VE difference was not found among those at different age of vaccination and VE waning over time was not found. Vaccination of 1 dose of live attenuated S₇₉ mumps vaccine as early as possible is of necessity among children and the second dose in time is advised.Vaccination as well as normative training on inoculation practitioners are the key for mumps control.