S_(79)株腮腺炎减毒活疫苗人群免疫保护效果研究
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摘要
腮腺炎病毒感染是儿童及早期成人一个潜在的严重危险,可导致脑膜炎(15%)、感觉神经型耳聋(5/10万)、胰腺炎(4%)、睾丸炎(20%-30%青春后期的男性感染者)及流产(25%,通常发生于孕期的前三个月)。国外成功的经验表明对儿童进行腮腺炎疫苗接种是预防控制流行性腮腺炎的重要措施。我国于1979年从美国引入Jeryl-Lynn毒株,在原代鸡胚细胞减毒传3代后生成S_(79)毒株。1990年开始卫生部上海、北京和兰州生物制品研究所获许生产含S_(79)株的腮腺炎疫苗,至今已经超过1亿剂腮腺炎疫苗用于中国儿童预防腮腺炎。国内有关该疫苗的研究多为人群血清抗体阳转研究,但该疫苗是否有积极的免疫保护效果,尚未达成共识。
循证医学(Evidence-based medicine,EBM)现在已形成了以最佳、最新的科研结果为依据的科学评价文献的方法学和重证据的科学思维方法,可对文献进行综合分析,可得到定量的指标结果。循证疫苗学概念也被相继提出,目前国内尚未见到循证医学在疫苗效果评价方面应用的报道。
国内对于疫苗的研究往往限于研制和开发过程,缺乏正式使用后大范围人群的评估。随机对照现场试验研究通常是在良好的条件下对疫苗效力进行评估,得来的疫苗保护效力数据不能直接转变成疫苗的保护效果。因为在实际的常规免疫中,不是所有的易感儿童在暴露于危险因素前会被免疫或者接受全程的疫苗接种。而且,实际的接种者不只是那些健康且对于疫苗反应很好的儿童,而这部分人通常在临床试验中被采纳,对于减毒活疫苗而言,实际应用中的冷链保持也是一个问题。只有从病人及人群进行研究才能更好地对疫苗免疫效果进行评估,临床试验证明有效的疫苗应继续进行上市后大规模人群应用后的研究,这样才能得到真实的保护效果。从公共卫生的角度而言,对于疫苗的实际保护效果应予以研究。
分类与回归树分析是一种非参数回归模型,当应变量是分类变量时为分类树分析,近年来在国外开始大量应用,该模型利用递归分型将人群分为不同的亚群进行分析,它对预测变量的数据类型无任何要求,可用于多因素研究数据的统计分析,尤其适合于自变量有相关关系时。第一部分S_(79)株腮腺炎疫苗人群抗体阳转研究系统评价
利用模糊数学Meta分析法和病例系列研究分析方法,通过复习既往关于该疫苗在儿童中抗体阳转研究的文献,探讨S_(79)株腮腺炎减毒活疫苗在人群中的血清阳转效果。
方法
1.以主题词包括腮腺炎和疫苗,检索MEDLINE、中国医学文献全文数据库和中国医院数字图书馆(1994-2008),以及近10年国内免疫生物制品会议论文集,收集符合条件的文献资料。
2.模糊数学Meta分析:对象为设置对照的血清阳转研究,按疫苗组(V)及对照组(C)的接种疫苗后抗体分为阳转和未阳转2个等级,以每一等级阳转的发生百分率为指标,分别计算疫苗组和对照组的效果值(L),最后得综合疗效相对值(M)。
3.病例系列研究综合分析:对象为未设置对照的血清阳转研究,纳入的文献要求观察期限在2个月内,腮腺炎抗体检测方法一致。
结果
1.通过文献检索共获得182篇相关文献,对这些文献的总体质量进行评估后,13篇最终入选,其中2篇设置对照,11篇无对照。
2.模糊数学Meta分析:共2项含对照的研究纳入,列出疫苗与对照的抗体阳转情况,计算每个单项研究的权重,归一化得疫苗综合效果相对值:M_V=L'_(ZV)/L'_(ZC)=1.92/1.63=1.18
M_V＞1.05,故疫苗的阳转效果优于对照组,疫苗组接种3年后的抗体阳转效果优于对照组18%。
3.病例系列研究综合分析:共收集有关S_(79)腮腺炎减毒活疫苗的抗体阳转病例系列报道11篇,发表时间为1992-2007年,涉及国内10个不同地区。山东、嘉兴、桐乡和杭州的病例系列研究的样本量大于100人,阳性率为76.2%-84.2%。1剂疫苗免后2个月内抗体的阳性率为54.3%-86.4%,其中免后1个月内抗体的阳转研究有3项,为54.3%-79.4%;免后时间1-2月的研究有8项,为66.2%-86.4%。报道24月龄前的阳转率研究有5项,为54.3%-86.4%;报道2-13岁的研究有6项,为66.2%-84.4%。
小结
人群血清阳转研究是采集受试者双份血,统计阴性者接种疫苗后一段时间后发生抗体阳转的比例,我们利用两种研究方法,对S_(79)株腮腺炎疫苗的血清阳转研究进行系统评价,发现不同年龄段儿童对1剂S_(79)株腮腺炎减毒活疫苗短期内有较好的、相近的抗体反应,接种1剂S_(79)株腮腺炎减毒活疫苗3年后仍有一定的保护性抗体。第二部分S_(79)株腮腺炎疫苗对腮腺炎临床发病保护效果的配对病例对照研究
腮腺炎是对广州市儿童健康的一个重大威胁,2004年及2005年广州市分别报道5171和7934名腮腺炎病例(发病率分别为70.36/10万和105.53/10万)。S_(79)疫苗自1995年起在广州应用,为评估该疫苗应用于人群的公共卫生角色,我们对其疫苗的保护效果进行回顾性调查研究。
方法
1.病例来源于中国疾病预防控制传染病监测信息系统,2006年9月至2007年3月间广州市报告的腮腺炎临床诊断病例。
2.对照为从来未出现过单侧或双侧腮腺或唾液腺肿大者,由调查人员根据监护人联系电话确认或面对面对儿童的监护人进行访谈确认。按照性别、年龄和居住地(如同一个居委或村)进行配对。利用广州市儿童预防接种管理信息系统选择对照,为每个病例选取3个候选的对照进行配对,最终选取1个和病例出生日期最近的儿童作为对照。
3.在广州市儿童预防接种管理信息系统有免疫接种记录,且年龄在8月龄至12岁的儿童作为研究对象,获取的信息包括儿童的基本信息及接种情况。
4.疫苗的保护效果(Vaccine Effectiveness,VE)=1-调整OR,此处OR为病例及对照的接种和未接种的暴露率的比值比。利用Epidata 3.1录入数据,导出成Excel格式后对原始数据进行清理。以COX回归模型拟合条件Logistic回归模型(conditional logistic regression model,CLRM),计算OR及其95%可信限(CI)。
结果
1.共获得469名儿童病例(年龄8.57±3.10岁,男女人数性别比为1.97:1),每1对配对的病例及对照的年龄(岁)、性别及居住地信息一致。
2.938名研究对象中,638名无S_(79)株腮腺炎疫苗接种史,300名儿童曾经接种过1或2剂S_(79)株疫苗(其中只有1个儿童接种过2剂疫苗),对照组的接种率为病例组的近2倍(分别为43.9%和20.0%)。
3.S_(79)腮腺炎疫苗对腮腺炎临床病例的保护效果为86.2%,1剂疫苗的保护效果稍低(86.0%,95%CI 77.2%-91.5%),未得到统计学意义的2剂疫苗的保护效果(限于样本量,保护效果的95%CI,0%-100%)。
4.对1剂疫苗保护效果分析,共有147个不一致的对子数(即病例和对照的接种史不一致的对子数),占全部对子数的31.4%。S_(79)腮腺炎疫苗对0、1、2、3、11及12岁儿童的保护效果无统计学意义。4-10岁之间的7个年龄保护效果之间的差别无统计学意义(95%可信限包含共同区间)。对0-5岁及6岁以上的保护效果的差别无统计学意义(87.9%和64.6%,95%CI分别为65.8%-95.7%和73.0%-91.2%)。
小结
疫苗上市后研究发现1剂S_(79)腮腺炎减毒活疫苗对预防临床腮腺炎存在有效的保护效果,不同年龄的儿童的既往保护效果相近。第三部分S_(79)株腮腺炎疫苗在腮腺炎暴发中的保护效果配对病例对照研究
为评估国产S_(79)株腮腺炎减毒活疫苗在人群应用后的实际公共卫生保护效果,我们利用广州市小学的暴发腮腺炎病例,进行该疫苗对暴发病例保护效果的配对病例对照研究。
方法
1.取广州市小学2007年腮腺炎暴发的临床诊断病例,腮腺炎暴发的定义为1个学校1周内发生至少3名病例。
2.按照性别、年龄和居住地进行配对,对照为既往未出现过单侧或双侧腮腺或唾液腺肿大,由班主任协助调查员进行电话确认或面对面对儿童的监护人进行访谈确认。
结果
1.共调查49起194名暴发腮腺炎病例,暴发病例分布于从小学一年级到五年级。
2.每一对配对的病例及对照的年龄(岁)、性别及居住地的信息一致。388名研究对象中,187名无S_(79)株腮腺炎疫苗接种史,201名儿童曾经接种过1或2剂S_(79)株疫苗(其中22个儿童接种过2剂疫苗。
3.1剂S_(79)株腮腺炎疫苗保护效果为80.4%(95%CI,60.0%-90.4%),共有55个不一致的对子数;10岁以下及以上两个年龄组儿童的保护效果差别无统计学意义(两者95%C1分别为47.2%-93.7%及45.4%-92.1%)。2剂疫苗保护效果为90.0%(95%CI,57.2%-97.7%),不一致的对子数为22。
小结
疫苗上市后保护效果研究发现S_(79)腮腺炎减毒活疫苗对腮腺炎暴发存在有效的保护作用。第四部分1剂S_(79)腮腺炎疫苗不同接种起始年龄及接种后保护效果衰减研究
之前分别对社区的临床腮腺炎病例及学校暴发腮腺炎病例进行1:1配对,得出1剂S_(79)腮腺炎减毒活疫苗的保护效果分别是86.0%(95%CI,77.2%-91.5%)及80.4%(95%CI,60.0%-90.4%)。我们将1剂S_(79)疫苗保护效果的数据库合并,进一步分析相关指标。
方法
将第二部分及第三部分论述的数据库(1剂S_(79)疫苗)的主要变量合并,计算1剂S_(79)腮腺炎减毒活疫苗总的保护效果、不同接种年龄的保护效果及接种该疫苗在接种后不同时间的保护效果。
结果
1.对640名研究对象既往的接种史进行分析,共有165名病例接种过S_(79)疫苗,接种比例为25.8%;对照313名接种过该疫苗,接种比例为48.9%。病例接种对照未接种的对子数为27,病例未接种对照接种的对子数为175,1剂S79疫苗总体保护效果为84.6%(76.9%-89.7%)。
2.接种起始月龄为8-11者的保护效果为78.4%(58.6%-88.8%),接种起始月龄为12-23者的保护效果为86.1%(73.8%-92.6%),接种起始月龄为≥24者的保护效果为87.2%(95%CI,67.5%-94.9%),三者差别无统计学意义(三者95%CI交叉)。
3.对接种后不同年度的保护效果分别为:98.5%(95%CI,0%-100%)(第1年)、98.5%(95%CI,0%-100%)(第2年)、85.7%(95%CI,0%-98.2%)(第3年)、66.7%(95%CI,8.3%-87.9%)(第4年)、90.0%(95%CI,67.2%-96.9%)(第5年)、76.9%(95%CI,19.0%-93.4%)(第6年)、93.3%(95%CI,72.1%-98.4%)(第7年)、77.8%(95%CI,34.3%-92.5%)(第8年)、92.9%(95%CI,70.0%-98.3%)(第9年)及60.0%(95%CI,0%-100%)(第10年及以后)。接种后第4、5、6、7、8、9年保护效果有保护意义,其中第5、7及9年的保护效果95%CI跨度更小。
4.接种后第1-3年内和4年以上的保护效果分别是94.7%(60.7%-99.3%)和83.3%(95%CI,74.5%-89.1%),两者相近(95%CI交叉);接种后第1-4年内和5年以上的保护效果分别是82.4%(95%CI,58.0%-92.6%)和85.2%(95%CI,76.3%-90.7%),两者相近(95%CI交叉)。
5.接种年龄为8-11月龄受种者接种后第1-3年的保护效果为98.5%(95%CI,0%-100%),接种后第4-年内为76.7%(95%CI,53.7%-88.3%);接种年龄为12-23月龄受种者接种后第1-3年的保护效果为75.0%(95%CI,0%-97.2%),接种后第4-年内为86.7%(95%CI,74.2%-93.1%);接种年龄为≥24月龄受种者接种后第1-3年的保护效果为98.5%(95%CI,0%-100%),接种后第4-年内为84.4%(95%CI,59.9%-93.9%)。
小结
接种1剂该疫苗的保护效果为84.6%(95%CI,76.9%-89.7%),未发现不同接种起始年龄的保护效果的统计学差别,接种后保护效果衰退不明显。说明该疫苗具有较好的保护作用,且一旦接种成功,具有较好的远期保护效果。第五部分预防接种从业人员培训模式研究及成绩影响因素分类树分析
为提高广州市预防接种从业人员的业务水平,实施以预防接种为主的综合干预措施,降低广州市流行性腮腺炎的发病,我们自2003至2005年对全市所有在岗及新上岗的从业人员进行了系统培训并进行严格考核。利用分类树分析模型,对广州市3年来培训考核的成绩的影响因素进行探讨,分析预防工作人员上岗培训模式及培训重点对象。
方法
参加培训人员为广州市所有预防接种门诊的从业人员,集中授课四天时间。考核1天,包括操作及理论部分,其中操作采用标准化形式,分为10个标准评分步骤,学员间循环进行皮内注射法操作;建立考试试题库,每次自题库中随机抽取考试题目。主要采用CART 5.0进行多因素分析。
结果
1.共举办23期培训班(不含补考班),考试成绩为61.0±12.1分,其中最高分数90.5,最低18.5,及格率为83.2%(66.7%-93.1%)。
2.有1824名研究对象纳入分类树模型分析,其中不及格303名,及格1521名。主分类树有23个中间结,24个终结点。
3.预测变量的相对重要性:以年龄为100分,按重要性从大到小依次是工作年限(45.84分)、是否中级职称(20.72分)、是否本科及以上(16.93分)、是否大专(13.99分)、是否初级(11.93分)、是否城乡结合地区(7.75分)、是否农村(6.36分)、是否科长(5.39分)、是否副高及以上(4.56分)、是否中专(2.96分)、性别(2.08分)、是否护±长(1.64分)。
小结
此种培训模式可作为一种上岗培训模式来推广。对考试及格与否的多因素分类树分析中,年龄和工作年限是最强的影响因素。此后培训的重点对象应该是年龄高于42.5岁而工作年限低者。分类树模型结果容易理解,是一种值得推广的多因素分析方法。
结论
我们利用模糊数学Meta分析及病例系列研究方法,对S_(79)腮腺炎减毒活疫苗的血清免疫反应性研究的文献进行系统评价,发现不同年龄段儿童对1剂S_(79)株腮腺炎减毒活疫苗短期内有较好的、相近的抗体反应,接种1剂S_(79)株腮腺炎减毒活疫苗3年后仍有一定的保护性抗体。利用1:1配对病例对照研究对社区散发和学校集中暴发进行S_(79)疫苗保护效果的研究,发现1剂S_(79)疫苗对受种者提供有效的保护作用,不同接种起始年龄的保护效果不明显,接种后保护效果衰退不明显。应对适龄儿童及早接种1剂该疫苗,以提供及时、良好的免疫保护效果;并适时进行第2剂的接种,同时应坚持对接种人员的培训模式,确保预防接种效果,是控制腮腺炎的免疫预防策略。
BACKGROUND & OBJECTIVE
Mumps 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 S_(79) 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 S_(79) 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.
PartⅠSystematic review on S_(79) mumps vaccine seroconversion studies
Methods of fuzzy mathematical meta analysis and case series analysis on S_(79) mumps vaccine seroconversion studies were used to evaluate immunogenicity in population.
Methods
i.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.
Results
i.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=1.18
Vaccine 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%.
Summary
Two 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.
PartⅡEffectiveness of live attenuated S_(79) mumps vaccine against clinical mumps:a matched case-control study
Mumps 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 S_(79) 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.
Methods
i.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 S_(79) 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)
Results
i.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 S_(79) 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%).
Summary
This post-licensing study of the VE of the live attenuated S_(79) mumps vaccine found that 1 versus 0 doses was effective in preventing mumps and similar VEs were seen among those with different brith years.
PartⅢEvaluation of Live Attenuated S_(79) Mumps Vaccine Effectiveness in Mumps Outbreaks:a Matched Case-control Study
An assessment of the public health role of the S_(79) vaccine under the real-world conditions of clinical practice is now needed and we accordingly carried out a study among mumps outbreaks cases.
Methods
i.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.
Results
i.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 S_(79) mumps vaccine,22 were vaccinated with 2 doses.
iii.As for 1 dose of S_(79) 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 S_(79) mumps vaccine, there were altoghther 22 distants and VE was 90.0%(95%CI,57.2%-97.7%).
Sumarry
This post-licensing study of the VE of the live attenuated S_(79) mumps vaccine found that 1(versus 0) doses was effective in preventing mumps outbreaks.
PartⅣStudy on the vaccine effectiveness of different time of vaccination and different time since vaccination
Using 1:1 paired case control studies,we get VE of 1 dose of S_(79) 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.
Methods
Total VE,VE of different age of vaccination and different time since vaccination of 1 dose of S_(79) mumps vaccine were calculated by combining main variables mentioned in PartⅡand PartⅢ.
Results
i.Among 640 enrollees,165 cases were vaccinated with S_(79) mumps vaccine (25.8%percent vaccinated) and 313 controls were vaccinated(48.9%percent vaccinated).Overall VE of 1 dose of S_(79) 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%).
Summary
VE of 1 dose of S_(79) 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.
PartⅤStudy on training mode of inoculation practitioners and Classification tree analysis on influencing factors of achievements
To 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.
Methods
All 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.
Results
i.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.
Summary
Score 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.
Conclusions
By 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 S_(79) 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 S_(79) 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.
循证医学(Evidence-based medicine,EBM)现在已形成了以最佳、最新的科研结果为依据的科学评价文献的方法学和重证据的科学思维方法,可对文献进行综合分析,可得到定量的指标结果。循证疫苗学概念也被相继提出,目前国内尚未见到循证医学在疫苗效果评价方面应用的报道。
国内对于疫苗的研究往往限于研制和开发过程,缺乏正式使用后大范围人群的评估。随机对照现场试验研究通常是在良好的条件下对疫苗效力进行评估,得来的疫苗保护效力数据不能直接转变成疫苗的保护效果。因为在实际的常规免疫中,不是所有的易感儿童在暴露于危险因素前会被免疫或者接受全程的疫苗接种。而且,实际的接种者不只是那些健康且对于疫苗反应很好的儿童,而这部分人通常在临床试验中被采纳,对于减毒活疫苗而言,实际应用中的冷链保持也是一个问题。只有从病人及人群进行研究才能更好地对疫苗免疫效果进行评估,临床试验证明有效的疫苗应继续进行上市后大规模人群应用后的研究,这样才能得到真实的保护效果。从公共卫生的角度而言,对于疫苗的实际保护效果应予以研究。
分类与回归树分析是一种非参数回归模型,当应变量是分类变量时为分类树分析,近年来在国外开始大量应用,该模型利用递归分型将人群分为不同的亚群进行分析,它对预测变量的数据类型无任何要求,可用于多因素研究数据的统计分析,尤其适合于自变量有相关关系时。第一部分S_(79)株腮腺炎疫苗人群抗体阳转研究系统评价
利用模糊数学Meta分析法和病例系列研究分析方法,通过复习既往关于该疫苗在儿童中抗体阳转研究的文献,探讨S_(79)株腮腺炎减毒活疫苗在人群中的血清阳转效果。
方法
1.以主题词包括腮腺炎和疫苗,检索MEDLINE、中国医学文献全文数据库和中国医院数字图书馆(1994-2008),以及近10年国内免疫生物制品会议论文集,收集符合条件的文献资料。
2.模糊数学Meta分析:对象为设置对照的血清阳转研究,按疫苗组(V)及对照组(C)的接种疫苗后抗体分为阳转和未阳转2个等级,以每一等级阳转的发生百分率为指标,分别计算疫苗组和对照组的效果值(L),最后得综合疗效相对值(M)。
3.病例系列研究综合分析:对象为未设置对照的血清阳转研究,纳入的文献要求观察期限在2个月内,腮腺炎抗体检测方法一致。
结果
1.通过文献检索共获得182篇相关文献,对这些文献的总体质量进行评估后,13篇最终入选,其中2篇设置对照,11篇无对照。
2.模糊数学Meta分析:共2项含对照的研究纳入,列出疫苗与对照的抗体阳转情况,计算每个单项研究的权重,归一化得疫苗综合效果相对值:M_V=L'_(ZV)/L'_(ZC)=1.92/1.63=1.18
M_V＞1.05,故疫苗的阳转效果优于对照组,疫苗组接种3年后的抗体阳转效果优于对照组18%。
3.病例系列研究综合分析:共收集有关S_(79)腮腺炎减毒活疫苗的抗体阳转病例系列报道11篇,发表时间为1992-2007年,涉及国内10个不同地区。山东、嘉兴、桐乡和杭州的病例系列研究的样本量大于100人,阳性率为76.2%-84.2%。1剂疫苗免后2个月内抗体的阳性率为54.3%-86.4%,其中免后1个月内抗体的阳转研究有3项,为54.3%-79.4%;免后时间1-2月的研究有8项,为66.2%-86.4%。报道24月龄前的阳转率研究有5项,为54.3%-86.4%;报道2-13岁的研究有6项,为66.2%-84.4%。
小结
人群血清阳转研究是采集受试者双份血,统计阴性者接种疫苗后一段时间后发生抗体阳转的比例,我们利用两种研究方法,对S_(79)株腮腺炎疫苗的血清阳转研究进行系统评价,发现不同年龄段儿童对1剂S_(79)株腮腺炎减毒活疫苗短期内有较好的、相近的抗体反应,接种1剂S_(79)株腮腺炎减毒活疫苗3年后仍有一定的保护性抗体。第二部分S_(79)株腮腺炎疫苗对腮腺炎临床发病保护效果的配对病例对照研究
腮腺炎是对广州市儿童健康的一个重大威胁,2004年及2005年广州市分别报道5171和7934名腮腺炎病例(发病率分别为70.36/10万和105.53/10万)。S_(79)疫苗自1995年起在广州应用,为评估该疫苗应用于人群的公共卫生角色,我们对其疫苗的保护效果进行回顾性调查研究。
方法
1.病例来源于中国疾病预防控制传染病监测信息系统,2006年9月至2007年3月间广州市报告的腮腺炎临床诊断病例。
2.对照为从来未出现过单侧或双侧腮腺或唾液腺肿大者,由调查人员根据监护人联系电话确认或面对面对儿童的监护人进行访谈确认。按照性别、年龄和居住地(如同一个居委或村)进行配对。利用广州市儿童预防接种管理信息系统选择对照,为每个病例选取3个候选的对照进行配对,最终选取1个和病例出生日期最近的儿童作为对照。
3.在广州市儿童预防接种管理信息系统有免疫接种记录,且年龄在8月龄至12岁的儿童作为研究对象,获取的信息包括儿童的基本信息及接种情况。
4.疫苗的保护效果(Vaccine Effectiveness,VE)=1-调整OR,此处OR为病例及对照的接种和未接种的暴露率的比值比。利用Epidata 3.1录入数据,导出成Excel格式后对原始数据进行清理。以COX回归模型拟合条件Logistic回归模型(conditional logistic regression model,CLRM),计算OR及其95%可信限(CI)。
结果
1.共获得469名儿童病例(年龄8.57±3.10岁,男女人数性别比为1.97:1),每1对配对的病例及对照的年龄(岁)、性别及居住地信息一致。
2.938名研究对象中,638名无S_(79)株腮腺炎疫苗接种史,300名儿童曾经接种过1或2剂S_(79)株疫苗(其中只有1个儿童接种过2剂疫苗),对照组的接种率为病例组的近2倍(分别为43.9%和20.0%)。
3.S_(79)腮腺炎疫苗对腮腺炎临床病例的保护效果为86.2%,1剂疫苗的保护效果稍低(86.0%,95%CI 77.2%-91.5%),未得到统计学意义的2剂疫苗的保护效果(限于样本量,保护效果的95%CI,0%-100%)。
4.对1剂疫苗保护效果分析,共有147个不一致的对子数(即病例和对照的接种史不一致的对子数),占全部对子数的31.4%。S_(79)腮腺炎疫苗对0、1、2、3、11及12岁儿童的保护效果无统计学意义。4-10岁之间的7个年龄保护效果之间的差别无统计学意义(95%可信限包含共同区间)。对0-5岁及6岁以上的保护效果的差别无统计学意义(87.9%和64.6%,95%CI分别为65.8%-95.7%和73.0%-91.2%)。
小结
疫苗上市后研究发现1剂S_(79)腮腺炎减毒活疫苗对预防临床腮腺炎存在有效的保护效果,不同年龄的儿童的既往保护效果相近。第三部分S_(79)株腮腺炎疫苗在腮腺炎暴发中的保护效果配对病例对照研究
为评估国产S_(79)株腮腺炎减毒活疫苗在人群应用后的实际公共卫生保护效果,我们利用广州市小学的暴发腮腺炎病例,进行该疫苗对暴发病例保护效果的配对病例对照研究。
方法
1.取广州市小学2007年腮腺炎暴发的临床诊断病例,腮腺炎暴发的定义为1个学校1周内发生至少3名病例。
2.按照性别、年龄和居住地进行配对,对照为既往未出现过单侧或双侧腮腺或唾液腺肿大,由班主任协助调查员进行电话确认或面对面对儿童的监护人进行访谈确认。
结果
1.共调查49起194名暴发腮腺炎病例,暴发病例分布于从小学一年级到五年级。
2.每一对配对的病例及对照的年龄(岁)、性别及居住地的信息一致。388名研究对象中,187名无S_(79)株腮腺炎疫苗接种史,201名儿童曾经接种过1或2剂S_(79)株疫苗(其中22个儿童接种过2剂疫苗。
3.1剂S_(79)株腮腺炎疫苗保护效果为80.4%(95%CI,60.0%-90.4%),共有55个不一致的对子数;10岁以下及以上两个年龄组儿童的保护效果差别无统计学意义(两者95%C1分别为47.2%-93.7%及45.4%-92.1%)。2剂疫苗保护效果为90.0%(95%CI,57.2%-97.7%),不一致的对子数为22。
小结
疫苗上市后保护效果研究发现S_(79)腮腺炎减毒活疫苗对腮腺炎暴发存在有效的保护作用。第四部分1剂S_(79)腮腺炎疫苗不同接种起始年龄及接种后保护效果衰减研究
之前分别对社区的临床腮腺炎病例及学校暴发腮腺炎病例进行1:1配对,得出1剂S_(79)腮腺炎减毒活疫苗的保护效果分别是86.0%(95%CI,77.2%-91.5%)及80.4%(95%CI,60.0%-90.4%)。我们将1剂S_(79)疫苗保护效果的数据库合并,进一步分析相关指标。
方法
将第二部分及第三部分论述的数据库(1剂S_(79)疫苗)的主要变量合并,计算1剂S_(79)腮腺炎减毒活疫苗总的保护效果、不同接种年龄的保护效果及接种该疫苗在接种后不同时间的保护效果。
结果
1.对640名研究对象既往的接种史进行分析,共有165名病例接种过S_(79)疫苗,接种比例为25.8%;对照313名接种过该疫苗,接种比例为48.9%。病例接种对照未接种的对子数为27,病例未接种对照接种的对子数为175,1剂S79疫苗总体保护效果为84.6%(76.9%-89.7%)。
2.接种起始月龄为8-11者的保护效果为78.4%(58.6%-88.8%),接种起始月龄为12-23者的保护效果为86.1%(73.8%-92.6%),接种起始月龄为≥24者的保护效果为87.2%(95%CI,67.5%-94.9%),三者差别无统计学意义(三者95%CI交叉)。
3.对接种后不同年度的保护效果分别为:98.5%(95%CI,0%-100%)(第1年)、98.5%(95%CI,0%-100%)(第2年)、85.7%(95%CI,0%-98.2%)(第3年)、66.7%(95%CI,8.3%-87.9%)(第4年)、90.0%(95%CI,67.2%-96.9%)(第5年)、76.9%(95%CI,19.0%-93.4%)(第6年)、93.3%(95%CI,72.1%-98.4%)(第7年)、77.8%(95%CI,34.3%-92.5%)(第8年)、92.9%(95%CI,70.0%-98.3%)(第9年)及60.0%(95%CI,0%-100%)(第10年及以后)。接种后第4、5、6、7、8、9年保护效果有保护意义,其中第5、7及9年的保护效果95%CI跨度更小。
4.接种后第1-3年内和4年以上的保护效果分别是94.7%(60.7%-99.3%)和83.3%(95%CI,74.5%-89.1%),两者相近(95%CI交叉);接种后第1-4年内和5年以上的保护效果分别是82.4%(95%CI,58.0%-92.6%)和85.2%(95%CI,76.3%-90.7%),两者相近(95%CI交叉)。
5.接种年龄为8-11月龄受种者接种后第1-3年的保护效果为98.5%(95%CI,0%-100%),接种后第4-年内为76.7%(95%CI,53.7%-88.3%);接种年龄为12-23月龄受种者接种后第1-3年的保护效果为75.0%(95%CI,0%-97.2%),接种后第4-年内为86.7%(95%CI,74.2%-93.1%);接种年龄为≥24月龄受种者接种后第1-3年的保护效果为98.5%(95%CI,0%-100%),接种后第4-年内为84.4%(95%CI,59.9%-93.9%)。
小结
接种1剂该疫苗的保护效果为84.6%(95%CI,76.9%-89.7%),未发现不同接种起始年龄的保护效果的统计学差别,接种后保护效果衰退不明显。说明该疫苗具有较好的保护作用,且一旦接种成功,具有较好的远期保护效果。第五部分预防接种从业人员培训模式研究及成绩影响因素分类树分析
为提高广州市预防接种从业人员的业务水平,实施以预防接种为主的综合干预措施,降低广州市流行性腮腺炎的发病,我们自2003至2005年对全市所有在岗及新上岗的从业人员进行了系统培训并进行严格考核。利用分类树分析模型,对广州市3年来培训考核的成绩的影响因素进行探讨,分析预防工作人员上岗培训模式及培训重点对象。
方法
参加培训人员为广州市所有预防接种门诊的从业人员,集中授课四天时间。考核1天,包括操作及理论部分,其中操作采用标准化形式,分为10个标准评分步骤,学员间循环进行皮内注射法操作;建立考试试题库,每次自题库中随机抽取考试题目。主要采用CART 5.0进行多因素分析。
结果
1.共举办23期培训班(不含补考班),考试成绩为61.0±12.1分,其中最高分数90.5,最低18.5,及格率为83.2%(66.7%-93.1%)。
2.有1824名研究对象纳入分类树模型分析,其中不及格303名,及格1521名。主分类树有23个中间结,24个终结点。
3.预测变量的相对重要性:以年龄为100分,按重要性从大到小依次是工作年限(45.84分)、是否中级职称(20.72分)、是否本科及以上(16.93分)、是否大专(13.99分)、是否初级(11.93分)、是否城乡结合地区(7.75分)、是否农村(6.36分)、是否科长(5.39分)、是否副高及以上(4.56分)、是否中专(2.96分)、性别(2.08分)、是否护±长(1.64分)。
小结
此种培训模式可作为一种上岗培训模式来推广。对考试及格与否的多因素分类树分析中,年龄和工作年限是最强的影响因素。此后培训的重点对象应该是年龄高于42.5岁而工作年限低者。分类树模型结果容易理解,是一种值得推广的多因素分析方法。
结论
我们利用模糊数学Meta分析及病例系列研究方法,对S_(79)腮腺炎减毒活疫苗的血清免疫反应性研究的文献进行系统评价,发现不同年龄段儿童对1剂S_(79)株腮腺炎减毒活疫苗短期内有较好的、相近的抗体反应,接种1剂S_(79)株腮腺炎减毒活疫苗3年后仍有一定的保护性抗体。利用1:1配对病例对照研究对社区散发和学校集中暴发进行S_(79)疫苗保护效果的研究,发现1剂S_(79)疫苗对受种者提供有效的保护作用,不同接种起始年龄的保护效果不明显,接种后保护效果衰退不明显。应对适龄儿童及早接种1剂该疫苗,以提供及时、良好的免疫保护效果;并适时进行第2剂的接种,同时应坚持对接种人员的培训模式,确保预防接种效果,是控制腮腺炎的免疫预防策略。
BACKGROUND & OBJECTIVE
Mumps 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 S_(79) 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 S_(79) 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.
PartⅠSystematic review on S_(79) mumps vaccine seroconversion studies
Methods of fuzzy mathematical meta analysis and case series analysis on S_(79) mumps vaccine seroconversion studies were used to evaluate immunogenicity in population.
Methods
i.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.
Results
i.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=1.18
Vaccine 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%.
Summary
Two 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.
PartⅡEffectiveness of live attenuated S_(79) mumps vaccine against clinical mumps:a matched case-control study
Mumps 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 S_(79) 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.
Methods
i.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 S_(79) 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)
Results
i.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 S_(79) 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%).
Summary
This post-licensing study of the VE of the live attenuated S_(79) mumps vaccine found that 1 versus 0 doses was effective in preventing mumps and similar VEs were seen among those with different brith years.
PartⅢEvaluation of Live Attenuated S_(79) Mumps Vaccine Effectiveness in Mumps Outbreaks:a Matched Case-control Study
An assessment of the public health role of the S_(79) vaccine under the real-world conditions of clinical practice is now needed and we accordingly carried out a study among mumps outbreaks cases.
Methods
i.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.
Results
i.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 S_(79) mumps vaccine,22 were vaccinated with 2 doses.
iii.As for 1 dose of S_(79) 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 S_(79) mumps vaccine, there were altoghther 22 distants and VE was 90.0%(95%CI,57.2%-97.7%).
Sumarry
This post-licensing study of the VE of the live attenuated S_(79) mumps vaccine found that 1(versus 0) doses was effective in preventing mumps outbreaks.
PartⅣStudy on the vaccine effectiveness of different time of vaccination and different time since vaccination
Using 1:1 paired case control studies,we get VE of 1 dose of S_(79) 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.
Methods
Total VE,VE of different age of vaccination and different time since vaccination of 1 dose of S_(79) mumps vaccine were calculated by combining main variables mentioned in PartⅡand PartⅢ.
Results
i.Among 640 enrollees,165 cases were vaccinated with S_(79) mumps vaccine (25.8%percent vaccinated) and 313 controls were vaccinated(48.9%percent vaccinated).Overall VE of 1 dose of S_(79) 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%).
Summary
VE of 1 dose of S_(79) 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.
PartⅤStudy on training mode of inoculation practitioners and Classification tree analysis on influencing factors of achievements
To 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.
Methods
All 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.
Results
i.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.
Summary
Score 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.
Conclusions
By 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 S_(79) 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 S_(79) 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.
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