麻疹疫苗接种策略及其免疫原性与安全性的系统评价

  本文关键词：麻疹疫苗接种策略及其免疫原性与安全性的系统评价，由笔耕文化传播整理发布。

        研究背景麻疹是由麻疹病毒通过呼吸道引起的高度接触性、急性传染病。当前麻疹的流行特点是重症病例减少,轻型病例增多,隐性感染普遍存在,局部仍有散发甚至爆发流行,一岁内儿童病例增加。麻疹疫苗可有效提高人群抗体水平,降低发病率。然而对于当前的免疫程序,存在诸多不同意见,疫苗的选用也存在国产和进口两种选择,同时,能否在保证免疫效果的前提下,使用联合疫苗来减少预防接种次数,降低疫苗管理难度及预防接种工作成本,从而提高免疫接种的依从性,尚未形成定论。目的为消除区域研究的片面性,应对麻疹发病新情况,甄选安全性强、高效能的麻疹疫苗,优化免疫程序,有效的预防和控制麻疹的发生,需要我们对现有疫苗的免疫效能、安全性、免疫程序以及与其它疫苗联合免疫的有效性和安全性等进行系统评价,进而为实现全面消除麻疹的目标提供科学依据。方法分别收集已公开发表的关于比较麻疹疫苗6月龄与8月龄初免效果的RCTs;比较国产MMR与进口MMR免疫原性和安全性的RCTs;比较MMRV与MMR和水痘疫苗分开接种免疫原性和安全性的RCTs,按照Cochrane协作网推荐的系统评价方法,对以上三方面麻疹疫苗免疫策略及其效果进行Meta分析。结果①纳入评价的不同初免月龄初免效果研究文献共10篇。系统评价结果显示:6月龄组和8月龄组接种前母传麻疹抗体阳性率差异有统计学意义[ RR=2.54, 95% CI(1.80 3.59), P<0.00001],6月龄组接种前母传抗体阳性率显著高于8月龄组;6月龄组和8月龄组接种后麻疹抗体阳性率差异有统计学意义[ RR=0.97, 95% CI(0.94 0.99), P=0.01],两组接种后免疫成功率差异有统计学意义[ RR=0.92, 95% CI(0.88 0.96), P=0.0003],6月龄组和8月龄组接种后麻疹抗体GMT差异有统计学意义[SMD=-96.32, 95%CI(-147.35 -43.29), P=0.0003],接种后8月龄组麻疹抗体阳性率、免疫成功率和麻疹抗体GMT均显著高于6月龄组。②纳入比较国产与进口MMR接种效果的文献共4篇,分析结果显示:国产MMR组和进口MMR组接种后麻疹抗体阳性率差异有统计学意义[ RR=1.06, 95% CI(1.12 1.29), P<0.00001],国产MMR组和进口MMR组麻疹抗体GMT差异有统计学意义[WMD=13.05, 95%CI(5.11 20.99), P=0.001] ,国产MMR接种后麻疹抗体阳性率和麻疹抗体GMT均高于进口MMR组;国产MMR组和进口MMR组接种后腮腺炎抗体阳性率差异无统计学意义[RR=0.96, 95%CI (0.92 1.01), P=0.16],两接种组风疹抗体GMT差异无统计学意义[WMD=-9.54, 95%CI(-72.70 53.61), P=0.77]。国产MMR组和进口MMR组接种后发热率差异有统计学意义[RR=2.29, 95%CI(1.21 4.33), P=0.01],接种后国产MMR组发热率显著高于进口MMR组;国产MMR组和进口MMR组接种后接种对象全身皮疹率差异无统计学意义[RR=1.49, 95%CI(0.53 4.19), P=0.44]。③共纳入5篇MMRV组和MMR+V组的免疫效果评价研究文献,Meta分析结果显示,对于MMRV组和MMR+V组:接种后发热率差异有统计学意义[RR=1.20, 95%CI(1.12 1.29), P<0.00001],MMRV组接种后发热率显著高于MMR+V组;接种部位疼痛发生率差异无统计学意义[RR=0.94, 95%CI(0.83 1.05) , P=0.28];接种部位红肿发生率差异无统计学意义[RR=1.08, 95%CI(0.90 1.29), P=0.40];接种部位硬结发生率差异无统计学意义[RR=1.16, 95%CI(0.95 1.43), P=0.14];接种后全身皮疹发生率差异无统计学意义[RR=1.18, 95%CI(1.00 1.41), P=0.05]。对于MMRV组和MMR+V组:接种后血清麻疹抗体阳性率差异无统计学意义[RR=1.00, 95%CI(0.99 1.01), Z=0.25, P=0.80];血清腮腺炎抗体阳性率差异无统计学意义[RR=0.99, 95%CI(0.50 1.01), P=0.11];血清风疹抗体阳性率差异无统计学意义[RR=1.00, 95%CI(0.99 1.01), P=0.68];血清水痘抗体阳性率差异无统计学意义[RR=1.00, 95%CI(0.99 1.01), P=0.58]。结论在麻疹的流行季节或麻疹流行、高发的地区,可将麻疹初免月龄提前至6月龄,将此作为一种应急性的保护措施,对低龄的易感儿童提供确实有效的保护。在未受到麻疹爆发威胁或发病率较低的地区,仍然坚持原有的8月龄初免接种,以保证疫苗接种的成功率和有效性;与进口MMR相比,国产MMR表现出较好的免疫原性,虽接种后发热率高于进口组,但考虑到国产疫苗的成本较低,适于现阶段在我国推广;与MMR三联疫苗+水痘疫苗分开接种相比,MMRV四联疫苗具有同等的免疫效果,在免疫安全性方面,除接种后发热率稍高外,其他局部和全身反应性良好。麻疹-腮腺炎-风疹-水痘联合疫苗可以作为儿童预防接种的候选疫苗进行接种。

    Background: Measles is highly contagious and acute infectious disease. It is spread by respiratory. The current measles epidemic is characterized by that severe cases are reduced while light cases are increased. Prevalence of latent infections are prevalent, the local outbreak is still distributed, the cases of children one year old are increased. Measles vaccine can efficiently increase the people’s antibody level and reduce morbidity. But there are still two choices about domestic and imported vaccine selection. Base on ensure the immune effect, can we take combined vaccines to reduce the vaccination number, cost and vaccine management difficulty, thereby increase the immunization dependence, there are no formed conclusion.Object To eliminate the one-sideness of regitional studies and deal with new measles situation and select measles vaccine with strong security and high-performance , optimize the immunization program, efficiently prevent and control the occurrence of measles, we must carry on system evaluation on immunization effect, security ,program of existing measles vaccine or combined with orther vaccines. Then we can provide scientific basis to completely eliminate measles .Methods The PubMed, BIOSIS Previews, CDSR, Cochrane Library, CBM, CNKI and VIP were searched between Jan 1990 and April 2010. Studies were included in the review if they were randomized controlled trials (RCTs) about measles vaccine in 6-months or 8-months old infants or measles(M)– mumps(M)– rubella(R) vaccine, or measles(M)– mumps(M)– rubella(R) and varicella (V) vaccine. Trial screening, data exaction and quality assessment of included trials were conducted by method recommended by Cochrane Collaboration.Results①10 RCTs were involved. Quality evaluation on included trials was carried on by Jadad method. Among those there were 1 trials 2 points and 9 trials 1point. Meta analysis shows that to measles vaccine in 6 or 8 month-old infants. Measles antibody positive rate of 6 or 8 month-old infants before vaccination was statistically significant with RR 2.54 and 95%CI 1.80 to 3.59 (P<0.00001). Measles antibody positive rate of 6 or 8 month-old infants after vaccination was statistically significant with RR 0.97 and 95%CI 0.94 to 0.99 (P=0.01). Measles antibody immunization success rate of 6 or 8 month-old infants after vaccination was statistically significant with RR 0.92 and 95%CI 0.88 to 0.96 (P=0.0003). Measles antibody GMT of 6 or 8 month-old infants after vaccination was statistically significant with SMD -96.32, 95%CI -147.35 to -43.29 (P=0.0003).②4 RCTs were involved. Among those there were 3 trials B degree and 1 trials C degree. Meta analysis show that to different inoculation method (MMRV or MMR+V) the rate of pain was not statistically significant with RR 0.94 and 95%CI 0.83to 1.05 (P=0.28).The rate of redness was not statistically significant with RR 1.08 and 95%CI 0.90 to 1.29 (P=0.40). The rate of hardening was not statistically significant with RR 1.16 and 95%CI 0.95 to 1.43 (P=0.14). The rate of fever was statistically significant with RR 1.20 and 95%CI 1.12 to 1.29 (P<0.00001). The rate of skin rash was not statistically significant with RR 1.18 and 95%CI 1.00 to 1.41 (P=0.05). The serum measles antibody positive rate was not statistically significant with RR 1.00 and 95%CI 0.99 to 1.01 (P=0.68). The serum mumps antibody positive rate was not statistically significant with RR 0.99 and 95%CI 0.50 to 1.01 (P=0.11). The serum rubella antibody positive rate was not statistically significant with RR 1.00 and 95%CI 0.99 to 1.01 (P=0.68). The serum varicella antibody positive rate was not statistically significant with RR 1.00 and 95%CI 0.99 to 1.01 (P=0.58).③5 RCTs were involved. Among those there were 2 trials B degree and 3 trials C degree. Meta analysis show that to different inoculation method (MMRV or MMR+V) the rate of pain was not statistically significant with RR 0.94 and 95%CI 0.83to 1.05 (P=0.28).The rate of redness was not statistically significant with RR 1.08 and 95%CI 0.90 to 1.29 (P=0.40). The rate of hardening was not statistically significant with RR 1.16 and 95%CI 0.95 to 1.43 (P=0.14). The rate of fever was statistically significant with RR 1.20 and 95%CI 1.12 to 1.29 (P<0.00001). The rate of skin rash was not statistically significant with RR 1.18 and 95%CI 1.00 to 1.41 (P=0.05). The serum measles antibody positive rate was not statistically significant with RR 1.00 and 95%CI 0.99 to 1.01 (P=0.68). The serum mumps antibody positive rate was not statistically significant with RR 0.99 and 95%CI 0.50 to 1.01 (P=0.11). The serum rubella antibody positive rate was not statistically significant with RR 1.00 and 95%CI 0.99 to 1.01 (P=0.68). The serum varicella antibody positive rate was not statistically significant with RR 1.00 and 95%CI 0.99 to 1.01 (P=0.58).Conclusion Through 6 month-old immunity can decrease the infection chance and play an active role in the protection of little infants. In measles epidemic season or popular areas, the first immune time could be moved up to 6 month-old as emergency protective measures. During the areas with low incidence or not threatened by measles outbreak, we can adhere to original 8 month-old immune time to ensure the immunogenicity of vaccine.In respect of immune safety, in addition to higher rate of fever after vaccination other local or systemic reaction was good. For the role of reducing vaccination times and good performance on immune effect and safety, the MMRV vaccine can be regarded as candidate vaccine for child.Compared with MMR+V vaccine the MMRV vaccine had the same immune effect. In respect of immune safety, in addition to higher rate of fever after vaccination other local or systemic reaction was good. For the role of reducing vaccination times and good performance on immune effect and safety, the MMRV vaccine can be regarded as candidate vaccine for child.

麻疹疫苗接种策略及其免疫原性与安全性的系统评价

英汉缩略语名词对照5-6摘要6-10ABSTRACT10-14前言15-18第一部分 麻疹疫苗6 月龄与8 月龄初免效果的系统评价18-29    1 材料与方法18-23    2 结果23-27    3 讨论27-29第二部分 国产与进口麻疹-腮腺炎-风疹三联疫苗免疫原性与安全性的系统评价29-42    1 材料与方法29-32    2 结果32-39    3 讨论39-42第三部分 麻疹-腮腺炎-风疹-水痘联合疫苗免疫原性与安全性的系统评价42-54    1 材料与方法42-45    2 结果45-51    3 讨论51-54结论54-55参考文献55-60文献综述60-68    参考文献65-68附录68-79致谢79-80攻读学位期间发表的学术论文目录80

  本文关键词：麻疹疫苗接种策略及其免疫原性与安全性的系统评价，由笔耕文化传播整理发布。