本文關(guān)鍵詞：麻疹疫苗接種策略及其免疫原性與安全性的系統(tǒng)評(píng)價(jià)，由筆耕文化傳播整理發(fā)布。

        研究背景麻疹是由麻疹病毒通過(guò)呼吸道引起的高度接觸性、急性傳染病。當(dāng)前麻疹的流行特點(diǎn)是重癥病例減少,輕型病例增多,隱性感染普遍存在,局部仍有散發(fā)甚至爆發(fā)流行,一歲內(nèi)兒童病例增加。麻疹疫苗可有效提高人群抗體水平,降低發(fā)病率。然而對(duì)于當(dāng)前的免疫程序,存在諸多不同意見(jiàn),疫苗的選用也存在國(guó)產(chǎn)和進(jìn)口兩種選擇,同時(shí),能否在保證免疫效果的前提下,使用聯(lián)合疫苗來(lái)減少預(yù)防接種次數(shù),降低疫苗管理難度及預(yù)防接種工作成本,從而提高免疫接種的依從性,尚未形成定論。目的為消除區(qū)域研究的片面性,應(yīng)對(duì)麻疹發(fā)病新情況,甄選安全性強(qiáng)、高效能的麻疹疫苗,優(yōu)化免疫程序,有效的預(yù)防和控制麻疹的發(fā)生,需要我們對(duì)現(xiàn)有疫苗的免疫效能、安全性、免疫程序以及與其它疫苗聯(lián)合免疫的有效性和安全性等進(jìn)行系統(tǒng)評(píng)價(jià),進(jìn)而為實(shí)現(xiàn)全面消除麻疹的目標(biāo)提供科學(xué)依據(jù)。方法分別收集已公開(kāi)發(fā)表的關(guān)于比較麻疹疫苗6月齡與8月齡初免效果的RCTs;比較國(guó)產(chǎn)MMR與進(jìn)口MMR免疫原性和安全性的RCTs;比較MMRV與MMR和水痘疫苗分開(kāi)接種免疫原性和安全性的RCTs,按照Cochrane協(xié)作網(wǎng)推薦的系統(tǒng)評(píng)價(jià)方法,對(duì)以上三方面麻疹疫苗免疫策略及其效果進(jìn)行Meta分析。結(jié)果①納入評(píng)價(jià)的不同初免月齡初免效果研究文獻(xiàn)共10篇。系統(tǒng)評(píng)價(jià)結(jié)果顯示:6月齡組和8月齡組接種前母?jìng)髀檎羁贵w陽(yáng)性率差異有統(tǒng)計(jì)學(xué)意義[ RR=2.54, 95% CI(1.80 3.59), P<0.00001],6月齡組接種前母?jìng)骺贵w陽(yáng)性率顯著高于8月齡組;6月齡組和8月齡組接種后麻疹抗體陽(yáng)性率差異有統(tǒng)計(jì)學(xué)意義[ RR=0.97, 95% CI(0.94 0.99), P=0.01],兩組接種后免疫成功率差異有統(tǒng)計(jì)學(xué)意義[ RR=0.92, 95% CI(0.88 0.96), P=0.0003],6月齡組和8月齡組接種后麻疹抗體GMT差異有統(tǒng)計(jì)學(xué)意義[SMD=-96.32, 95%CI(-147.35 -43.29), P=0.0003],接種后8月齡組麻疹抗體陽(yáng)性率、免疫成功率和麻疹抗體GMT均顯著高于6月齡組。②納入比較國(guó)產(chǎn)與進(jìn)口MMR接種效果的文獻(xiàn)共4篇,分析結(jié)果顯示:國(guó)產(chǎn)MMR組和進(jìn)口MMR組接種后麻疹抗體陽(yáng)性率差異有統(tǒng)計(jì)學(xué)意義[ RR=1.06, 95% CI(1.12 1.29), P<0.00001],國(guó)產(chǎn)MMR組和進(jìn)口MMR組麻疹抗體GMT差異有統(tǒng)計(jì)學(xué)意義[WMD=13.05, 95%CI(5.11 20.99), P=0.001] ,國(guó)產(chǎn)MMR接種后麻疹抗體陽(yáng)性率和麻疹抗體GMT均高于進(jìn)口MMR組;國(guó)產(chǎn)MMR組和進(jìn)口MMR組接種后腮腺炎抗體陽(yáng)性率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=0.96, 95%CI (0.92 1.01), P=0.16],兩接種組風(fēng)疹抗體GMT差異無(wú)統(tǒng)計(jì)學(xué)意義[WMD=-9.54, 95%CI(-72.70 53.61), P=0.77]。國(guó)產(chǎn)MMR組和進(jìn)口MMR組接種后發(fā)熱率差異有統(tǒng)計(jì)學(xué)意義[RR=2.29, 95%CI(1.21 4.33), P=0.01],接種后國(guó)產(chǎn)MMR組發(fā)熱率顯著高于進(jìn)口MMR組;國(guó)產(chǎn)MMR組和進(jìn)口MMR組接種后接種對(duì)象全身皮疹率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=1.49, 95%CI(0.53 4.19), P=0.44]。③共納入5篇MMRV組和MMR+V組的免疫效果評(píng)價(jià)研究文獻(xiàn),Meta分析結(jié)果顯示,對(duì)于MMRV組和MMR+V組:接種后發(fā)熱率差異有統(tǒng)計(jì)學(xué)意義[RR=1.20, 95%CI(1.12 1.29), P<0.00001],MMRV組接種后發(fā)熱率顯著高于MMR+V組;接種部位疼痛發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=0.94, 95%CI(0.83 1.05) , P=0.28];接種部位紅腫發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=1.08, 95%CI(0.90 1.29), P=0.40];接種部位硬結(jié)發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=1.16, 95%CI(0.95 1.43), P=0.14];接種后全身皮疹發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=1.18, 95%CI(1.00 1.41), P=0.05]。對(duì)于MMRV組和MMR+V組:接種后血清麻疹抗體陽(yáng)性率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=1.00, 95%CI(0.99 1.01), Z=0.25, P=0.80];血清腮腺炎抗體陽(yáng)性率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=0.99, 95%CI(0.50 1.01), P=0.11];血清風(fēng)疹抗體陽(yáng)性率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=1.00, 95%CI(0.99 1.01), P=0.68];血清水痘抗體陽(yáng)性率差異無(wú)統(tǒng)計(jì)學(xué)意義[RR=1.00, 95%CI(0.99 1.01), P=0.58]。結(jié)論在麻疹的流行季節(jié)或麻疹流行、高發(fā)的地區(qū),可將麻疹初免月齡提前至6月齡,將此作為一種應(yīng)急性的保護(hù)措施,對(duì)低齡的易感兒童提供確實(shí)有效的保護(hù)。在未受到麻疹爆發(fā)威脅或發(fā)病率較低的地區(qū),仍然堅(jiān)持原有的8月齡初免接種,以保證疫苗接種的成功率和有效性;與進(jìn)口MMR相比,國(guó)產(chǎn)MMR表現(xiàn)出較好的免疫原性,雖接種后發(fā)熱率高于進(jìn)口組,但考慮到國(guó)產(chǎn)疫苗的成本較低,適于現(xiàn)階段在我國(guó)推廣;與MMR三聯(lián)疫苗+水痘疫苗分開(kāi)接種相比,MMRV四聯(lián)疫苗具有同等的免疫效果,在免疫安全性方面,除接種后發(fā)熱率稍高外,其他局部和全身反應(yīng)性良好。麻疹-腮腺炎-風(fēng)疹-水痘聯(lián)合疫苗可以作為兒童預(yù)防接種的候選疫苗進(jìn)行接種。

    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.

麻疹疫苗接種策略及其免疫原性與安全性的系統(tǒng)評(píng)價(jià)

英漢縮略語(yǔ)名詞對(duì)照5-6摘要6-10ABSTRACT10-14前言15-18第一部分 麻疹疫苗6 月齡與8 月齡初免效果的系統(tǒng)評(píng)價(jià)18-29    1 材料與方法18-23    2 結(jié)果23-27    3 討論27-29第二部分 國(guó)產(chǎn)與進(jìn)口麻疹-腮腺炎-風(fēng)疹三聯(lián)疫苗免疫原性與安全性的系統(tǒng)評(píng)價(jià)29-42    1 材料與方法29-32    2 結(jié)果32-39    3 討論39-42第三部分 麻疹-腮腺炎-風(fēng)疹-水痘聯(lián)合疫苗免疫原性與安全性的系統(tǒng)評(píng)價(jià)42-54    1 材料與方法42-45    2 結(jié)果45-51    3 討論51-54結(jié)論54-55參考文獻(xiàn)55-60文獻(xiàn)綜述60-68    參考文獻(xiàn)65-68附錄68-79致謝79-80攻讀學(xué)位期間發(fā)表的學(xué)術(shù)論文目錄80

  本文關(guān)鍵詞：麻疹疫苗接種策略及其免疫原性與安全性的系統(tǒng)評(píng)價(jià)，由筆耕文化傳播整理發(fā)布。