麻疹风疹联合减毒活疫苗接种后抗体产生时程和有疫苗免疫史麻疹病例诊断研究
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摘要
目的探索麻疹风疹联合减毒活疫苗(MR)或麻腮风联合减毒活疫苗(MMR)接种后麻疹、风疹抗体产生时程和有MR免疫史麻疹监测病例的诊断。方法在某接种门诊随机抽取MR和MMR常规免疫适龄儿童(8-10月龄、18月龄),采集接种MR后10d、15d、20d、1月、2月、3月、6月和复种MMR 10d血标本,检测血清麻疹、风疹IgM和IgG以及血CD4+细胞数,分析抗体产生时程;对2例有MR免疫史麻疹监测病例的诊断进行个案分析。结果 59.09%(13/22)的儿童麻疹IgM在接种MR后15d产生,维持45d;75.00%(15/20)的儿童风疹IgM在接种MR后30d产生,维持30d。95.45%(21/22)的儿童麻疹IgG在接种MR后15d产生,40.00%(8/20)和90.47%(19/21)的儿童风疹IgG分别在接种MR后1月和2月产生。儿童复种MMR后10d麻疹、风疹IgG几何平均浓度(GMC)分别为1 682.00mI U/mL、93.46 IU/mL,阳性率分别为96.00%(24/25)、88.00%(22/25);而复种前GMC分别为584.39 mIU/mL、78.39 IU/mL,阳性率分别为90.47%(19/21)、95.23%(20/21)。接种MR后15d、2月的儿童平均血CD4+细胞数为2 178/μL、2 524/μL。个案分析显示,2例麻疹监测病例应诊断为风疹,因接种MR后麻疹IgM阳性而误诊为麻疹。结论接种MR后麻疹抗体产生较早;风疹抗体产生受到免疫抑制而推迟,且复种MMR后无明显免疫应答。有MR免疫史的麻疹监测病例应根据临床症状和/或病毒核酸(而非仅血清学)检测结果进行诊断。
Objective To explore the timing of antibodies induced by measles and rubella combined attenuated live vaccine(MR), or measles, mumps and rubella combined attenuated live vaccine(MMR), and the diagnosis of measles among suspected cases with a history of MR vaccination. Methods We recruited a random sample of children visiting a vaccination clinic who were age-eligible for routine MR or MMR vaccination(8-10 months and 18 months). We collected blood samples from participants 10 days, 15 days, 20 days, 1 month, 2 months, 3 months, and 6 months after MR vaccination, and 10 days after MMR vaccination. We tested serum samples for IgM and IgG antibodies to measles and rubella and blood CD4+ cells to determine when antibodies were induced. We also conducted a case study on the diagnosis of two suspected measles cases that had histories of receiving MR vaccine. Results The measles IgM positivity rate was 59.09%(13/22) 15 days after MR vaccination, lasting for 45 days. The rubella IgM positivity rate was 75.00%(15/20) 30 days after MR vaccination, lasting for 30 days. The measles IgG positivity rate was 95.45%(21/22) 15 days after MR vaccination, while the rubella IgG positivity rates were 40.00%(8/20) and 90.47%(19/21)1 month and 2 months after MR vaccination. Geometric mean concentrations(GMCs) of measles and rubella IgG antibody in children were 1 682.00 mIU/mL and 93.46 IU/mL 10 days after MMR vaccination, with positivity rates of 96.00%(24/25) and 88.00%(22/25), compared with GMCs of 584.39 mIU/mL and 78.39 IU/mL, and positivity rates of 90.47%(19/21) and 95.23%(20/21) before MMR vaccination. CD4+ cell counts were 2 178/μL and 2 524/μL15 days and 2 months after MR vaccination. The case study showed that the 2 suspected measles cases should have been diagnosed as rubella, but were misdiagnosed as measles due to positive measles IgM antibody tests, likely fromearlier MR vaccination. Conclusions Measles antibody was induced early after MR vaccination; rubella antibody was delayed, probably due to immunosuppression. No measles or rubella immune response was induced after routine MMR vaccination, as MMR vaccine was administered to children who received routine MR vaccination. The diagnosis of measles in a child who recently received MR vaccine should be based on clinical symptoms and/or viral nucleic acid testing, not just serological testing.
Objective To explore the timing of antibodies induced by measles and rubella combined attenuated live vaccine(MR), or measles, mumps and rubella combined attenuated live vaccine(MMR), and the diagnosis of measles among suspected cases with a history of MR vaccination. Methods We recruited a random sample of children visiting a vaccination clinic who were age-eligible for routine MR or MMR vaccination(8-10 months and 18 months). We collected blood samples from participants 10 days, 15 days, 20 days, 1 month, 2 months, 3 months, and 6 months after MR vaccination, and 10 days after MMR vaccination. We tested serum samples for IgM and IgG antibodies to measles and rubella and blood CD4+ cells to determine when antibodies were induced. We also conducted a case study on the diagnosis of two suspected measles cases that had histories of receiving MR vaccine. Results The measles IgM positivity rate was 59.09%(13/22) 15 days after MR vaccination, lasting for 45 days. The rubella IgM positivity rate was 75.00%(15/20) 30 days after MR vaccination, lasting for 30 days. The measles IgG positivity rate was 95.45%(21/22) 15 days after MR vaccination, while the rubella IgG positivity rates were 40.00%(8/20) and 90.47%(19/21)1 month and 2 months after MR vaccination. Geometric mean concentrations(GMCs) of measles and rubella IgG antibody in children were 1 682.00 mIU/mL and 93.46 IU/mL 10 days after MMR vaccination, with positivity rates of 96.00%(24/25) and 88.00%(22/25), compared with GMCs of 584.39 mIU/mL and 78.39 IU/mL, and positivity rates of 90.47%(19/21) and 95.23%(20/21) before MMR vaccination. CD4+ cell counts were 2 178/μL and 2 524/μL15 days and 2 months after MR vaccination. The case study showed that the 2 suspected measles cases should have been diagnosed as rubella, but were misdiagnosed as measles due to positive measles IgM antibody tests, likely fromearlier MR vaccination. Conclusions Measles antibody was induced early after MR vaccination; rubella antibody was delayed, probably due to immunosuppression. No measles or rubella immune response was induced after routine MMR vaccination, as MMR vaccine was administered to children who received routine MR vaccination. The diagnosis of measles in a child who recently received MR vaccine should be based on clinical symptoms and/or viral nucleic acid testing, not just serological testing.
引文
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[3]卓家同,钟革,郑志刚.流行高峰间隔法在麻疹爆发高危县预测甄别中的研究及其初步应用[J].中国计划免疫,2006,12(6):486-488.ZHUO Jiatong,ZHONG Ge,ZHENG Zhigang.Research and primary application on identifying measles high-risk counties with historic epidemic curve interval[J].Chinese Journal of Vaccines and Immunization.2006,12(6):486-488.
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[5]中国疾病预防控制中心.全国麻疹监测方案[S].2014-02-21.Chinese Center for Disease Cont rol and Prevent ion.National guideline for measles surveillance[S].2014-02-21.
[6]LEMAN SJ,BOLLINGER M,BRUNKEN JM.Clinical and serologic evaluation of measles,mumps and rubella(HPV-77,DE-5 and RA27/3)virus vaccines singly and in combination[J].Pediatrics,1981,68:18-22.
[7]迮文远,陈海平,宋继萍.感染性疾病的免疫预防[M].北京:人民卫生出版社,2010:239.Z E Wenyuan,CHEN Haiping,SONG Jiping.Immunoprophylaxis ofinfectious diseases[M].People’s Medical Publishing House,Beijing,2010:239.
[8]OKADA H,KOBUNE F,SATO TA,et al.Extensive lymphopenia due to apoptosis ofinfected lymphocytes in acute measles patients[J].Arch Virol,2000,145:905-920.
[9]梁晓峰,罗凤基,封多佳,主译.疫苗学[M].北京:人民卫生出版社,2011:26-27.LIANG Xiaofeng,LUO Fengji,FENG Duojia(translators).Vaccines[M].Bei jing:People’s Medical Publishing House,Beijing,2011:26-27.
[2]ZHUO J,GENG W,HOEKSTRA EJ,et al.Impact of supplementary immunization activities in measles-endemic areas:a case study from Guangxi,China[J].The Journal of Infectious Diseases,2011,204(S1):455-462.
[3]卓家同,钟革,郑志刚.流行高峰间隔法在麻疹爆发高危县预测甄别中的研究及其初步应用[J].中国计划免疫,2006,12(6):486-488.ZHUO Jiatong,ZHONG Ge,ZHENG Zhigang.Research and primary application on identifying measles high-risk counties with historic epidemic curve interval[J].Chinese Journal of Vaccines and Immunization.2006,12(6):486-488.
[4]迮文远,陈海平,宋继萍.感染性疾病的免疫预防[M].北京:人民卫生出版社,2010:94-101.ZE Wenyuan,CHEN Haiping,SONG Jiping.Immunoprophylaxis ofinfectious diseases[M].Bei jing:People’s Medical Publishing House,Beijing,2010:94-101.
[5]中国疾病预防控制中心.全国麻疹监测方案[S].2014-02-21.Chinese Center for Disease Cont rol and Prevent ion.National guideline for measles surveillance[S].2014-02-21.
[6]LEMAN SJ,BOLLINGER M,BRUNKEN JM.Clinical and serologic evaluation of measles,mumps and rubella(HPV-77,DE-5 and RA27/3)virus vaccines singly and in combination[J].Pediatrics,1981,68:18-22.
[7]迮文远,陈海平,宋继萍.感染性疾病的免疫预防[M].北京:人民卫生出版社,2010:239.Z E Wenyuan,CHEN Haiping,SONG Jiping.Immunoprophylaxis ofinfectious diseases[M].People’s Medical Publishing House,Beijing,2010:239.
[8]OKADA H,KOBUNE F,SATO TA,et al.Extensive lymphopenia due to apoptosis ofinfected lymphocytes in acute measles patients[J].Arch Virol,2000,145:905-920.
[9]梁晓峰,罗凤基,封多佳,主译.疫苗学[M].北京:人民卫生出版社,2011:26-27.LIANG Xiaofeng,LUO Fengji,FENG Duojia(translators).Vaccines[M].Bei jing:People’s Medical Publishing House,Beijing,2011:26-27.
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