Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands.
Expanded Programme on Immunization, Department of Immunization, Vaccines, and Biologicals, World Health Organization, Geneva, Switzerland.
Lancet Infect Dis. 2019 Nov;19(11):1235-1245. doi: 10.1016/S1473-3099(19)30395-0. Epub 2019 Sep 20.
Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles. To assess whether bringing forward the age of MCV1 is beneficial, we did a systematic review and meta-analysis of the benefits and risks of MCV1 in infants younger than 9 months.
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, Proquest, Global Health, the WHO library database, and the WHO Institutional Repository for Information Sharing database, and consulted experts. We included randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We assessed: proportion of infants seroconverted, geometric mean antibody titre, avidity, cellular immunity, duration of immunity, vaccine efficacy, vaccine effectiveness, and safety. We used random-effects models to derive pooled estimates of the endpoints, where appropriate. We assessed methodological quality using the Grading of Recommendations, Assessment, Development, and Evaluation guidelines.
Our search identified 1156 studies, of which 1071 were screened for eligibility. 351 were eligible for full-text screening, and data from 56 studies that met all inclusion criteria were used for analysis. The proportion of infants who seroconverted increased from 50% (95% CI 29-71) for those vaccinated with MCV1 at 4 months of age to 85% (69-97) for those were vaccinated at 8 months. The pooled geometric mean titre ratio for infants aged 4-8 months vaccinated with MCV1 compared with infants vaccinated with MCV1 at age 9 months or older was 0·46 (95% CI 0·33-0·66; I=99·9%, p<0·0001). Only one study reported on avidity and suggested that there was lower avidity and a shorter duration of immunity following MCV1 administration at 6 months of age than at 9 months of age (p=0·0016) or 12 months of age (p<0·001). No effect of age at MCV1 administration on cellular immunity was found. One study reported that vaccine efficacy against laboratory-confirmed measles virus infection was 94% (95% CI 74-98) in infants vaccinated with MCV1 at 4·5 months of age. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% CI 9-80; I=84·9%, p<0·0001). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 were 51% (95% CI -44 to 83; I=92·3%, p<0·0001), and for those aged 9 months and older at vaccination it was 83% (76-88; I=93·8%, p<0·0001). No differences in the risk of adverse events after MCV1 administration were found between infants younger than 9 months and those aged 9 months of older. Overall, the quality of evidence ranged from moderate to very low.
MCV1 administered to infants younger than 9 months induces a good immune response, whereby the proportion of infants seroconverted increases with increased age at vaccination. A large proportion of infants receiving MCV1 before 9 months of age are protected and the vaccine is safe, although higher antibody titres and vaccine effectiveness are found when MCV1 is administered at older ages. Recommending MCV1 administration to infants younger than 9 months for those at high risk of measles is an important step towards reducing measles-related mortality and morbidity.
WHO.
麻疹是儿童死亡的一个重要原因，尽管有安全且具有成本效益的含麻疹成分疫苗（MCV）可用。在麻疹持续传播的国家，推荐在 9 月龄时接种第一剂 MCV（MCV1），而在麻疹风险低的国家则推荐在 12 月龄时接种。为了评估提前接种 MCV1 是否有益，我们对小于 9 月龄婴儿接种 MCV1 的益处和风险进行了系统评价和荟萃分析。
为了进行这项系统评价和荟萃分析，我们在 MEDLINE、EMBASE、Scopus、Proquest、全球卫生、世卫组织图书馆数据库和世卫组织机构知识库数据库中进行了检索，并咨询了专家。我们纳入了随机和准随机对照试验、暴发调查以及队列和病例对照研究，不限制发表日期，其中 MCV1 被用于小于 9 月龄的婴儿。我们于 2015 年 6 月 2 日进行文献检索，并于 2019 年 1 月 14 日更新。我们评估了：婴儿血清转化率、几何平均抗体滴度、亲合力、细胞免疫、免疫持续时间、疫苗效力、疫苗效果和安全性。我们适当地使用随机效应模型来推导终点的汇总估计值。我们使用推荐评估、制定和评估分级指南来评估方法学质量。
我们的检索共确定了 1156 项研究，其中 1071 项进行了资格筛选。351 项进行了全文筛选，符合所有纳入标准的 56 项研究的数据用于分析。4 月龄时接种 MCV1 的婴儿血清转化率从 50%（95%CI 29-71）增加到 8 月龄时接种 MCV1 的婴儿的 85%（69-97）。4-8 月龄婴儿接种 MCV1 与 9 月龄或以上婴儿接种 MCV1 相比，几何平均抗体滴度比值为 0.46（95%CI 0.33-0.66；I=99.9%，p<0.0001）。只有一项研究报告了亲合力，表明 6 月龄时接种 MCV1 比 9 月龄或 12 月龄时接种 MCV1 的亲合力较低，免疫持续时间较短（p=0.0016）。未发现 MCV1 接种年龄对细胞免疫的影响。一项研究报告称，在 4.5 月龄婴儿中接种 MCV1 的疫苗效力为 94%（95%CI 74-98），可预防实验室确诊的麻疹病毒感染。小于 9 月龄婴儿接种 MCV1 的疫苗效果的汇总估计值为 58%（95%CI 9-80；I=84.9%，p<0.0001）。在小于 9 月龄的婴儿中进行的研究内比较中，接种 MCV1 的婴儿的疫苗效果估计值为 51%（95%CI -44 至 83；I=92.3%，p<0.0001），而在 9 月龄或以上的婴儿中接种的疫苗效果估计值为 83%（76-88；I=93.8%，p<0.0001）。在 MCV1 接种后，小于 9 月龄和 9 月龄以上婴儿的不良事件风险无差异。总体而言，证据质量从中等到极低不等。
小于 9 月龄婴儿接种 MCV1 可诱导良好的免疫反应，随着接种年龄的增加，血清转化率增加。很大一部分在 9 月龄之前接种 MCV1 的婴儿得到了保护，疫苗是安全的，尽管当 MCV1 在较晚的年龄接种时，抗体滴度和疫苗效力更高。对于那些麻疹风险高的婴儿，建议在 9 月龄之前接种 MCV1 是减少麻疹相关死亡和发病的重要一步。
世卫组织。
