Jefferson Tom, Rivetti Alessandro, Di Pietrantonj Carlo, Demicheli Vittorio, Ferroni Eliana
The Cochrane Collaboration, Roma, Italy.
Cochrane Database Syst Rev. 2012 Aug 15;2012(8):CD004879. doi: 10.1002/14651858.CD004879.pub4.
The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years of age.
To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children, assess vaccine efficacy (prevention of confirmed influenza) and effectiveness (prevention of influenza-like illness (ILI)) and document adverse events associated with influenza vaccines.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3) which includes the Acute Respiratory Infections Group's Specialised Register, OLD MEDLINE (1950 to 1965), MEDLINE (1966 to November 2011), EMBASE (1974 to November 2011), Biological Abstracts (1969 to September 2007), and Science Citation Index (1974 to September 2007).
Randomised controlled trials (RCTs), cohort and case-control studies of any influenza vaccine in healthy children under 16 years of age.
Four review authors independently assessed trial quality and extracted data.
We included 75 studies with about 300,000 observations. We included 17 RCTs, 19 cohort studies and 11 case-control studies in the analysis of vaccine efficacy and effectiveness. Evidence from RCTs shows that six children under the age of six need to be vaccinated with live attenuated vaccine to prevent one case of influenza (infection and symptoms). We could find no usable data for those aged two years or younger.Inactivated vaccines in children aged two years or younger are not significantly more efficacious than placebo. Twenty-eight children over the age of six need to be vaccinated to prevent one case of influenza (infection and symptoms). Eight need to be vaccinated to prevent one case of influenza-like-illness (ILI). We could find no evidence of effect on secondary cases, lower respiratory tract disease, drug prescriptions, otitis media and its consequences and socioeconomic impact. We found weak single-study evidence of effect on school absenteeism by children and caring parents from work. Variability in study design and presentation of data was such that a meta-analysis of safety outcome data was not feasible. Extensive evidence of reporting bias of safety outcomes from trials of live attenuated influenza vaccines (LAIVs) impeded meaningful analysis. One specific brand of monovalent pandemic vaccine is associated with cataplexy and narcolepsy in children and there is sparse evidence of serious harms (such as febrile convulsions) in specific situations.
AUTHORS' CONCLUSIONS: Influenza vaccines are efficacious in preventing cases of influenza in children older than two years of age, but little evidence is available for children younger than two years of age. There was a difference between vaccine efficacy and effectiveness, partly due to differing datasets, settings and viral circulation patterns. No safety comparisons could be carried out, emphasising the need for standardisation of methods and presentation of vaccine safety data in future studies. In specific cases, influenza vaccines were associated with serious harms such as narcolepsy and febrile convulsions. It was surprising to find only one study of inactivated vaccine in children under two years, given current recommendations to vaccinate healthy children from six months of age in the USA, Canada, parts of Europe and Australia. If immunisation in children is to be recommended as a public health policy, large-scale studies assessing important outcomes, and directly comparing vaccine types are urgently required. The degree of scrutiny needed to identify all global cases of potential harms is beyond the resources of this review. This review includes trials funded by industry. An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry-funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favourable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in the light of this finding.
流感对儿童和成人的主要影响是导致缺课和旷工。然而，儿童及65岁以上人群出现并发症的风险最高。
评估所有比较流感疫苗对健康儿童影响的研究，评估疫苗效力（预防确诊流感）和效果（预防流感样疾病（ILI）），并记录与流感疫苗相关的不良事件。
我们检索了Cochrane对照试验中心注册库（CENTRAL）（《Cochrane图书馆》2011年第3期），其中包括急性呼吸道感染组的专业注册库、旧版医学期刊数据库（1950年至1965年）、医学期刊数据库（1966年至2011年11月）、EMBASE数据库（1974年至2011年11月）、生物学文摘数据库（1969年至2007年9月）以及科学引文索引数据库（1974年至2007年9月）。
针对16岁以下健康儿童使用任何流感疫苗的随机对照试验（RCT）、队列研究和病例对照研究。
四位综述作者独立评估试验质量并提取数据。
我们纳入了75项研究，约有三十万条观察数据。在分析疫苗效力和效果时，我们纳入了17项随机对照试验、19项队列研究和11项病例对照研究。随机对照试验的证据表明，6岁以下儿童中，每6名接种减毒活疫苗才能预防1例流感（感染及出现症状）。对于2岁及以下儿童，我们未找到可用数据。2岁及以下儿童使用的灭活疫苗并不比安慰剂更有效。6岁以上儿童中，每28名接种疫苗才能预防1例流感（感染及出现症状）。每8名接种疫苗才能预防1例流感样疾病（ILI）。我们未发现疫苗对二代病例、下呼吸道疾病、药物处方、中耳炎及其后果以及社会经济影响有效果的证据。我们发现有单项研究提供了微弱证据，表明疫苗对儿童缺课及照顾儿童的家长旷工有影响。研究设计和数据呈现的差异使得对安全性结果数据进行荟萃分析不可行。来自减毒活流感疫苗（LAIV）试验的安全性结果存在广泛报告偏倚的证据，妨碍了有意义的分析。一种特定品牌的单价大流行疫苗与儿童猝倒症和发作性睡病有关，在特定情况下有严重危害（如高热惊厥）的证据较少。
流感疫苗对2岁以上儿童预防流感病例有效，但2岁以下儿童的相关证据很少。疫苗效力和效果存在差异，部分原因是数据集、环境和病毒传播模式不同。无法进行安全性比较，这凸显了未来研究中方法标准化和疫苗安全性数据呈现标准化的必要性。在特定情况下，流感疫苗与严重危害如发作性睡病和高热惊厥有关。鉴于美国、加拿大、欧洲部分地区和澳大利亚目前建议对6个月以上健康儿童进行免疫接种，令人惊讶的是，我们仅找到一项针对2岁以下儿童使用灭活疫苗的研究。如果要将儿童免疫接种作为一项公共卫生政策推荐，迫切需要开展大规模研究来评估重要结果，并直接比较不同疫苗类型。识别所有全球潜在危害病例所需的审查程度超出了本综述的资源范围。本综述纳入了行业资助的试验。一项对截至2007年发表的274项流感疫苗研究的早期系统综述发现，行业资助的研究发表在更具声望的期刊上，且被引用次数多于其他研究，与方法质量和规模无关。公共来源资助的研究得出有利于疫苗结论的可能性显著更低。该综述表明，关于流感疫苗的可靠证据很少，但有证据表明存在广泛的结论操纵和研究的虚假声誉。应根据这一发现来解释本综述的内容和结论。
