Vaccines for preventing influenza in healthy adults.
Vaccines for preventing influenza in healthy adults.
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DOI：
10.1002/14651858.cd001269.pub6
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发表时间：
2018-02-01
期刊：
影响因子：
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通讯作者：
Di Pietrantonj, Carlo
中科院分区：
文献类型：
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作者：
Demicheli, Vittorio;Jefferson, Tom;Di Pietrantonj, Carlo
背景：成人流感的后果主要是下班时间。国际上建议孕妇接种疫苗。这是对2014年发表的一篇评论的更新。只有当新的试验或疫苗可用时，才会对该综述进行进一步更新。由于历史原因，本综述先前版本中包含的观察数据被保留，但由于其对综述结论缺乏影响，因此未进行更新。方法：我们检索了科克伦中心对照试验登记处，（CENTRAL; 2016，第12期）、MEDLINE（1966年1月至2016年12月31日）、Embase（1990年至2016年12月31日）、WHO国际临床试验注册平台（ICTRP; 2017年7月1日）和ClinicalTrials.gov（2017年7月1日），以及检查检索文章的参考书目。选择标准：随机对照试验（RCT）或准RCT，在16至65岁的健康个体中比较流感疫苗与安慰剂或无干预措施对自然发生的流感的影响。本综述的先前版本包括评估严重和罕见伤害的观察性比较研究队列和病例对照研究。由于观察性（即非随机化）研究的质量不确定，并且它们对综述结论缺乏影响，我们决定仅更新随机化证据。数据收集和分析：两名综述作者独立评估了试验质量并提取了数据。我们使用GRADE对关键结果（流感、流感样疾病（ILI）、住院和不良反应）的证据确定性进行了评级。主要结果：我们纳入了52项临床试验，超过80，000人评估了流感疫苗的安全性和有效性。我们介绍了25项研究的结果，这些研究比较了灭活肠外流感疫苗与安慰剂或不做任何事情的对照组，认为它们与决策最相关。这些研究是在1969年至2009年期间在北美，南美和欧洲的单一流感季节进行的。我们不认为存在高偏倚风险的研究会影响我们的结果，但住院治疗除外。灭活流感疫苗可能将健康成人的流感从未接种疫苗的2.3%降至0.9%。（风险比（RR）0.41，95%置信区间（CI）0.36至0.47; 71，221名参与者;中等确定性证据），它们可能将ILI从21.5%降低到18.1%（RR 0.84，95% CI 0.75至0.95; 25，795名参与者;中等确定性证据; 71名健康成年人需要接种疫苗，以防止其中一人患流感，29名健康成年人需要接种疫苗，以防止其中一人患ILI。两个疫苗接种所需数量（NNV）值之间的差异取决于研究人群中ILI和确诊流感的不同发病率。接种疫苗可能导致健康成人住院风险小幅降低，从14.7%降至14.1%，但CI较宽，不排除较大获益（RR 0.96，95%CI 0.85至1.08; 11，924例受试者;低确定性证据）。接种疫苗可能导致很少或不小的休假天数减少（-0.04天，95% CI -0.14天至0.06;低确定性证据）。灭活疫苗引起的发热从1.5%增加到2.3%。我们确定了一项随机对照试验和一项对照临床试验，评估了孕妇接种疫苗的效果。含pH 1 N1的灭活疫苗对母亲（NNV 55）和24周内婴儿（NNV 56）的流感有效性分别为50%（95% CI 14%-71%）和49%（95% CI 12%-70%）。没有关于妊娠期间预防季节性流感的有效性的数据。来自观察性研究的证据表明，流感疫苗对孕妇的ILI的有效性为24%（95% CI 11%至36%，NNV 94），对接种疫苗妇女的新生儿的流感的有效性为41%（95% CI 6%至63%，NNV 27）。1968年至1969年大流行性流感疫苗的单剂或两剂全病毒粒子疫苗对ILI（NNV 16）和流感（NNV 35）的性能更高。1968年至1969年大流行（NNV 94）对住院的影响有限。在怀孕期间接种季节性流感疫苗和2009年流感大流行疫苗对流产或新生儿死亡没有显著影响，但这是基于观察数据集的结论：接受灭活肠外流感疫苗而不是没有疫苗的健康成年人可能经历更少的流感，从略高于2%到略低于1%（中等确定性证据）。他们在接种疫苗后也可能经历较少的ILI，但以绝对值表示的获益程度在不同环境中有所不同。对ILI的保护变化可能部分是由于不一致的症状分类。住院和休假时间略有减少的证据不足。母亲和新生儿对流感和ILI的保护作用小于本综述中考虑的其他人群。疫苗增加了一些不良事件的风险，包括发热的小幅增加，但恶心和呕吐的发生率尚不确定。孕妇和新生儿接种疫苗的保护作用也非常有限。我们没有发现任何证据表明流感疫苗接种和严重不良事件之间的联系，在本次审查中考虑的比较研究。纳入的15项RCT由行业资助（29%）。
BACKGROUND: The consequences of influenza in adults are mainly time off work. Vaccination of pregnant women is recommended internationally. This is an update of a review published in 2014. Future updates of this review will be made only when new trials or vaccines become available. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated due to their lack of influence on the review conclusions.OBJECTIVES: To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy adults, including pregnant women.SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE (January 1966 to 31 December 2016), Embase (1990 to 31 December 2016), the WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017), as well as checking the bibliographies of retrieved articles.SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy individuals aged 16 to 65 years. Previous versions of this review included observational comparative studies assessing serious and rare harms cohort and case-control studies. Due to the uncertain quality of observational (i.e. non-randomised) studies and their lack of influence on the review conclusions, we decided to update only randomised evidence. The searches for observational comparative studies are no longer updated.DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We rated certainty of evidence for key outcomes (influenza, influenza-like illness (ILI), hospitalisation, and adverse effects) using GRADE.MAIN RESULTS: We included 52 clinical trials of over 80,000 people assessing the safety and effectiveness of influenza vaccines. We have presented findings from 25 studies comparing inactivated parenteral influenza vaccine against placebo or do-nothing control groups as the most relevant to decision-making. The studies were conducted over single influenza seasons in North America, South America, and Europe between 1969 and 2009. We did not consider studies at high risk of bias to influence the results of our outcomes except for hospitalisation.Inactivated influenza vaccines probably reduce influenza in healthy adults from 2.3% without vaccination to 0.9% (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.36 to 0.47; 71,221 participants; moderate-certainty evidence), and they probably reduce ILI from 21.5% to 18.1% (RR 0.84, 95% CI 0.75 to 0.95; 25,795 participants; moderate-certainty evidence; 71 healthy adults need to be vaccinated to prevent one of them experiencing influenza, and 29 healthy adults need to be vaccinated to prevent one of them experiencing an ILI). The difference between the two number needed to vaccinate (NNV) values depends on the different incidence of ILI and confirmed influenza among the study populations. Vaccination may lead to a small reduction in the risk of hospitalisation in healthy adults, from 14.7% to 14.1%, but the CI is wide and does not rule out a large benefit (RR 0.96, 95% CI 0.85 to 1.08; 11,924 participants; low-certainty evidence). Vaccines may lead to little or no small reduction in days off work (-0.04 days, 95% CI -0.14 days to 0.06; low-certainty evidence). Inactivated vaccines cause an increase in fever from 1.5% to 2.3%.We identified one RCT and one controlled clinical trial assessing the effects of vaccination in pregnant women. The efficacy of inactivated vaccine containing pH1N1 against influenza was 50% (95% CI 14% to 71%) in mothers (NNV 55), and 49% (95% CI 12% to 70%) in infants up to 24 weeks (NNV 56). No data were available on efficacy against seasonal influenza during pregnancy. Evidence from observational studies showed effectiveness of influenza vaccines against ILI in pregnant women to be 24% (95% CI 11% to 36%, NNV 94), and against influenza in newborns from vaccinated women to be 41% (95% CI 6% to 63%, NNV 27).Live aerosol vaccines have an overall effectiveness corresponding to an NNV of 46. The performance of one- or two-dose whole-virion 1968 to 1969 pandemic vaccines was higher (NNV 16) against ILI and (NNV 35) against influenza. There was limited impact on hospitalisations in the 1968 to 1969 pandemic (NNV 94). The administration of both seasonal and 2009 pandemic vaccines during pregnancy had no significant effect on abortion or neonatal death, but this was based on observational data sets.AUTHORS' CONCLUSIONS: Healthy adults who receive inactivated parenteral influenza vaccine rather than no vaccine probably experience less influenza, from just over 2% to just under 1% (moderate-certainty evidence). They also probably experience less ILI following vaccination, but the degree of benefit when expressed in absolute terms varied across different settings. Variation in protection against ILI may be due in part to inconsistent symptom classification. Certainty of evidence for the small reductions in hospitalisations and time off work is low. Protection against influenza and ILI in mothers and newborns was smaller than the effects seen in other populations considered in this review.Vaccines increase the risk of a number of adverse events, including a small increase in fever, but rates of nausea and vomiting are uncertain. The protective effect of vaccination in pregnant women and newborns is also very modest. We did not find any evidence of an association between influenza vaccination and serious adverse events in the comparative studies considered in this review. Fifteen included RCTs were industry funded (29%).