Department of Geriatrics and Gerontology, Universidade Federal de São Paulo, São Paulo, Brazil.
Cochrane Brazil, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, Brazil.
Cochrane Database Syst Rev. 2023 Oct 2;10(10):CD008858. doi: 10.1002/14651858.CD008858.pub5.
BACKGROUND: Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of ageing is associated with a reduction in cellular immunity, and this predisposes older adults to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. Two types of herpes zoster vaccines are currently available. One of them is the single-dose live attenuated zoster vaccine (LZV), which contains the same live attenuated virus used in the chickenpox vaccine, but it has over 14-fold more plaque-forming units of the attenuated virus per dose. The other is the recombinant zoster vaccine (RZV) which does not contain the live attenuated virus, but rather a small fraction of the virus that cannot replicate but can boost immunogenicity. The recommended schedule for the RZV is two doses two months apart. This is an update of a Cochrane Review first published in 2010, and updated in 2012, 2016, and 2019. OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. SEARCH METHODS: For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2022, Issue 10), MEDLINE (1948 to October 2022), Embase (2010 to October 2022), CINAHL (1981 to October 2022), LILACS (1982 to October 2022), and three trial registries. SELECTION CRITERIA: We included studies involving healthy older adults (mean age 60 years or older). We included randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine (any dose and potency) versus any other type of intervention (e.g. varicella vaccine, antiviral medication), placebo, or no intervention (no vaccine). Outcomes were cumulative incidence of herpes zoster, adverse events (death, serious adverse events, systemic reactions, or local reaction occurring at any time after vaccination), and dropouts. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two new studies involving 1736 participants in this update. The review now includes a total of 26 studies involving 90,259 healthy older adults with a mean age of 63.7 years. Only three studies assessed the cumulative incidence of herpes zoster in groups that received vaccines versus placebo. Most studies were conducted in high-income countries in Europe and North America and included healthy Caucasians (understood to be white participants) aged 60 years or over with no immunosuppressive comorbidities. Two studies were conducted in Japan and one study was conducted in the Republic of Korea. Sixteen studies used LZV. Ten studies tested an RZV. The overall certainty of the evidence was moderate, which indicates that the intervention probably works. Most data for the primary outcome (cumulative incidence of herpes zoster) and secondary outcomes (adverse events and dropouts) came from studies that had a low risk of bias and included a large number of participants. The cumulative incidence of herpes zoster at up to three years of follow-up was lower in participants who received the LZV (one dose subcutaneously) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate-certainty evidence) in the largest study, which included 38,546 participants. There were no differences between the vaccinated and placebo groups for serious adverse events (RR 1.08, 95% CI 0.95 to 1.21) or deaths (RR 1.01, 95% CI 0.92 to 1.11; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of one or more adverse events (RR 1.71, 95% CI 1.38 to 2.11; RD 23%; number needed to treat for an additional harmful outcome (NNTH) 4.3) and injection site adverse events (RR 3.73, 95% CI 1.93 to 7.21; RD 28%; NNTH 3.6; moderate-certainty evidence) of mild to moderate intensity. These data came from four studies with 6980 participants aged 60 years or older. Two studies (29,311 participants for safety evaluation and 22,022 participants for efficacy evaluation) compared RZV (two doses intramuscularly, two months apart) versus placebo. Participants who received the new vaccine had a lower cumulative incidence of herpes zoster at 3.2 years follow-up (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate-certainty evidence), probably indicating a favourable profile of the intervention. There were no differences between the vaccinated and placebo groups in cumulative incidence of serious adverse events (RR 0.97, 95% CI 0.91 to 1.03) or deaths (RR 0.94, 95% CI 0.84 to 1.04; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of adverse events, any systemic symptom (RR 2.23, 95% CI 2.12 to 2.34; RD 33%; NNTH 3.0), and any local symptom (RR 6.89, 95% CI 6.37 to 7.45; RD 67%; NNTH 1.5). Although most participants reported that their symptoms were of mild to moderate intensity, the risk of dropouts (participants not returning for the second dose, two months after the first dose) was higher in the vaccine group than in the placebo group (RR 1.25, 95% CI 1.13 to 1.39; RD 1%; NNTH 100, moderate-certainty evidence). Only one study reported funding from a non-commercial source (a university research foundation). All other included studies received funding from pharmaceutical companies. We did not conduct subgroup and sensitivity analyses AUTHORS' CONCLUSIONS: LZV (single dose) and RZV (two doses) are probably effective in preventing shingles disease for at least three years. To date, there are no data to recommend revaccination after receiving the basic schedule for each type of vaccine. Both vaccines produce systemic and injection site adverse events of mild to moderate intensity. The conclusions did not change in relation to the previous version of the systematic review.
背景:带状疱疹,俗称带状疱疹,是由引起水痘(水痘)的病毒重新激活引起的神经皮肤疾病。在水痘发作缓解后,病毒可能潜伏在脊柱敏感的背神经节中。数年后,随着免疫力下降,水痘带状疱疹病毒(VZV)可能重新激活并导致带状疱疹,这是一种极其痛苦的疾病,可持续数周或数月,严重影响受影响者的生活质量。衰老的自然过程与细胞免疫的下降有关,这使老年人易患带状疱疹。接种减毒形式的 VZV 可激活特定的 T 细胞产生,避免病毒重新激活。目前有两种类型的带状疱疹疫苗。其中一种是单剂量活减毒带状疱疹疫苗(LZV),它含有与水痘疫苗相同的活减毒病毒,但每剂的减毒病毒形成单位数是其 14 倍以上。另一种是重组带状疱疹疫苗(RZV),它不含活减毒病毒,而是含有一小部分不能复制但能增强免疫原性的病毒。RZV 的推荐方案是两剂,间隔两个月。这是对 2010 年首次发表的 Cochrane 综述的更新,并且在 2012 年、2016 年和 2019 年进行了更新。
目的:评估接种疫苗预防老年人带状疱疹的有效性和安全性。
检索方法:对于 2022 年的这次更新,我们在 Cochrane 对照试验中心注册库(CENTRAL 2022,第 10 期)、MEDLINE(1948 年至 2022 年 10 月)、Embase(2010 年至 2022 年 10 月)、CINAHL(1981 年至 2022 年 10 月)、LILACS(1982 年至 2022 年 10 月)和三个试验注册处进行了搜索。
选择标准:我们纳入了研究健康老年人(平均年龄 60 岁或以上)的研究。我们纳入了比较带状疱疹疫苗(任何剂量和效力)与任何其他类型干预(例如水痘疫苗、抗病毒药物)、安慰剂或无干预(无疫苗)的随机对照试验(RCT)或准 RCT。结局为带状疱疹的累积发生率、不良事件(死亡、严重不良事件、全身反应或接种疫苗后任何时间发生的局部反应)和脱落。
数据收集和分析:我们使用了 Cochrane 预期的标准方法程序。
主要结果:本次更新中我们纳入了两项新的研究,共纳入了 1736 名参与者。该综述现在共包括 26 项研究,涉及 90259 名健康的老年人,平均年龄为 63.7 岁。只有三项研究评估了疫苗组与安慰剂组之间带状疱疹的累积发生率。大多数研究在高收入国家(理解为白种人参与者)进行,包括 60 岁或以上、无免疫抑制合并症的健康白种人。两项研究在日本进行,一项研究在大韩民国进行。16 项研究使用了 LZV。10 项研究测试了 RZV。主要结局(带状疱疹的累积发生率)和次要结局(不良事件和脱落)的数据主要来自于偏倚风险低且纳入大量参与者的研究。在最大的研究中,接受 LZV(皮下单次剂量)的参与者的带状疱疹累积发生率低于接受安慰剂的参与者(风险比(RR)0.49,95%置信区间(CI)0.43 至 0.56;风险差异(RD)2%;每增加一次有益结果需要治疗的人数(NNTB)为 50;中等确定性证据),该研究纳入了 38546 名参与者。在严重不良事件(RR 1.08,95%CI 0.95 至 1.21)或死亡(RR 1.01,95%CI 0.92 至 1.11;中等确定性证据)方面,疫苗组与安慰剂组之间没有差异。接种组的累积不良事件(RR 1.71,95%CI 1.38 至 2.11;RD 23%;需要治疗的额外不良结果的人数(NNTH)为 4.3)和注射部位不良事件(RR 3.73,95%CI 1.93 至 7.21;RD 28%;NNTH 3.6;中等确定性证据)的累积发生率更高,这些不良事件为轻度至中度强度。这些数据来自四项研究,涉及 6980 名 60 岁或以上的参与者。两项研究(29311 名参与者用于安全性评估和 22022 名参与者用于疗效评估)比较了 RZV(两次肌内注射,间隔两个月)与安慰剂。接受新疫苗的参与者在 3.2 年随访时带状疱疹的累积发生率较低(RR 0.08,95%CI 0.03 至 0.23;RD 3%;NNTB 33;中等确定性证据),这可能表明干预措施具有有利的特征。在严重不良事件(RR 0.97,95%CI 0.91 至 1.03)或死亡(RR 0.94,95%CI 0.84 至 1.04;中等确定性证据)方面,疫苗组与安慰剂组之间没有差异。接种组的累积不良事件发生率更高,任何全身症状(RR 2.23,95%CI 2.12 至 2.34;RD 33%;NNTH 3.0)和任何局部症状(RR 6.89,95%CI 6.37 至 7.45;RD 67%;NNTH 1.5)更高。尽管大多数参与者报告他们的症状为轻度至中度,但与安慰剂组相比,疫苗组的脱落率(接种第一剂后两个月未返回接种第二剂的参与者)更高(RR 1.25,95%CI 1.13 至 1.39;RD 1%;NNTH 100;中等确定性证据)。只有一项研究报告了非商业来源(大学研究基金会)的资助。所有其他纳入的研究都收到了制药公司的资助。我们没有进行亚组和敏感性分析。
作者结论:LZV(单剂量)和 RZV(两剂)可能在至少三年内有效预防带状疱疹。迄今为止,尚无数据推荐在每种疫苗的基本方案之后进行再接种。两种疫苗均产生轻度至中度强度的全身和注射部位不良事件。结论与之前的系统评价版本没有变化。
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