Are rotavirus vaccines safe and effective in preventing rotavirus diarrhoea in infants and children?

What is the aim of this review?

The aim of this Cochrane Review was to find out if rotavirus vaccines are effective in preventing diarrhoea and deaths in infants and young children. We also aimed to find out if the rotavirus vaccines are safe. We collected and analysed all relevant studies to answer these questions.

Key messages

Rotarix,RotateQ,Rotasiil和Rotavac在儿童生命的第一年中,在腹泻最危险的第一年中,大部分大部分轮状病毒腹泻发作,在第二年的功效略低。我们发现,严重不良事件(中度至高确定性证据)的风险没有增加,包括肠suse脚(肠子本身就是肠望远镜,可能会引起阻塞)。

What was studied in the review?

轮状病毒感染是婴儿和幼儿腹泻的常见原因,可能导致轻度疾病,住院和死亡。自2009年以来,世界卫生组织(WHO)建议将轮状病毒疫苗包括在所有国家婴儿和儿童免疫计划中。迄今为止,有96个国家遵循了这一建议。在婴儿和儿童开始接受轮状病毒疫苗的几年中,轮状病毒感染导致五岁以下的儿童每年约有半百万人死亡,主要是低收入国家和中等收入国家。

In this review, we included randomized controlled trials in infants and young children that evaluated rotavirus vaccination with Rotarix (GlaxoSmithKline) or RotaTeq (Merck). These vaccines have been evaluated in several large trials and are approved for use in many countries. We also included trials that evaluated Rotavac (Bharat Biotech Ltd.) and Rotasiil (Serum Institute of India Ltd.), rotavirus vaccines which are currently used in India only. The rotavirus vaccines were compared with placebo or with no vaccine. The included studies did not allow comparisons between the different rotavirus vaccines.

What are the main results of the review?

We found 60 relevant studies with a total of 228,233 participants. The trials took place in several locations worldwide. The vaccines tested were Rotarix (36 trials with 119,114 participants), RotaTeq (15 trials with 88,934 participants), Rotasiil (five trials with 11,753 participants), and Rotavac (four trials with 8432 participants). Fifty-six studies were funded or co-funded by vaccine manufacturers, while four were independent of manufacturer funding.

在生命的头两年中,我们发现轮状病毒疫苗在儿童死亡率低的国家 /地区预防了90%以上的轮状病毒腹泻病例,中等儿童死亡率的国家中有75%以上,35%至58%在儿童死亡率较高的国家中。

轮状病毒疫苗可能预防儿童死亡率低的国家 /地区的所有原因(例如任何病毒感染,细菌感染或寄生虫感染)的严重腹泻病例中的50%以上,在儿童死亡率较高的国家中,没有到27%。

儿童死亡率低和中等的国家的证据来自对Rotarix和RotateQ疫苗的研究。这两种疫苗在所有情况下均已评估。Rotasiil和Rotavac疫苗仅在儿童死亡率较高的国家进行了评估。

We found little or no difference in the number of serious adverse events between those receiving rotavirus vaccines compared with placebo or with no vaccine.

轮状病毒vaccines may make little to no difference to the number of deaths or to intussusception cases, compared with placebo or no vaccine, but the certainty of the evidence was limited for these rare outcomes.

How up-to-date is this review?

We searched for studies that had been published up to 30 November 2020.

Authors' conclusions:

Rotarix, RotaTeq, Rotasiil, and Rotavac prevent episodes of rotavirus diarrhoea. The relative effect estimate is smaller in high-mortality than in low-mortality countries, but more episodes are prevented in high-mortality settings as the baseline risk is higher. In high-mortality countries some results suggest lower efficacy in the second year. We found no increased risk of serious adverse events, including intussusception, from any of the prequalified rotavirus vaccines.

阅读完整的抽象...
背景:

轮状病毒是腹泻,与腹泻有关的住院和与腹泻有关的死亡的常见原因。轮状病毒疫苗由世界卫生组织(WHO)(WHO)提供资格,包括Rotarix(GlaxoSmithkline),RotateQ(Merck),以及最近的Rotasiil(印度血清研究所有限公司)和Rotavac(Bharat Biotech Ltd.)。

Objectives:

评估轮状病毒疫苗由WHO预先资格的儿童疗效和安全性。

搜索策略:

On 30 November 2020, we searched PubMed, the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, Science Citation Index Expanded, Social Sciences Citation Index, Conference Proceedings Citation Index-Science, Conference Proceedings Citation Index-Social Science & Humanities. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies, and relevant systematic reviews.

选择标准:

We selected randomized controlled trials (RCTs) conducted in children that compared rotavirus vaccines prequalified for use by the WHO with either placebo or no intervention.

数据收集和分析:

Two authors independently assessed trial eligibility and assessed risk of bias. One author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analyses by under-five country mortality rate and used GRADE to evaluate evidence certainty.

Main results:

如果xty trials met the inclusion criteria and enrolled a total of 228,233 participants. Thirty-six trials (119,114 participants) assessed Rotarix, 15 trials RotaTeq (88,934 participants), five trials Rotasiil (11,753 participants), and four trials Rotavac (8432 participants).

Rotarix

婴儿接种疫苗并随访第一年

In low-mortality countries, Rotarix prevented 93% of severe rotavirus diarrhoea cases (14,976 participants, 4 trials; high-certainty evidence), and 52% of severe all-cause diarrhoea cases (3874 participants, 1 trial; moderate-certainty evidence).

在中期国家,rotarix预防了79%的严重轮状病毒腹泻病例(31,671名参与者,4项试验;高确定性证据),而36%的严重全因腹泻病例(26,479例参与者,2例试验;高度确定性证据)。

在高年龄较大的国家中,rotarix预防了58%的严重轮状病毒腹泻病例(15,882名参与者,4项试验;高确定性证据)和27%的严重全因腹泻病例(5639名参与者,2个试验;高度确定性证据;高确定性证据)。

Children vaccinated and followed up for two years

In low-mortality countries, Rotarix prevented 90% of severe rotavirus diarrhoea cases (18,145 participants, 6 trials; high-certainty evidence), and 51% of severe all-cause diarrhoea episodes (6269 participants, 2 trials; moderate-certainty evidence).

In medium-mortality countries, Rotarix prevented 77% of severe rotavirus diarrhoea cases (28,834 participants, 3 trials; high-certainty evidence), and 26% of severe all-cause diarrhoea cases (23,317 participants, 2 trials; moderate-certainty evidence).

In high-mortality countries, Rotarix prevented 35% of severe rotavirus diarrhoea cases (13,768 participants, 2 trials; moderate-certainty evidence), and 17% of severe all-cause diarrhoea cases (2764 participants, 1 trial; high-certainty evidence).

rotateq

婴儿接种疫苗并随访第一年

In low-mortality countries, RotaTeq prevented 97% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence).

In medium-mortality countries, RotaTeq prevented 79% of severe rotavirus diarrhoea cases (3863 participants, 1 trial; low-certainty evidence).

In high-mortality countries, RotaTeq prevented 57% of severe rotavirus diarrhoea cases (6775 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (1 trial, 4085 participants; moderate-certainty evidence).

Children vaccinated and followed up for two years

In low-mortality countries, RotaTeq prevented 96% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence).

In medium-mortality countries, RotaTeq prevented 79% of severe rotavirus diarrhoea cases (3863 participants, 1 trial; low-certainty evidence).

在高年龄较高的国家中,RotateQ可预防44%的严重轮状病毒腹泻病例(6744名参与者,2个试验;高确定性证据),而严重全因腹泻病例中有15%(5977名参与者,2例参与者,2例试验;高确定性证据)。

We did not identify RotaTeq studies reporting on severe all-cause diarrhoea in low- or medium-mortality countries.

Rotasiil

Rotasiil has not been assessed in any RCT in countries with low or medium child mortality.

婴儿接种疫苗并随访第一年

在高年龄率的国家,旋转植物阻止了48%的严重轮状病毒腹泻病例(11,008名参与者,2个试验;高确定性证据),并且严重全因腹泻病例几乎没有差异(11,008例参与者,2个试验;高度试验;高度- 确定性证据)。

Children vaccinated and followed up for two years

In high-mortality countries, Rotasiil prevented 44% of severe rotavirus diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence), and resulted in little to no difference in severe all-cause diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence).

Rotavac

Rotavac has not been assessed in any RCT in countries with low or medium child mortality.

婴儿接种疫苗并随访第一年

在高年龄率的国家中,rotavac防止了57%的严重轮状病毒腹泻病例(6799名参与者,1例试验;中度确定性证据),而严重全因腹泻病例中有16%(6799名参与者,1例试验;中度确定性证据)。

Children vaccinated and followed up for two years

In high-mortality countries, Rotavac prevented 54% of severe rotavirus diarrhoea cases (6541 participants, 1 trial; moderate-certainty evidence); no Rotavac studies have reported on severe all-cause diarrhoea at two-years follow-up.

Safety

没有增加严重不良事件(SAE)的风险(SAE)(103,714名参与者,31个试验;高确定性证据),RotateQ(82,502名参与者,14个试验;中度至高度证据),Rotasiil(11,646参与者,3个试验);高确定性证据)或rotavac(8210名参与者,3个试验;中度确定性证据)。

死亡很少发生,分析没有足够的证据表明对全因死亡率产生影响。肠se脚很少见。