Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial
Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(10)60889-6
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发表时间：
2010-08-21
期刊：
影响因子：
168.9
通讯作者：
Neuzil, Kathleen M.
中科院分区：
文献类型：
--
作者：
Armah, George E.;Sow, Samba O.;Neuzil, Kathleen M.
背景 轮状病毒胃肠炎导致撒哈拉以南非洲地区许多婴儿死亡。由于轮状病毒疫苗在发达国家已被证明有效，但尚未在发展中国家进行测试，因此我们于 2007 年 4 月至 2009 年 3 月期间在加纳、肯尼亚和马里评估了五价轮状病毒疫苗对严重疾病的功效。 方法 在我们在加纳和肯尼亚农村地区以及马里城市地区进行的多中心、双盲、安慰剂对照试验中，我们随机分配 4-12 周龄的婴儿，胃肠道疾病症状按 1:1 的比例在 6 周、10 周和 14 周龄左右接受 3 剂口服五价轮状病毒疫苗 2 mL 或安慰剂。不排除感染艾滋病毒的婴儿。随机化是通过计算机生成的随机化序列以六个为一组进行的。我们从父母到医疗保健机构就诊时获得了胃肠道症状的数据，并由临床医生前瞻性地获得了临床数据。主要终点是通过酶免疫分析检测到的严重轮状病毒胃肠炎（Vesikari 评分≥ 11），发生在第三剂安慰剂或疫苗后 14 天或更长时间至研究结束（2009 年 3 月 31 日；大约 21 个月大）。分析按照方案进行；接受预定剂量的疫苗或安慰剂且在第三次接种后 14 天以内未干预实验室确认的自然发生的轮状病毒病且具有完整临床和实验室结果的婴儿被纳入分析。这项研究已在 ClinicalTrials.gov 注册，编号为 NCT00362648。结果 5468 名婴儿被随机分配接受五价轮状病毒疫苗 (n=2733) 或安慰剂 (n=2735)。 2357 名婴儿被分配接种疫苗，2348 名婴儿被分配安慰剂被纳入符合方案分析。疫苗组在 2610.6 人年中报告了 79 例严重轮状病毒胃肠炎，而安慰剂组在 2585.9 人年中报告了 129 例严重轮状病毒胃肠炎，导致疫苗对严重轮状病毒胃肠炎的功效为 39.3%（95% CI 19.1-54.7，功效 >0% 时 p=0.0003）。从给予第三剂疫苗或安慰剂后 14 天开始，两组的中位随访时间均为 527 天。被分配接受疫苗的 2723 名婴儿中有 42 名 (1.5%) 和被分配接受安慰剂的 2724 名婴儿中有 45 名 (1.7%) 在任何剂量后 14 天内出现严重不良事件。最常见的严重不良事件是胃肠炎（疫苗 17 [0.6%]；安慰剂 17 [0.6%]）。 解释 在 5 岁以下婴儿死亡率较高的非洲国家，五价轮状病毒疫苗可有效预防出生后 2 年内发生的严重轮状病毒胃肠炎。我们支持世卫组织关于将轮状病毒疫苗纳入非洲国家扩大免疫规划的建议。
Background Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa. Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries, we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and Mali between April, 2007, and March, 2009.Methods In our multicentre, double-blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and an urban area of Mali, we randomly assigned infants aged 4-12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants with HIV infection were not excluded. Randomisation was done by computer-generated randomisation sequence in blocks of six. We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospectively by clinicians. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >= 11), detected by enzyme immunoassay, arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31,2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648.Findings 5468 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735). 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group, compared with 129 cases in 2585.9 person-years in the placebo group, resulting in a vaccine efficacy against severe rotavirus gastroenteritis of 39.3% (95% CI 19.1-54.7, p=0.0003 for efficacy >0%). Median follow-up in both groups was 527 days starting 14 days after the third dose of vaccine or placebo was given. 42 (1.5%) of 2723 infants assigned to receive vaccine and 45 (1.7%) of 2724 infants assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was gastroenteritis (vaccine 17 [0.6%]; placebo 17 [0.6%]).Interpretation Pentavalent rotavirus vaccine is effective against severe rotavirus gastroenteritis in the first 2 years of life in African countries with high mortality in infants younger than 5 years. We support WHO's recommendation for adoption of rotavirus vaccine into national expanded programmes on immunisation in Africa.