低成本、热稳定型口服轮状病毒疫苗在尼日尔的疗效。

Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger.

机构信息

From the Department of Research, Epicentre, Paris (S.I., C.L., R.F.G.); the Departments of Nutrition and Global Health and Population, Harvard T.H. Chan School of Public Health, Boston (S.I.); Epicentre (O.G., A.M.S., N.S.-M.), National Hospital (E.A.), and University of Niamey (A.D.), Niamey, Niger; BioStat Consulting, Jasper, GA (B.D.P.); Laboratory of Specialized Clinical Studies, Cincinnati Children's Hospital Medical Center, Cincinnati (M.M.M., N.M.); and Médecins sans Frontières Operational Center, Geneva (B.J.).

出版信息

N Engl J Med. 2017 Mar 23;376(12):1121-1130. doi: 10.1056/NEJMoa1609462.

DOI:10.1056/NEJMoa1609462

PMID:28328346

Abstract

BACKGROUND

Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa.

METHODS

We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3.

RESULTS

Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception.

CONCLUSIONS

Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).

摘要

背景

每年，轮状病毒肠胃炎导致全世界 5 岁以下儿童腹泻死亡的比例约为 37%，其中撒哈拉以南非洲地区的影响尤为严重。

方法

我们在尼日尔进行了一项随机、安慰剂对照试验，以评估口服牛轮状病毒五价疫苗（BRV-PV，印度血清研究所）预防严重轮状病毒肠胃炎的效果。健康婴儿在 6、10 和 14 周龄时分别接受 3 剂疫苗或安慰剂。通过主动和被动监测评估肠胃炎发作情况，并根据 Vesikari 评分（范围为 0 至 20，得分越高表示疾病越严重）进行分级。主要终点是与安慰剂相比，3 剂疫苗对首次实验室确诊的严重轮状病毒肠胃炎（Vesikari 评分≥11）的疗效，从第 3 剂后 28 天开始。

结果

在符合方案的疗效分析中，3508 名婴儿中有 31 例发生严重轮状病毒肠胃炎，疫苗组 87 例，安慰剂组分别为 2.14 和 6.44 例/100 人年，疫苗效力为 66.7%（95%置信区间[CI]：49.9 至 77.9）。意向治疗分析也显示出类似的疗效，疫苗效力为 69.1%（95%CI：55.0 至 78.7）。两组间不良事件风险无显著差异，疫苗组和安慰剂组分别有 68.7%和 67.2%的婴儿报告不良事件，严重不良事件风险也无显著差异（疫苗组 8.3%，安慰剂组 9.1%）；疫苗组有 27 例死亡，安慰剂组有 22 例死亡。无婴儿确诊为肠套叠。