Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal
Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal
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DOI：
10.1056/nejmoa1905047
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发表时间：
2019-12-05
影响因子：
158.5
通讯作者：
Pollard, Andrew J.
中科院分区：
文献类型：
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作者：
Shakya, Mila;Colin-Jones, Rachel;Pollard, Andrew J.
背景伤寒沙门氏菌是低收入和中等收入国家儿童发烧的主要原因。最近通过世界卫生组织资格预审的伤寒结合疫苗 (TCV) 在人类攻击模型中被证明是有效的，但缺乏伤寒流行地区的功效试验数据。 方法在尼泊尔拉利特布尔进行的这项第 3 阶段随机对照试验中，参与者和观察者都不知道试验组分配情况，我们以 1:1 的比例随机分配 9 个月至 16 岁之间的儿童。比例，接受 TCV 或 A 组荚膜脑膜炎球菌结合疫苗 (MenA) 作为对照。主要结局是经血培养证实为伤寒。我们提出了主要和主要次要结果（包括免疫原性亚组）的预设分析；为期 2 年的试验随访正在进行中。 结果 共有 10,005 名参与者接种了 TCV，10,014 名参与者接种了 MenA 疫苗。接受 TCV 的 7 名参与者（每 10 万人年 79 例）和接受 MenA 疫苗的 38 名参与者（每 10 万人年 428 例）出现血培养证实的伤寒（疫苗功效，81.6%；95% 置信区间，58.8 至 91.8；P
BACKGROUNDSalmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking.METHODSIn this phase 3, randomized, controlled trial in Lalitpur, Nepal, in which both the participants and observers were unaware of the trial-group assignments, we randomly assigned children who were between 9 months and 16 years of age, in a 1:1 ratio, to receive either a TCV or a capsular group A meningococcal conjugate vaccine (MenA) as a control. The primary outcome was typhoid fever confirmed by blood culture. We present the prespecified analysis of the primary and main secondary outcomes (including an immunogenicity subgroup); the 2-year trial follow-up is ongoing.RESULTSA total of 10,005 participants received the TCV and 10,014 received the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 7 participants who received TCV (79 cases per 100,000 person-years) and in 38 who received MenA vaccine (428 cases per 100,000 person-years) (vaccine efficacy, 81.6%; 95% confidence interval, 58.8 to 91.8; P