Background

Typhoid fever is a major public health problem in low-resource settings. Vaccination can help curb the disease and might reduce transmission. We have previously reported an interim analysis of the efficacy of typhoid conjugate vaccine (TCV) in Nepali children. Here we report the final results after 2 years of follow-up.

Methods

We did a participant-masked and observer-masked individually randomised trial in Lalitpur, Nepal, in which 20 019 children aged 9 months to younger than 16 years were randomly assigned in a 1:1 ratio to receive a single dose of TCV (Typbar TCV, Bharat Biotech International, India) or capsular group A meningococcal conjugate vaccine (MenA). Participants were followed up until April 9, 2020. The primary outcome was blood culture-confirmed typhoid fever. Cases were captured via passive surveillance and active telephone surveillance followed by medical record review. The trial is registered at ISRCTN registry, ISRCTN43385161 and is ongoing.

Findings

From Nov 20, 2017, to April 9, 2018, of 20 119 children screened, 20 019 participants were randomly assigned to receive TCV or MenA vaccine. There were 75 cases of blood culture-confirmed typhoid fever included in the analysis (13 in the TCV group and 62 in the MenA group) over the 2-year period. The protective efficacy of TCV against blood culture-confirmed typhoid fever at 2 years was 79·0% (95% CI 61·9–88·5; p<0·0001). The incidence of typhoid fever was 72 (95% CI 38–123) cases per 100 000 person-years in the TCV group and 342 (95% CI 262–438) cases per 100 000 person-years in the MenA group. Adverse events occurring within the first 7 days post-vaccination were reported previously.

Interpretation

The final results of this randomised, controlled trial are in keeping with the results of our published interim analysis. There is no evidence of waning protection over a 2-year period. These findings add further support for the WHO recommendations on control of enteric fever.

Funding

Bill & Melinda Gates Foundation.

中文翻译：

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尼泊尔伤寒结合疫苗的功效：3 期随机对照试验的最终结果

背景

伤寒是资源匮乏地区的主要公共卫生问题。接种疫苗可以帮助遏制这种疾病，并可能减少传播。我们之前曾报道过伤寒结合疫苗 (TCV) 在尼泊尔儿童中的疗效的中期分析。在这里，我们报告了 2 年随访后的最终结果。

方法

我们在尼泊尔拉利特布尔进行了一项参与者掩蔽和观察者掩蔽的个体随机试验，其中 20019 名 9 个月至 16 岁以下的儿童以 1:1 的比例随机分配接受单剂 TCV（Typbar TCV , Bharat Biotech International, India) 或荚膜 A 组脑膜炎球菌结合疫苗 (MenA)。参与者随访至 2020 年 4 月 9 日。主要结果是血培养确诊的伤寒。通过被动监视和主动电话监视捕获病例，然后进行病历审查。该试验已在 ISRCTN 注册中心 ISRCTN43385161 注册并正在进行中。

发现

从 2017 年 11 月 20 日到 2018 年 4 月 9 日，在筛查的 20 119 名儿童中，20 019 名参与者被随机分配接受 TCV 或 MenA 疫苗。在 2 年期间，分析中包括 75 例血培养确诊的伤寒病例（TCV 组 13 例，MenA 组 62 例）。2 年时 TCV 对血培养确诊伤寒的保护效力为 79·0%（95% CI 61·9–88·5；p<0·0001）。TCV 组伤寒的发生率为每 100 000 人年 72 (95% CI 38–123) 例，MenA 组为每 100 000 人年 342 (95% CI 262–438) 例。疫苗接种后前 7 天内发生的不良事件先前已报告。

解释

这项随机对照试验的最终结果与我们公布的中期分析结果一致。没有证据表明保护作用在 2 年内减弱。这些发现进一步支持了世卫组织关于控制肠道热的建议。

资金

比尔和梅琳达盖茨基金会。