Background

Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa.

Methods

We conducted a phase 3, double-blind trial in Blantyre, Malawi, to assess the efficacy of Vi polysaccharide typhoid conjugate vaccine (Vi-TCV). We randomly assigned children who were between 9 months and 12 years of age, in a 1:1 ratio, to receive a single dose of Vi-TCV or meningococcal capsular group A conjugate (MenA) vaccine. The primary outcome was typhoid fever confirmed by blood culture. We report vaccine efficacy and safety outcomes after 18 to 24 months of follow-up.

Results

The intention-to-treat analysis included 28,130 children, of whom 14,069 were assigned to receive Vi-TCV and 14,061 were assigned to receive the MenA vaccine. Blood culture–confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 cases per 100,000 person-years) and in 62 children in the MenA group (243.2 cases per 100,000 person-years). Overall, the efficacy of Vi-TCV was 80.7% (95% confidence interval [CI], 64.2 to 89.6) in the intention-to-treat analysis and 83.7% (95% CI, 68.1 to 91.6) in the per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including 6 deaths (all in the MenA group). No serious adverse events were considered by the investigators to be related to vaccination.

Conclusions

Among Malawian children 9 months to 12 years of age, administration of Vi-TCV resulted in a lower incidence of blood culture–confirmed typhoid fever than the MenA vaccine. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT03299426.)

中文翻译：

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马拉维儿童伤寒结合疫苗的安全性和有效性

背景

由耐多药 H58伤寒沙门氏菌引起的伤寒是撒哈拉以南非洲日益严重的公共卫生威胁。

方法

我们在马拉维布兰太尔进行了一项 3 期双盲试验，以评估 Vi 多糖伤寒结合疫苗 (Vi-TCV) 的功效。我们以 1:1 的比例将 9 个月至 12 岁的儿童随机分配到接受单剂 Vi-TCV 或脑膜炎球菌 A 群结合物 (MenA) 疫苗接种。主要结果是血培养证实的伤寒。我们在 18 至 24 个月的随访后报告疫苗有效性和安全性结果。

结果

意向治疗分析包括 28,130 名儿童，其中 14,069 名被分配接受 Vi-TCV，14,061 名被分配接受 MenA 疫苗。Vi-TCV 组 12 名儿童（每 10 万人年 46.9 例）和 MenA 组 62 名儿童（每 10 万人年 243.2 例）发生血培养证实伤寒。总体而言，Vi-TCV 的疗效在意向治疗分析中为 80.7%（95% 置信区间 [CI]，64.2 至 89.6），在符合方案分析中为 83.7%（95% CI，68.1 至 91.6） . 在疫苗接种后的前 6 个月内，总共发生了 130 起严重不良事件（Vi-TCV 组 52 起，MenA 组 78 起），其中 6 起死亡（均在 MenA 组中）。研究人员认为没有严重的不良事件与疫苗接种有关。

结论

在 9 个月至 12 岁的马拉维儿童中，与 MenA 疫苗相比，接种 Vi-TCV 导致血培养确诊伤寒的发生率更低。（由比尔和梅琳达盖茨基金会资助；ClinicalTrials.gov 编号，NCT03299426。）