From the Malawi-Liverpool-Wellcome Program (P.D.P., P.P., J.E.M., T.M., F.M., C.M., H.M., D.B., M.M., M.H., M.G., M.A.G.), the Blantyre Malaria Project (N.N., O.M.N.), the Department of Paediatrics, Queen Elizabeth Central Hospital (Q.D.), the District Health Office, Blantyre District Council (G.K.), and Kamuzu University of Health Sciences (M.A.G.) - all in Blantyre, Malawi; the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (Y.L., J.K.T., F.A., K.S., E.R., M.B., K.K., M.B.L., K.M.N.); and Oxford Vaccine Group, the Department of Paediatrics, Oxford University, Oxford (J.E.M.), Liverpool School of Tropical Medicine (C.M., M.H., M.G.), and the Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool (M.A.G.), and the Division of Infection and Immunity, University College London, London (R.S.H.) - all in the United Kingdom.
N Engl J Med. 2021 Sep 16;385(12):1104-1115. doi: 10.1056/NEJMoa2035916.
Typhoid fever caused by multidrug-resistant H58 Typhi is an increasing public health threat in sub-Saharan Africa.
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.
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.
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.).
由 H58 耐药伤寒沙门氏菌引起的伤寒在撒哈拉以南非洲地区是日益严重的公共卫生威胁。
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）的疗效。我们将年龄在 9 个月至 12 岁之间的儿童以 1:1 的比例随机分配，接受单次剂量的 Vi-TCV 或脑膜炎球菌 A 群结合疫苗（MenA）疫苗。主要结局是通过血培养证实的伤寒。我们报告了 18 至 24 个月随访后的疫苗疗效和安全性结果。
意向治疗分析包括 28130 名儿童，其中 14069 名被分配接受 Vi-TCV，14061 名被分配接受 MenA 疫苗。Vi-TCV 组发生 12 例血培养确诊伤寒（每 100000 人年 46.9 例），MenA 组发生 62 例（每 100000 人年 243.2 例）。总体而言，Vi-TCV 在意向治疗分析中的疗效为 80.7%（95%置信区间[CI]，64.2%至 89.6%），在方案分析中的疗效为 83.7%（95%CI，68.1%至 91.6%）。接种后 6 个月内共发生 130 例严重不良事件（Vi-TCV 组 52 例，MenA 组 78 例），包括 6 例死亡（均在 MenA 组）。研究者认为没有严重不良事件与疫苗接种有关。
在马拉维 9 个月至 12 岁的儿童中，接种 Vi-TCV 可降低血培养确诊伤寒的发病率，低于 MenA 疫苗。（由比尔和梅琳达盖茨基金会资助；临床试验.gov 编号，NCT03299426。）
