Malawi-Liverpool-Wellcome Program, Kamuzu University of Health Sciences, Blantyre, Malawi.
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Lancet. 2024 Feb 3;403(10425):459-468. doi: 10.1016/S0140-6736(23)02031-7. Epub 2024 Jan 25.
Randomised controlled trials of typhoid conjugate vaccines among children in Africa and Asia have shown high short-term efficacy. Data on the durability of protection beyond 2 years are sparse. We present the final analysis of a randomised controlled trial in Malawi, encompassing more than 4 years of follow-up, with the aim of investigating vaccine efficacy over time and by age group.
In this phase 3, double-blind, randomised controlled efficacy trial in Blantyre, Malawi, healthy children aged 9 months to 12 years were randomly assigned (1:1) by an unmasked statistician to receive a single dose of Vi polysaccharide conjugated to tetanus toxoid vaccine (Vi-TT) or meningococcal capsular group A conjugate (MenA) vaccine. Children had to have no previous history of typhoid vaccination and reside in the study areas for inclusion and were recruited from government schools and health centres. Participants, their parents or guardians, and the study team were masked to vaccine allocation. Nurses administering vaccines were unmasked. We did surveillance for febrile illness from vaccination until follow-up completion. The primary outcome was first occurrence of blood culture-confirmed typhoid fever. Eligible children who were randomly assigned and vaccinated were included in the intention-to-treat analyses. This trial is registered at ClinicalTrials.gov, NCT03299426.
Between Feb 21, 2018, and Sept 27, 2018, 28 130 children were vaccinated; 14 069 were assigned to receive Vi-TT and 14 061 to receive MenA. After a median follow-up of 4·3 years (IQR 4·2-4·5), 24 (39·7 cases per 100 000 person-years) children in the Vi-TT group and 110 (182·7 cases per 100 000 person-years) children in the MenA group were diagnosed with a first episode of blood culture-confirmed typhoid fever. In the intention-to-treat population, efficacy of Vi-TT was 78·3% (95% CI 66·3-86·1), and 163 (129-222) children needed to be vaccinated to prevent one case. Efficacies by age group were 70·6% (6·4-93·0) for children aged 9 months to 2 years; 79·6% (45·8-93·9) for children aged 2-4 years; and 79·3% (63·5-89·0) for children aged 5-12 years.
A single dose of Vi-TT is durably efficacious for at least 4 years among children aged 9 months to 12 years and shows efficacy in all age groups, including children younger than 2 years. These results support current WHO recommendations in typhoid-endemic areas for mass campaigns among children aged 9 months to 15 years, followed by routine introduction in the first 2 years of life.
Bill & Melinda Gates Foundation.
在非洲和亚洲开展的儿童伤寒结合疫苗随机对照试验显示出了短期的高疗效。关于保护作用持续时间超过 2 年的数据很少。我们报告了马拉维一项随机对照试验的最终分析结果，该试验随访时间超过 4 年，旨在研究随时间推移和按年龄组的疫苗效果。
在马拉维布兰太尔进行的这项 3 期、双盲、随机对照的疗效试验中，9 个月至 12 岁的健康儿童按 1:1 的比例被随机分配（由未设盲的统计人员）接受单次伤寒多糖结合破伤风类毒素疫苗（Vi-TT）或脑膜炎球菌 A 群结合疫苗（MenA）接种。儿童必须没有以前的伤寒疫苗接种史，并居住在研究区域以进行纳入，从政府学校和保健中心招募。参与者、其父母或监护人以及研究团队对疫苗分配情况不知情。接种疫苗的护士则是知情的。我们从接种疫苗开始一直到随访完成，对发热性疾病进行了监测。主要结局是首次发生经血液培养确认的伤寒。随机分配并接种疫苗的合格儿童被纳入意向治疗分析。该试验在 ClinicalTrials.gov 注册，编号为 NCT03299426。
2018 年 2 月 21 日至 2018 年 9 月 27 日期间，共有 28130 名儿童接种了疫苗；14069 名被分配接受 Vi-TT，14061 名接受 MenA。中位随访 4.3 年（IQR 4.2-4.5）后，Vi-TT 组有 24 名（每 100000 人年 39.7 例）和 MenA 组有 110 名（每 100000 人年 182.7 例）儿童被诊断出首次发生经血液培养确认的伤寒。在意向治疗人群中，Vi-TT 的疗效为 78.3%（95%CI 66.3-86.1），需要接种 163 名（129-222 名）儿童才能预防 1 例发病。按年龄组的疗效为 9 个月至 2 岁儿童 70.6%（6.4-93.0）；2-4 岁儿童 79.6%（45.8-93.9）；5-12 岁儿童 79.3%（63.5-89.0）。
9 个月至 12 岁儿童接种一剂 Vi-TT 至少 4 年的效果持久，在所有年龄组均有效，包括 2 岁以下的儿童。这些结果支持目前世卫组织在伤寒流行地区的建议，即对 9 个月至 15 岁的儿童开展大规模疫苗接种运动，随后在生命的头 2 年常规引入。
比尔及梅琳达·盖茨基金会。
Zotero 插件
