马拉维Kamuzu健康科学大学（KUHeS）Melita A. Gordon团队研究了马拉维儿童伤寒结合疫苗的安全性和有效性。该研究成果于2021年9月15日发表于《新英格兰医学杂志》上。

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

研究组在马拉维布兰太尔进行了一项临床3期双盲试验，以评估Vi多糖伤寒结合疫苗（Vi-TCV）的疗效。招募9个月至12岁的儿童，按1：1的比例随机分配，分别接种单剂量Vi-TCV或脑膜炎球菌荚膜A组结合疫苗（MenA）。主要结局是血液培养证实的伤寒。研究组报告了18至24个月随访后的疫苗疗效和安全性结局。

意向治疗分析共包括28130名儿童，其中14069名接种Vi-TCV疫苗，14061名接种MenA疫苗。Vi-TCV组有12名儿童（每10万人-年46.9例）经血液培养确诊伤寒，MenA组有62名儿童（每10万人-年243.2例），组间差异显著。总体而言，在意向治疗分析中，Vi-TCV的疗效为80.7%，在按方案分析中，Vi-TCV的疗效为83.7%。在接种疫苗后的前6个月内，共发生了130起严重不良事件，其中Vi-TCV组52起，MenA组78起，包括6起死亡事件（全部在MenA组）。研究人员认为未发生与疫苗接种相关的严重不良事件。

研究结果表明，对于9个月至12岁的马拉维儿童，与MenA疫苗相比，使用Vi-TCV可降低血液培养证实的伤寒发病率。

附：英文原文

Title: Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

Author: Priyanka D. Patel, M.B., B.S.,, Pratiksha Patel, M.B., B.S.,, Yuanyuan Liang, Ph.D.,, James E. Meiring, Ph.D.,, Theresa Misiri, M.P.H.,, Felistas Mwakiseghile, M.Sc.,, J. Kathleen Tracy, Ph.D.,, Clemens Masesa, M.Sc.,, Harrison Msuku, B.Sc.,, David Banda, B.Sc.,, Maurice Mbewe, B.Sc.,, Marc Henrion, Ph.D.,, Fiyinfolu Adetunji, M.P.H.,, Kenneth Simiyu, Ph.D.,, Elizabeth Rotrosen, A.B.,, Megan Birkhold, M.D.,, Nginache Nampota, M.B., B.S.,, Osward M. Nyirenda, B.Sc.,, Karen Kotloff, M.D.,, Markus Gmeiner, M.Sc.,, Queen Dube, Ph.D.,, Gift Kawalazira, M.B., B.S.,, Matthew B. Laurens, M.D.,, Robert S. Heyderman, Ph.D.,, Melita A. Gordon, M.D.,, and Kathleen M. Neuzil, M.D.

Issue&Volume: 2021-09-15

Abstract:

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.

DOI: 10.1056/NEJMoa2035916

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2035916