伤寒结合疫苗可有效降低尼泊尔儿童伤寒发病率，这一成果由英国丘吉尔医院Merryn Voysey研究组取得。该项研究成果发表在2019年12月5日的《新英格兰医学杂志》上。

伤寒沙门菌是中低收入国家儿童发热的主要原因。最近通过世界卫生组织资格预审的伤寒结合疫苗（TCV） 在人类挑战模型中被证明有效，但在伤寒流行地区的疗效仍有待观察。

研究组在尼泊尔拉利特布尔进行了一项临床3期、双盲、随机对照的试验，招募9个月至16岁的儿童，按1：1随机分组，其中10005名儿童接受TCV，10014名接受A群脑膜炎球菌结合疫苗（MenA，对照组）。

TCV组中有7名儿童经血液培养确诊为伤寒，发病率为每10万人年79例，对照组中有38名，发病率为每10万人年428例，疫苗效力为81.6%。接种6个月内共发生严重不良事件132例，其中TCV组61例，对照组71例，1例被认为与疫苗有关。

两组间不良事件发生率相似，TCV组有5.0%的儿童接种1周内出现发热，对照组为5.4%。在免疫原性亚组中，TCV组的血清转化率（Vi-lgG 接种28天后至少增加4倍）为99%，而对照组为2%。

总之，单剂量TCV具有免疫原性，可有效降低9个月至16岁儿童伤寒杆菌血症的发病率。

附：英文原文

Title: Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal

Author: Mila Shakya, M.P.H.,, Rachel Colin-Jones, M.A.,, Katherine Theiss-Nyland, Ph.D.,, Merryn Voysey, D.Phil.,, Dikshya Pant, F.C.P.S.,, Nicola Smith, M.B., B.Chir.,, Xinxue Liu, Ph.D.,, Susan Tonks, B.Sc.,, Olga Mazur, B.Sc.,, Yama G. Farooq, M.Sc.,, Jenny Clarke, Ph.D.,, Jennifer Hill, Ph.D.,, Anup Adhikari, M.A.,, Sabina Dongol, D.Phil.,, Abhilasha Karkey, D.Phil.,, Binod Bajracharya, M.D.,, Sarah Kelly, M.Sc.,, Meeru Gurung, M.D.,, Stephen Baker, Ph.D.,, Kathleen M. Neuzil, M.D.,, Shrijana Shrestha, M.D.,, Buddha Basnyat, F.R.C.P.E.,, and Andrew J. Pollard, F.Med.Sci.

Issue&Volume: 2019-12-04

Abstract:

Background

Salmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking.

Methods

In this phase 3, randomized, controlled trial in Lalitpur, Nepal, in which both the participants and observers were unaware of the trial-group assignments, we randomly assigned children who were between 9 months and 16 years of age, in a 1:1 ratio, to receive either a TCV or a capsular group A meningococcal conjugate vaccine (MenA) as a control. The primary outcome was typhoid fever confirmed by blood culture. We present the prespecified analysis of the primary and main secondary outcomes (including an immunogenicity subgroup); the 2-year trial follow-up is ongoing.

Results

A total of 10,005 participants received the TCV and 10,014 received the MenA vaccine. Blood culture–confirmed typhoid fever occurred in 7 participants who received TCV (79 cases per 100,000 person-years) and in 38 who received MenA vaccine (428 cases per 100,000 person-years) (vaccine efficacy, 81.6%; 95% confidence interval, 58.8 to 91.8; P<0.001). A total of 132 serious adverse events (61 in the TCV group and 71 in the MenA vaccine group) occurred in the first 6 months, and 1 event (pyrexia) was identified as being vaccine-related; the participant remained unaware of the trial-group assignment. Similar rates of adverse events were noted in the two trial groups; fever developed in 5.0% of participants in the TCV group and 5.4% in the MenA vaccine group in the first week after vaccination. In the immunogenicity subgroup, seroconversion (a Vi IgG level that at least quadrupled 28 days after vaccination) was 99% in the TCV group (677 of 683 participants) and 2% in the MenA vaccine group (8 of 380 participants).

Conclusions

A single dose of TCV was immunogenic and effective in reducing S. Typhi bacteremia in children 9 months to 16 years of age.

DOI: 10.1056/NEJMoa1905047

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1905047