Typhoid is a serious public health threat in many low-income and middle-income countries. Several vaccines for typhoid have been recommended by WHO for typhoid prevention in endemic countries. This study aimed to review the efficacy of typhoid vaccines against culture-confirmed serovar Typhi. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for studies published in English between Jan 1, 1986 and Nov 2, 2023. We included randomised controlled trials (RCTs) comparing typhoid vaccines with a placebo or another vaccine. This meta-analysis evaluated the efficacy and safety of several typhoid vaccines, including live attenuated oral Ty21a vaccine, Vi capsular polysaccharide (Vi-PS), Vi polysaccharide conjugated to recombinant Pseudomonas aeruginosa exotoxin A vaccine (Vi-rEPA), and Vi-tetanus toxoid conjugate vaccine (TCV). The certainty of evidence for key outcomes was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. The outcome of interest was typhoid fever confirmed by the isolation of serovar Typhi in blood and adverse events following immunisation. This study is registered with PROSPERO (CRD42021241043). We included 14 RCTs assessing four different vaccines (Ty21a: four trials; Vi-PS: five trials; Vi-rEPA: one trial; TCV: four trials) involving 585 253 participants. All trials were conducted in typhoid endemic countries and the age of participants ranged from 6 months to 50 years. The pooled efficacy against typhoid fever was 45% (95% CI 33–55%; four trials; 247 649 participants; 59%; moderate certainty) for Ty21a and 58% (44–69%; five trials; 214 456 participants; 34%; moderate certainty) for polysaccharide Vi-PS. The cumulative efficacy of two doses of Vi-rEPA vaccine at 2 years was 91% (88–96%; one trial; 12 008 participants; moderate certainty). The pooled efficacy of a single shot of TCV at 2 years post-immunisation was 83% (77–87%; four trials; 111 130 participants; 0%; moderate certainty). All vaccines were safe, with no serious adverse effects reported in the trials. The existing data from included trials provide promising results regarding the efficacy and safety of the four recommended typhoid vaccines. TCV and Vi-rEPA were found to have the highest efficacy at 2 years post-immunisation. However, follow-up data for Vi-rEPA are scarce and only TCV is pre-qualified by WHO. Therefore, roll-out of TCV into routine immunisation programmes in typhoid endemic settings is highly recommended. There was no funding source for this study.

中文翻译：

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伤寒疫苗对伤寒流行国家经培养证实的伤寒沙门氏菌的功效：系统评价和荟萃分析

伤寒是许多低收入和中等收入国家的严重公共卫生威胁。世界卫生组织推荐了几种伤寒疫苗用于伤寒流行国家的预防。本研究旨在评价伤寒疫苗对经培养证实的伤寒血清型的功效。我们检索了 Cochrane 对照试验中心注册库、MEDLINE 和 Embase，查找 1986 年 1 月 1 日至 2023 年 11 月 2 日期间以英文发表的研究。我们纳入了将伤寒疫苗与安慰剂或其他疫苗进行比较的随机对照试验 (RCT)。这项荟萃分析评估了几种伤寒疫苗的功效和安全性，包括口服减毒活 Ty21a 疫苗、Vi 荚膜多糖 (Vi-PS)、Vi 多糖缀合重组铜绿假单胞菌外毒素 A 疫苗 (Vi-rEPA) 和 Vi-破伤风疫苗类毒素结合疫苗（TCV）。使用建议分级、评估、制定和评估方法来评估关键结果证据的确定性。感兴趣的结果是通过在血液中分离伤寒血清和免疫接种后的不良事件证实伤寒。本研究已在 PROSPERO 注册（CRD42021241043）。我们纳入了 14 项随机对照试验，评估四种不同的疫苗（Ty21a：四项试验；Vi-PS：五项试验；Vi-rEPA：一项试验；TCV：四项试验），涉及 585 253 名参与者。所有试验均在伤寒流行国家进行，参与者年龄从 6 个月到 50 岁不等。 Ty21a 治疗伤寒的综合疗效为 45%（95% CI 33–55%；四项试验；247 649 名受试者；59%；中等确定性），Ty21a 为 58%（44–69%；五项试验；214 456 名受试者；34） %；中等确定性）对于多糖Vi-PS。两剂 Vi-rEPA 疫苗 2 年的累积疗效为 91%（88-96%；一项试验；12 008 名参与者；中等确定性）。免疫后 ​​2 年单次 TCV 注射的汇总疗效为 83%（77-87%；四项试验；111 130 名受试者；0%；中等确定性）。所有疫苗都是安全的，试验中没有报告严重的副作用。纳入试验的现有数据提供了关于四种推荐伤寒疫苗的功效和安全性的有希望的结果。研究发现 TCV 和 Vi-rEPA 在免疫后 2 年具有最高功效。然而，Vi-rEPA 的后续数据很少，并且只有 TCV 通过了 WHO 的资格预审。因此，强烈建议在伤寒流行地区将 TCV 纳入常规免疫计划。这项研究没有资金来源。