在伤寒Vi结合疫苗的整群随机试验中评估疫苗群体保护效果：进一步分析结果
Assessment of vaccine herd protection in a cluster-randomised trial of Vi conjugate vaccine against typhoid fever: results of further analysis.
作者信息
Khanam Farhana, Kim Deok Ryun, Liu Xinxue, Voysey Merryn, Pitzer Virginia E, Zaman K, Pollard Andrew J, Qadri Firdausi, Clemens John D
机构信息
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
International Vaccine Institute, Seoul, South Korea.
出版信息
EClinicalMedicine. 2023 Apr 4;58:101925. doi: 10.1016/j.eclinm.2023.101925. eCollection 2023 Apr.
BACKGROUND
A cluster-randomised trial of Vi-tetanus toxoid (Vi-TT) conjugate vaccine conducted in urban Bangladeshi children found a high level of direct protection by Vi-TT but no significant vaccine herd protection. We reassessed the trial using a "fried egg" analysis to evaluate whether herd protection might have been obscured by transmission of typhoid into the clusters from the outside.
METHODS
A participant- and observer-blind, cluster-randomised trial was conducted between February 14, 2018 and August 12, 2019 in three wards of Mirpur, a densely populated urban area of Dhaka, Bangladesh. Children 9 months to under 16 years of age in 150 geographic clusters, which had a total of 311,289 persons present at baseline or entering during follow-up, were randomised by cluster to a single-dose of Vi-TT or Japanese encephalitis (JE) vaccine. Vi-TT protection against typhoid fever, detected at 8 treatment centres serving the study population, was compared in the original clusters for the trial, and for progressively more central subclusters ("yolks" of the "fried egg") of the cluster residents. If transmission of typhoid into the clusters had diluted observed vaccine herd protection, we hypothesised that analysis of the innermost "yolks" would reveal vaccine herd protection that was not evident in analysis of the entire clusters. The trial is registered at www.isrctn.com as ISRCTN11643110.
FINDINGS
At ≤18 months of follow-up, total vaccine effectiveness (protection of Vi-TT recipients relative to JE vaccine recipients) was 85% (95% CI: 76%, 90%); indirect effectiveness (protection of non-Vi-TT recipients in Vi-TT clusters relative to non-JE vaccine recipients in JE vaccine clusters) was 17% (95% CI: -13%, 40%); and overall effectiveness (protection of all residents in the Vi-TT clusters relative to all residents of the JE vaccine clusters) was 57% (95% CI: 44%, 66%). Analyses of subpopulations in inner 75%, 50% and 25% "yolks" of the clusters failed to reveal significant changes in any of these estimates.
INTERPRETATION
Our analysis did not reveal Vi-TT herd protection in the trial. Consideration should be given to exploring whether targeting adults as well as children with Vi-TT yields appreciable levels of vaccine herd protection.
FUNDING
Bill & Melinda Gates Foundation (OPP1151153, INV-025388).
背景
在孟加拉国城市儿童中进行的一项伤寒Vi多糖-破伤风类毒素（Vi-TT）结合疫苗的整群随机试验发现，Vi-TT具有高水平的直接保护作用，但没有显著的疫苗群体保护作用。我们使用“煎蛋”分析重新评估了该试验，以评估群体保护作用是否可能因伤寒从外部传入各群组而被掩盖。
方法
2018年2月14日至2019年8月12日，在孟加拉国达卡人口密集的城市地区米尔布尔的三个病房进行了一项参与者和观察者双盲的整群随机试验。150个地理群组中9个月至16岁以下的儿童，基线时共有311289人或在随访期间进入，按群组随机分配接受单剂量Vi-TT或日本脑炎（JE）疫苗。在为研究人群服务的8个治疗中心检测到的Vi-TT对伤寒热的保护作用，在试验的原始群组以及群组居民中逐渐更中心的子群组（“煎蛋”的“蛋黄”）中进行了比较。如果伤寒传入群组稀释了观察到的疫苗群体保护作用，我们推测对最内层“蛋黄”的分析将揭示在对整个群组的分析中不明显的疫苗群体保护作用。该试验在www.isrctn.com上注册为ISRCTN11643110。
结果
在随访≤18个月时，总疫苗效力（Vi-TT接种者相对于JE疫苗接种者的保护作用）为85%（95%CI：76%，90%）；间接效力（Vi-TT群组中非Vi-TT接种者相对于JE疫苗群组中非JE疫苗接种者的保护作用）为17%（95%CI：-13%，40%）；总体效力（Vi-TT群组中所有居民相对于JE疫苗群组中所有居民的保护作用）为57%（95%CI：44%，66%）。对群组内部75%、50%和25%“蛋黄”中的亚人群进行的分析未能揭示这些估计值中的任何显著变化。
解读
我们的分析未在试验中发现Vi-TT的群体保护作用。应考虑探索将Vi-TT同时针对成人和儿童是否能产生可观水平的疫苗群体保护作用。
资金来源
比尔及梅琳达·盖茨基金会（OPP1151153，INV-025388）。
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