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沃尔巴克氏体介导的不育技术降低登革热发病率的效果:新加坡的合成对照研究。

Efficacy of Wolbachia-mediated sterility to reduce the incidence of dengue: a synthetic control study in Singapore.

机构信息

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Environmental Health Institute, National Environment Agency, Singapore.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.

出版信息

Lancet Microbe. 2024 May;5(5):e422-e432. doi: 10.1016/S2666-5247(23)00397-X. Epub 2024 Feb 8.

Abstract

BACKGROUND

Due to the absence of available therapeutics and good vaccines, vector control solutions are needed to mitigate the spread of dengue. Matings between male Aedes aegypti mosquitoes infected with the wAlbB strain of Wolbachia and wildtype females yield non-viable eggs. We evaluated the efficacy of releasing wAlbB-infected A aegypti male mosquitoes to suppress dengue incidence.

METHODS

In this synthetic control study, we conducted large-scale field trials in Singapore involving release of wAlbB-infected A aegypti male mosquitoes for dengue control via vector population suppression, from epidemiological week (EW) 27, 2018, to EW 26, 2022. We selected two large towns (Yishun and Tampines) to adopt an expanding release strategy and two smaller towns (Bukit Batok and Choa Chu Kang) to adopt a targeted-release approach. Releases were conducted two times a week in high-rise public housing estates. All intervention and control locations practised the same baseline dengue control protocol. The main outcome was weekly dengue incidence rate caused by any dengue virus serotype. We used incidence data collected by the Singapore Ministry of Health to assess the efficacy of the interventions. To compare interventions, we used the synthetic control method to generate appropriate counterfactuals for the intervention towns using a weighted combination of 30 control towns between EW 1, 2014 and EW 26, 2022.

FINDINGS

Our study comprised an at-risk population of 607 872 individuals living in intervention sites and 3 894 544 individuals living in control sites. Interventions demonstrated up to 77·28% (121/156, 95% CI 75·81-78·58) intervention efficacy despite incomplete coverage across all towns until EW 26, 2022. Intervention efficacies increased as release coverage increased across all intervention sites. Releases led to 2242 (95% CI 2092-2391) fewer cases per 100 000 people in intervention sites during the study period. Secondary analysis showed that these intervention effects were replicated across all age groups and both sexes for intervention sites.

INTERPRETATION

Our results demonstrated the potential of Wolbachia-mediated incompatible insect technique for strengthening dengue control in tropical cities, where dengue burden is the greatest.

FUNDING

Singapore Ministry of Finance, Ministry of Sustainability, and the National Environment Agency, and the Singapore National Robotics Program.

摘要

背景

由于缺乏有效的治疗方法和良好的疫苗,需要采用病媒控制措施来减轻登革热的传播。感染沃尔巴克氏体wAlbB 株的埃及伊蚊雄蚊与野生型雌蚊交配会产生不育卵。我们评估了释放感染 wAlbB 的埃及伊蚊雄蚊以抑制登革热发病率的效果。

方法

在这项综合对照研究中,我们在新加坡进行了大规模的现场试验,从 2018 年流行病学周 27 日到 2022 年流行病学周 26 日,通过种群抑制手段,释放感染 wAlbB 的埃及伊蚊雄蚊来控制登革热。我们选择了两个较大的城镇(义顺和淡滨尼)采用扩展释放策略,两个较小的城镇(武吉巴督和蔡厝港)采用有针对性的释放方法。每周在高层公共住宅区进行两次释放。所有干预和对照地点都采用相同的登革热控制基线协议。主要结果是由任何登革热病毒血清型引起的每周登革热发病率。我们使用新加坡卫生部收集的发病率数据来评估干预措施的效果。为了比较干预措施,我们使用综合对照方法,使用 2014 年流行病学周 1 日至 2022 年流行病学周 26 日期间的 30 个对照城镇的加权组合,为干预城镇生成适当的反事实情况。

结果

我们的研究包括居住在干预地点的 607872 名高危人群和居住在对照地点的 3894544 名高危人群。尽管到 2022 年流行病学周 26 日,所有城镇的覆盖范围都不完整,但干预措施仍显示出高达 77.28%(121/156,95%CI 75.81-78.58)的干预效果。随着所有干预地点的释放覆盖范围增加,干预效果也随之增加。在研究期间,释放导致干预地点每 10 万人减少 2242 例(95%CI 2092-2391)病例。二次分析表明,这些干预效果在干预地点的所有年龄组和性别中均得到复制。

解释

我们的研究结果表明,沃尔巴克氏体介导的不相容昆虫技术在登革热负担最大的热带城市加强登革热控制方面具有潜力。

资金

新加坡财政部、可持续发展部和国家环境局以及新加坡国家机器人计划。

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