BACKGROUND The introduction of Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Randomised and non-randomised studies in multiple countries have shown significant reductions in dengue incidence following field releases of wMel-infected Ae. aegypti. We report the public health outcomes from phased, large-scale releases of wMel-Ae. aegypti mosquitoes throughout three contiguous cities in the Aburrá Valley, Colombia. METHODOLOGY/PRINCIPAL FINDINGS Following pilot releases in 2015-2016, staged city-wide wMel-Ae. aegypti deployments were undertaken in the cities of Bello, Medellín and Itagüí (3.3 million people) between October 2016 and April 2022. The impact of the Wolbachia intervention on dengue incidence was evaluated in two parallel studies. A quasi-experimental study using interrupted time series analysis showed notified dengue case incidence was reduced by 95% in Bello and Medellín and 97% in Itagüí, following establishment of wMel at ≥60% prevalence, compared to the pre-intervention period and after adjusting for seasonal trends. A concurrent clinic-based case-control study with a test-negative design was unable to attain the target sample size of 63 enrolled virologically-confirmed dengue (VCD) cases between May 2019 and December 2021, consistent with low dengue incidence throughout the Aburrá Valley following wMel deployments. Nevertheless, VCD incidence was 45% lower (OR 0.55 [95% CI 0.25, 1.17]) and combined VCD/presumptive dengue incidence was 47% lower (OR 0.53 [95% CI 0.30, 0.93]) among participants resident in wMel-treated versus untreated neighbourhoods. CONCLUSIONS/SIGNIFICANCE Stable introduction of wMel into local Ae. aegypti populations was associated with a significant and sustained reduction in dengue incidence across three Colombian cities. These results from the largest contiguous Wolbachia releases to-date demonstrate the real-world effectiveness of the method across large urban populations and, alongside previously published results, support the reproducibility of this effectiveness across different ecological settings. TRIAL REGISTRATION NCT03631719.

中文翻译：

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在哥伦比亚三个城市全市范围内释放沃尔巴克氏菌蚊子后，登革热发病率降低：中断时间序列分析和前瞻性病例对照研究。

背景技术将沃尔巴克氏体（wMel菌株）引入埃及伊蚊会降低其传播登革热和其他虫媒病毒的能力。多个国家的随机和非随机研究表明，在现场释放受 wMel 感染的白伊蚊后，登革热发病率显着降低。埃及伊蚊。我们报告了分阶段、大规模释放 wMel-Ae 的公共卫生结果。哥伦比亚阿布拉山谷三个毗邻城市的埃及蚊子。方法/主要发现 继 2015 年至 2016 年试点发布后，在全市范围内举办了 wMel-Ae。2016 年 10 月至 2022 年 4 月期间，在贝洛、麦德林和伊塔圭（330 万人）等城市部署了埃及伊蚊。两项平行研究评估了沃尔巴克氏菌干预对登革热发病率的影响。一项使用间断时间序列分析的准实验研究表明，在确定 wMel 患病率≥60% 后，与干预前和调整后相比，贝洛和麦德林报告的登革热病例发病率降低了 95%，伊塔圭降低了 97%季节性趋势。一项采用测试阴性设计的并行临床病例对照研究无法达到 2019 年 5 月至 2021 年 12 月期间登记的 63 例病毒学确诊登革热 (VCD) 病例的目标样本量，这与整个阿布拉山谷的登革热发病率较低相一致以下 wMel 部署。尽管如此，在接受 wMel 治疗的参与者中，VCD 发病率降低了 45%（OR 0.55 [95% CI 0.25, 1.17]），并且 VCD/推定登革热综合发病率降低了 47%（OR 0.53 [95% CI 0.30, 0.93]）。与未经处理的社区相比。结论/意义 将 wMel 稳定引入当地 Ae。埃及伊蚊种群与哥伦比亚三个城市登革热发病率的显着持续下降有关。这些来自迄今为止最大的连续沃尔巴克氏体释放的结果证明了该方法在大型城市人口中的现实有效性，并且与之前发布的结果一起支持了这种有效性在不同生态环境中的可重复性。试用注册 NCT03631719。