Lim Jue Tao, Mailepessov Diyar, Chong Chee Seng, Dickens Borame, Lai Yee Ling, Ng Youming, Lu Deng, Lee Caleb, Tan Li Yun, Chain Grace, Ho Soon Hoe, Chang Chia-Chen, Ma Pei, Bansal Somya, Lee Vernon, Sim Shuzhen, Tan Cheong Huat, Ng Lee Ching
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Environmental Health Institute, National Environment Agency, Singapore, Singapore.
BMC Med. 2025 Mar 28;23(1):184. doi: 10.1186/s12916-025-03941-2.
Matings between male Aedes aegypti mosquitoes infected with wAlbB strain of Wolbachia and wild-type females yield non-viable eggs, thereby suppressing Ae. aegypti abundance in the field. We evaluated the spillover efficacy of releasing wAlbB-infected Ae. aegypti male mosquitoes to suppress dengue in sites adjacent to release sites (spillover sites).
The protocol of a two-arm cluster-randomised test-negative controlled trial (cRCT) was specified and emulated using a nationally representative dengue test-negative/positive database of 454,437 individuals reporting for febrile illness to primary or secondary care in public healthcare institutions. Spillover intervention sites were defined by geolocating locations which were adjacent to, i.e. shared geographical borders with, actual Wolbachia intervention sites. We built a cohort of individuals who resided in spillover sites versus a comparator control group who resided in sites which did not receive Wolbachia interventions. We emulated a constrained randomisation protocol used in cRCTs to balance dengue risk between spillover and control arms in the pre-intervention period. We matched individuals reporting for testing in intervention and control groups by calendar time and a high-dimensional battery of sociodemographic, environmental and anthropogenic variables. Intention-to-treat analysis was conducted to estimate the protective efficacy against dengue given spillover Wolbachia exposure.
The final cohort consisted of 2354 matched individuals residing in Wolbachia spillover and control sites for at least 3 months in the study period. Compared to the controls, individuals residing in spillover sites for 3 or more months were associated with a 45% (OR: 0.55, 95% CI: 0.42‒0.74) reduction in risk of contracting dengue. Higher durations of spillover Wolbachia exposure also modestly increased protective efficacies. Compared to the control arm, the proportion of virologically confirmed dengue cases was lower in the spillover arm overall and across each subgroup. Protective efficacies were found across all years, age and sex subgroups.
Our results demonstrated the potential of Wolbachia-mediated sterility for reducing the risk of contracting dengue even in sites which were not directly treated by the intervention.
感染沃尔巴克氏体wAlbB菌株的雄性埃及伊蚊与野生型雌性交配会产生无法孵化的卵，从而抑制野外埃及伊蚊的数量。我们评估了释放感染wAlbB的埃及伊蚊雄蚊在释放地点（溢出地点）附近的地点抑制登革热的溢出效果。
使用一个具有全国代表性的包含454437名因发热疾病到公共医疗机构的初级或二级护理机构就诊的个体的登革热检测阴性/阳性数据库，指定并模拟了双臂整群随机试验阴性对照试验（cRCT）的方案。溢出干预地点通过对与实际沃尔巴克氏体干预地点相邻（即共享地理边界）的位置进行地理定位来确定。我们建立了一个居住在溢出地点的个体队列，并与一个居住在未接受沃尔巴克氏体干预地点的对照比较组进行对比。我们模拟了cRCT中使用的受限随机化方案，以在干预前期平衡溢出组和对照组之间的登革热风险。我们按日历时间以及一系列社会人口学、环境和人为变量对干预组和对照组中报告进行检测的个体进行匹配。进行意向性分析以估计在有溢出沃尔巴克氏体暴露情况下对登革热的保护效果。
最终队列由2354名在研究期间至少3个月居住在沃尔巴克氏体溢出地点和对照地点的匹配个体组成。与对照组相比，在溢出地点居住3个月或更长时间的个体感染登革热的风险降低了45%（比值比：0.55，95%置信区间：0.42‒0.74）。更长时间的溢出沃尔巴克氏体暴露也适度提高了保护效果。与对照组相比，总体上以及在每个亚组中，溢出组病毒学确诊的登革热病例比例更低。在所有年份、年龄和性别亚组中均发现了保护效果。
我们的结果表明，即使在未直接接受干预的地点，沃尔巴克氏体介导的不育技术也有降低感染登革热风险的潜力。
