背景:感染WolbachiawAlbB品系的雄性埃及伊蚊与野生型雌性之间的交配产生了无法存活的卵。我们评估了释放wAlbB感染的Ae的功效。埃及伊蚊雄性蚊子抑制登革热。
方法:我们指定了一项双臂整群随机测试阴性对照试验(cRCT)的方案,并使用全国代表性的测试阴性/阳性数据库对其进行了仿真,该数据库包括向任何一家公立医院报告发热疾病的个人,全科医生或综合诊所。我们回顾性地建立了一组居住在Wolbachia地区的个体与一个不居住在Wolbachia地区的比较对照组,使用具有全国代表性的数据库,该数据库包含所有报告发热性疾病并在环境卫生研究所/医院实验室/商业诊断实验室进行登革热检测的个人,通过全科医生诊所,从EW12019-EW262022起,综合诊所或公立/私立医院。我们模拟了cRCT中使用的约束随机化方案,以平衡干预前干预组和控制组之间的登革热风险。我们使用逆概率加权方法来进一步平衡干预和对照组,使用一系列算法选择的社会人口统计学,环境和人为变量。进行了意向治疗分析,以评估暴露于Wolbachia的登革热风险降低。
结果:意向治疗分析显示,与对照组相比,3、6、12个月或更长时间的Wolbachia释放与47%(95CI:25-69%)相关,44%(33-77%)和61%(38-78%)的登革热保护功效,分别。当暴露于12个月或更长时间的Wolbachia释放时,不同年份的保护效果从49%(13-72%)到77%(60-94%)不等。在干预组中,病毒学证实的登革热病例的比例总体较低。所有年份都发现了保护性功效,年龄和性别亚组,Wolbachia暴露时间延长与登革热风险降低相关。
结论:结果表明,Wolbachia介导的不育可以加强热带城市的登革热控制,登革热负担最大的地方。
BACKGROUND: Matings between male Aedes aegypti mosquitoes infected with wAlbB strain of
Wolbachia and wildtype females yield non-viable eggs. We evaluated the efficacy of releasing wAlbB-infected Ae. aegypti male mosquitoes to suppress dengue.
METHODS: We specified the protocol of a two-arm cluster-randomized test-negative controlled trial (cRCT) and emulated it using a nationally representative test-negative/positive database of individuals reporting for febrile illness to any public hospital, general practitioner or polyclinic. We retrospectively built a cohort of individuals who reside in
Wolbachia locations versus a comparator control group who do not reside in
Wolbachia locations, using a nationally representative database of all individuals whom report for febrile illness and were tested for dengue at the Environmental Health Institute/hospital laboratories/commercial diagnostic laboratories, through general practitioner clinic, polyclinic or public/private hospital from EW1 2019-EW 262022. We emulated a constrained randomization protocol used in cRCTs to balance dengue risk between intervention and control arms in the pre-intervention period. We used the inverse-probability weighting approach to further balance the intervention and control groups using a battery of algorithmically selected sociodemographic, environmental and anthropogenic variables. Intention-to-treat analyses was conducted to estimate the risk reduction of dengue given Wolbachia exposure.
RESULTS: Intention-to-treat analyses revealed that, compared with controls, Wolbachia releases for 3, 6, 12 or more months was associated to 47%(95%CI:25-69%), 44%(33-77%) and 61%(38-78%) protective efficacy against dengue, respectively. When exposed to 12 or more months of
Wolbachia releases, protective efficacies ranged from 49%(13-72%) to 77%(60-94%) across years. The proportion of virologically confirmed dengue cases was lower overall in the intervention arm. Protective efficacies were found across all years, age and sex subgroups, with higher durations of Wolbachia exposure associated to greater risk reductions of dengue.
CONCLUSIONS: Results demonstrated that
Wolbachia-mediated sterility can strengthen dengue control in tropical cities, where dengue burden is the greatest.