Quanitifying the Epidemiological Impact of Targeted Indoor Residual Spraying on Aedes-borne Diseases

项目总结/摘要 同期城市病媒控制（车载超低量喷雾、热雾化、 杀幼虫剂）未能控制登革热的流行，也未能防止伊蚊在全球范围内的扩张- 传播的病毒（ABV：登革热、基孔肯雅热、寨卡）。维持有效ABV的部分挑战 控制出现了显着缺乏证据的流行病学影响的任何 矢量控制法此外，应对临床病例的典型干预措施 未能说明外出人员流动和无症状感染的重要贡献。 迫切需要新的病媒控制方法和干预措施提供战略，以遏制ABV。 有针对性的室内滞留喷洒（TIRS），对正在休息的埃及伊蚊施用残留杀虫剂 暴露的矮墙[<1.5米]、家具下和深色表面等场所）是合理的矢量 控制方法，利用Ae。埃及伊蚊的休息行为，集中杀虫剂的应用， 残留疗效无损失。最近发表的系统综述已经确定TIRS是一种非常 ABD预防的有希望的方法，但强调这种干预措施的证据基础有限， 缺乏来自随机对照试验的疗效估计， 在地方病环境中。为了满足这种迫切的需求，我们将采用一种双臂、平行、非盲的 一项量化TIRS在减轻实验室检查负担方面的总体疗效的随机分组试验， 确认的（病毒学或血清学）ABV临床疾病（例如，登革热、寨卡病毒或基孔肯雅病毒） （主要终点）。次要终点将包括： 或ZIKV血清转化; B）Ae.埃及蚊感染率， DENV、CHIKV或ZIKV; c）Ae.埃及室内昆虫学指标审判将在 梅里达（尤卡坦州，墨西哥，人口约100万），我们将前瞻性地跟踪人口 4，600名2-15岁的儿童入学，分布在50个5x 5城市街区的集群中（每个街区约92名儿童）。 集群），随机分配接受TIRS治疗（n=25）或不接受TIRS治疗（n=25）。培训人员来自 联邦卫生部将在治疗集群的所有房屋中进行TIRS， ABV传播高峰期的开始积极监测症状性ABD感染将 由外地护士和医生通过每周家访和加强监测（电话） 电话，监测梅里达的医院/诊所系统的疑似病例），而年度血清调查将 在每个传播季节之后进行。如果有效，TIRS将通过以下方式推动伊蚊控制的范式转变： 考虑到E。埃及的行为，以指导杀虫剂的应用;改变先发制人的控制（前ABV 传播季节，而不是针对有症状的病例）;使用杀虫剂制剂， 其中Ae。埃及人很敏感。

Project Summary/Abstract Contemporaneous urban vector control (truck-mounted ultra-low volume spraying, thermal fogging, larviciding) has failed to contain dengue epidemics and to prevent the global range expansion of Aedes- borne viruses (ABVs: dengue, chikungunya, Zika). Part of the challenge in sustaining effective ABV control emerges from the remarkable paucity of evidence about the epidemiological impact of any vector control method. Furthermore, the classic deployment of interventions in response to clinical cases fails to account for the important contribution of out-of-home human mobility and asymptomatic infections. Novel vector control approaches and intervention delivery strategies to contain ABVs are urgently needed. Targeted indoor residual spraying (TIRS, applying residual insecticides on Aedes aegypti resting sites such as exposed low walls [<1.5m], under furniture, and on dark surfaces) is a rational vector control approach that exploits Ae. aegypti resting behavior to focalize insecticide applications with no loss in residual efficacy. Recently published systematic reviews have identified TIRS as a very promising approach for ABD prevention, but highlighted the limited evidence-base for this intervention due to the absence of efficacy estimates from randomized controlled trials with epidemiological endpoints performed in endemic settings. In response to such critical need, we will pursue a two-arm, parallel, unblinded cluster randomized trial to quantify the overall efficacy of TIRS in reducing the burden of laboratory- confirmed (virologically or serologically) ABV clinical disease (e.g., dengue, Zika or chikungunya) (primary endpoint). Secondary endpoints will include: a) Laboratory-confirmed (serologically) DENV, CHIKV or ZIKV seroconversion in children aged 2-15 at enrollment; b) Ae. aegypti mosquito infection rates with DENV, CHIKV or ZIKV; c) Ae. aegypti indoor entomological indices. The trial will be conducted in the city of Merida (Yucatan State, Mexico, population ~1million), where we will prospectively follow a population of 4,600 children 2-15 years at enrollment, distributed in 50 clusters of 5x5 city blocks each (~92 children per cluster), randomly allocated to receive either TIRS treatment (n=25) or not (n=25). Trained personnel from the Federal Ministry of Health will perform TIRS in all houses from the treatment clusters ~1-2 months prior to the beginning of the peak ABV transmission season. Active monitoring for symptomatic ABD infections will be performed by field nurses and doctors through weekly household visits and enhanced surveillance (phone calls, monitoring of suspected cases to Merida’s hospital/clinic system), whereas annual sero-surveys will be performed after each transmission season. If efficacious, TIRS will drive a paradigm shift in Aedes control by: considering Ae. aegypti behavior to guide insecticide applications; change to preemptive control (pre- ABV transmission season rather than in response to symptomatic cases); the use of insecticide formulations to which Ae. Aegypti is susceptible.