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

项目摘要/摘要 同期城市病媒控制(车载超低量喷雾、热喷雾、 (杀幼虫)未能遏制登革热流行，并未能阻止伊蚊在全球范围内的范围扩大- 传播病毒(ABV：登革热、基孔肯雅热、寨卡病毒)。维持有效的ABV面临的部分挑战 控制的出现来自关于任何一种流行病影响的明显缺乏的证据 矢量控制法。此外，针对临床病例部署干预措施的经典做法 没有考虑到离家出走的人类流动性和无症状感染的重要贡献。 迫切需要新的媒介控制方法和干预传递战略来遏制ABV。 靶向室内滞留喷洒(TIR)，对埃及伊蚊进行残留杀虫剂喷洒 裸露的低墙[1.5米]、家具下和黑暗的表面等场所是有理的载体 利用Ae的控制方法。埃及伊蚊的休眠行为，以集中使用杀虫剂 残留药效无损失。最近发表的系统评价发现，TIR是一种非常 对于ABD的预防很有希望，但强调了这种干预的证据基础有限，因为 流行病学终点的随机对照试验缺乏疗效评估 在地方性环境中。为了满足这种迫切需要，我们将追求一种双臂、平行、不盲目的 整群随机试验量化TIR在减轻实验室负担方面的总体效果 确诊(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热) (主端点)。次要终点将包括：a)实验室确认的(血清学)DENV、CHIKV 或在2-15岁儿童登记时ZIKV血清转换；b)Ae。埃及伊蚊感染率与 DENV、CHIKV或ZIKV；c)Ae.埃及埃及室内昆虫学指数。审判将在该市进行。 梅里达(墨西哥尤卡坦州，人口约100万)，我们将在那里前瞻性地跟踪人口 入学时有4600名2-15岁的儿童，分布在50个5x5城市街区的集群中(每个集群约92名儿童 组)，随机分配接受TRS治疗(n=25)或不接受TRS治疗(n=25)。受过培训的人员来自 联邦卫生部将在治疗群组的所有房屋中提前1-2个月进行TIR ABV传播高峰期的开始。积极监测有症状的ABD感染将 由现场护士和医生通过每周家访和加强监测(电话)进行 电话，监测梅里达医院/诊所系统的疑似病例)，而年度血清调查将 在每个传输季节之后执行。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Ae.埃及伊蚊行为以指导杀虫剂的使用；改为先发制人控制(PRE-ABV 传播季节，而不是对症状病例的反应)；使用杀虫剂配方来 哪一个是..。埃及伊蚊很容易感染。

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.