The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial
The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial
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DOI：
10.1371/journal.pmed.1001993
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发表时间：
2016-04-01
期刊：
影响因子：
15.8
通讯作者：
Cox, Jonathan
中科院分区：
文献类型：
--
作者：
Bousema, Teun;Stresman, Gillian;Cox, Jonathan
背景疟疾传播是高度异质性的，产生疟疾热点，可以在更广泛的地区助长疟疾传播。瞄准热点可能是减少疟疾传播的有效战略。我们确定了针对疟疾血清学定义的热点地区的干预措施对疟疾传播的影响，包括在热区内和周围社区的影响。方法和发现2011年6月24日至7月31日进行的一项调查中，在肯尼亚Rachuonyo南区100公里(2)的区域内检测到27个血清学定义的疟疾热点，其中包括来自3,213个化合物的17,503人。在2012年3月22日至4月15日的一项整群随机试验中，我们随机分配了5个群组，进行热点针对性干预，包括杀幼虫、分发长效驱虫蚊帐、室内残留喷洒和重点集体用药(432个化合物中2,082人)；5个对照群组根据肯尼亚国家政策接受疟疾控制(512个化合物中2,468人)。我们的主要结果测量是评估区域在热点外500米范围内的寄生虫流行率，由技术人员盲目干预后基线和干预后8周(2012年6月16日至7月6日)和16周(2012年8月21日至9月10日)通过套式聚合酶链式反应(NPCR)确定。次要结果指标是火锅内的寄生虫流行率、评估区内的寄生虫流行率与距离热点边界的距离、按蚊密度、蚊子繁殖地的生产力、被动病例发现的疟疾发病率以及干预措施的安全性和可接受性。所有干预措施覆盖率均超过87%。针对热点的干预措施没有导致热点边界外非聚合酶链球菌寄生虫流行率的变化(p>；=0.187)。我们观察到，在干预后8周，热点地区的nPCR型寄生虫患病率平均下降了10.2%(95%CI-1.3%至21.7%)，在调整协变量后有统计学意义(p=0.024)，但在干预后16 wk没有统计学意义(p=0.265)。在干预后8wk(p=0.27)或16wk(p=0.75)距离热点边界的距离方面，我们没有观察到干预对评估区npcr寄生虫流行率的影响有统计学意义的趋势。经快速诊断试验确诊的36例临床疟疾患者可归入干预组或对照组，研究组之间无明显差异。在干预组中，我们在热点区域内平均捕获了1.14条雌性按蚊，在评估区域内捕获了0.47条；在对照集群中，我们在热点内捕获了0.90条雌性按蚊，在评估区域内捕获了0.50条雌性按蚊，两个研究组之间没有明显差异。我们的试验不是为了检测针对热点的干预措施的细微影响，也不是为了检测干预措施在多个传播季节的效果。结论尽管覆盖率很高，针对疟疾媒介和人类感染的干预措施对NPCR寄生虫流行率的影响是温和的、短暂的，并且仅限于目标热点地区。我们的发现表明，传播可能不会主要发生在热点地区和周围地区，疟疾传播高度异质性但广泛传播的地区目前可能从无针对性的全社区方法中受益最大。针对热点的方法在人类住区更加核心的环境中可能更有效。
BackgroundMalaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities.Methods and FindingsTwenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km(2) area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June-6 July 2012) and 16 wk (21 August-10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p >= 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI -1.3 to 21.7%) inside hotspots 8 wk post-intervention that was statistically significant after adjustment for covariates (p = 0.024), but not 16 wk post-intervention (p = 0.265). We observed no statistically significant trend in the effect of the intervention on nPCR parasite prevalence in the evaluation zone in relation to distance from the hotspot boundary 8 wk (p = 0.27) or 16 wk post-intervention (p = 0.75). Thirty-six patients with clinical malaria confirmed by rapid diagnostic test could be located to intervention or control clusters, with no apparent difference between the study arms. In intervention clusters we caught an average of 1.14 female anophelines inside hotspots and 0.47 in evaluation zones; in control clusters we caught an average of 0.90 female anophelines inside hotspots and 0.50 in evaluation zones, with no apparent difference between study arms. Our trial was not powered to detect subtle effects of hotspot-targeted interventions nor designed to detect effects of interventions over multiple transmission seasons.ConclusionsDespite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear.