Data from: The impact of hotspot-targeted interventions on malaria transmission in Rachuonyo south district in the western Kenyan highlands: a cluster-randomized controlled trial

Background: Malaria 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 Findings: Twenty-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-km2 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. Conclusions: Despite 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. Trial registration: ClinicalTrials.gov NCT01575613.研究背景：疟疾传播具有高度异质性，会形成可在更大范围内助推疟疾传播的疟疾热点区。针对热点区开展干预，或可成为降低疟疾传播的有效策略。本研究旨在明确以血清学定义的疟疾热点区（serologically defined malaria hotspots）为目标的干预措施，对热点区内部及周边社区疟疾传播的影响。 研究方法与结果：2011年6月24日至7月31日，研究团队在肯尼亚拉乔尼奥南区100平方公里范围内开展流行病学调查，共纳入来自3213户的17503名个体，检出27个血清学定义的疟疾热点区。2012年3月22日至4月15日开展整群随机试验（cluster-randomized trial）：将5个整群随机分配至热点靶向干预组，实施幼虫灭杀（larviciding）、长效杀虫蚊帐（long-lasting insecticide-treated nets）发放、室内残留喷洒（indoor residual spraying）及局部大规模药物治疗（focal mass drug administration），共覆盖432户的2082名个体；另5个整群作为对照组，按照肯尼亚国家疟疾防控政策开展工作，覆盖512户的2468名个体。本研究的主要结局指标为热点区周边500米范围内评估区域的疟原虫感染率，由对干预分组不知情的技术人员分别在基线、干预后8周（2012年6月16日至7月6日）及干预后16周（2012年8月21日至9月10日）采用巢式聚合酶链式反应（nested PCR, nPCR）进行检测。次要结局指标包括：热点区内部的疟原虫感染率、随与热点边界距离变化的评估区域疟原虫感染率、按蚊（Anopheles mosquito）密度、蚊媒孳生地滋生能力、被动病例监测（passive case detection）的疟疾发病率，以及干预措施的安全性与可接受性。所有干预措施的实施覆盖度均超过87%。热点靶向干预未使热点边界外的nPCR检测疟原虫感染率发生显著变化（p≥0.187）。研究团队观察到，干预后8周热点区内部的nPCR检测疟原虫感染率平均降低10.2%（95%置信区间：-1.3%~21.7%），经协变量调整后差异具有统计学意义（p=0.024），但干预后16周该差异无统计学意义（p=0.265）。无论干预后8周（p=0.27）还是16周（p=0.75），干预对评估区域nPCR检测疟原虫感染率的影响均未随与热点边界的距离变化呈现显著趋势。本研究共纳入36例经快速诊断试验确诊的临床疟疾患者，可将其分配至干预组或对照组，两组间未观察到显著差异。干预组在热点区内部平均捕获1.14只雌性按蚊，在评估区域内平均捕获0.47只；对照组在热点区内部平均捕获0.90只雌性按蚊，在评估区域内平均捕获0.50只，两组间未观察到显著差异。本研究的检验效能不足以检测热点靶向干预的细微效应，且研究设计未覆盖多轮传播季节内的干预效果评估。 研究结论：尽管干预覆盖度较高，但针对疟疾媒介与人类感染的热点靶向干预措施对nPCR检测疟原虫感染率的影响较为微弱、短暂，且仅局限于目标热点区。本研究结果提示，疟疾传播可能并非主要由热点区向周边区域扩散；对于存在高度异质性但广泛传播的疟疾流行区，当前或可从无差别社区全员防控策略中获得更大收益。热点靶向防控策略在人类聚居更为集中的区域可能更具应用价值。 试验注册：ClinicalTrials.gov NCT01575613。