Targeted malaria elimination interventions reduce Plasmodium falciparum infections up to 3 kilometers away.

Jade Benjamin-Chung, Haodong Li, Anna Nguyen, Gabriella Barratt Heitmann, Adam Bennett, Henry Ntuku, Lisa M Prach, Munyaradzi Tambo, Lindsey Wu, Chris Drakeley, Roly Gosling, Davis Mumbengegwi, Immo Kleinschmidt, Jennifer L Smith, Alan Hubbard, Mark van der Laan, Michelle S Hsiang
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Abstract

Malaria elimination interventions in low-transmission settings aim to extinguish hot spots and prevent transmission to nearby areas. In malaria elimination settings, the World Health Organization recommends reactive, focal interventions targeted to the area near malaria cases shortly after they are detected. A key question is whether these interventions reduce transmission to nearby uninfected or asymptomatic individuals who did not receive interventions. Here, we measured direct effects (among intervention recipients) and spillover effects (among non-recipients) of reactive, focal interventions delivered within 500m of confirmed malaria index cases in a cluster-randomized trial in Namibia. The trial delivered malaria chemoprevention (artemether lumefantrine) and vector control (indoor residual spraying with Actellic) separately and in combination using a factorial design. We compared incidence, infection prevalence, and seroprevalence between study arms among intervention recipients (direct effects) and non-recipients (spillover effects) up to 3 km away from index cases. We calculated incremental cost-effectiveness ratios accounting for spillover effects. The combined chemoprevention and vector control intervention produced direct effects and spillover effects. In the primary analysis among non-recipients within 1 km from index cases, the combined intervention reduced malaria incidence by 43% (95% CI 20%, 59%). In secondary analyses among non-recipients 500m-3 km from interventions, the combined intervention reduced infection by 79% (6%, 95%) and seroprevalence 34% (20%, 45%). Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 37%. Our findings provide the first evidence that targeting hot spots with combined chemoprevention and vector control interventions can indirectly benefit non-recipients up to 3 km away.

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有针对性的消除疟疾干预措施可减少3公里外的恶性疟原虫感染。
在低传播环境中进行的消除疟疾干预措施旨在扑灭热点地区,防止传播到附近地区。在消除疟疾的环境中,世界卫生组织建议在发现疟疾病例后不久,针对疟疾病例附近地区采取反应性、重点干预措施。一个关键问题是,这些干预措施是否会减少向附近未感染或未接受干预的无症状个体的传播。在这里,我们在纳米比亚的一项集群随机试验中,测量了在确诊疟疾指数病例5亿范围内实施的反应性重点干预措施的直接影响(在干预接受者中)和溢出影响(在非接受者中)。该试验采用析因设计,分别和联合进行疟疾化学预防(蒿甲醚-流明三烯)和媒介控制(Actellic室内残留喷洒)。我们比较了干预受试者和非受试者(溢出效应)在距离指标病例3公里的研究组之间的发病率、感染流行率和血清流行率。我们计算了考虑溢出效应的增量成本效益比。化学预防和媒介控制相结合的干预产生了直接效应和溢出效应。在距离指标病例1公里以内的非受试者的初步分析中,联合干预将疟疾发病率降低了43%(95%CI 20%,59%)。在距离干预措施500m-3km的非受试者的二次分析中,联合干预使感染率降低了79%(6%,95%),血清流行率降低了34%(20%,45%)。考虑到溢出效应,联合干预的成本效益提高了37%。我们的研究结果首次证明,通过化学预防和媒介控制相结合的干预措施来靶向热点地区,可以间接使3公里外的非接受者受益。重要声明:在疟疾传播正在下降并接近消除的环境中,新的疟疾病例在空间和时间上都是聚集性的。先前的研究发现,在新发现的疟疾病例周围地区,靶向预防性抗疟药物和病媒控制可以减少整个社区的疟疾。在这里,我们发现,当在最近病例附近的地区将抗疟药物和病媒控制作为一种联合策略时,没有接受干预的人在3公里外的疟疾发病率降低了。考虑到这些对非接受者的好处,增加了干预的成本效益。总的来说,我们的研究结果表明,有针对性的综合疟疾干预措施可以减少当地传播,并支持其用于消除疟疾。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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