Ecology of African Highland Malaria

说明（申请方提供）：在过去十年中，大规模推广驱虫蚊帐和室内滞留喷洒，加上采用青蒿素复方疗法，使非洲高地的疟疾流行率和发病率大幅下降。然而，杀虫剂抗药性的上升和室外传播的增加大大阻碍了驱虫蚊帐和室内滞留喷洒的有效性，因为目前的室内干预措施并不针对室外叮咬的蚊子。因此，大多数高原地区保持持续的低水平传播，而其他一些地区的疟疾发病率最近有所回升。因此，迫切需要新的补充干预措施来解决户外传播和拟除虫菊酯杀虫剂耐药性问题。这一竞争性更新申请的中心目标是确定环境保护局批准的长效微生物杀幼虫剂在减少肯尼亚西部高地疟疾传播和临床疟疾发病率方面的功效和成本效益。这三个具体目标是：1）检查调节幼虫栖息地生产力的机制，2）使用随机分组研究确定长效微生物杀幼虫剂在减少疟疾传播和临床疟疾发病率方面的功效，以及3）确定长效微生物杀幼虫方案与其他疟疾控制干预措施相比的成本效益，并评估其对非目标生物的影响。通过对潜在的具有成本效益的长效微生物杀幼虫剂进行全面评价，该项目将提供急需的数据，说明长效微生物杀幼虫剂是否可以扩大规模，作为进一步降低非洲高地疟疾发病率的补充疟疾控制工具。疟疾户外传播控制是目前非洲疟疾控制中一个非常重要和紧迫的问题，因此，我们的研究结果将对非洲疟疾流行区和流行区的疟疾预防和控制产生广泛的影响。

DESCRIPTION (provided by applicant): In the past decade, massive scale-up of insecticide-treated nets (ITN) and indoor residual spraying (IRS), together with the introduction of artemisinin-combination treatments, have led to substantial reductions in malaria prevalence and incidence in African highlands. However, rising insecticide resistance and increased outdoor transmission have greatly hampered the effectiveness of ITN and IRS because the current indoor-based interventions do not target the outdoor-biting mosquitoes. Consequently, most highland sites maintain sustained low- level transmission while some others have recently experienced resurgence in malaria rates. Therefore, new supplemental interventions that can tackle outdoor transmission and pyrethroid insecticide resistance are urgently needed. The central objective of this competing renewal application is to determine the efficacy and cost-effectiveness of EPA-approved long-lasting microbial larvicides in reducing malaria transmission and clinical malaria incidence in western Kenya highlands. The three specific aims are: 1) to examine mechanisms regulating larval habitat productivity, 2) to determine the efficacy of long-lasting microbial larvicides on the reduction of malaria transmission and clinical malaria incidence using a cluster randomized study, and 3) to determine the cost-effectiveness of the long-lasting microbial larviciding program as compared to other malaria control interventions and evaluate its impact on non-target organisms. Through comprehensive evaluation of potentially cost-effective long-lasting microbial larvicides, this project will provide critically needed data on whether long-lasting microbial larvicides can be scaled up as a supplemental malaria control tool to further reduce malaria incidence in African highlands. Malaria outdoor transmission control is presently a highly significant and urgent issue in malaria control across Africa, and thus, our results will have broad implications on malaria prevention and control in endemic and epidemic regions of Africa.