Ivermectin for Malaria Control

描述（由申请人提供）：蚊媒疾病给发展中国家，特别是非洲带来了巨大的公共卫生和经济负担。疟疾在全球蚊媒疾病发病率和死亡率中所占比例最大。目前迫切需要新的病媒控制工具，以不同于传统杀虫剂的方式减少蚊子传播疟疾，包括在蚊子体内具有新的分子靶点的工具、新的给蚊子递送模式的工具，以及能够针对经杀虫剂处理的蚊帐或室内残留喷洒无法很好控制的病媒传播的工具。为了在发展中国家资源有限的环境中发挥最大的作用，这些工具还必须能够与现有的疟疾控制干预措施和现有的人类卫生基础设施相结合。我们的广泛假设是，在非洲村庄的人类驱虫运动中使用的伊维菌素可以作为这些有前途的新工具之一，我们已经证明它可以破坏塞内加尔村庄的疟疾寄生虫传播。伊维菌素是一种口服药物，在发展中国家已经大量给人服用以控制盘尾丝虫病，疟疾病媒在这些大量给药后叮咬人，可能被这种药物摄入并杀死。我们的数据表明，在疟疾流行社区更频繁地施用伊维菌素将导致疟疾寄生虫传播的持续减少。为了实现这一目标，有必要在现场和实验室对伊维菌素对疟疾病媒的作用进行彻底检查。我们提出两个具体目标：目标1：在塞内加尔对野生疟疾病媒摄入伊维菌素的影响进行实地人口研究。目标2：对伊维菌素可能对蚊子和疟疾寄生虫传播产生的影响进行实验室和建模研究。

DESCRIPTION (provided by applicant): The public health and economic burden imposed by mosquito-borne diseases on the developing world, and especially Africa, is enormous. Malaria accounts for the largest portion of global mosquito-borne disease morbidity and mortality. There is an urgent need for novel vector control tools that reduce malaria transmission by mosquitoes in distinct ways from traditional insecticides, including tools that have new molecular targets in mosquitoes, new modes of delivery to the mosquito, and tools that can target transmission by vectors not well- controlled by insecticide-treated nets or indoor residual spraying. To be maximally effective in resource- constrained environments of the developing world, such tools must also be able to integrate with existing malaria control interventions and existing human health infrastructures. Our broad hypothesis is that ivermectin used in human de-worming campaigns in African villages, and which we have shown can disrupt malaria parasite transmission in Senegalese villages, could serve as one of these promising new tools. Ivermectin is an oral drug, already given by mass administration to humans in the developing world for onchocerciasis control, and malaria vectors can ingest and be killed by this drug when they bite humans after these mass drug administrations. Our data suggests that more frequent administrations of ivermectin in malaria-endemic communities would result in sustained reductions in malaria parasite transmission. To get to this goal, a thorough examination of the ivermectin effects against malaria vectors in the field and laboratory is necessary. We propose two specific aims: Aim 1: Perform field population studies in Senegal on the effects of ivermectin ingested by wild malaria vectors. Aim 2: Perform laboratory and modeling studies on the effects ivermectin may have on mosquitoes and malaria parasite transmission.