Endectocides for Malaria Control

描述(申请人提供)：疟疾每年继续在世界各地导致数百万人患病和死亡，在撒哈拉以南非洲是一个特别棘手的问题。蚊子防腐剂是有效控制疟疾的基础，因为它们相对成本效益高，可以用于墙壁或蚊帐，而且它们针对的是疟疾传播模型中最关键的变量--成年蚊子存活率。然而，广泛的杀虫剂抗药性和疟疾的持续传播要求开发新的掺杂剂和新的使用方法。杀虫剂是一种广谱、低毒的药物，兼具抗蠕虫和抗体外寄生虫的特性，目前用于人类人群的丝虫病和淋巴丝虫病控制。目前作为蚊子肌肉神经连接谷氨酸和GABA门控氯离子通道激动剂的杀菌剂，也可有效地用于撒哈拉以南非洲的疟疾控制，由于其分子靶标、如何给人使用以及非洲疟疾媒介的生物学特性，将具有某些重大优势。本研究旨在确定谷氨酸和GABA门控氯离子通道激动剂杀灭成虫的有效剂量。当通过人造血粉给药时。其次，将在塞内加尔东南部大规模使用伊维菌素控制盘尾丝虫病，以测试其对吸血的成年按蚊的杀蚊效果。在实地，这一效应将暂时阻断疟疾在当地社区的传播。与公共卫生的相关性该项目寻求开发新的方法来控制撒哈拉以南非洲的疟疾，方法是评估目前用于抗击非洲疟疾媒介的抗蠕虫药物，并在自然野外试验中测试其效果。

DESCRIPTION (provided by applicant): Malaria continues to sicken and kill millions of people around the world every year, and is an especially intractable problem in sub-Saharan Africa. Mosquito adulticides are the bedrock of effective malaria control because they are relatively cost-effective, they can be applied to walls or bednets, and they target the most critical variable in malaria transmission models, adult mosquito survivor rates. However, widespread insecticide resistance and continued malaria transmission require the development of novel adulticides and novel ways to apply them. Endectocides are broad spectrum, low toxicity drugs with combined anti-helminthic and anti-ectoparasitic properties and are currently given to human populations for onchocerciasis and lymphatic filariasis control. Current endectocides that act as agonists to glutamate and GABA-gated chloride ion channels in mosquito myoneural junctions, could also be effectively used for malaria control in sub- Saharan Africa and would have certain major advantages over other adulticides due to their molecular targets, how they would be administered to the human population, and the bionomics of African malaria vectors. This research is intended to determine the effective doses of glutamate and GABA-gated chloride ion channel agonist endectocides (macrocyclic lactones, milbemycins, nodulasporamides) for killing adult Anopheles spp. when administered via an artificial bloodmeal. Secondly, mass-ivermectin administration for onchocerciasis control in Southeastern Senegal will be tested for mosquitocidal effects on bloodfeeding adult Anopheles spp. in the field, and that this effect will transiently interrupt malaria transmission in the local community. PUBLIC HEALTH RELEVANCE This project seeks to develop novel methods to control malaria in sub-Saharan Africa by evaluating current anti-helminth drugs for activity against African malaria vectors and testing their effects in a natural field experiment.