Endectocides for Malaria Control

描述（由申请人提供）：疟疾每年继续导致全世界数百万人患病和死亡，这在撒哈拉以南非洲地区是一个特别棘手的问题。成蚊杀剂是有效控制疟疾的基石，因为它们相对具有成本效益，可以应用于墙壁或蚊帐，并且针对疟疾传播模型中最关键的变量，即成蚊存活率。然而，广泛的杀虫剂抗药性和持续的疟疾传播需要开发新型杀虫剂和新的应用方法。杀内线虫剂是广谱、低毒的药物，具有抗蠕虫和抗体外寄生虫的特性，目前用于人类控制盘尾丝虫病和淋巴丝虫病。目前的杀虫剂可作为蚊子肌肉神经连接处谷氨酸和 GABA 门控氯离子通道的激动剂，也可有效用于撒哈拉以南非洲的疟疾控制，并且由于其分子靶点、对人群的给药方式以及非洲疟疾病媒的生物学特性，与其他杀成虫剂相比具有某些主要优势。本研究旨在确定谷氨酸和 GABA 门控氯离子通道激动剂杀虫剂（大环内酯、米尔倍霉素、结节孢酰胺）杀死成年按蚊的有效剂量。当通过人工血粉给药时。其次，将测试塞内加尔东南部用于控制盘尾丝虫病的大规模伊维菌素对吸血成年按蚊的杀蚊效果。这种效应将暂时中断当地社区的疟疾传播。公共卫生相关性 该项目旨在通过评估当前抗蠕虫药物对非洲疟疾病媒的活性并在自然现场实验中测试其效果，开发控制撒哈拉以南非洲疟疾的新方法。

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.