Endectocides for Malaria Control

描述（由申请人提供）：疟疾每年继续使世界各地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。杀成蚊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，并且它们针对疟疾传播模型中最关键的变量，即成蚊存活率。然而，广泛的杀虫剂耐药性和持续的疟疾传播需要开发新的杀成虫剂和新的应用方法。杀内寄生虫剂是广谱、低毒性药物，具有抗蠕虫和抗外寄生虫的特性，目前用于人群控制盘尾丝虫病和淋巴丝虫病。在蚊子肌神经接点中充当谷氨酸和GABA门控氯离子通道激动剂的现有杀内外寄生虫剂也可有效地用于撒哈拉以南非洲的疟疾控制，并且由于其分子靶标、其将如何施用于人群以及非洲疟疾媒介的生物学特性，其将具有优于其他杀成虫剂的某些主要优势。本研究旨在确定谷氨酸和GABA门控氯离子通道激动剂杀线虫剂（大环内酯类、米尔贝霉素类、节孢酰胺类）杀灭按蚊成虫的有效剂量。当通过人造血粉给药时。其次，将测试塞内加尔东南部用于控制盘尾丝虫病的大量伊维菌素给药对吸血按蚊成虫的杀蚊效果。这一效果将暂时阻断疟疾在当地社区的传播。该项目旨在通过评估目前抗蠕虫药物对非洲疟疾病媒的活性并在自然实地实验中测试其效果，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.