Endectocides for Malaria Control

用于控制疟疾的杀虫剂

• 批准号: 7512454
• 负责人: BRIAN David FOY
• 金额: $ 14.7万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7512454
• 关键词: Acids; Adult; Africa South of the Sahara; African; Age; Agonist; Agriculture; Anopheles Genus; Anopheles gambiae; Area; Bionomics; Blood; Characteristics; Chloride Channels; Cities; Class; Communities; Culicidae; Developed Countries; Developing Countries; Development; Dose; Drug toxicity; Exhibits; Feeding behaviors; Female; Filarial Elephantiases; Fogs; Generations; Glutamates; Habits; Health; Helminths; Housing; Human; Infection; Insecticide Resistance; Insecticides; Ivermectin; Lactones; Link; Logistic Regressions; Malaria; Malathion; Mammals; Measures; Membrane; Methods; Modeling; Molecular Target; Nematoda; Neuromuscular Junction; Onchocerciasis; Pesticides; Pharmaceutical Preparations; Plasmodium; Population; Property; Public Health; Rate; Research; Resistance; Rest; Safety; Score; Senegal; Sporozoites; Structure; Survival Rate; Survivors; Testing; Time; Treatment Protocols; cost; day; disease transmission; drug testing; egg; feeding; killings; mathematical model; milbemycin; milbemycins; mosquitocidal; moxidectin; novel; prevent; pyrethroid; research study; stem; transmission process; vector

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.

描述（由申请人提供）：疟疾每年继续使全世界数百万人患病和死亡，这是撒哈拉以南非洲地区一个特别棘手的问题。灭蚊剂是有效控制疟疾的基础，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式中最关键的变量，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菌剂和新的施用方法。杀内灭剂是广谱、低毒的药物，具有抗寄生虫和抗体外寄生虫的综合特性，目前用于控制盘尾丝虫病和淋巴丝虫病。目前的灭虫剂作为激动剂作用于蚊子肌神经连接中的谷氨酸和gaba门控氯离子通道，也可以有效地用于撒哈拉以南非洲的疟疾控制，并且由于其分子靶点、对人群的施用方式以及非洲疟疾媒介的生物学特性，与其他灭虫剂相比，它们具有一定的主要优势。本研究旨在确定谷氨酸和gaba门控氯离子通道激动剂（大环内酯、米贝霉素、球孢酰胺）通过人工血粉杀灭成年按蚊的有效剂量。其次，将在塞内加尔东南部对用于控制盘尾丝虫病的伊维菌素大规模施用进行实地测试，以确定对吸血成年按蚊的杀蚊效果，以及这种效果将暂时阻断疟疾在当地社区的传播。本项目旨在通过评估目前抗寄生虫药物对非洲疟疾病媒的活性并在自然实地试验中测试其效果，开发控制撒哈拉以南非洲疟疾的新方法。