Snail-Related Studies of Transmission & Control of Schistosomiasis in Kenya

与蜗牛相关的传播研究

基本信息

批准号：
10611300
负责人：
ERIC SAMUEL LOKER
金额：
$ 35.12万
依托单位：
UNIVERSITY OF NEW MEXICO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-15 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10611300
关键词：
Address Affect Africa Africa South of the Sahara African Alleles Area Asexual Reproduction Biomphalaria CRISPR/Cas technology Castration Cattle Characteristics Climate Collaborations Coupled Development Exposure to Fibrinogen Fresh Water Funding General Practitioners Genes Goals Histologic Human Immune Immune response In Vitro Individual Infection Instruction Interruption Intestines Kenya Larva Learning Life Cycle Stages Mediating Medical Medical Research Methods Modeling Monitor Outcome Parasites Persons Phenotype Play Population Predisposition Production Progress Reports Proteins Proteomics RNA Interference Reproduction Research Institute Resistance Role Schistosoma Schistosoma mansoni Schistosome Parasite Schistosomiasis Scientist Snails Sporocysts Stream Techniques Temperature Testing Training Water Work chemotherapy climate change experimental study field study immune resistance in vivo infection rate innovation metabolomics mindfulness neglected tropical diseases novel performance site prevent resilience resistance mechanism response success transcriptome sequencing transcriptomics transmission process vector vector competence

项目摘要

Sc histosomiasis is one of the world's most common neglected tropical diseases, currently infecting over 200 million people, with 90% of cases occurring in tropical Africa. The involvement of freshwater snails as vectors imparts considerable stability to the schistosome life cycle because snails support the prolific production by asexual reproduction of cercariae, the infective stage of the parasite for people. Efforts thus far to control schistosomes in snails have had but limited success. Our work's overall goal is to identify innovative new ways to interrupt the development and transmission of Schistosoma mansoni in its obligatory Biomphalaria snail hosts, especially in the context of the Lake Victoria basin. Rather than to attempt to suppress large snail populations across broad endemic areas, our approach is to find specific ways to target infected snails and the larval stages of schistosomes living within them . Our field studies also constantly remind us of the impact a warming c limate may have on vector snails and the schistosomes developing within them. Building on both lab- and field-based discoveries made in our ongoing funding period, we propose the following new aims: Aim 1. We seek to learn if immune responses we have shown to be relevant to resistance in a lab model, the Neotropical snail B. glabrata and S. mansoni, are also at play in African Biomphalaria taxa in western Kenya. The transcriptomics and other studies we propose will identify novel characteristics of the responses of African snails to schistosome infection and how snail responses to S. mansoni might be affected by warming c limates. Aim 2. We aim to characterize the means whereby larval trematodes, especially ubiquitously common cattle-transmitted amphistomes, suppress and supplant the development of S. mansoni sporocysts in African Biomphalaria taxa . We will use a combination of in vivo and in vitro approaches coupled with transcriptomics, proteomics and metabolomics techniques to address this issue. Aim 3. We hypothesize that shore-dwelling B. sudanica suffers constant exposure to many different trematode species, including S. mansoni, and have developed a generalist immune strategy featuring tolerance to minimize trematode impact. In contrast, a close relative, B. choanomphala, lives in a deepwater refugium from infection, and we predict will show diminished immune responsiveness and lack of tolerance responses upon challenge with trematodes. Our aims all seek to characterize novel ways to interfere with the development of schistosome larval development in snai ls, build a two-way bridge between lab and field studies and will enable us to continue a 30+ year collaboration between biologists at UNM and the Kenya Medical Research Institute, emphasizing training of young scientists in medical malacology. RELEVANCE (See instructions): Schistosomiasis is one of the world's most common neglected tropical diseases. Its resilience is partly due to the reliance of schistosome parasites on freshwater snail vectors that support the production of prolific numbers of human-infective cercariae. We propose to explo it immune resistance mechanisms in snails and the means whereby competing larval trematodes interfere with larval schistosomes in snails to develop needed new means to control transmission of schistosome parasites to people in sub-Saharan Africa. P ROJ EC / P E R FO R M AN C E SI T E(S) (if ad ditional space is need ed , use ProjecU Performance Site Format

SC病变病是世界上最常见的被忽视的热带疾病之一，目前感染了200多种百万人，有90％的案件发生在热带非洲。淡水蜗牛作为向量的参与蜗牛支持蜗牛的生产，因此赋予了稳定的生命周期 Cercariae的无性繁殖，这是寄生虫的感染阶段。迄今为止努力控制蜗牛中的血吸虫虽然取得了有限的成功。我们工作的总体目标是确定创新的新方法在其强制性的蜗牛宿主中，中断曼尼尼血吸虫的发展和传播，特别是在维多利亚湖盆地的背景下。而不是试图抑制大型蜗牛种群在广泛的地方性地区，我们的方法是找到针对感染蜗牛和幼虫阶段的特定方法居住在其中的血块。我们的现场研究也不断地使我们想起变暖C的影响可能有矢量蜗牛和内部发展的血块。建立在实验室和现场的基础上在我们正在进行的资金期间发现的发现，我们提出以下新目标：目标1。我们试图学习是否是否免疫反应我们已证明与实验室模型中的抗性有关，新热带蜗牛B. glabrata 和曼森（S.转录组学和其他我们提出的研究将确定非洲蜗牛对黑素感染的反应的新特征以及蜗牛对曼氏链球菌的反应可能会受到变暖的c峰的影响。目标2。我们旨在表征幼虫trematododes，尤其是普通的牛经过的两栖动物，抑制和取代了非洲生物腔分类单元中的曼氏孢子孢子虫的发展。我们将使用IN的组合体内和体外方法以及转录组学，蛋白质组学和代谢组学技术来解决这个问题。目的3。我们假设居住在苏丹省海岸的B. 包括曼氏链球菌在内的Trematode物种，并制定了具有耐受性的通才免疫策略为了最大程度地减少Trematode的影响。相比之下，一个亲戚B. choanomphala生活在一个深水中感染，我们预测将显示免疫反应性降低，并且缺乏耐受反应带有trematodes的挑战。我们的目标都旨在表征新颖的方法来干预发展的发展 Snai ls中的阴谋体幼虫发展，在实验室和野外研究之间建立双向桥梁，并将使我们能够要继续在UNM和肯尼亚医学研究所的生物学家之间进行30多年的合作，强调对年轻科学家在医学疾病学方面的培训。相关性（请参阅说明）：血吸虫病是世界上最常见的被忽视的热带疾病之一。它的弹性部分是由于依赖于支持产生多产数量的淡水蜗牛载体对淡水蜗牛载体的依赖人体感染cercariae。我们建议利用蜗牛的免疫抗性机制和手段竞争幼虫差异竞争蜗牛中的幼虫血块的影响控制将血吸虫寄生虫传播给撒哈拉以南非洲的人们。 p roj ec / p e r fo r m an c e si t e（s）（如果需要广告空间，请使用projecu性能站点格式