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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

血吸虫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多名 100万人，其中90%的病例发生在热带非洲。淡水蜗牛作为媒介的参与赋予相当大的稳定性，因为蜗牛支持多产的生产，尾蚴的无性繁殖，即人体寄生虫的感染阶段。迄今为控制蜗牛中的寄生虫只取得了有限的成功。我们工作的总体目标是确定创新的新方法，阻断曼氏血吸虫在其专性双脐螺宿主中的发育和传播，特别是在维多利亚湖盆地的背景下。而不是试图抑制大量的蜗牛种群在广泛的流行地区，我们的方法是找到针对受感染蜗牛和幼虫阶段的具体方法生活在其中的人。我们的实地研究也不断提醒我们气候变暖的影响可能对媒介蜗牛和它们体内的寄生虫有影响。基于实验室和现场在我们正在进行的资助期间取得的发现，我们提出了以下新目标：目标1。我们想知道我们已经在实验室模型--新热带区蜗牛B--中证明了免疫应答与抗性相关。光滑和s. mansoni，也在肯尼亚西部的非洲双脐螺类群中发挥作用。转录组学和其他我们提出的研究将确定非洲蜗牛对寄生虫感染的反应的新特征，以及蜗牛对S. mansoni可能会受到气候变暖的影响。目标2.我们的目标是描述手段，使幼虫吸虫，特别是无处不在的常见牛传播的双口类，抑制和取代了S.非洲双脐螺分类群中的曼氏孢子囊。我们将结合使用in 体内和体外方法结合转录组学、蛋白质组学和代谢组学技术，这个问题目标3.我们假设岸边居民B.苏丹卡不断受到许多不同的吸虫种类包括S. mansoni，并开发了一种具有耐受性的通用免疫策略，以尽量减少吸虫的影响。相反，近亲B。choanomphala，生活在一个深水避难所，感染，我们预测将显示免疫反应性减弱，缺乏耐受性反应，挑战吸虫。我们的目标都是寻求以新颖的方式来干扰发展，研究蜗牛幼虫的发育，在实验室和现场研究之间建立一个双向桥梁，继续在UNM和肯尼亚医学研究所的生物学家之间的30多年的合作，强调培养医学软体动物学的青年科学家。相关性（参见说明）：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寄生虫对淡水蜗牛载体的依赖，这些载体支持大量的感染人类的尾蚴本文旨在探讨钉螺免疫抗性机制及防治方法从而使相互竞争的幼虫吸虫干扰蜗牛体内的幼虫体，来控制寄生虫在撒哈拉以南非洲的传播。 P ROJ EC/P E R FO R M AN C E SI T E（S）（如果需要艾德，请使用项目绩效现场格式