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

SC组织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多人 100万人，90%的病例发生在热带非洲。淡水蜗牛作为媒介的参与 给予血吸虫生命周期相当大的稳定性，因为蜗牛通过以下方式支持多产 尾蚴的无性繁殖，是寄生虫对人的感染阶段。到目前为止努力控制 蜗牛体内的血吸虫只取得了有限的成功。我们工作的总体目标是找到创新的新方法 阻断曼氏血吸虫在其必需的生物钉螺宿主中的发育和传播， 尤其是在维多利亚湖盆地的背景下。而不是试图压制大量的蜗牛种群 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 生活在它们体内的血吸虫。我们的实地研究也不断提醒我们气候变暖的影响。 可能有媒介蜗牛和在它们体内发育的血吸虫。建立在实验室和现场的基础上 在我们正在进行的资助期内的发现，我们提出了以下新的目标：目标1.我们寻求了解是否 在实验室模型中，我们已经证明免疫反应与抵抗力有关，这种新热带蜗牛是光滑蜗牛。 和S.mansoni也在肯尼亚西部的非洲Biomphalaria分类群中发挥作用。转录学和其他 我们提出的研究将确定非洲蜗牛对血吸虫感染的反应的新特征 以及气温升高如何影响蜗牛对曼氏血吸虫的反应。目标2.我们的目标是描述 幼虫吸虫，特别是普遍存在的牛传播的两栖动物，抑制和 替代非洲生物菌类群中曼氏葡萄球菌孢子囊的发育。我们将使用中的组合 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来解决 这个问题。目标3.我们假设居住在海岸的苏丹白僵菌持续暴露在许多不同的环境中 包括曼氏吸虫在内的吸虫物种，并已开发出一种具有耐受性的通用免疫策略 以将吸虫的影响降至最低。相比之下，一种近亲B.choonomphala生活在来自日本的深水避难所 感染，我们预测将表现出免疫反应减弱和缺乏耐受性反应 用吸虫挑战。我们的目标都是试图用新的方式来干预 血吸虫幼虫在蜗牛中的发育，在实验室和实地研究之间建立了双向桥梁，并将使我们能够 为了继续在UNM的生物学家和肯尼亚医学研究所之间30多年的合作， 重视培养青年科学家的医学软化学知识。 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。它的弹性在一定程度上是由于 血吸虫寄生虫对淡水蜗牛媒介的依赖，这些媒介支持产生大量的 人类感染的尾蚴。我们建议探索它在钉螺中的免疫抵抗机制和手段。 通过竞争的幼虫吸虫干扰蜗牛的幼虫血吸虫，以开发所需的新方法 以控制血吸虫寄生虫在撒哈拉以南非洲的传播。 P ROJ EC/P E R FO R M和C E SI T E(S)(如果需要其他空间，请使用ProjecU Performance站点格式

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