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

肯尼亚血吸虫病传播和控制的蜗牛相关研究

基本信息

批准号：
8469389
负责人：
ERIC SAMUEL LOKER
金额：
$ 31.98万
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 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8469389
关键词：
Adverse effects Africa Africa South of the Sahara African Area Bayluscide Biology Biomphalaria Buffers Child Chronic Communicable Diseases Complement Complex Development Doctor of Philosophy Dose Equilibrium Exposure to Future Gene Expression Genes Genotype Goals Habitats Health Homologous Gene Human Indigenous Infection Investigation Kenya Laboratory Study Larva Learning Life Life Cycle Stages Medical Research Methods Microarray Analysis Modeling Molecular Nature Parasites Pharmaceutical Preparations Physiological Play Population Praziquantel Predisposition Prevalence Production Property Protocols documentation RNA Interference Relative (related person)Research Institute Research Personnel Resistance Role Schistosoma Schistosoma mansoni Schistosomiasis Scientist Series Side Site Snails Source Stream Students Techniques Testing Time Training Trematoda Tropical Disease Work base deep sequencing egg experience insight knock-down neglect novel operation programs response stressor transmission process

Adverse effects Africa Africa South of the Sahara African Area Bayluscide Biology Biomphalaria Buffers Child Chronic Communicable Diseases Complement Complex Development Doctor of Philosophy Dose Equilibrium Exposure to Future Gene Expression Genes Genotype Goals Habitats Health Homologous Gene Human Indigenous Infection Investigation Kenya Laboratory Study Larva Learning Life Life Cycle Stages Medical Research Methods Microarray Analysis Modeling Molecular Nature Parasites Pharmaceutical Preparations Physiological Play Population Praziquantel Predisposition Prevalence Production Property Protocols documentation RNA Interference Relative (related person)Research Institute Research Personnel Resistance Role Schistosoma Schistosoma mansoni Schistosomiasis Scientist Series Side Site Snails Source Stream Students Techniques Testing Time Training Trematoda Tropical Disease Work base deep sequencing egg experience insight knock-down neglect novel operation programs response stressor transmission process

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项目摘要

DESCRIPTION (provided by applicant): Because of its endemic and chronic nature, schistosomiasis is easy to overlook relative to other more visible and publicized infectious diseases. It is a truly neglected and unconquered tropical disease, one for which we have consistently underestimated its health impact. Our means to control it are barely adequate and our expertise for dealing with it is limited and shrinking. Schistosomes undergo obligatory larval development in snails in which they produce human- infective cercariae in prodigious numbers. Control programs focus almost exclusively on treating people with the one widely available drug, praziquantel, yet drug-based control consistently fails to interrupt transmission because it ignores the central role of snails in supporting the schistosome life cycle. Over 90% of the world's victims of schistosomiasis live in sub-Saharan Africa, with one of the most prominent causal species being Schistosoma mansoni. This proposal focuses on the interactions between S. mansoni and its most common African snail host, Biomphalaria pfeifferi, as they co-occur in Kenya. We will provide new information regarding the role of snails in transmission, and how new methods of control could be developed to complement the existing uni-dimensional drug-centered programs. Throughout this project, the emphasis will be on B. pfeifferi snails taken straight from an active transmission site, and their interactions with S. mansoni miracidia derived directly from nearby infected children. Our four aims are united by the need to define the degree of compatibility that exists between wild snail and schistosome populations, and the factors that govern that level of compatibility. Building on work we have undertaken that has identified snail genes important in governing compatibility, we will attempt in the lab to alter expression of these genes in field- derived snails to learn if we can diminish compatibility. This would open the way for further studies in which snail compatibility might be manipulated to assist control efforts. Also, acknowledging that the impact of human infectious diseases can be reduced by ecological checks and balances, we will also explore the underappreciated role of natural enemies, including competing species of digenetic trematodes, in limiting S. mansoni's compatibility with, and prevalence in, B. pfeifferi. Finally, by applying modern techniques like microarray analysis and deep sequencing, we seek to define how snails respond to infection and to highlight physiological vulnerabilities of infected snails to enable us to better exploit thse weaknesses to selectively eliminate them in control efforts. This study is novel for its emphasis on applying modern molecular methods to wild snails and schistosomes in the African context, instead of dwelling on lab models. Also, this project is oriented around providing training for bot Kenyan and U.S. PhD students to maintain our expertise in an area that is suffering from a sharply dwindling number of investigators. Our work will ultimately favor development of more sustainable and successful means of schistosomiasis control in the part of the world where it is most urgently needed, tropical Africa.

描述（由申请人提供）：由于其特有和慢性的性质，相对于其他更明显和宣传的传染病，血吸虫病很容易忽略。这是一种真正被忽视和未被征服的热带疾病，我们一直低估了其健康影响。我们控制它的手段几乎没有足够的足够，而我们处理它的专业知识有限且萎缩。血块在蜗牛中经历了强制性的幼虫发育，在这些蜗牛中产生人类感染性尾car虫数量。控制程序几乎完全专注于用一种广泛使用的药物Praziquantel治疗人们，但是基于药物的控制始终无法中断传播，因为它忽略了蜗牛在支持Schistosome生命周期中的核心作用。世界上有90％以上的血吸虫病受害者生活在撒哈拉以南非洲，其中最杰出的因果物种之一是曼森。该提议着重于S. Mansoni与其最常见的非洲蜗牛宿主，Biomphalaria pfeifferi之间的相互作用，因为它们在肯尼亚共同发生。我们将提供有关蜗牛在传播中的作用的新信息，以及如何开发新的控制方法来补充现有的单维中心程序。在整个项目中，重点将集中在B. pfeifferi蜗牛直接从活跃的传输部位取出的蜗牛，以及它们与曼氏奇迹的相互作用直接来自附近受感染的儿童。我们的四个目标是由定义野性蜗牛和螺杆菌种群之间存在的兼容程度以及控制兼容性水平的因素而团结的。在我们进行的工作的基础上，我们确定了对兼容性重要的蜗牛基因，我们将在实验室中尝试改变这些基因在现场派生的蜗牛中的表达，以了解我们是否可以降低兼容性。这将为进一步的研究开辟道路，其中可能会操纵蜗牛兼容性以帮助控制工作。同样，承认人类传染病的影响可以通过生态检查和平衡来降低，我们还将探索自然敌人的作用不足，包括竞争性的挖掘爆发物种，在限制S. Mansoni与B. Pfeifferi在B. Pfeifferi中的兼容性和普遍性。最后，通过应用现代技术，例如微阵列分析和深度测序，我们试图定义蜗牛如何应对感染并突出感染蜗牛的生理脆弱性，以使我们能够更好地利用弱点，以选择性地消除它们在控制努力中。这项研究是新颖的，因为它强调在非洲背景下将现代分子方法应用于野生蜗牛和血块，而不是居住在实验室模型上。此外，该项目围绕为肯尼亚机器人和美国博士学位学生提供培训，以维持我们的专业知识，该领域遭受了大量调查人员的苦难。我们的工作最终将有利于在最迫切需要的世界中最迫切需要的热带非洲的世界中更可持续和成功的血吸虫病控制手段。