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

• 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
• 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

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）：由于血吸虫病具有地方性和慢性性，相对于其他更明显和公开的传染病，血吸虫病很容易被忽视。这是一种真正被忽视和未被征服的热带疾病，我们一直低估了它对健康的影响。我们控制它的手段几乎不够，我们处理它的专业知识也很有限并且正在萎缩。血吸虫在蜗牛中经历强制性幼虫发育，产生数量惊人的人类感染性尾蚴。控制计划几乎完全专注于使用一种广泛使用的药物吡喹酮来治疗患者，但基于药物的控制始终无法阻止传播，因为它忽视了蜗牛在支持血吸虫生命周期中的核心作用。世界上超过 90% 的血吸虫病受害者生活在撒哈拉以南非洲，其中最主要的致病物种之一是曼氏血吸虫。该提案重点关注曼氏蜗牛与其最常见的非洲蜗牛宿主 Biomphalaria pfeifferi 之间的相互作用，因为它们同时出现在肯尼亚。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以药物为中心的单维计划。在整个项目中，重点将放在直接从活跃传播地点采集的 B. pfeifferi 蜗牛，以及它们与直接来自附近受感染儿童的 S. mansoni miracidia 的相互作用。我们的四个目标是通过需要确定野生蜗牛和血吸虫种群之间存在的相容性程度以及控制该相容性水平的因素来实现的。基于我们已经确定的对控制相容性很重要的蜗牛基因的工作，我们将尝试在实验室中改变这些基因在田间来源的蜗牛中的表达，以了解是否可以降低相容性。这将为进一步研究开辟道路，通过控制蜗牛的相容性来协助控制工作。此外，我们认识到可以通过生态制衡来减少人类传染病的影响，因此我们还将探讨天敌（包括双遗传吸虫的竞争物种）在限制曼氏吸虫与菲弗氏吸虫的相容性和流行方面所发挥的未被充分认识的作用。最后，通过应用微阵列分析和深度测序等现代技术，我们试图定义蜗牛如何应对感染，并强调受感染蜗牛的生理脆弱性，使我们能够更好地利用这些弱点，在控制工作中选择性地消除它们。这项研究的新颖之处在于它强调将现代分子方法应用于非洲的野生蜗牛和血吸虫，而不是停留在实验室模型上。此外，该项目的目标是为肯尼亚和美国的博士生提供培训，以保持我们在研究人员数量急剧减少的领域的专业知识。我们的工作最终将有利于在世界上最迫切需要的热带非洲地区开发更可持续、更成功的血吸虫病控制手段。