The development of molecular diagnostics for antihelmintic drug resistance monitoring in human schistosomiasis.

血吸虫病是一种被忽视的热带疾病，疾病负担最重的是撒哈拉以南非洲地区。这种疾病是由血吸虫属的吸虫引起的。血吸虫病有一系列临床表现，包括血尿和肝、脾等器官肿大。世界卫生组织估计，在血吸虫病流行地区生活的7亿人中，有三分之一以上受到血吸虫病的影响。人类血吸虫病的唯一推荐治疗方法是单剂吡喹酮(PZQ)，因为它可以用于治疗所有主要血吸虫病物种。这种药物可以通过大规模药物管理(MDA)计划与治疗其他感染(如淋巴丝虫病)的药物一起使用。近年来，PZQ的通达性有了很大改善。例如，制药公司默克-KGaA将每年的捐赠量从2000万片扩大到2.5亿片。虽然这种扩大的覆盖率有助于减轻症状的严重性，但它增加了血吸虫寄生虫的药物选择压力。丙二醛计划的扩大可能会导致对PZQ具有抗性的寄生虫的出现。因此，有必要检测和跟踪耐药血吸虫寄生虫的出现，以抵消抗药性的威胁血吸虫病控制方案。该项目以全球感染健康为主题，有两个主要目标：1.开发基于分子的方法以早期检测血吸虫物种，并阐明与PZQ耐药性发展相关的遗传标记的存在和分布。产生数据，以指导在大规模药物管理血吸虫病控制方案中合理和明智地使用吡喹酮的未来模式。该项目将应用基于分子的实验室、现场和计算工具来实现项目目标。最初的工作将侧重于获得钉螺维护技能，在实验室建立耐PZQ的血吸虫株，并使用分子分析来确认所提出的和新的遗传标记。这将使我能够通过活体训练获得整个生物体生理学的技能。随后，将在接受PZQ丙二醛的地方性环境中进行实地工作，以阐明遗传标记的存在和分布。该项目期间产生的数据可以指导未来在MDA项目中使用PZQ来控制血吸虫病。这个项目将发展和拓宽我在分子技术、统计和流行病学分析以及功能和计算基因组学方面的技能。我从医学寄生虫学硕士那里获得了这些领域的基本经验，所以向专家学习将有助于发展我的跨学科技能。我计划最大限度地利用我在LSHTM和圣乔治大学这两个机构的可用资源。我已经开始学习流行病学模块，并与寄生虫基因组学模块签约，以发展与该项目相关的技能。我还参加了一个可转让的技能课程，以帮助进行文学搜索，并为未来预订了更多课程。如果可能的话，我打算参加一个使用R程序的课程，以提高我的统计分析和量化技能。

Schistosomiasis is a neglected tropical disease where the highest burden of disease occurs in sub-Saharan Africa. This disease is caused by trematodes belonging to the genus Schistosoma. Schistosomiasis has a range of clinical forms including haematuria and enlargement of organs such as the liver and spleen. The WHO estimate that schistosomiasis affects over one third of the 700 million people living in endemic areas. The only recommended treatment for schistosomiasis in humans is a single dose of praziquantel (PZQ), as it can be used against all major species of schistosomiasis. The drug can be administered through mass drug administration (MDA) programmes alongside drugs to treat other infections such as lymphatic filariasis. In recent years, the access to PZQ has been greatly improved. For example, the pharmaceutical company Merck-KGaA have expanded the annual donation from 20 million to 250 million PZQ tablets. Although this increased coverage has aided in reducing severity of symptoms, it heightens the drug selection pressures on Schistosoma parasites. The scale up of MDA programs could lead to the emergence of PZQ resistant parasites. Therefore, there is a need to detect and track the emergence of resistant Schistosoma parasites in order counteract the threat of resistance to schistosomiasis control programs. This project comes under the theme of Global Infectious Health and has two main aims:1. Develop molecular-based approaches for early detection of Schistosoma species and elucidate the presence and distribution of genetic markers associated with the development of PZQ resistance2. To generate data to guide future models of rational and judicious use of praziquantel in mass drug administration schistosomiasis control programmes. The project will apply molecular-based laboratory, field and computational tools to achieve the project aims. Work will initially focus on gaining skills in snail maintenance and establishing a PZQ resistant schistosome strain in the laboratory and using molecular assays to confirm proposed and novel genetic markers. This will allow me to gain skills in whole organism physiology through in vivo training. Following this, field work in endemic settings receiving MDA of PZQ, will be undertaken in order to elucidate the presence and distribution of the genetic markers. The data generated during this project can guide the future use of PZQ in MDA programs to control schistosomiasis. This project will develop and broaden my skills in molecular techniques, statistical and epidemiological analysis as well as functional and computation genomics. I have basic experience in these areas achieved from my MSc Medical Parasitology so learning from experts will be beneficial in developing my interdisciplinary skillset.I plan to make the most of the resources available to me at both institutions; LSHTM and St George's. I have already begun epidemiology modules and have signed up to a parasite genomics module to develop skills relevant to the project. I have also attended a transferable skills course to aid in literature searching with more courses booked for the future. When it is possible, I intend to attend a course on using the program R in order to improve my statistical analysis and quantitative skills.