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

点击翻译按钮获取中文摘要

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.