Immunological tools for a seroprevalence and immune status map of Burkholderia pseudomallei and thailandensis in Vietnam

这项牛顿基金申请旨在加强河内和伦敦帝国理工学院免疫学/微生物学研究人员之间现有的研究联系。生物医学研究问题涉及对越南类鼻疽病风险的评估。这是一种潜在的严重或致命的细菌感染，由许多温带国家的土壤和供水中发现的假氏伯克霍尔德菌引起。在邻国泰国，每年有数千人死于这种疾病。据预测，包括越南在内的其他几个国家可能对该病的诊断不足，但没有全面的数据。有了更精确的数据，就有可能为诊断和抗生素治疗方案制定适当的计划。因此，这一提议将来自河内和伦敦的研究人员聚集在一起，他们对这个问题有着强烈的、持续的兴趣。我们打算从几个层面来评估形势。第一种方法是从全国各地采集土壤样本，确定细菌的分布和负荷。作为这项工作的一部分，我们还将评估一种密切相关但非致病性的细菌——泰国伯克霍尔德氏菌的存在。这是很重要的，因为对这两种细菌的免疫部分是交叉反应的，并且有一种观点认为，接触泰国环境菌可以预防类鼻疽。然后，我们将与全国五家地区医院的合作者合作，在常规健康检查期间从每个中心的200名志愿献血者身上收集少量血液样本。这个样本将用于检查这两种细菌的抗体，从而提供一个“血清阳性率”数据集——也就是说，一个人类暴露于细菌的区域地图，它可以与绘制的土壤样本叠加在一起。这并不能告诉我们有多少人患有类鼻疽。相反，它将提供一幅图片，说明越南是否确实存在类似于泰国北部高风险地区的地区，在那里，大多数人在接触细菌后会产生高水平的抗体。由于那些对细菌有免疫力但没有疾病迹象的人一定有功能性保护，我们将进行合作研究，在白细胞（称为“T细胞”）的水平上描述这种保护的性质。一个密切相关的问题是，糖尿病是迄今为止暴露于细菌的个体发展成严重疾病的最强危险因素。因此，我们将使用血清样本来建立糖尿病患病率的平行区域地图，据信糖尿病在越南正在迅速增长。这项研究将包括即时血糖和胰腺自身抗体的分析。这项工作的一个重要组成部分将是互动和培训部分，包括在越南举行的年度讲习班

This Newton Fund application seeks to enhance existing research links between immunology/microbiology researchers in Hanoi and at Imperial College London. The biomedical research question concerns appraisal in Vietnam of the risk of melioidosis. This is a potentially severe or lethal bacterial infection caused by the bacterium, Burkholderia pseudomallei, found in many temperate countries in the soil and in the water supply. The disease is associated with thousands of deaths annually in neighbouring Thailand. It has been predicted that the disease may be under-diagnosed in several other countries including Vietnam, but no comprehensive data exists. With more precise data, it would be possible to put appropriate plans in place for diagnosis and antibiotic treatment protocols. This proposal thus brings together researchers who have a strong, ongoing, interest in this question, from Hanoi and London. We plan to appraise the situation at several levels. The first is to take soil samples from sites across the country, determining distribution and load of the bacterium. As part of this work we will also assess presence of a closely related but non-pathogenic bacterium called Burkholderia thailandensis. This is important as immunity to the two bacteria is partly cross-reactive and there is a view that exposure to environmental thailandensis may protect against melioidosis. We will then work with collaborators at five regional hospitals across the country, collecting a small blood sample from 200 volunteer donors at each centre, during routine health-checks. This sample will be used to check for antibodies to the two bacteria, giving a dataset for 'seroprevalence' - that is, a regional map of human exposure to the bacteria, which can be overlaid with the mapped soil samples. This will not tell us how many people have melioidosis. Rather, it will give a picture of whether or not there are indeed regions of Vietnam similar to high-risk regions of N. Thailand, where a majority of people develop high levels of antibody after bacterial exposure. Since those people who show immunity to the bacterium but show no signs of disease must have functional protection, we will do collaborative studies to characterise the nature of this protection at the level of white blood cells termed 'T cells.' A closely related issue is that diabetes is by far the strongest risk factor for development of severe disease in individuals exposed to the bacterium. For this reason, we will use the serum samples to build a parallel, regional map of the prevalence of diabetes, believed to be growing rapidly in Vietnam. This study will include point-of-care blood glucose and analysis of pancreatic autoantibodies. A strong component of the work will be the interactive and training component, including annual workshops held in Vietnam