Environmental Aetiology of Diarrhoeagenic Pathogens in Children in a Developing Country Setting

在许多发展中国家，儿童疾病仅由五种情况之一引起：肺炎、腹泻、麻疹、疟疾或营养不良。2002年，腹泻造成的死亡人数估计占全世界儿童死亡人数的13%。超过19%的急性腹泻发作会持续下去，其中高达50%的病例证明是致命的。人们普遍认为，引起腹泻的病原体通常具有环境来源，然而，由于致病病原体可能来源的多样性以及合并感染的存在，即使确定了来源，也很少确定。迄今为止有限的监测突出表明，源自动物的病原体是导致儿童腹泻的潜在重要因素。人类微生物组项目和世界各地的类似努力正在使我们对人类微生物的理解以及它们如何随着健康和疾病而变化。这些项目的深度和广度只是在过去几年才成为可能，因为？下一代？分子生物学技术传统微生物学侧重于将单个物种作为孤立单位进行研究，尽管大多数微生物从未被成功分离。这些新一代技术可以？又宽又深对微生物群落的公正检查，既快速又敏感，并且在培养有机体失败时通常成功。我们提出，新的分子生物学监测方法加上生物信息学（病原体DNA/RNA分析），不仅可以确认已知的病原体及其来源的相关性，但可能更重要的是，证明相关的未报告的病原体及其来源作为潜在的主要参与者在儿童的病原体感染。拟议的研究旨在利用“年轻生命”项目的知识库和基础设施，该项目是一个多国研究项目，调查儿童贫困性质的变化。Young Lives的综合观点和拟议的环境采样将为全面的系统战略提供基础，以了解驱动和控制儿童中病原体出现和传播的最重要因素。此外，该项目旨在提供证据基础，以促进制定战略，优先考虑有限的国家和国际资金，以减轻儿童中的致病性传染因子。将从气候变化的角度重新评估研究社区儿童致病病原体的性质和来源。

In many developing countries, childhood illnesses are caused by one of only five conditions: pneumonia, diarrhoea, measles, malaria or malnutrition. In 2002, diarrhoea caused an estimated 13% of child deaths worldwide. Upwards of 19% of acute diarrhoea episodes become persistent, with up to 50% of these cases proving fatal. It is widely recognised that pathogens that cause diarrhoea often have an environmental origin, however, owing to the diversity of possible sources of diarrhoeagenic pathogens, and the presence of co-infections, the origin is rarely if ever determined. Limited surveillance to date has highlighted pathogens originating from animals as potentially important factors in causing childhood diarrhoea. The Human Microbiome Project and similar efforts worldwide are making quantum leaps in our understanding of the microorganisms that colonise humans and how they change with health and disease. The depth and breadth of these projects have only become possible in the past few years because of ?next generation? molecular biology technologies. Traditional microbiology has focused on the study of individual species as isolated units despite the fact that most microbes have never been successfully isolated. These next generation technologies enable ?broad and deep? unbiased examination of microbial communities which are both rapid and sensitive, and often succeed when culturing the organism fails. We propose that novel molecular biology surveillance approaches coupled with bioinformatics (analysis of pathogen DNA/RNA), can not only confirm the relevance of known diarrhoeagenic pathogens and their sources, but, potentially more importantly, demonstrate the relevance of under-reported pathogens and their sources as potential major players in diarrhoeagenic infections in children. The proposed study aims to build upon the knowledge base and infrastructure of the Young Lives project, which is a multi-country research project investigating the changing nature of childhood poverty. The combined perspectives from Young Lives and the proposed environmental sampling will provide the foundation for a holistic systems strategy for understanding the most important factors driving and controlling the emergence and spread of diarrhoeagenic pathogens among children. In addition, the project aims to provide the evidence base to facilitate the development of strategies for prioritising limited national and international funds for mitigating diarrhoeagenic infectious agents in children. The nature and sources of diarrhoeagenic pathogens to children in the study communities will be re-assessed within the perspective of a changing climate.