Epidemiology and Genomics of Multidrug resistant Salmonella Typhi infections in Kenya: The role of carriage in an endemic setting

项目摘要 沙门氏菌是肠杆菌科，可引起人类和动物的一系列疾病，包括 肠（伤寒）热和胃肠炎。伤寒，主要由沙门氏菌引起 伤寒（S.伤寒），导致危及生命的全身性疾病，导致显著的发病率， 全球每年的死亡率。这种疾病在非洲许多地方流行，包括肯尼亚。1 - 5%的 感染S.伤寒成为胆囊（GB）作为持久性部位的慢性携带者。 S.伤寒是一种人类限制性病原体，因此无症状携带者是伤寒的关键宿主。 疾病的进一步传播。我们已经证明，胆结石（GS）的发展援助， 在小鼠模型和人类中维持GB携带，作为鲑鱼的底物， 附着并形成保护性生物膜。然而，关于沙门氏菌发展的流行病学 对急性和慢性携带者的慢性携带和疾病传播了解甚少。在这 建议，我们打算前瞻性地研究在肯尼亚伤寒流行地区的人口，以更好地 了解：（1）沙门氏菌的基因组学、耐药性和生物膜表型;伤寒菌株 发热和慢性携带，（2）GS与慢性携带者建立的联系，以及（3）当地 伤寒在目标城市社区的流行病学和地理空间分布。数据建模 收集将使人们更好地了解造成急性和慢性感染的菌株， 相关流行病学因素对S.伤寒在一个社区传播。这也将有助于医疗保健 从业人员更好地治疗和预测疾病传播的可能性以及无症状携带。

PROJECT SUMMARY Salmonellae are Enterobacteriaceae that cause a spectrum of diseases in humans and animals, including enteric (typhoid) fever and gastroenteritis. Typhoid fever, caused primarily by Salmonella enterica serovar Typhi (S. Typhi), results in a life-threatening systemic disease that is responsible for significant morbidity and mortality annually worldwide. The disease is endemic in many parts of Africa, including Kenya. 1-5% of individuals infected with S. Typhi become chronic carriers with the gallbladder (GB) as the site of persistence. S. Typhi is a human-restricted pathogen, therefore asymptomatic carriers represent a critical reservoir for further spread of disease. We have demonstrated that gallstones (GSs) aid in the development and maintenance of GB carriage in a mouse model and in humans, serving as a substrate to which salmonellae attach and form a protective biofilm. However, the epidemiology regarding the development of Salmonella chronic carriage and spread of the disease from both acute and chronic carriers is poorly understood. In this proposal, we intend to prospectively study a population in a typhoid fever endemic region in Kenya to better understand: (1) genomics, antibiotic resistance and biofilm phenotypes of the S. Typhi strains causing typhoid fever and chronic carriage, (2) the linkage of GSs to the establishment of chronic carriers, and (3) the local epidemiology and geospatial distribution of typhoid fever in the target urban community. Modeling the data gathered will allow a greater understanding of the strains causing acute and chronic infection and the associated epidemiologic factors contributing to S. Typhi spread in a community. This will also help healthcare practitioners better treat and predict the likelihood of disease transmission as well as asymptomatic carriage.