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

项目总结 沙门氏菌是肠杆菌科细菌，可引起人类和动物的一系列疾病，包括 肠道(伤寒)热和胃肠炎。伤寒主要由肠道沙门氏菌血清型引起 伤寒(S.Typhi)，导致一种危及生命的系统性疾病，导致严重的发病率和 全球每年的死亡率。这种疾病在非洲许多地区流行，包括肯尼亚。1-5% 感染伤寒沙门氏菌的人会成为慢性携带者，并以胆囊(GB)为持久性部位。 伤寒沙门氏菌是一种人类限制的病原体，因此无症状携带者代表着关键的宿主。 疾病的进一步传播。我们已经证明，胆结石(GSS)有助于发育和 在小鼠模型和人类中维持gB载体，作为沙门氏菌的底物 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 慢性携带者和慢性携带者对疾病的传播知之甚少。在这 建议，我们打算前瞻性地研究肯尼亚伤寒流行地区的人群，以更好地 了解：(1)伤寒沙门氏菌基因组学、耐药性和生物被膜表型 发热和慢性携带者，(2)GSS与慢性携带者建立的联系，以及(3)当地 目标城市社区伤寒的流行病学和地理空间分布。为数据建模 收集到的信息将使人们更好地了解导致急性和慢性感染的菌株以及 导致伤寒沙门氏菌在社区传播的相关流行病学因素。这也将有助于医疗保健 医生更好地治疗和预测疾病传播以及无症状携带者的可能性。

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.