Systems Biology for Molecular Analysis of Tuberculosis in Ethiopia

结核分枝杆菌（Mtb）估计感染了世界三分之一的人口， 皮肤结核菌素试验阳性的调查报告。全球有22个高负担国家，其中 在埃塞俄比亚，占所有活动性结核病病例的80%。循环菌株的克隆相关性 对人类和其他潜在的宿主了解甚少。分子流行病学在 跟踪菌株并应对关键的公共卫生挑战，以预防和控制传染病， 埃塞俄比亚，包括结核病。埃塞俄比亚牧民被忽视， 易感染各种传染病。这些地区对结核病的监测也很少。牧民 依赖畜牧产品，一个重大的，基本上未探索的挑战是潜在的高水平的 结核病在牲畜和人之间的传播。目前还没有有效的疫苗保护 人类对抗结核病由减毒分枝杆菌组成的卡介苗（BCG）疫苗 牛制剂是唯一批准的结核病疫苗，但不再提供保护性免疫， 一些人口。另一个挑战是需要长期的抗生素治疗， 完成后，加速了结核分枝杆菌多药耐药性的发展。结核病高发的主要问题 负担国家是人类和环境因素，有助于削弱免疫系统， 增加对Mtb感染易感性、潜伏感染复发以及高发病率和死亡率。现代 基因组学工具将大大影响传播动力学知识， 以及TB与其宿主环境的分子相互作用。在拟议的阿迪斯与 该项目是由美国农业大学（AAU）和J.克雷格文特尔研究所（JCVI）合作开展的，目标是建立AAU的基因组学能力， 重点对Mtb和M.牛使用Illumina Nextgen测序技术， 示范项目，了解活动性结核病与宿主成分的关系， 人类呼吸道微生物组和基于蛋白质的呼吸道免疫反应分析。 该提案包括创新的系统生物学研究以及培训埃塞俄比亚科学家的计划 在基因组学学科和传染病的应用。 2.

Mycobacterium tuberculosis (Mtb) is estimated to have infected one third of the world's population based on reports from surveys on positive skin tuberculin tests. There are 22 high-burden countries globally, among them Ethiopia, accounting for 80% of all active tuberculosis cases. The clonal relatedness of strains circulating in humans and other potential reservoirs is poorly understood. Molecular epidemiology is gaining importance in tracking strains and addressing key public health challenges to prevent and control communicable diseases in Ethiopia, including tuberculosis (TB). Ethiopian pastoralist populations have been neglected despite their vulnerability to various infectious diseases. Surveillance of TB in these areas is also minimal. As pastoralists rely on livestock products, a significant, largely unexplored challenge is the potentially high level of transmission of tuberculosis between livestock and people. There is currently no effective vaccine protecting humans against TB. The Bacillus Calmette Guerin (BCG) vaccine consisting of attenuated Mycobacterium bovis preparations is the only approved vaccine against TB, but no longer provides protective immunity in some populations. Another challenge is the need of prolonged antibiotic treatment which, if not properly completed, accelerates the development of Mtb multi-drug resistance. Major problems in high TB disease burden countries are human and environmental factors that contribute to a weakened immune system and can increase susceptibility to Mtb infection, recurrence of latent infection and high morbidity and mortality. Modern genomics tools will considerably impact the knowledge of transmission dynamics, the extent of strain diversity and molecular interactions of TB with its host environments. In the proposed partnership between Addis Ababa University (AAU) and J. Craig Venter Institute (JCVI), the objective is to build genomics capacity at AAU, with a focus on the typing of strains of Mtb and M. bovis using Illumina Nextgen sequencing technologies and, in demonstration projects, understanding the relationships of active TB disease with host components such as the human respiratory microbiome and protein-based analysis of immune responses in the respiratory tract. This proposal includes innovative systems biology research as well as a program training Ethiopian scientists in genomics disciplines and applications to infectious diseases. 2.