Systems Biology for Molecular Analysis of Tuberculosis in Ethiopia

据估计，结核分枝杆菌(Mtb)已经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 其中埃塞俄比亚占所有活动性结核病病例的80%。循环菌株的克隆亲缘关系 在人类和其他潜在的宿主中，人们对此知之甚少。分子流行病学在全球变得越来越重要 追踪毒株和应对关键公共卫生挑战，以预防和控制传染病 埃塞俄比亚，包括结核病(TB)。埃塞俄比亚的牧民被忽视了，尽管他们 对各种传染病的脆弱性。在这些地区对结核病的监测也很少。作为牧民 依赖畜产品，一个重大的、基本上未被探索的挑战是潜在的高水平 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。卡介苗(BCG)减毒分枝杆菌疫苗的研制 牛黄制剂是唯一被批准的结核病疫苗，但不再提供保护性免疫。 一些种群。另一个挑战是需要长期的抗生素治疗，如果不适当的话 完成后，加速了结核分枝杆菌多药耐药的发展。高发结核病面临的主要问题 负担国是导致免疫系统减弱的人类和环境因素，可以 增加对结核分枝杆菌感染的易感性，潜伏感染复发，发病率和死亡率高。现代 基因组学工具将对传播动力学的知识、菌株多样性的程度产生重大影响 以及结核病与宿主环境的分子相互作用。在亚的斯亚贝巴之间拟议的伙伴关系中 大学(AAU)和J·克雷格·文特尔研究所(JCVI)，目标是在AAU建设基因组学能力，通过 重点利用Illumina NextGen测序技术和In 示范项目，了解活动性结核病与宿主成分的关系，如 人体呼吸道微生物组和基于蛋白质的呼吸道免疫反应分析。 该提议包括创新的系统生物学研究以及一个培训埃塞俄比亚科学家的计划。 在基因组学学科和传染病应用方面。 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.