Enhancing basic and translational TB research in northern Vietnam

2014年，世界卫生组织估计，有150万人死于结核分枝杆菌(TB)感染(其中40万人为艾滋病毒阳性)。越南位于一个占世界结核病病例58%的地区，估计每年有13.7万越南人感染结核病(其中5000人获得抗药性结核病)。其中，估计每年有1.9万名越南人死于这种疾病。在目前的提案中，我们的目标是加强和加强伊利诺伊大学芝加哥分校(UIC)、越南科学院海洋生物化学研究所(IMBC-Vavast)和越南河内国家卫生与流行病学研究所(NIHE)之间的研究培训计划。我们的目标是加强东道国的基础和翻译研究能力，重点是发现和开发结核病的抗生素先导。自20世纪90年代以来，疾病控制和预防中心在越南的临床实验室和艾滋病毒/艾滋病/结核病监测系统上投入了大量资金，尽管这些努力和其他几项努力主要集中在建设医疗基础设施上。我们的提议将通过加强基础和转化科学研究基础设施和研究人员培训计划来弥合这一差距，该计划侧重于利用东道国的资源来发现治疗结核病的抗生素线索，并通过河内协调的抗生素线索筛选计划探索其致病的基本机制。这项计划的成功是由短期和长期的研究、培训和教育推动的。UIC在与Vavast的合作方面有着良好的记录。在过去的20年里，通过美国国立卫生研究院和麦克阿瑟基金会的资助，该团队致力于建立一个基于植物的药物先导发现和资源保护计划。然而，越南拥有超过3000公里的海岸线，拥有世界上一些最丰富的海洋生物多样性，本提案旨在开采这些海洋生物多样性。该项目的目标是1)通过在UIC的长期博士后培训，在IMBC-VAST/NIHE建立三名独立的研究人员；2)在项目期间为9名IMBC/NIHE博士后学生提供短期和长期的针对抗生素的培训；3)通过在NIHE创建结核分枝杆菌体外筛查项目，加强生物检测研究基础设施。在五年的时间里，我们的计划将产生12名训练有素的科学家，他们专门从事结核病抗生素的发现和开发。12名科学家中的3名--在各自研究所所长和所长的大量机构支持下--将建立独立的研究小组，以补充一个更广泛的计划，该计划利用越南的自然资源发现结核病抗生素，并利用这些线索探索结核分枝杆菌的致病机制。在五年的项目期后，IMBC和NIHE研究能力的显著增强将使越南北部成为结核病的转化性筛查中心，并将促进与越南国内外机构的合作。

In 2014, the World Health Organization estimated that there were 1.5 million deaths as a result of Mycobacterium tuberculosis (TB) infection (0.4 million of which were HIV-positive). Vietnam is located in a region that accounts for 58% of the world's TB cases, and an estimated 137,000 Vietnamese are infected with TB per year (5,000 of which acquire drug-resistant TB). Of these, the disease kills an estimated 19,000 Vietnamese annually. In the current proposal, we aim to enhance and strengthen a research training program between the University of Illinois at Chicago (UIC), the Institute of Marine Biochemistry at the Vietnam Academy of Science and Technology (IMBC-VAST), and the National Institute of Hygiene and Epidemiology (NIHE) in Hanoi, Vietnam. We aim to enhance host country basic and translational research capacity that focuses on the discovery and development of antibiotic leads for TB. Since the 1990s, the Centers for Disease Control and Prevention have invested heavily in both clinical labs and HIV/AIDS/TB surveillance systems in Vietnam, though these and several other efforts have focused predominantly on building medical infrastructure. Our proposal will bridge this gap by enhancing basic and translational science research infrastructure and a researcher training program that focuses on utilizing host-country resources to discover antibiotic leads that will treat TB and probe its basic mechanisms of pathogenicity through coordinated antibiotic lead screening programs in Hanoi. The success of this program is driven by short- and long-term research training and education. UIC has a strong track record of collaboration with VAST. Through NIH and MacArthur Foundation funding in the past 20 years, the team has worked to build a plant-based drug-lead discovery and resource conservation program. However, with greater than 3,000 km of coastline, Vietnam harbors some of the richest marine biodiversity in the world, from which this proposal aims to mine. The aims of this program are 1) Establish three independent investigators at IMBC-VAST/NIHE via long-term postdoctoral training at UIC; 2) Provide short- and long-term antibiotic-specific training to nine IMBC/NIHE predoctoral students over the course of the program period; 3) Enhance biological assay research infrastructure through creation of an in vitro M. tuberculosis screening program at NIHE. In a five-year period, our program will generate twelve highly trained scientists who specialize in TB antibiotic discovery and development. Three of the twelve scientists – with considerable institutional support from the Director and President of their respective institutes – will establish independent research groups that complement a broader program that uses Vietnam's natural resources to discover TB antibiotics, and to use these leads to explore mechanisms of M. tuberculosis pathogenicity. Beyond the five-year project period, the significant enhancement in research capacity at IMBC and NIHE will establish northern Vietnam as a translational screening center for TB, and will facilitate collaboration with institutions across and outside Vietnam.