Analysis of XDR-TB and MDR-TB strains: safety, diagnosis and pathogenesis

描述（由申请人提供）：结核病控制日益受到全球耐多药/广泛耐药结核病上升的影响。有效的耐多药/广泛耐药结核病流行病学调查和病例管理，以及开发新的诊断方法和抗结核药物，需要强大的实验室能力，例如，确定正在接受结核病治疗的患者的耐药性概况。这种广泛的实验室支持并不是结核病控制规划的常规组成部分，而是研究实验室的领域。虽然南非的一些研究实验室在技术能力和科学专门知识方面具有高度的复杂性，但受过训练的人员数量有限，因此难以显著扩大诊断和研究能力。此外，只有少数研究地点拥有最先进的BSL3设施，而且需要发展耐多药/广泛耐药结核病感染控制知识。因此，目前在培训和扩大应对南非不断扩大的耐多药/广泛耐药结核病流行所需的熟练实验室和研究活动方面的需求尚未得到满足。我们申请全球传染病培训计划就是为了满足这一需求。提供的培训将在多个层面进行：(1)建立和管理功能性生物安全-3设施的培训，以安全地开展耐多药/广泛耐药结核病研究的支持微生物学；(2)特定分子技术的培训，如分子流行病学和新诊断方法；(3)先进研究方法的培训，以支持耐多药/广泛耐药结核病的特定项目，包括免疫学和发病机理。培训将主要包括短期课程，而不是学位课程或完整的博士后奖学金。该方案将在新泽西州纽瓦克UMDNJ公共卫生研究所的设施中进行。为了实现我们的目标，我们将招募不同专业水平的人员，包括参与南非结核病研究项目的博士生和博士后候选人。培训模块旨在加强现有和正在扩大或启动耐多药/广泛耐药结核病新项目的新研究小组的研究能力。必要时，受训者将多次访问美国接受额外的培训，以支持他们正在进行的研究项目。我们预计，其中一些培训将成为正在进行的合作的一部分，其他培训将演变为南非研究人员与美国研究人员之间的新合作，以应对新出现的耐多药/广泛耐药结核病流行。这一GID培训计划将通过加强调查人员和卫生专业人员的科学专业知识和促进合作联系，帮助在南非建立可持续的耐多药/广泛耐药结核病研究能力。由于MTB等病原体很容易通过现代运输方式在国际上传播，因此该项目也与美国及其公民的公共卫生高度相关。

DESCRIPTION (provided by applicant): TB control is increasingly compromised by the global rise in M/XDR-TB. Effective M/XDR-TB epidemiologic surveys and case management, as well as the development of new diagnostics and anti-TB drugs, require strong laboratory capabilities, for example, to define drug resistance profiles in patients undergoing TB therapy. Such extensive laboratory support has not been a routine component of TB control programs but, rather, the domain of research labs. While some research labs in South Africa have high levels of sophistication in their technical capabilities and scientific expertise, the numbers of trained personnel are limited, making significant expansion of diagnostic and research capacities difficult. In addition, state-of-the-art BSL3 facilities are available at only a few research sites, and knowledge of infection control for M/XDR-TB is in need of development. Thus, there is currently an unmet need for training and scale-up of the skilled laboratory and research activities required to address the expanding M/XDR-TB epidemic in South Africa. Our application for the Global Infectious Disease Training Program is designed to address this need. The training offered will be at multiple levels: (1) training in establishment and management of functional BSL-3 facilities to safely carry out the supporting microbiology for M/XDR-TB research, (2) training in specific molecular techniques, such as molecular epidemiology and new diagnostic methods, and (3) training in advanced research approaches to support specific projects on M/XDR-TB, including immunology and pathogenesis. Training will predominantly comprise short term periods, rather than degree programs or full post-doctoral fellowships. The program will be carried out in the facilities of the Public Health Research Institute at UMDNJ in Newark, NJ. To achieve our goals, we will recruit individuals at different levels of expertise, including pre- and post-doctoral candidates that are involved in TB research programs in South Africa. The training modules are intended to strengthen the research capacity of pre-existing and new research groups that are either expanding or initiating new projects on M/XDR-TB. When necessary, trainees will make repeat visits to the US for additional training to support their ongoing research projects. We anticipate that some of these traineeships will be part of ongoing collaborations and others will evolve into new collaborations between South African investigators and US investigators addressing the emerging M/XDR-TB epidemic. PUBLICE HEATLH RELEVANCE This GID Training Program will help to build sustainable M/XDR-TB research capacity in South Africa by enhancing the scientific expertise of investigators and health professionals and fostering collaborative links. Since pathogens such as MTB can be easily transmitted internationally via modern transportation modes, the project is also highly relevant to the public health of the United States and its citizens.