Clinical Phenotyping: Pediatric HIV and TB Cohort

临床表型：儿童艾滋病毒和结核病队列

• 批准号: 10247056
• 负责人: Mogomotsi Sandy Matshaba
• 金额: $ 19.56万
• 依托单位: BOTSWANA BAYLOR CHILD/CLINCAL CTR/EXCELL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247056
• 关键词: AIDS/HIV problem; Achievement; Acquired Immunodeficiency Syndrome; Address; Adolescent; Adult; Affect; Africa; Africa South of the Sahara; African; Aliquot; Archives; Automobile Driving; Award; Bacteria; Bioinformatics; Blood specimen; Botswana; Candidate Disease Gene; Caring; Case-Control Studies; Child; Childhood; Chronic Disease; Clinical; Clinical Data; Collection; Communities; Complex; Computerized Medical Record; Consent; Country; DNA; Data; Detection; Diagnosis; Diagnostic; Disease; Disease Progression; Doctor of Philosophy; Education; Educational Materials; Enrollment; Ethics; Exposure to; Family; Foundations; Future; Genes; Genetic; Genomics; Goals; Grant; HIV; HIV Infections; HIV Seropositivity; HIV/TB; Health; Home; Household; Human Genetics; Individual; Infection; Institution; Investments; Knowledge; Laboratories; Link; Morbidity - disease rate; Mycobacterium tuberculosis; Outcome; Participant; Patient Recruitments; Patients; Pediatric cohort; Peripheral Blood Mononuclear Cell; Phenotype; Play; Population; Process; Prophylactic treatment; RNA; Research; Research Personnel; Research Project Grants; Resources; Role; Sampling; Science; Secure; Ships; Site; South Africa; Students; Swaziland; System; Technology; Training; Tuberculosis; Uganda; Underrepresented Populations; United States; Visit; base; case control; clinical center; clinical phenotype; clinical research site; cohort; community engagement; comorbidity; doctoral student; ethical legal social implication; experience; genomic data; innovation; insight; meetings; mortality; next generation sequencing; novel; pediatric human immunodeficiency virus; recruit; sample collection

Project Summary HIV/AIDS remains a major cause of morbidity and mortality in sub-Saharan Africa and children are particularly vulnerable. The progression of HIV disease to AIDS is complex. Although studies in adult, mostly Western populations have clearly demonstrated a consistent role for host genetic factors in this progression, the host genetic factors influencing disease progression in sub-Saharan populations, and in particular, pediatric African populations, remains largely unknown. In the same way, tuberculosis (TB) remains a significant cause of morbidity and mortality in sub-Saharan Africa, particularly in those co-infected with HIV. Hence there is a pressing need to find new and effective strategies for managing and diagnosing TB infections. Exposure to M. tuberculosis – the causative agent of TB – typically results in either active TB disease (ATB), latent TB infection (LTBI), or no TB. The driving mechanisms behind these outcomes, however, are not well understood, making the diagnostics employed for their detection imprecise, particularly in children. Nonetheless, there is growing evidence that host genomic factors play a prominent role, and can be diagnostically exploited. The availability of advanced genomic technologies presents a valuable opportunity to investigate the host genetics of HIV and TB disease progression in sub-Saharan children, and this is at the scientific core of the Collaborative African Genomics Network (CAfGEN) – an H3Africa Collaborative Center spanning six institutions in Uganda, Botswana, Swaziland, and the United States. During the previous award period, despite unavoidable challenges, CAfGEN was able to use next-generation sequencing to identify candidate genes influencing pediatric HIV progression and TB disease progression; leverage scientific studies to establish and develop genomics capacity, technology, and expertise in Uganda and Botswana; and effectively engage local communities in addressing ethical, legal and social issues (ELSI) related to genomics research. In the next grant period CAfGEN will build on these achievements by a) expanding genomics studies of pediatric HIV and TB disease progression in children to include new populations and new science; b) providing additional genomics and bioinformatics training on the continent; c) assisting the six PhD students who received two-years of graduate training in human genetics to transition into independent investigators in their home countries; and d) continuing the use of innovative approaches to engage local communities in addressing ELSI related to genomics research in Africa. In so doing, CAfGEN will contribute novel and important mechanistic insights to pediatric HIV and HIV-TB disease progression, whilst creating a sustainable, synergistic, knowledgeable African genomic alliance capable of transforming the future of health on the African continent – the ultimate goal of the H3Africa Initiative.

项目概要 艾滋病毒/艾滋病仍然是撒哈拉以南非洲地区发病和死亡的一个主要原因，儿童尤其如此 虽然艾滋病毒疾病发展为艾滋病的过程很复杂，但研究对象大多是西方人。 人群已经清楚地证明了宿主遗传因素在这一进展中的一致作用，宿主 影响撒哈拉以南人口，特别是非洲儿童疾病进展的遗传因素 同样，结核病 (TB) 仍然是导致结核病的一个重要原因。 撒哈拉以南非洲地区的发病率和死亡率，特别是同时感染艾滋病毒的人。 迫切需要找到新的有效策略来管理和诊断结核分枝杆菌感染。 结核病——结核病的病原体——通常会导致活动性结核病（ATB）、潜伏性结核病 然而，这些结果背后的驱动机制尚不清楚。 然而，用于检测的诊断方法并不精确，尤其是在儿童中。 越来越多的证据表明宿主基因组因素发挥着重要作用，并且可以用于诊断。 先进基因组技术的出现为研究宿主提供了宝贵的机会 撒哈拉以南儿童艾滋病毒和结核病进展的遗传学，这是该研究的科学核心 非洲基因组学合作网络 (CAfGEN) – 一个跨越六个的 H3Africa 合作中心 尽管在上一个奖项期间乌干达、博茨瓦纳、斯威士兰和美国的机构。 面对不可避免的挑战，CAfGEN 能够利用新一代测序来识别候选基因 儿科艾滋病毒进展和结核病进展；利用科学研究来确定和 发展乌干达和博茨瓦纳的基因组学能力、技术和专业知识，并有效地吸引当地的参与； 与基因组学研究相关的道德解决、法律和社会问题 (ELSI) 社区。 在下一个资助期内，CAfGEN 将在这些成就的基础上，通过以下方式扩大基因组学研究： 儿童艾滋病毒和结核病的进展，包括新人群和新科学 b) 提供 c) 为非洲大陆的六名博士生提供额外的基因组学和生物信息学培训； 接受了两年的人类遗传学研究生培训，以转变为独立研究人员 母国；和 d) 继续使用创新方法让当地社区参与 CAfGEN 将致力于解决与非洲基因组学研究相关的 ELSI。 对儿科艾滋病毒和艾滋病毒结核病进展的重要机制见解，同时创造可持续的、 协同、知识渊博的非洲基因组联盟能够改变非洲健康的未来 非洲大陆——H3非洲倡议的最终目标。