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.

项目摘要 艾滋病毒/艾滋病仍然是撒哈拉以南非洲发病率和死亡率的主要原因，尤其是儿童 易受伤害的。艾滋病毒疾病向艾滋病的发展很复杂。虽然在成人中进行研究，但大多是西方 人群清楚地表明了宿主遗传因素在此进展中的作用一致，宿主 影响撒哈拉以下人群的疾病进展的遗传因素，尤其是小儿非洲 人口，在很大程度上仍然未知。以同样的方式，结核病（TB）仍然是 撒哈拉以南非洲的发病率和死亡率，特别是与艾滋病毒共同感染的人。因此有一个 迫切需要寻找用于管理和诊断性结核病感染的新有效策略。暴露于M 结核病 - 结核病的病因 - 通常会导致活性结核病（ATB），潜在结核病 感染（LTBI）或没有结核病。然而，这些结果背后的驾驶机制尚不清楚 使诊断对他们的检测进行了暗示，尤其是在儿童中。但是，有 越来越多的证据表明宿主基因组因素起着重要作用，可以诊断出来。 高级基因组技术的可用性为调查宿主提供了宝贵的机会 撒哈拉以下儿童的艾滋病毒和结核病遗传学进展，这是科学的核心 非洲协作基因组学网络（CAFGEN） - H3africa合作中心跨越了六个 乌干达，博茨瓦纳，斯威士兰和美国的机构。在上一个奖项期间，之前 不可避免的挑战，Cafgen能够使用下一代测序来识别候选基因 影响小儿艾滋病毒的进展和结核病疾病进展；利用科学研究来建立和 在乌干达和博茨瓦纳开发基因组能力，技术和专业知识；并有效地参与本地 解决与基因组学研究有关的道德，法律和社会问题（ELSI）的社区。 在下一个赠款期间，Cafgen将通过a）扩大基因组学研究来建立这些成就 儿童的小儿艾滋病毒和结核病疾病的进展包括新的人群和新科学； b）提供 继续进行的其他基因组学和生物信息学培训； c）协助六位博士学位的学生 接受了两年的人类遗传学研究生培训，以过渡到独立研究者。 本国； d）继续使用创新方法来吸引当地社区参与 解决与非洲基因组学研究有关的ELSI。这样，Cafgen将贡献小说，并且 小儿艾滋病毒和HIV-TB疾病进展的重要机理见解，同时创造了可持续的， 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 大陆 - H3africa倡议的最终目标。