Vitamin D supplementations as adjunct to anti-tuberculosis drugs in Mongolia

蒙古将维生素 D 补充剂作为抗结核药物的辅助药物

• 批准号: 8534237
• 负责人: Ganmaa Davaasambuu
• 金额: $ 19.27万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8534237
• 关键词: Antitubercular Agents; Award; Back; Body Weight Changes; CD3 Antigens; CD8B1 gene; Cause of Death; Cell Count; Cells; Cessation of life; Child; Clinical; Consent; Developed Countries; Developing Countries; Development; Epidemiology; Evaluation; Goals; Health Benefit; Health Professional; Immune; Immune response; Immunology; Infection; Interleukin-12; Interleukin-17; Interleukin-2; Interleukin-4; Lead; Measures; Mediating; Mentors; Mongolia; Outcome; Patients; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Plasma; Prevention; Production; Public Health; Recruitment Activity; Regimen; Relapse; Schools; Specimen; Sputum; Supplementation; TNF gene; Testing; Tuberculosis; United States; Vitamin D; Vitamin D Deficiency; Work; antimicrobial; cytokine; disorder prevention; follow-up; global health; immune function; improved; in vitro testing; lymphocyte proliferation; macrophage; meetings; monocyte; nutrition; nutritional epidemiology; protective effect; randomized trial; tuberculosis drugs

DESCRIPTION (provided by applicant): Our enthusiasm for this project reflects our commitment to Mongolian public health sector development as well as our sense of urgency to resolve the vitamin D crisis and tuberculosis in Mongolia. My immediate and long term goals are to broaden my expertise in global health and nutritional epidemiology. With this award I intend to successfully complete the proposed aims and begin to establish myself as a global health professional with a focus in nutrition-related disease prevention. I plan to take formal course works, interact regularly with my mentors with formal evaluations of the progress and attend national meetings annually. Tuberculosis is predicted to be the largest single infectious cause of death between 1990 and 2020. More than 95% of the estimated TB cases and deaths due to TB occur in developing countries. We propose to examine the inter-relationships of nutrition, immunology, and epidemiology with respect to TB in Mongolia. Specifically, we propose a pilot study to test the effect of a daily vitamin D supplementation on the ability of subjects to control TB infection. We will also perform corollary studies on the effect of vitamin D supplementation on immune parameters. Aim 1: A. To recruit subjects, obtain consent, distribute vitamin D supplements to the children in the schools, obtain biologic specimens and to transport those specimens intact back to the United States. B. To test the hypothesis that daily vitamin D supplementation will increase plasma levels of 25(OH) D, and restore TLR-induced antimicrobial activity in monocytes/macrophages tested in vitro. Aim 2: To determine the efficacy of vitamin D supplement as an adjunct to multi drug therapy in enhancing the anti-microbial immune response to TB. Bacteriologic cure after the start of vitamin D therapy will be determined by ascertaining conversion of sputum culture to negative. The clinical outcomes include sputum culture conversion, relapse, or death. Cell-mediated immune endpoints will be measured including CD4+, CD8+, and CD3+ cell counts; ex vivo lymphocyte proliferation; and cytokine production. Relevance: Tuberculosis is one of the priorities in global health. Vitamin D deficiency is prevalent almost everywhere, both in developed and developing countries, the full potential of vitamin D is unknown but positive results would mean an inexpensive, non-toxic means, with possible other health benefits, to control a major killer in the world.

描述（由申请人提供）： 我们对该项目的热情反映了我们对蒙古公共卫生部门发展的承诺以及我们对解决蒙古维生素D危机和结核病的紧迫感。我的近期和长期目标是扩大我在全球健康和营养流行病学方面的专业知识。有了这个奖项，我打算成功地完成拟议的目标，并开始建立自己作为一个全球卫生专业人士，重点是营养相关的疾病预防。我计划参加正式的课程工作，定期与我的导师互动，对进展情况进行正式评估，并每年参加国家会议。结核病预计将是1990年至2020年期间最大的单一传染性死亡原因。据估计，95%以上的结核病病例和结核病死亡发生在发展中国家。我们建议研究蒙古结核病的营养、免疫学和流行病学之间的相互关系。具体来说，我们提出了一项试点研究，以测试每日补充维生素D对受试者控制结核感染能力的影响。我们还将对补充维生素D对免疫参数的影响进行推论研究。目标1：A.招募受试者，获得同意，向学校的儿童分发维生素D补充剂，获取生物标本并将这些标本完好无损地运回美国。B。检验每日补充维生素D会增加血浆25（OH）D水平，并恢复体外检测的单核细胞/巨噬细胞中TLR诱导的抗菌活性的假设。目的2：确定维生素D补充剂作为多药治疗的辅助治疗在增强结核病抗微生物免疫反应方面的功效。开始维生素D治疗后的细菌学治愈将通过确定痰培养转为阴性来确定。临床结局包括痰培养转化、复发或死亡。将测量细胞介导的免疫终点，包括CD 4+、CD 8+和CD 3+细胞计数;离体淋巴细胞增殖;和细胞因子产生。相关性：结核病是全球卫生的优先事项之一。维生素D缺乏症几乎在世界各地都很普遍，无论是在发达国家还是在发展中国家，维生素D的全部潜力都是未知的，但积极的结果将意味着一种廉价，无毒的手段，以及可能的其他健康益处，以控制世界上的主要杀手。