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

描述(由申请人提供)： 我们对这个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，并开始将自己确立为一名专注于与营养相关的疾病预防的全球卫生专业人员。我计划参加正式的课程作业，定期与我的导师互动，对进展进行正式评估，并每年参加全国会议。据预测，在1990至2020年间，结核病将成为最大的单一传染病死因。估计的结核病病例和死于结核病的95%以上发生在发展中国家。我们建议研究与蒙古结核病相关的营养学、免疫学和流行病学的相互关系。具体地说，我们建议进行一项初步研究，以测试每日补充维生素D对受试者控制结核病感染能力的影响。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，征得同意，向学校的孩子们分发维生素D补充剂，获得生物标本，并将这些标本完整地运回美国。B.检验每天补充维生素D将增加血浆25(OH)D水平的假设，并在体外测试的单核/巨噬细胞中恢复TLR诱导的抗菌活性。目的：探讨补充维生素D作为多种药物治疗的辅助手段在增强结核病抗微生物免疫应答中的作用。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。临床结果包括痰培养转换、复发或死亡。将测量细胞介导的免疫终点，包括CD4+、CD8+和CD3+细胞计数；体外淋巴细胞增殖；以及细胞因子的产生。相关性：结核病是全球卫生领域的优先事项之一。维生素D缺乏症几乎在任何地方都很普遍，无论是在发达国家还是发展中国家，维生素D的全部潜力尚不清楚，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，以控制世界上的一种主要杀手。

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.