Community Health and Neuropathy: Nutritional and Environmental Links in Zambia (CHANNELZ)

项目摘要/摘要 这个项目的主要目标是促进对远端关节的复杂病理生理学的了解。 对称性多发性神经病(DSP)与赞比亚营养性神经病的未来干预 通过：1)对赞比亚玉米和大豆的基于人口的估计和风险因素进行评估 木薯主食区域；2)基于人口的估计和风险因素与以前诊所的比较- 基于相同玉米主产区的数据；3)评估特定微量营养素的几率 在DSP病例和来自相同地区的年龄、性别和艾滋病毒匹配的对照中存在缺陷。至 为了实现这些目标，Kvalsund博士将专注于获得更多的专业知识和经验 以下关键领域：1)先进的流行病学方法和分析；2)临床试验方法；3) 全球卫生政策；4)神经病变结果评估；5)艾滋病毒和营养。所需技能将是 通过有组织的指导、课程安排以及务实的临床试验和健康政策来实现 经历。研究-培训计划将为Kvalsund博士提供必要的额外熟练程度 开展旨在减少赞比亚营养相关神经发病率的未来干预研究 以及对产生DSP的病理生理机制的科学知识的提高 表型。中心假设是以前在临床人群中观察到的DSP的高比率 由于常见的地方性传染病，赞比亚在医疗保健环境之外同样普遍存在 他们的神经毒性治疗、食物不安全和饮食多样性低、反复出现的营养挑战、特定的 微量营养素缺乏及其相互作用，以及可能存在的其他不明潜伏因素。我们假设 这种叶酸缺乏将与赞比亚社区的数字信号处理器高度相关，这已在 临床人群，并可能需要有针对性的公共卫生干预，鉴于可预防的性质和 一系列其他神经系统疾病也与叶酸缺乏有关。具体目标是：1) 确定赞比亚基于总体的数字信号处理器估计数；2)比较和对比数字信号处理器估计数和风险 与赞比亚临床环境中的因素相一致；3)考虑城市化的相对贡献， 农业生态/主食区域和特定微量营养素缺乏对DSP流行率的影响；以及4)评估 在这种环境中，潜在的环境或有毒饮食因素是导致DSP的因素。这项研究是 期望为未来的R-01干预和观测研究提供基础，并改进 科学地理解不同的病因、多重接触和相互作用如何导致共同的 临床病理的DSP表型，至今仍知之甚少。

Project Summary/Abstract The overarching goals of this project are to advance knowledge of the complex pathophysiology of distal symmetric polyneuropathies (DSP) and frame future interventions for nutritional neuropathies in Zambia through: 1) assessment of population-based estimates and risk factors for DSP in Zambia’s maize and cassava staple food zones; 2) comparison of population-based estimates and risk factors to previous clinic- based data from the same maize-staple districts; 3) and assessing the odds of specific micronutrient deficiencies among DSP cases and age, gender, and HIV-matched controls from the same districts. To accomplish these goals, Dr. Kvalsund will focus on acquisition of additional expertise and experience in the following key areas: 1) advanced epidemiological methods and analysis; 2) clinical trials methodologies, 3) global health policy; 4) neuropathy outcome assessments; and 5) HIV and nutrition. The needed skills will be achieved through structured mentorship, coursework, and pragmatic clinical trials and health policy experiences. The research-training plan will provide Dr. Kvalsund with the additional proficiency necessary to undertake future intervention research aimed at reducing nutrition-associated neurologic morbidity in Zambia and advancing scientific knowledge of the pathophysiologic mechanisms that generate DSP as a common phenotype. The central hypothesis is that the high rate of DSP previously observed in clinic populations in Zambia is equally prevalent outside healthcare settings owing to common endemic infectious diseases and their neurotoxic treatments, food insecurity and low dietary diversity, recurrent nutritional challenges, specific micronutrient deficiencies and their interactions, and possibly other unidentified latent factors. We hypothesize that folate-deficiency will be highly associated with DSP in Zambian communities, as has been documented in clinic populations, and may warrant a targeted public health intervention given the preventable nature and range of other neurologic morbidities also associated with folate deficiencies. The specific aims are to: 1) Determine population-based DSP estimates in Zambia; 2) Compare and contrast DSP estimates and risk factors with those from clinical settings in Zambia; 3) to consider the relative contributions of urbanicity, agroecological/staple food zone, and specific micronutrient deficiencies on DSP prevalence; and 4) Evaluate for latent environmental or toxico-dietary factors as contributors to DSP in this environment. The research is expected to provide the foundation for future R-01 intervention and observational research and to improve scientific understanding of how diverse etiologies, multiple exposures and interactions lead to a common clinicopathologic DSP phenotype, which remains poorly understood to date.