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

项目概要/摘要 该项目的总体目标是促进对远端神经系统疾病复杂病理生理学的了解。 赞比亚对称性多发性神经病（DSP）和营养性神经病未来干预框架 通过：1）评估赞比亚玉米中DSP的基于人口的估计和风险因素， 木薯主食区; 2）基于人口的估计数和风险因素与以前诊所的比较- 基于来自同一玉米主食区的数据; 3）并评估特定微量营养素的可能性 DSP病例与来自同一地区的年龄、性别和HIV匹配对照之间的缺陷。到 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）神经病结果评估; 5）艾滋病毒和营养。所需的技能将是 通过结构化的指导，课程和务实的临床试验和卫生政策实现 经验研究培训计划将为Kvalsund博士提供必要的额外能力， 开展未来干预研究，旨在降低赞比亚与营养相关的神经系统发病率 和推进的病理生理机制，产生DSP作为一个共同的科学知识， 表型中心假设是先前在临床人群中观察到的高DSP率， 由于常见的地方性传染病，赞比亚在医疗保健机构之外也同样普遍， 他们的神经毒性治疗，粮食不安全和饮食多样性低，经常性的营养挑战，具体 微量营养素缺乏及其相互作用，以及可能的其他未确定的潜在因素。我们假设 叶酸缺乏症将与赞比亚社区的DSP高度相关，如文献所述， 诊所人群，并可能需要有针对性的公共卫生干预，因为可预防的性质， 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） 确定赞比亚基于人口的DSP估计值; 2）比较和对比DSP估计值和风险 因素与赞比亚临床环境中的因素; 3）考虑城市化的相对贡献， 农业生态/主食区和特定微量营养素缺乏症对DSP患病率的影响;以及4）评估 潜在的环境或有毒饮食因素在这种环境中作为DSP的贡献者。这项研究是 预计将为未来的R-01干预和观察研究提供基础， 科学地了解不同的病因、多重暴露和相互作用如何导致共同的 临床病理学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.