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)，并通过以下方式制定赞比亚营养性神经病的未来干预措施： 1)对赞比亚玉米和木薯主食中DSP的人口估计和风险因素的评估 食品区；2)基于人口的估计和风险因素与以前基于诊所的数据的比较 相同的玉米主产区；3)评估在DSP病例中特定微量营养素缺乏症的几率 以及来自相同地区的年龄、性别和艾滋病毒匹配的对照组。为了实现这些目标，Kvalsund博士 将专注于在以下关键领域获得更多的专业知识和经验：1)高级 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；以及5)艾滋病毒和营养。所需技能将通过结构化的方式实现 指导，课程安排，以及务实的临床试验和卫生政策经验。研究-培训计划 将为Kvalsund博士提供进行未来干预研究所需的额外熟练程度 旨在减少赞比亚与营养相关的神经疾病发病率，并促进对 产生DSP的病理生理机制是一种常见的表型。中心假设是 以前在赞比亚临床人群中观察到的高DSP率在医疗保健以外也同样普遍 环境由于常见的地方性传染病及其神经毒性治疗、粮食不安全和低 饮食多样性、经常性的营养挑战、特定的微量营养素缺乏及其相互作用； 可能还有其他不明原因的潜在因素。我们假设叶酸缺乏与 赞比亚社区的数字信号处理器，正如在临床人群中记录的那样，可能需要有针对性的公众 考虑到其他神经系统疾病的可预防性质和范围，健康干预也与 叶酸缺乏。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；2) 将数字信号处理器的估计和风险因素与赞比亚临床环境中的数字信号处理器估计值和风险因素进行比较；3)考虑 城市化、农业生态/主食区和特定微量营养素缺乏症的相对贡献 4)评估潜在的环境或毒物-饮食因素对儿童DSP的影响 这种环境。本研究有望为今后的R-01干预和 观察性研究并提高对不同病因、多重暴露的科学理解 相互作用导致了一种常见的临床病理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.