Onchocerciasis-associated Neurodevelopmental Deficits: The Hit Squad

描述(由申请人提供)：我们提出了一个美国/刚果民主共和国合作项目，以阐明患有丝虫病的受试者中癫痫和神经发育缺陷(ENDD)的风险因素。盘尾丝虫病是一种丝虫病(蠕虫)，居住在热带地区的数亿人中具有显著的残疾。我们将探索饮食氰化(神经毒性)和伊维菌素治疗的盘尾丝虫病之间可能的相互作用与END的关系。我们将在接受伊维菌素治疗的盘尾丝虫病患者中测试木薯氰化物生成是ENDD的风险因素的假设。来自盘尾丝虫病社区的儿童将接受以下方面的评估：(1)癫痫(和脑电异常)；(2)眼底镜检查确定的视神经病变、视野缺陷(倍频技术视野检查)和视网膜神经纤维层变薄(扫描激光偏振仪)；以及(3)认知障碍(KABC-II测试)。丝虫与沃尔巴克氏菌内共生菌的混合感染将被包括在我们的模型中，作为临床盘尾丝虫病的潜在效应修饰物(目标1)。这一目标与 能力建设的目标是继续培训一支由卫生部和大学系统的年轻刚果调查人员组成的多学科小组，内容涉及研究设计、神经眼科评估和分子生物学技术(目标2)。我们的发现将为刚果国家和全球防治盘尾丝虫病的卫生计划提供信息，以完善根除盘尾丝虫病的治疗方案。我们将为未来的研究建立一个基本的框架，以阐明复杂的相互作用在撒哈拉以南非洲的ENDD中的作用，例如营养、感染和化学(有毒或药物)暴露之间的作用。

DESCRIPTION (provided by applicant): We propose a USA/DRC collaborative project to elucidate risk factors for epilepsy and neurodevelopmental deficits (ENDD) among subjects affected by onchocerciasis, a filarial (worm) disease with significant disability among hundreds of millions of people dwelling under the tropics. We will explore the putative interaction between dietary cyanogenesis (neurotoxicity) and ivermectin-treated onchocerciasis in relation to ENDD. We will test the hypothesis that cassava cyanogenesis is a risk factor for ENDD in onchocerciasis-affected subjects treated with ivermectin. Children from an onchocerciasis-community that has benefited from mass treatment with ivermectin while reliant on cassava as staple food will be assessed for (1) epilepsy (and EEG abnormalities); (2) optic neuropathy determined by fundoscopy, visual field deficits (frequency doubling technology perimetry), and retinal nerve fiber layer thinning (scanning laser polarimetry); and (3) for cognition impairments (KABC-II testing). Filarial co-infection with wolbachia endosymbiotic bacteria will be included in our model as potential effect modifier of clinical onchocerciasis (Aim 1). This aim is tied up with a capacity- building aim to continue training a multidisciplinary team of young Congolese investigators from the Ministry of Health and the university system in study design, neuro-ophthalmologic assessment, and techniques of molecular biology (Aim 2). Our findings will be informative for the Congo national and global health programs against onchocerciasis to refine treatment protocols in place for the eradication of onchocerciasis. We will establish a foundational framework for future studies to elucidate the role of complex interactions such as those between nutrition, infection, and chemical (toxic or pharmaceutical) exposures in ENDD in sub-Saharan Africa.