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，以阐明盘尾丝虫病（一种丝虫病）影响的受试者癫痫和神经发育缺陷（ENDD）的危险因素，盘尾丝虫病是生活在热带地区的数亿人的一种严重残疾的丝虫病。我们将探讨饮食中的氰化（神经毒性）和伊维菌素治疗的盘尾丝虫病与end之间可能的相互作用。我们将检验木薯发紫是接受伊维菌素治疗的盘尾丝虫病患者终末死亡的危险因素这一假设。来自盘尾丝虫病社区的儿童受益于伊维菌素的大规模治疗，同时依赖木薯作为主食，将被评估：(1)癫痫（和脑电图异常）；(2)眼底镜检查确定视神经病变，视野缺损（倍频技术验光），视网膜神经纤维层变薄（扫描激光偏振法）；(3)认知障碍（KABC-II测试）。丝虫与沃尔巴克氏体内共生细菌的共同感染将被纳入我们的模型，作为临床盘尾丝虫病的潜在效应修饰因子（目的1）。这个目标与

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.