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，以阐明受盘尾丝虫病影响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，在热带地区居住的数亿人中具有重大残疾。我们将探讨膳食生氰（神经毒性）和伊维菌素治疗的盘尾丝虫病与ENDD之间的假定相互作用。我们将检验这一假设，即木薯生氰是伊维菌素治疗的盘尾丝虫病受试者ENDD的一个危险因素。将对来自依赖木薯作为主食并受益于伊维菌素大规模治疗的盘尾丝虫病社区的儿童进行以下评估：（1）癫痫（和EEG异常）;（2）通过眼底镜检查确定的视神经病变、视野缺损（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感染将作为临床盘尾丝虫病的潜在效应调节剂纳入我们的模型（目的1）。这一目标与 能力建设的目标是继续培训一个由刚果卫生部和大学系统的年轻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）。我们的研究结果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础框架，以阐明撒哈拉以南非洲ENDD中营养，感染和化学品（有毒或药物）暴露之间的复杂相互作用的作用。

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.