Onchocerciasis-associated Neurodevelopmental Deficits: The Hit Squad

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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.