Abstract
INTRODUCTION: Onchocerciasis, commonly known as river blindness, is a parasitic disease caused by Onchocerca volvulus affecting millions predominantly in sub-Saharan Africa. Robust epidemiological evidence points to a clinical relationship between onchocerciasis and epilepsy, a condition termed onchocerciasis-associated epilepsy (OAE). Despite extensive research and various successful elimination programmes over the past decades, the pathogenesis of OAE is still unknown. Current hypotheses propose that O. volvulus microfilaria, their excretory-secretory products or the newly discovered filarial O. volvulus RNA virus 1 (OVRV1) virus may traverse the blood-brain barrier, triggering seizures or immune responses that result in neurological damage. However, direct evidence of microfilaria or their DNA in cerebrospinal fluid (CSF) or brain tissue remains elusive, likely due to immune-mediated parasite clearance. Additionally, investigations into the potential neurotoxicity of these novel filarial viruses have yet to be pioneered. METHODS AND ANALYSIS: This prospective cohort study will involve 100 ivermectin-naïve children aged 2-5 years, recruited from rural communities in the Aketi health zone, located in the Democratic Republic of Congo. This region is known to be an onchocerciasis-endemic area with a high prevalence and transmission of OAE, despite years of community-directed treatment with ivermectin. Lumbar punctures (LP) will be performed in children presenting with complex febrile seizures according to WHO's paediatric guidelines. CSF samples will be examined for white blood cells, protein levels, glycorrhachia, microfilaria, OVRV1 and O. volvulus biomarkers. Children will be followed annually, monitoring the development of epilepsy and O. volvulus infection. This approach aims to elucidate the presence of O. volvulus and OVRV1 in the brain and their role in the pathogenesis of epileptic seizures and the myriad of clinical symptoms observed in OAE. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the University of Kisangani (UNIKIS/CE/KGB/001/2025) and the University of Antwerp (project ID 7323-Edge n/a-BUN B3002025000078). Written informed consent will be obtained from all parents and/or legal guardians of children for whom an LP is considered. Findings will be disseminated at national and international levels via meetings and peer-reviewed open-source publications. Study data will be stored in an open repository. TRIAL REGISTRATION NUMBER: Pan African Clinical Trials Registry (PACTR202507670131109).