# Onchocerciasis-associated epilepsy: an explorative case-control study with viral metagenomic analyses on   Onchocerca volvulus

## TL;DR

This study explores the link between a parasitic infection and epilepsy by analyzing the virus content of the parasite in an area of South Sudan.

## Contribution

The study introduces a novel approach to understanding onchocerciasis-associated epilepsy by examining the virome of Onchocerca volvulus.

## Key findings

- The study will compare the virome of O. volvulus in individuals with and without epilepsy.
- It will describe the number, size, and location of onchocerciasis nodules in relation to epilepsy.
- The effect of nodulectomy on seizure frequency will be assessed.

## Abstract

Background: A high prevalence of onchocerciasis-associated epilepsy (OAE) has been observed in onchocerciasis-endemic areas with high ongoing
Onchocerca volvulus transmission. However, the pathogenesis of OAE remains to be elucidated. We hypothesise that the
O. volvulus virome could be involved in inducing epilepsy. With this study, we aim to describe the
O. volvulus virome and identify potential neurotropic viruses linked to OAE.

Methods: In Maridi County, an onchocerciasis endemic area in South Sudan with a high prevalence of OAE, we will conduct an exploratory case-control study enrolling 40 persons aged 12 years and above with palpable onchocerciasis nodules. Cases will be participants with OAE (n=20), who will be age- and village-matched with controls without epilepsy (n=20). For each study participant, two skin snips at the iliac crest will be obtained to collect
O. volvulus microfilariae, and one nodulectomy will be performed to obtain adult worms. A viral metagenomic study will be conducted on microfilariae and adult worms, and the
O. volvulus virome of persons with and without OAE will be compared. The number, size, and localisation of onchocerciasis nodules in persons with and without OAE will be described. Moreover, the pre- and post-nodulectomy frequency of seizures in persons with OAE will be compared.

Ethics and dissemination: The protocol has been approved by the Ethics Committee of the University of Antwerp and the Ministry of Health of South Sudan. Findings will be disseminated nationally and internationally via meetings and peer-reviewed publications.

Registration:
https://clinicaltrials.gov/ registration NCT05868551 (
https://clinicaltrials.gov/study/NCT05868551)

Protocol version: 1.1, dated 09/05/2023