Joseph Nelson Siewe Fodjo

Filarial parasites cause over 200 million infections globally. Filarial morbidity was presumably limited to the skin, eyes, and lymphatic vessels. However, my research generated evidence that Onchocerca volvulus infection also induces neurological disease including Onchocerciasis-Associated Epilepsy (OAE). However, the causal mechanisms for neurological symptoms linked to O. volvulus infection are still unknown. Recently my research group co-discovered a virus (OVRV1) within O. volvulus. Being related to the rabies virus family, OVRV1 could potentially cause OAE. I will investigate the clinical implications of this virus in >1600 persons from 3 affected countries. Case-control studies will verify whether OVRV1 is a risk factor for OAE. In a cohort study of onchocerciasis-exposed children with neurological symptoms, I will investigate the presence of OVRV1 in cerebrospinal fluid and assess its neurotoxicity by seeding OVRV1-positive samples on neural organoids. Viral metagenomics on Mansonella perstans (most common filarial disease, >110 million infections) will determine if it also harbours OVRV1 or other viruses. Finally, I will establish a prospective pregnancy cohort (n=900) and follow-up their children to investigate the materno-foetal consequences of in utero exposure to filarial parasites and/or viruses.

This project is expected to unveil new disease mechanisms and may lead to new diagnostic/treatment options. If OVRV1 is shown to be associated with OAE, it could serve as a biomarker to diagnose this condition. However if OVRV1 is found to be an O. volvulus-specific endosymbiont, it could be used to improve the performance of the current onchocerciasis diagnostic tests. It could even become a target for the development of new (macro)filaricidal drugs. Demonstrating that filarial infections can adversely impact pregnancy/child health will justify research on safe approaches to treat pregnant women and under-fives with ivermectin during mass drug administration.