Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns

Abstract

Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, β-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.

Emerging and Re-Emerging Parasitic Infections of the Central Nervous System (CNS) in Europe

“…Nodding syndrome, a severe neurological disorder affecting children, is also found in areas with onchocerciasis. The relationship between onchocerciasis and nodding syndrome is intricate, involving potential neuroinflammation and interactions between O. volvulus antigens and the immune system, which could be implicated in the syndrome's pathogenesis [124].…”

Active infection with Onchocerca volvulus and the linkage to epilepsy/nodding syndrome

“…In our study [ 2 ], we focused on the presence of an active Onchocerca volvulus (OV) infection, determined by polymerase chain reaction (PCR) from skin snips, in the context of epilepsy/nodding syndrome (NS) and not on the immune profiles of onchocerciasis-associated epilepsy (OAE) patients. Therefore, we did not present the OAE criteria.…”

Onchocerciasis-associated epilepsy and biomarkers

“…However, the pathogenesis of OAE remains to be elucidated [6].So far, little was known about the immunological processes associated with OAE. In a recent PNTD paper, Arndts et al [7] describe the immune profile (cytokine, chemokine, and immunoglobulin levels) of persons with epilepsy including NS that were examined at the Mahenge epilepsy clinic in Tanzania between November 2014 and April 2015. Profiles of persons with epilepsy were compared with profiles of individuals without neurological disorders residing in the same endemic area.…”