Effect of Ivermectin Treatment on the Frequency of Seizures in Persons with Epilepsy Infected with Onchocerca volvulus.

Alfred Dusabimana,Solomon Tsebeni Wafula,Robert Colebunders,Floribert Tepage,Joseph Nelson Siewe Fodjo,An Hotterbeekx,Dan Bhwana,Stephen Jada Raimon,Gasim Abd-Elfarag,Steven Abrams

doi:10.3390/pathogens10010021

Abstract

A clinical trial performed in the Democratic Republic of Congo (DRC), among persons with epilepsy (PWE) infected with Onchocerca volvulus treated with anti-seizure medication suggested that ivermectin reduces the seizure frequency. We assessed the effect of ivermectin treatment on seizure frequency in PWE with and without anti-seizure medication in three onchocerciasis endemic areas (Maridi, South Sudan; Aketi, DRC; and Mahenge, Tanzania). Pre- and 3–5 months post-ivermectin microfilariae densities in skin snips and seizure frequency were assessed. After ivermectin, the median (IQR) percentage reduction in seizure frequency in the study sites ranged from 73.4% (26.0–90.0) to 100% (50.0–100.0). A negative binomial mixed model showed that ivermectin significantly reduced the seizure frequency, with a larger decrease in PWE with a high baseline seizure frequency. Mediation analysis showed that ivermectin reduced the seizure frequencies indirectly through reduction in microfilariae densities but also that ivermectin may have a direct anti-seizure effect. However, given the short half-life of ivermectin and the fact that ivermectin does not penetrate the healthy brain, such a direct anti-seizure effect is unlikely. A randomized controlled trial assessing the ivermectin effect in people infected with O. volvulus who are also PWE on a stable anti-seizure regimen may be needed to clarify the causal relationship between ivermectin and seizure frequency.

Highlights

The filarial nematode Onchocerca volvulus (O. volvulus) is known to cause skin disease, and ocular problems
We study the effect of ivermectin on the frequency of seizures in people infected with O. volvulus who are persons with epilepsy (PWE) whereby some individuals were on anti-epileptic treatment and others were not
This study assessed the effect of ivermectin on the frequency of seizures among PWE living in onchocerciasis-endemic areas

Summary

Introduction

The filarial nematode Onchocerca volvulus (O. volvulus) is known to cause skin disease, and ocular problems (river blindness). Ivermectin does not kill the adult filarial worm, it decreases its fertility, kills the microfilariae, and has an excellent safety profile with adverse events occurring only as a consequence of an immunological response against the killed microfilariae [3]. These effects termed as “Mazzotti reactions” are usually mild and disappear within days without further treatment [4,5]. If microfilarial density plays a role in causing OAE, it is expected that a reduction in microfilarial density following treatment with ivermectin may be able to decrease the frequency of seizures

Methods

Results

Conclusion