Single versus Multiple Dose Ivermectin Regimen in Onchocerciasis-Infected Persons with Epilepsy Treated with Phenobarbital: A Randomized Clinical Trial in the Democratic Republic of Congo.

Michel Mandro,Steven Haesendonckx,Richard Lokonda,An Hotterbeekx,Deby Mukendi,Germain Abhafule,Robert Colebunders,Alfred Dusabimana,Francoise Nyisi,Joseph Nelson Siewe Fodjo,Swabra Nakato,D Wonya’Rossi,Steven Abrams

doi:10.3390/pathogens9030205

Abstract

Background: There is anecdotal evidence that ivermectin may decrease seizure frequency in Onchocerca volvulus-infected persons with epilepsy (PWE). Methods: In October 2017, a 12-month clinical trial was initiated in rural Democratic Republic of Congo. PWE with onchocerciasis-associated epilepsy experiencing ≥2 seizures/month were randomly allocated to receive, over a one-year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). All participants also received anti-epileptic drugs. Data was analyzed using multiple logistic regression. Results: We enrolled 197 participants. In an intent-to-treat analysis (data from group 1 and 2 combined), seizure freedom was more likely among OIPWE treated with ivermectin thrice (OR: 5.087, 95% CI: 1.378–19.749; p = 0.018) and twice (OR: 2.471, 95% CI: 0.944–6.769; p = 0.075) than in those treated once. Similarly, >50% seizure reduction was more likely among those treated with ivermectin twice (OR: 4.469, 95% CI: 1.250–16.620) and thrice (OR: 2.693, 95% CI: 1.077–6.998). Absence of microfilariae during the last 4 months increased the odds of seizure freedom (p = 0.027). Conclusions: Increasing the number of ivermectin treatments was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures.

Highlights

An association between onchocerciasis and epilepsy was reported as early as 1938 [1]
We present the seizure outcomes of a single versus multiple dose ivermectin regimen in persons with epilepsy (PWE) after 12 months of follow-up
One hundred ninety-seven PWE (50.9%) with evidence of O. volvulus infection were included in the trial

Summary

Introduction

An association between onchocerciasis (river blindness) and epilepsy was reported as early as 1938 [1]. To investigate the role of O. volvulus in triggering and aggravating seizures, we evaluated the effect of ivermectin on the frequency of seizures in onchocerciasis-infected persons with epilepsy (OIPWE). Demonstrating such an effect would provide additional support that infection with O. volvulus is able to cause epilepsy. We initially performed a four months proof-of-concept trial to investigate the effect of ivermectin on the frequency of seizures in OIPWE treated with phenobarbital. PWE with onchocerciasis-associated epilepsy experiencing ≥2 seizures/month were randomly allocated to receive, over a one-year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). In an intent-to-treat analysis (data from group 1 and 2 combined), seizure freedom was more likely among

Methods

Results

Conclusion