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

Abstract

Background There is anecdotal evidence that ivermectin may decrease the frequency of seizures 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 with ≥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 (AED). Study outcomes included seizure freedom during the last four months (primary endpoint), decrease in microfilarial density, and occurrence of adverse events. A multiple logistic regression model was used to evaluate the primary outcome. Results Of the 197 OIPWE enrolled, 100 were randomized to receive ivermectin thrice, 52 twice, and 45 once. In an intent-to-treat combined analysis of data from group 1 and 2, the probability to become seizure-free for OIPWE treated with ivermectin twice per year was significantly higher than in those treated once (OR: 5.087, 95% CI: 1.378-19.749; p=0.018) and individuals who received ivermectin twice had a 4.471 (95% CI: 0.944-6.769, p=0.075) times higher odds of seizure freedom than those received ivermectin once per year. Absence of microfilariae during the last 4 months was associated with a higher probability of seizure freedom (p=0.027). Conclusions Increasing the number of ivermectin treatments per year was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures. Registration: www.clinicaltrials.gov; NCT03852303

Community perceptions and attitudes regarding epilepsy and disease cost after implementation of a community-based epilepsy treatment program in onchocerciasis-endemic communities in the Democratic Republic of Congo

“…The full impact of the CBETP cannot be evaluated using only a qualitative study. Moreover, the program included only the PWE and their families who participated in the trial to evaluate the effect of ivermectin on the frequency of seizures [8]. Persons not included in the trial who were followed up less strictly may have had different and less positive experiences.…”

“…Some PWE and their family members who participated in a clinical trial to evaluate the added value of ivermectin on the frequency of seizures in O. volvulus infected PWE [8,16] were asked to participate in a study to evaluate the epilepsy-related cost for the family. The direct and indirect costs due to epilepsy were assessed by interviewing PWE and their family using a questionnaire that was used prior to the implementation of the CBETP [6].…”

“…In October 2017, a clinical trial was initiated in the Logo health zone to investigate whether ivermectin is able to decrease the frequency of seizures [8]. During that project, we also aimed at establishing a community-based epilepsy treatment program (CBETP) to treat all PWE in the area [9].…”