Single versus multiple dose ivermectin regimen in onchocerciasis-infected persons with epilepsy: A randomized clinical trial

Abstract

Background: Recent epidemiological studies have shown that onchocerciasis (river blindness) is an important cause of epilepsy in certain onchocerciasis-endemic regions in sub Saharan Africa with ongoing Onchocerca volvulus transmision. Moreover, there is anecdotal evidence that ivermectin (the treatment of onchocerciasis) may decrease the frequency of seizures in O. volvulus-infected persons with epilepsy (PWE). 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). Methods & Materials: In October 2017, a 12 months randomised clinical trial was initiated in rural Democratic Republic of Congo. PWE meeting the criteria for onchocerciasis-associated epilepsy with ≥2 seizures/month were randomly allocated to receive over a one year period, ivermectin once or thrice, while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice. 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 PWE enrolled, 100 received ivermectin thrice, 52 twice, and 45 once. The probability to become seizure-free for OIPWE treated with ivermectin twice and thrice was significantly higher than those treated once in an intent-to-treat analysis (OR: 5.087, 95% CI: 1.378–19.749; p = 0.018) and (OR: 2.471, 95% CI: 0.944–6.769; p = 0.075). Similar results were obtained in as-treated analysis, with higher odds of seizure freedom in those who received ivermectin twice and thrice vs once (OR: 10.033, 95% CI: 2.670–42.496, p = 0.001) and (OR: 4.795, 95% CI: 1.790–14.089; p = 0.003). Absence of microfilariae during the last 4 months was associated with a higher probability of seizure freedom (p < 0.027). One participant developed a phenobarbital-induced toxic epidermal necrolysis but survived, and one woman delivered a child with a cleft lip. Conclusion: 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.