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 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.

Onchocerca volvulus and epilepsy: A comprehensive review using the Bradford Hill criteria for causation

“…Furthermore, a randomized trial in the DRC, comparing a single versus a multiple dose of ivermectin treatment regimen in O . volvulus -infected persons with epilepsy treated with phenobarbital showed that the multiple dose ivermectin regimen was associated with a reduced frequency of seizures [ 91 ]. The PWE included in this trial were all initially treated with phenobarbital despite having different seizure types, which may have affected the overall study outcomes.…”

Comparison of Diagnostic Tests for Onchocerca volvulus in the Democratic Republic of Congo

“…Samples were collected during a cross-sectional onchocerciasis assessment in persons with epilepsy (PWE), as part of a clinical trial conducted in onchocerciasis-endemic villages in the Logo health zone, Ituri province, DRC [ 14 , 15 ]. In these villages (Draju, Kanga, Wala, Tedheja, and Ulyeko), ivermectin mass drug administration was never implemented.…”

Ivermectin Treatment Response in Onchocerca Volvulus Infected Persons with Epilepsy: A Three-Country Short Cohort Study

“…The four study sites were the Aketi health zone, Bas Uélé province and the Logo health zone, Ituri province in the Democratic Republic of Congo (DRC), Mahenge, Ulanga district in Tanzania and Maridi in South Sudan. In Maridi, Aketi and Mahenge participants were enrolled only for a short follow up study, while in the Logo health zone, the 132 participants were enrolled in a randomized clinical trial to evaluate the potential added value of ivermectin in decreasing the frequency of seizures in PWE with O. volvulus infection treated with phenobarbital [ 15 ]. Right and left skin snips were obtained from each participant before ivermectin treatment intake.…”

“…In October 2017, a proof-of-concept randomized clinical trial investigating the effect of ivermectin on seizure frequency in O. volvulus infected PWE was initiated in the Logo health zone, an onchocerciasis-endemic area with a high epilepsy prevalence (4.6%) where ivermectin had never been distributed before [ 13 ]. In February 2018, PWE were asked to participate in a randomized clinical trial to evaluate the effect of ivermectin on the frequency of seizures in O. volvulus infected PWE [ 15 ]. In 392 PWE, skin snips were obtained and 143 (36.5%) of them had detectable mf [ 17 ].…”