Onchocerciasis-associated epilepsy in the Democratic Republic of Congo: Clinical description and relationship with microfilarial density

Abstract

Background High epilepsy prevalence and incidence were observed in onchocerciasis-endemic villages in the Democratic Republic of Congo (DRC). We investigated the clinical characteristics of onchocerciasis-associated epilepsy (OAE), and the relationship between seizure severity and microfilarial density. Methods In October 2017, ivermectin-naive persons with epilepsy (PWE) were recruited from onchocerciasis-endemic areas in the Logo health zone in the DRC. Additional PWE were enrolled in the Aketi health zone, where ivermectin had been distributed annually for 14 years. Past medical history, clinical characteristics and skin snips for Onchocerca volvulus detection were obtained from participants. Bivariate and multivariable analyses were used to investigate associations with microfilarial density. Results Of the 420 PWE in the Logo health zone, 392 were skin snipped (36.5% positive). Generalized motor seizures were most frequent (392 PWE, 93.3%), and nodding seizures were reported in 32 (7.6%) participants. Twelve PWE (3.1%) presented Nakalanga features. Sixty-three (44.1%) skin snip-positive PWE had a family history of epilepsy, compared to only 82 (32.9%) skin snip-negative PWE (p = 0.027). Eighty-one onchocerciasis-infected PWE were recruited in the Aketi health zone. Positive correlations between seizure frequency and microfilarial density were observed in Logo (Spearman-rho = 0.175; p<0.001) and Aketi (Spearman-rho = 0.249; p = 0.029). In the multivariable model adjusted for age, gender, and previous treatment, high seizure frequency was associated with increasing microfilarial density in Aketi (p = 0.025) but not in Logo (p = 0.148). Conclusion In onchocerciasis-endemic regions in the DRC, a wide spectrum of seizures was observed. The occurrence of Nodding seizures and Nakalanga features, as well as an association between seizure severity and O . volvulus microfilarial density suggest a high OAE prevalence in the study villages. Trial registration ClinicalTrials.gov NCT03052998 .

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

“…Most likely the advantage of the multiple dose ivermectin is explained by the lower mf density by the end of the study period in participants on a multiple dose ivermectin regimen, confirming the previously documented positive association between seizure frequency and mf density [14]. Our findings strongly suggest that O. volvulus mf may induce seizures and that the beneficial effect of ivermectin was not caused by a direct anti-seizure mechanism.…”

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

“…However, the penetration of ivermectin into murine CNS must be interpreted in the light of evidence demonstrating an increased permeability of their blood-brain barrier (BBB) during the neonatal period [20]. Ivermectin given at therapeutic doses is unlikely to cross the human BBB [21] and therefore cannot elicit a direct anti-epileptic effect in the CNS The relative superiority of the multiple dose ivermectin in reducing seizures during our study is probably explained by the lower mf density at the end of the study period in participants on this regimen, thus confirming the previously documented positive association between seizure frequency and mf density [22]. A small study conducted in a non-onchocerciasis-endemic area reported that treatment with ivermectin decreased the frequency of seizures in persons with refractory epilepsy [23].…”

Prevalence and incidence of nodding syndrome and other forms of epilepsy in onchocerciasis-endemic areas in northern Uganda after the implementation of onchocerciasis control measures

“…Most cases of NS have been described in the onchocerciasis-endemic regions in northern Uganda [3,6], western Uganda [7], South Sudan [8], and the Mahenge area in Tanzania [9]. More recent studies have reported nodding seizures among persons with epilepsy (PWE) in the onchocerciasis-endemic regions in Cameroon [10] and the Democratic Republic of Congo [11]. A high prevalence of epilepsy has also been reported in many onchocerciasis meso-and hyper-endemic regions [12][13][14][15] particularly where transmission is poorly controlled [16][17][18][19].…”