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

Background: High epilepsy prevalence and incidence were observed in onchocerciasis-endemic villages in the Democratic Republic of Congo (DRC). We sought to investigate the clinical characteristics of onchocerciasis-associated epilepsy (OAE), and the relationship with 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. More skin snip-positive participants reported a family history of epilepsy (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=0.181; p=0.0003) and Aketi (Spearman-rho=0.228; p=0.046). In the multivariable analysis which adjusted for age, gender and previous anti-epileptic drug use, factors associated with high seizure frequency included: high microfilarial density (RR=1.004, 95% CI: 1.002-1.007; p<0.001), history of nodding seizures (RR=3.852, 95% CI: 2.926-5.082; p<0.001) and shorter duration of epilepsy (RR=0.948, 95% CI: 0.928-0.968; p<0.001). In Aketi, previous ivermectin use was associated with reduced seizures (RR=0.69, 95% CI: 0.58-0.83; p<0.001). Conclusion: In onchocerciasis-endemic regions in the DRC, a wide spectrum of seizures was observed. Nodding seizures, Nakalanga features, and a positive association between microfilarial density and seizures suggest a high OAE prevalence in the study villages, requiring a double management strategy: treatment with anti-epileptic drugs and stronger onchocerciasis elimination programs.