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.
In June 2020, a door-to-door household survey was conducted in Mvolo County, an onchocerciasis-endemic area in South Sudan. A total of 2357 households containing 15,699 individuals agreed to participate in the study. Of these, 5046 (32.1%, 95% CI: 31.4–32.9%) had skin itching and 445 (2.8%, 95% CI: 2.6–3.1%) were blind. An epilepsy screening questionnaire identified 813 (5.1%) persons suspected of having epilepsy. Of them, 804 (98.9%) were seen by a medical doctor, and in 798 (98.1%) the diagnosis of epilepsy was confirmed. The overall epilepsy prevalence was 50.8/1000 (95% CI: 47.6–54.4/1000), while the prevalence of nodding syndrome was 22.4/1000 (95% CI: 20.1–24.9/1000). Younger age, being male, skin itching, blindness, and living in a neighbourhood or village close to the Naam River were risk factors for epilepsy. The annual incidence of epilepsy was 82.8/100,000 (95% CI: 44.1–141.6/100,000). Among children 7–9 years old without epilepsy, 34% were Ov16 seropositive, suggesting high ongoing Onchocerca volvulus transmission, but only 41.9% of them took ivermectin during the last mass distribution. In conclusion, a high prevalence and incidence of epilepsy was observed in Mvolo, South Sudan. Strengthening of the onchocerciasis elimination programme is urgently needed in order to prevent epilepsy in this region.
Introduction Recent findings from onchocerciasis-endemic foci uphold that increasing ivermectin coverage reduces the epilepsy incidence, and anecdotal evidence suggests seizure frequency reduction in persons with onchocerciasis-associated epilepsy, when treated with ivermectin. We conducted a randomized clinical trial to assess whether ivermectin treatment decreases seizure frequency. Methods A proof-of-concept randomized clinical trial was conducted in the Logo health zone in the Ituri province, Democratic Republic of Congo, to compare seizure frequencies in onchocerciasisinfected persons with epilepsy (PWE) randomized to one of two treatment arms: the anti-epileptic drug phenobarbital supplemented with ivermectin, versus phenobarbital alone. The primary endpoint was defined as the probability of being seizure-free at month 4. A secondary endpoint was defined as >50% reduction in seizure frequency at month 4, compared to baseline. Both endpoints were analyzed using multiple logistic regression. In longitudinal analysis, the probability of seizure freedom during the follow-up period was assessed for both treatment arms by fitting a logistic regression model using generalized estimating equations (GEE). Results Ninety PWE enrolled between October and November 2017 were eligible for analysis. A multiple logistic regression analysis showed a borderline association between ivermectin
Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 antibodies by a cell-based assay (CBA) and Western blot (WB). These samples were also investigated for the presence of auto-antibodies cross-reacting with rat brain tissue by immunohistochemistry (IHC). Additionally, IHC was used to detect the leiomodin-1 protein in post-mortem brain samples of persons with OAE who died. Leiomodin-1 antibodies were detected by CBA in 6/52 (12%) and by WB in 23/54 (43%) persons with OAE compared to in 14/61 (23%) (p = 0.113) and 23/54 (43%) (p = 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between O. volvulus infection or epilepsy status and the presence of leiomodin-1. Leiomodin-1 antibodies were not detected in 12 CSF samples from persons with OAE or in 16 CSF samples from persons with acute-onset neurological conditions, as well as not being detected in serum from European controls. Moreover, the leiomodin-1 protein was only detected in capillary walls in post-mortem brain tissues and not in brain cells. IHC on rat brain slides with serum samples from persons with OAE or controls from persons with or without O. volvulus infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies.
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