BackgroundNodding syndrome (NS) is a disabling childhood-onset epilepsy occurring in onchocerciasis-endemic regions. High Onchocerca volvulus microfilarial loads in childhood are a key risk factor, but not all heavily infected individuals develop NS, suggesting a possible role for host genetic susceptibility. Human leukocyte antigen (HLA) haplotypes have been implicated in susceptibility to various infectious and autoimmune diseases, including onchocerciasis. We investigated potential associations between HLA haplotypes and onchocerciasis-associated epilepsy (OAE), including NS, in Tanzania.MethodsA case-control study was conducted in an onchocerciasis-endemic area in the Mahenge area, Tanzania, including 98 persons with epilepsy and 112 controls. DNA was extracted from dry blood spots and HLA sequence-based typing was performed by Histogenetics (Ossining, USA). A total of 11 HLA loci (HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1) were exon sequenced. The HLA-typed dataset was analysed using pyHLA, including Bonferroni as multi-test adjustment, to test for associations with O. volvulus anti-Ov16 seropositivity, epilepsy, OAE and NS.ResultsAnti-Ov16 seropositivity was significantly higher in cases than controls (76.5% vs 58.9%; p = 0.01). No HLA alleles were significantly associated with epilepsy, OAE, NS, or anti-Ov16 seropositivity after correction. Before adjustment, HLA-C07:01 appeared to be a risk factor for epilepsy, HLA-DQB106:02 was associated with OAE, HLA-B35:01 with NS, and HLA-C08:02 and DRB1*03:01 with anti-Ov16 seropositivity. Post-hoc power analysis indicated that substantially larger sample sizes would be required to confirm these associations.ConclusionsThis study did not identify statistically significant HLA associations with epilepsy, OAE, NS, or O. volvulus exposure. However, several alleles-particularly HLA-B*35:01, also reported in a previous South Sudanese study-emerged as potential candidates for further investigation. Larger, multi-country studies with sufficient power are needed to clarify whether host genetic factors contribute to susceptibility to OAE and NS. Strengthening onchocerciasis elimination programmes remains essential, as NS is a preventable disease.

Epilepsy remains a significant public health concern in Tanzania, with affected individuals enduring stigma, whether through actions or perceptions. Myths, misunderstandings, and misconceptions about epilepsy have persisted due to a multitude of factors. Here, we assessed attitudes and perceptions toward epilepsy in Mahenge. A cross-sectional study utilising a mixed-methods approach was undertaken in eight villages in the Ulanga district of Mahenge, integrating a semi-structured questionnaire and focus group discussions (FGDs). The questionnaire involved 778 community members, and 15 FGDs were conducted (seven groups with people with epilepsy and eight without). Descriptive statistics, chi-square, and logistic regression were used for quantitative analysis, while we used NVivo version 14 for thematic analysis of qualitative data. Of 778 participants, over half were women (425, 54.6

OBJECTIVE:In onchocerciasis-endemic areas, limited access to antiseizure medications (ASMs) contributes to a high epilepsy burden. This study evaluated the impact of a community-based epilepsy care program in Mahenge, Tanzania, an onchocerciasis-endemic area with high epilepsy prevalence. METHODS:A baseline survey (2017-2018) identified persons with epilepsy (PWE) in four rural villages. Subsequently, PWE were invited to enroll in the epilepsy treatment program (2019-2022), where trained community health workers (CHWs) screened for epilepsy, promoted ivermectin intake to treat onchocerciasis, distributed ASMs, and monitored seizure frequency and ASM adherence monthly under supervision from the project clinician trained in epilepsy diagnosis and treatment. A concluding survey (2022) collected sociodemographic data and participants' status as alive, deceased, or lost to follow-up. Mixed-effects negative binomial regression analyzed risk factors for weekly seizure incidence rate. RESULTS:Of 206 participants, 77.7% reported bilateral tonic-clonic seizures, and 32.0% reported focal seizures. More than one third (38.5%) were suspected of having nodding syndrome. Weekly seizure frequency decreased significantly from a mean of 1.9 seizures (interquartile range [IQR] = 0-2) at enrollment to .4 seizures (IQR = 0-0) at the last follow-up (Wilcoxon test p < .0001), with significantly improved ASM adherence (57.5%-94.7%, McNemar test p < .0001). Factors associated with lower weekly seizure incidence included longer program participation, ASM adherence, carbamazepine use compared to phenobarbital, and ivermectin intake in 2022. ASM adverse events were associated with increased seizure frequency. The mortality rate was 32.7 deaths per 1000 person-years, with most deceased not fully adhering to ASM (88%) and having epilepsy-related causes of death (60%). SIGNIFICANCE:The community-based program using CHWs was associated with a significant reduction in seizure frequency and improved ASM adherence. In onchocerciasis-endemic areas, it should be investigated whether carbamazepine should be a preferred ASM in PWE. Ivermectin's impact on seizure frequency merits further investigation in onchocerciasis-endemic areas. Community-based epilepsy care is a promising strategy for scaling up epilepsy care in rural areas in Africa.

BACKGROUND:There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures, reinforcing the concept of onchocerciasis-associated epilepsy (OAE). The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem. MAIN TEXT:During the 2nd International Workshop on OAE held on 19-21 September, 2023, in Antwerp, Belgium, participants recognised OAE as a substantial yet neglected public health problem, particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic. Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence. There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care. It is expected that raising awareness about OAE will boost the population uptake of ivermectin. The implementation of a community-based epilepsy treatment programme offering free anti-seizure medications (ASMs) has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy. CONCLUSIONS:To reduce OAE burden, enhanced collaboration between onchocerciasis and mental health programmes at community, national, and international levels is required. Urgent efforts are needed to ensure the uninterrupted provision of free ASMs in onchocerciasis-endemic areas. Furthermore, OAE should be included in the quantification of the onchocerciasis disease burden.

INTRODUCTION:Epidemiological evidence suggests that Onchocerca volvulus is associated with epilepsy, although the exact pathophysiological mechanism is unknown. Mahenge is an endemic focus of onchocerciasis, with the longest-running ivermectin treatment intervention in Tanzania. We assessed the prevalence of onchocerciasis and epilepsy after 25 years of control using ivermectin. METHODS:This was a population-based cross-sectional study in 34 villages in Mahenge in 2021. Community health workers conducted door-to-door household surveys to enumerate the population and screen for individuals suspected of epilepsy using a standardised questionnaire. Trained physicians confirmed epilepsy. Children aged 6-11 years were screened for onchocerciasis antibodies using the Ov16 rapid test. Villages were stratified into three altitude levels (low [<400], medium [400-950], and high [>950 meters above sea level]) as a proxy for rapids, which black flies favour for breeding sites. Incidence of epilepsy was estimated as a ratio of new cases in the year preceding the survey per 100,000 population. RESULTS:56,604 individuals (median age 20.2 years, 51.1% females) were surveyed. Onchocerciasis prevalence in children was 11.8% and was highest in villages at medium (21.7%) and lowest in low altitudes (3.2%), p<0.001. Self-reported use of ivermectin was 88.4%. Epilepsy prevalence was 21.1 (95%CI: 19.9-22.3) cases per 1000 persons and was highest in medium (29.5%) and lowest in the lowlands (12.7%). The odds ratio (OR) of having epilepsy was significantly higher in females (OR = 1.22, 95%CI: 1.08-1.38), middle altitudes (OR = 2.34 [95%CI: 2.04-2.68]), and in individuals positive for OV16 (OR = 1.98 [95%CI:1.57-2.50]). The incidence of epilepsy a year before the survey was 117 (95%CI: 99.7-160.4) cases per 100,000 person-years. CONCLUSION:Despite ivermectin use for 25 years, the prevalence of onchocerciasis and epilepsy remains high. It is crucial to strengthen bi-annual ivermectin treatment and initiate interventions targeting vectors to control onchocerciasis and epilepsy in the area.

IntroductionDespite over 20 years of community-directed treatment with ivermectin (CDTI) in Mahenge area in Tanzania, the prevalence of onchocerciasis has remained high (over 40% in children 6-10 years using antibody testing and 49% using skinsnips in adults). The area has one of the highest prevalence of epilepsy, exceeding 3.5% in some of rural villages.MethodsBetween June and July 2019, in four rural villages using qualitative methods, we assessed factors potentially associated with the persistence of high Onchocerca volvulus transmission.ResultsEleven focus group discussions were organized with persons with epilepsy and their caretakers, community resource persons, and community drug distributors (CDDs), and two in-depth interviews with district programme coordinators of neglected tropical diseases (NTD). Factors considered being responsible for the persistence of onchocerciasis transmission included not taking ivermectin during CDTI for fear of adverse reactions such as itching, swelling and misconception that the drug causes infertility. Challenges for high CDTI coverage included, long walking distance by CDDs to deliver drugs to households, persons being away for farming, low awareness of the disease including the association between onchocerciasis and epilepsy and limited supervision by the NTD coordinators.ConclusionIvermectin uptake in Mahenge should be optimised by continuous advocacy about the importance of taking ivermectin to prevent onchocerciasisassociated morbidity and by improving supervision during CDTI.

Background: Epilepsy is estimated to affect 50 million people globally, with 80% living in sub-Saharan Africa (SSA). Children with epilepsy (CWE) in SSA are often socially isolated, and many do not get access to school. This study aimed to explore the barriers hindering accessibility to formal education among CWE in Mahenge, Tanzania. Methods: The study was conducted in June 2022 in four villages (Mdindo, Msogezi, Mzelezi and Sali) using quantitative and qualitative methods. The quantitative included 203 persons with epilepsy (PWE), while the qualitative involved six focus group discussions and 17 in-depth interviews. Quantitative and qualitative data were analyzed using Stata and Nvivo software, respectively. Results: Of the 203 PWE, 62 (30.5%) had never enrolled in school, while 77 (54.6%) of those enrolled dropped-out before completing it. The perceived barriers to accessing education were categorized as indi-vidual barriers (such as frequent seizures, learning difficulties, anti-seizure medication side effects and perceived stigma), Community barriers (such as stigma and discrimination, negative beliefs and misconceptions, relocation to farms and poor socio-economic status), and Institutional barriers (including lack of knowledge about epilepsy among stake-holders, topography and distance to schools).Conclusion: There is a high rate of dropouts and non-enrolment of CWE in schools within the Mahenge area. Negative beliefs and low awareness of the community about epilepsy and formal education con-tribute to this issue. This calls for more advocacy to raise community awareness on epilepsy. The government should enforce an inclusive education policy and provide free and uninterrupted anti-seizure medication for seizure control.(c) 2023 Elsevier Inc. All rights reserved.

Objective: This study investigated the quality of life (QoL) of adults with epilepsy living in Mahenge, an onchocerciasis-endemic area in Tanzania with a high prevalence of onchocerciasis-associated epilepsy (OAE).Methods: Between February and December 2020, persons with epilepsy (PWE) were recruited from four rural villages in Mahenge: Mdindo, Msogezi, Mzelezi, and Sali. For PWE who could not answer the questionnaire due to their mental or physical disability, a family member was asked to answer the questions instead. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) questionnaire used contained seven domains. The raw domain scores were transformed to 0-100% subscales, with higher scores indicating better QoL. The global QoL was calculated from the subscales using the overall QOLIE-31 score formula.Results: In total, 96 PWE were enrolled in the study with a median age of 28 (range: 18-60) years, of whom 45 (47%) were male. The questionnaires were answered by PWE (54.8%) or one of their family members (45.2%). Most PWE were single (81%), and half never attended school. About two-thirds (65%) of PWE were suspected of having OAE, and a third (31%) had a history of head nodding seizures. Most PWE were treated with phenobarbital (85.4%) and had high treatment adherence (96.9%). Still, the number of seizures per week ranged from 0 to 7, with a median of one. The mean global QOLIE-31 score was 66.9 (range: 38.3-92.1) out of 100.0. Predictors of lower QoL were living in Sali Village and experiencing seizures the week before the interview. In contrast, completing primary school and switching to second-line anti-seizure medication were predictors of higher QoL.Conclusion: In order to improve the QoL of PWE in Mahenge, it is vital to optimize anti-seizure medication regimens to decrease the frequency of seizures and to increase the schooling of PWE.& COPY; 2023 Elsevier Inc. All rights reserved.

BACKGROUND:Nodding syndrome (NS) has been consistently associated with onchocerciasis. Nevertheless, a positive association between NS and a Mansonella perstans infection was found in South Sudan. We aimed to determine whether the latter parasite could be a risk factor for NS in Mahenge. METHODS:Cases of epilepsy were identified in villages affected by NS in Mahenge, Tanzania, and matched with controls without epilepsy of the same sex, age and village. We examined blood films of cases and controls to identify M. perstans infections. The participants were also asked for sociodemographic and epilepsy information, examined for palpable onchocercal nodules and onchocerciasis-related skin lesions and tested for anti-Onchocerca volvulus antibodies (Ov16 IgG4) by ELISA. Clinical characteristics of cases and controls, O. volvulus exposure status and relevant sociodemographic variables were assessed by a conditional logistic regression model for NS and epilepsy status matched for age, sex and village. RESULTS:A total of 113 epilepsy cases and 132 controls were enrolled, of which, respectively, 56 (49.6%) and 64 (48.5%) were men. The median age in cases and controls was 28.0 (IQR: 22.0-35.0) and 27.0 (IQR: 21.0-33.3) years. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria and 106 (93.8%) had onchocerciasis-associated epilepsy (OAE). M. perstans infection was absent in all participants, while Ov16 seroprevalence was positively associated with probable NS (odds ratio (OR): 5.05, 95%CI: 1.79-14.27) and overall epilepsy (OR: 2.03, 95%CI: 1-07-3.86). Moreover, onchocerciasis-related skin manifestations were only found in the cases (n = 7, p = 0.0040), including persons with probable NS (n = 4, p = 0.0033). Residing longer in the village and having a family history of seizures were positively correlated with Ov16 status and made persons at higher odds for epilepsy, including probable NS. CONCLUSION:In contrast to O. volvulus, M. perstans is most likely not endemic to Mahenge and, therefore, cannot be a co-factor for NS in the area. Hence, this filaria is unlikely to be the primary and sole causal factor in the development of NS. The main risk factor for NS remains onchocerciasis.

Background Community-directed treatment with ivermectin (CDTi) is used to eliminate onchocerciasis. However, despite 25 years of annual CDTi in Mahenge, Tanzania, the prevalence of onchocerciasis and onchocerciasis-associated epilepsy remained high in certain rural villages. Therefore, in 2019, bi-annual CDTi was introduced in the area. This study assessed the impact of the programme on the incidence of epilepsy in four villages. Methodology Door-to-door epilepsy surveys were conducted prior to (2017/18) and after (2021) implementing a bi-annual CDTi program. All household members were screened for epilepsy symptoms using a validated questionnaire, and suspected cases were examined by a medical doctor to confirm/reject the diagnosis of epilepsy. The prevalence and annual incidence of epilepsy, including nodding syndrome, were calculated with 95% Wilson confidence intervals with continuity correction. The latter was also done for CDTi coverage in 2016 and 2021. Results Precisely 5,444 and 6,598 persons were screened for epilepsy before and after implementing the intervention. The CDTi coverage of the overall population was 82.3% (95%CI: 81.3–83.2%) in 2021 and sustained in both distribution rounds (81.5% and 76.8%). The coverage was particularly high in children and teenagers aged 6 to 18 years (93.2%, 95%CI: 92.1–94.2%). The epilepsy prevalence remained similar: 3.3% (95%CI: 2.9–3.9%) in 2017/18 versus 3.1% (95%CI: 2.7–3.5%) in 2021. However, the incidence of epilepsy declined from 177.6 (95%CI: 121.2–258.5) in 2015–2017 and 2016–2018 to 45.5 (95%CI: 22.2–89.7) in 2019–2021 per 100,000 persons-years. The incidence of probable nodding syndrome varied from 18.4 (95%CI: 4.7–58.5) to 5.1 (95%CI: 0.3–32.8). None of the nine incidence cases of epilepsy for which information on ivermectin intake was available took ivermectin in the year they developed their first seizures. Conclusion A bi-annual CDTi programme should be implemented in areas with high prevalence of onchocerciasis and epilepsy. High CDTi coverage among children is particularly important to prevent onchocerciasis-associated epilepsy.

Background: A high prevalence of epilepsy has been observed in the onchocerciasis-endemic focus of Mahenge, Tanzania. This study sought to assess the degree of disability experienced by persons with epilepsy (PWE) in Mahenge and identify associations with sociodemographic and clinical features. Method: This cross-sectional study was conducted in Mahenge, Tanzania, between February and July 2020. PWE were recruited from the Mahenge epilepsy clinic and four neighbouring rural villages (Mdindo, Mzogezi, Mzelezi and Sali). Data were collected using the 36-item version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire for adults. For children aged 5-17 years, we used the Module on Child Functioning developed by UNICEF and the Washington Group. Questionnaires were administered by trained research assistants. Descriptive statistics were performed, and multivariable analyses (gamma and logistic regressions) were conducted. Results: A total of 321 adults (45.5% males) and 48 children (55.3% males) with epilepsy participated. The overall median WHODAS 2.0 score was 4.8% (IQR: 0.9-18.9). The most affected disability domain was 'participating in the society' (median score: 12.5%, IQR: 0-29.2). Fifteen (31.3%) of the children with epilepsy had a disability in at least one domain of the child functioning module, with the 'accepting change' domain harbouring the highest proportion of disabled children (12.5%). Higher seizure frequency and longer epilepsy duration were associated with more disability. Conclusion: PWE in Mahenge experience variable degrees of disability. The affected domains indicate the need for societal rehabilitation of PWE in various community and/or social activities. Peer-support groups were instituted at the study sites to address these needs.

Onchocerciasis is known to cause skin lesions and blindness, but there is also epidemiological evidence that onchocerciasis is associated with epilepsy, including nodding syndrome. We carried out ocular exams in persons with epilepsy in Mahenge, an onchocerciasis endemic area with a high prevalence of epilepsy in Tanzania. We recruited 278 consecutive persons with epilepsy attending the epilepsy clinic at Mahenge hospital and satellite clinics in rural villages. They underwent a general physical and a detailed ocular examination and were tested for onchocerciasis Ov16 IgG4 antibodies. Glaucoma was defined by a raised intraocular pressure above 21 mmHg with evidence of typical glaucomatous disc changes in one or both eyes. Among the 278 participants, median age 27 (IQR 21–38) years, 55.4% were female; 151/210 (71.9%) (95% CI: 65.3–77.9) were Ov16 positive. The most frequent ophthalmic lesions were glaucoma (33.1%), vitreous opacities (6.5%) and cataracts (2.9%). In multivariate analysis, glaucoma (adjusted IRR = 1.46; 95% CI: 1.24–1.70) and age (adjusted IRR = 1.01; 95% CI: 1.01–1.02) were significantly associated with onchocerciasis. In conclusion, a high prevalence of glaucoma was observed among Ov16 positive persons with epilepsy. Persons with epilepsy with O. volvulus infection should undergo screening for glaucoma to prevent one of the causes of preventable blindness.

Common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 1.25-2.5 mg/kg s.c., twice a week) for 5-10 consecutive months. The initial doses of MPTP produced a severe parkinsonian syndrome but motor activity was partially recovered at the end of treatment. Fifteen days or 6 months after the last MPTP dose, monkeys were sacrificed. In addition to a strong decrease of dopamine in the striatum, there were significant reductions in substance P and Met-enkephalin content in the substantia nigra, caudate nucleus and putamen. In the globus pallidus, the reduction in peptide levels did not reach statistical significance as compared to controls. Neurotensin levels were also decreased in the caudate nucleus. The chronic administration of MPTP for 5-10 months induces changes in substance P and Met-enkephalin systems which resemble the degeneration found in brains from parkinsonian patients.

Background Despite 20 years of ivermectin mass distribution in the Mahenge area, Tanzania, the prevalence of onchocerciasis and epilepsy has remained high in rural villages. Objectives We investigated the efficacy of ivermectin in reducing Onchocerca volvulus microfilariae and predictors for parasitic load following ivermectin treatment in persons with (PWE) and without epilepsy (PWOE). Methods Between April and September 2019, 50 PWE and 160 randomly selected PWOE from Msogezi and Mdindo villages participated in a follow-up study. Skin snips were obtained pre (baseline) and three months post-ivermectin treatment. Results The overall prevalence of O. volvulus positive skin snips at baseline was 49% (103/210), with no significant difference between PWE (58.0%) and PWOE (46.3%); p=0.197. The overall mean microfilarial density was significantly higher at baseline 1.45(95%CI:0.98–2.04)) than three-month post-ivermectin treatment (0.23(95%CI:0.11–0.37), p<0.001. Three months after ivermectin, the microfilarial density had decreased by ≥80% in 54 (81.8%, 95%CI: 72.3–91.4) of the 66 individuals with positive skin snips at baseline. High microfilarial density at baseline was the only significant predictor associated with higher microfilarial density in the post-ivermectin skin snips. Conclusion Our study reports a decrease in microfilarial density following ivermectin treatment in most individuals. Optimizing ivermectin coverage will address the ongoing onchocerciasis transmission in Mahenge.

Despite of over 20 years of community directed treatment with ivermectin (CDTI), a high prevalence of onchocerciasis and onchocerciasis-associated epilepsy were observed in rural villages in Mahenge, Tanzania. Therefore, we assessed the knowledge, attitude and practice about onchocerciasis in four rural villages in the Mahenge area. This was a qualitative study conducted between June and July 2019. Eleven focus group discussions were organized with persons with epilepsy and their caretakers, community resource persons, and community drug distributors (CDDs), and two in-depth interviews with district programme coordinators of neglected tropical diseases (NTD). Most participants were aware about symptoms of onchocerciasis using local terminologies such as &ldquo;ukurutu/rough dry skin&rdquo; and &ldquo;kuwashwa/itching&rdquo;. A small proportion of people did not take ivermectin during CDTI for fear of adverse reactions such as itching and swelling. Some men believed that ivermectin may decrease libido. Challenges for high CDTI coverage included, long walking distance by CDDs to deliver drugs to households, persons being away for farming, low awareness of the disease and limited supervision by the NTD coordinators. In conclusion, ivermectin uptake in Mahenge should be optimised by continuous advocacy about the importance of taking ivermectin to prevent onchocerciasis-associated morbidity and by improving supervision during CDTI.

A high burden of epilepsy has been reported in sub-Saharan Africa (SSA) particularly in onchocerciasis endemic areas. To improve the quality of life of persons with epilepsy (PWE) in Mahenge, an onchocerciasis-endemic area in Tanzania, we established peer support groups (PSG) in two out of four rural villages (Mdindo, Msogezi, Mzelezi and Sali). One year later (between February and July 2020), we carried out a cross-sectional survey among PWE and their caregivers in the four rural villages with the aim of comparing perceived stigma among PWE in study sites with and without PSG. Perceived stigma was measured using the validated Kilifi stigma scale of epilepsy (KSSE), whose total score ranges from 0-30. A generalized linear mixed regression model was used to identify factors associated with high stigma scores. A total of 161 PWE participated in the study; 76 (47.2%) resided in villages where a PSG intervention was implemented. The overall mean stigma score was 3.7 +/- 4.6, with no significant difference between villages with and without PSG (p = 0.537). Only one PWE (0.6%) scored above 20 (very high perceived stigma). Experiencing more seizures during the past week (Coef = 1.013 [0.568, 1.457]), having attended school (Coef = 1.821 0.345, 3.297], and a history of physical abuse (Coef = 3.200 [0.574, 5.827]) were associated with higher stigma scores. Perceived stigma in rural villages in Mahenge is a major public health problem. A follow-up study is needed to determine the medium-to long-term effect of the PSG intervention on perceived epilepsy-related stigma. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

A clinical trial performed in the Democratic Republic of Congo (DRC), among persons with epilepsy (PWE) infected with Onchocerca volvulus treated with anti-seizure medication suggested that ivermectin reduces the seizure frequency. We assessed the effect of ivermectin treatment on seizure frequency in PWE with and without anti-seizure medication in three onchocerciasis endemic areas (Maridi, South Sudan; Aketi, DRC; and Mahenge, Tanzania). Pre- and 3–5 months post-ivermectin microfilariae densities in skin snips and seizure frequency were assessed. After ivermectin, the median (IQR) percentage reduction in seizure frequency in the study sites ranged from 73.4% (26.0–90.0) to 100% (50.0–100.0). A negative binomial mixed model showed that ivermectin significantly reduced the seizure frequency, with a larger decrease in PWE with a high baseline seizure frequency. Mediation analysis showed that ivermectin reduced the seizure frequencies indirectly through reduction in microfilariae densities but also that ivermectin may have a direct anti-seizure effect. However, given the short half-life of ivermectin and the fact that ivermectin does not penetrate the healthy brain, such a direct anti-seizure effect is unlikely. A randomized controlled trial assessing the ivermectin effect in people infected with O. volvulus who are also PWE on a stable anti-seizure regimen may be needed to clarify the causal relationship between ivermectin and seizure frequency.

There is growing epidemiological evidence that onchocerciasis may induce epilepsy. High prevalence of onchocerciasis has been reported in onchocerciasis-meso and hyper-endemic regions. We aimed to determine the OV16 antibody prevalence in persons with epilepsy (PWE) in four onchocerciasis-endemic regions. PWE were identified during studies in Mahenge area (Tanzania), Kitgum and Pader districts (Uganda), the Mbam and Sanaga river valleys (Cameroon), and the Logo health zone (Democratic Republic of Congo). Exposure to Onchocerca volvulus was assessed by testing PWE for OV16 IgG4 antibodies using a rapid diagnostic test. The OV16 seroprevalence among PWE in the four onchocerciasis-endemic study sites ranged from 35.2% to 59.7%. OV16 seroprevalence increased with age until the age of 39 years, after which it decreased drastically. Our study suggests that, in onchocerciasis-endemic regions, epilepsy in young people is often associated with onchocerciasis, while epilepsy in older persons seems unrelated to O. volvulus exposure.

Information about the genetic attribution to Parkinson's disease (PD) in Sub Sahara Africa (SSA) is limited. PRKN gene (PARK2, parkin) mutations [1] have been described in individuals from various ethnic backgrounds but were found in only three individuals across three large studies from Nigeria, South Africa and Zambia [2–5]. This is a first PRKN-related parkinsonism family from Eastern Africa. (see Fig. 1)