Purpose To determine the prevalence and incidence of epilepsy in an onchocerciasis endemic region of South Sudan. Methods In May 2018, a door-to-door household survey was conducted in 8 study sites in an onchocerciasis endemic area in Maridi County. Results A total of 2511 households agreed to participate in the study, corresponding to 17,652 individuals. An epilepsy screening questionnaire identified 799 persons suspected to have epilepsy (4.5%); in 736 of the 766 persons (96.1%) seen by a clinical officer the diagnosis of epilepsy was confirmed. Adding 38 persons who were not seen but with a positive answer to a combination of screening questions, 774 persons (4.4%) had epilepsy. Epilepsy prevalence was highest in the 11–20 age group (10.5%); 66 persons with epilepsy (PWE) developed their first seizures in the year preceding the survey (annual incidence = 373.9/100.000). Neurocysticercosis cannot explain the high epilepsy prevalence since no pigs are kept in the area. Independent risk factors for epilepsy included male gender, belonging to a “permanent household” and a farming family, and living in a village bordering the Maridi River. Only 7209 (40.8%) of the population took ivermectin in 2017. Conclusion A very high prevalence and incidence of epilepsy was observed in several villages in Maridi County located close to the Maridi River and the Maridi dam. Urgent action is needed to prevent children in Maridi County from developing OAE by strengthening the onchocerciasis elimination program.

High prevalence of onchocerciasis-associated epilepsy in villages in Maridi County, Republic of South Sudan: A community-based survey.

Nodding syndrome (NS) is an epileptic disorder occurring in children in African onchocerciasis endemic regions. Here, we describe the pathological changes in 9 individuals from northern Uganda who died with NS (n = 5) or other forms of onchocerciasis-associated epilepsy (OAE) (n = 4). Postmortem examinations were performed and clinical information was obtained. Formalin-fixed brain samples were stained by hematoxylin and eosin and immunohistochemistry was used to stain astrocytes (GFAP), macrophages (CD68), ubiquitin, α-synuclein, p62, TDP-43, amyloid β, and tau (AT8). The cerebellum showed atrophy and loss of Purkinje cells with hyperplasia of the Bergmann glia. Gliosis and features of past ventriculitis and/or meningitis were observed in all but 1 participant. CD68-positive macrophage clusters were observed in all cases in various degrees. Immunohistochemistry for amyloid β, α-synuclein, or TDP-43 was negative. Mild to sparse AT8-positive neurofibrillary tangle-like structures and threads were observed in 4/5 NS and 2/4 OAE cases, preferentially in the frontal and parietal cortex, thalamic- and hypothalamic regions, mesencephalon and corpus callosum. Persons who died with NS and other forms of OAE presented similar pathological changes but no generalized tauopathy, suggesting that NS and other forms of OAE are different clinical presentations of a same disease with a common etiology.

/pdf/neuroinflammation-and-not-tauopathy-is-a-predominant-2se4dm49ia.pdf

Neuroinflammation and Not Tauopathy Is a Predominant Pathological Signature of Nodding Syndrome.

Around 2007, a nodding syndrome (NS) epidemic appeared in onchocerciasis-endemic districts of northern Uganda, where ivermectin mass distribution had never been implemented. This study evaluated the effect of community-directed treatment with ivermectin (CDTI) and ground larviciding of rivers initiated after 2009 and 2012 respectively, on the epidemiology of NS and other forms of epilepsy (OFE) in some districts of northern Uganda. In 2012, a population-based community survey of NS/epilepsy was carried out by the Ugandan Ministry of Health in Kitgum and Pader districts. In August 2017, we conducted a new survey in selected villages of these districts and compared our findings with the 2012 data. In addition, two villages in Moyo district (where CDTI was ongoing since 1993) served as comparative onchocerciasis-endemic sites in which larviciding had never been implemented. The comparison between 2012 and 2017 prevalence and cumulative incidence were done using the Fisher’s and Pearson’s Chi-square tests at 95% level of significance. A total of 2138 individuals in 390 households were interviewed. In the selected villages of Kitgum and Pader, there was no significant decrease in prevalence of NS and OFE between 2012 and 2017. However, the cumulative incidence of all forms of epilepsy decreased from 1165 to 130 per 100 000 persons per year (P = 0.002); that of NS decreased from 490 to 43 per 100 000 persons per year (P = 0.037); and for OFE from 675 to 87 per 100 000 persons per year (P = 0.024). The median age of affected persons (NS and OFE) shifted from 13.5 (IQR: 11.0–15.0) years in 2012 to 18.0 (IQR: 15.0–20.3) years in 2017; P <  0.001. The age-standardized prevalence of OFE in Moyo in 2017 was 4.6%, similar to 4.5% in Kitgum and Pader. Our findings support the growing evidence of a relationship between infection by Onchocerca volvulus and some types of childhood epilepsy, and suggest that a combination of bi-annual mass distribution of ivermectin and ground larviciding of rivers is an effective strategy to prevent NS and OFE in onchocerciasis-hyperendemic areas.

/pdf/prevalence-and-incidence-of-nodding-syndrome-and-other-forms-3iyk2d1spn.pdf

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.

1 Global Health Institute, University of Antwerp, Antwerp, Belgium, 2 Neglected and Disabling Diseases of Poverty Consultant, Kent, United Kingdom, 3 Neglected Tropical Diseases Control Programme, Ministry of Health, Kampala, Uganda, 4 National institute for Medical Research, Ministry of Health, Dar es Salaam, Tanzania, 5 Neglected Tropical Diseases Unit, Ministry of Health, Juba, South Sudan, 6 London Centre for Neglected Tropical Disease Research and MRC Centre for Global Infectious Disease Analysis (MRC-GIDA), Imperial College London, London, United Kingdom

/pdf/from-river-blindness-to-river-epilepsy-implications-for-4hd2jtgl31.pdf

From river blindness to river epilepsy: Implications for onchocerciasis elimination programmes.

Background
The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association.
Methods
PubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection with O. volvulus and epilepsy, including the nodding syndrome.
Results
Onchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and
analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including
nodding and Nakalanga syndromes.
Conclusion
Applying the Bradford Hill criteria suggests consistent epidemiological evidence that O. volvulus infection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.

/pdf/onchocerca-volvulus-and-epilepsy-a-comprehensive-review-zsv45cwcra.pdf

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

Purpose To describe the clinical manifestations of persons with epilepsy (PWE) in onchocerciasis endemic villages in South Sudan. Methods During a survey in Maridi County in May 2018, PWE were interviewed and examined in their households by a clinical officer or medical doctor. Onchocerciasis-associated epilepsy (OAE) was defined as ≥2 seizures without any obvious cause, starting between the ages of 3–18 years in previously healthy persons who had resided for at least 3 years in the onchocerciasis endemic area. Results Seven hundred and thirty-six PWE were included in the study; 315 (42.8%) were females; median age was 18 years. A variety of seizure types were reported: generalized tonic-clonic seizures in 511 PWE (69.4%), absences in 15 (2.0%), focal motor seizures with full awareness in 7 (1.0%), focal motor seizures with impaired awareness in 25 (3.4%), brief episodes of hallucinations in 316 (43.9%) and nodding seizures in 335 (45.5%). The median age of onset of all seizures was 10 years, and 8 years for nodding seizures. PWE with nodding seizures presented with more cognitive disabilities. The diagnostic criteria for OAE were met by 414 (85.2%) of the 486 PWE with complete information. Eighty (11.0%) PWE presented with Nakalanga features. Only 378 (51.4%) PWE were taking anti-epileptic treatment. Conclusion PWE presented with a wide spectrum of seizures. The high percentage of PWE who met the diagnostic criteria for OAE suggests that better onchocerciasis control could prevent new cases. Urgent action is needed to close the anti-epileptic treatment gap.

Clinical characteristics of onchocerciasis-associated epilepsy in villages in Maridi County, Republic of South Sudan.

Aims. Following previous reports of very high epilepsy prevalence in the onchocerciasis-endemic villages in Maridi County, South Sudan, a study was conducted to investigate the association between the level of Onchocerca volvulus infection, epilepsy, and related outcomes. Methods. In December 2018, persons with epilepsy (PWE) were recruited from villages where an epilepsy prevalence of 4.4% (range: 3.5–11.9%) was documented. We enrolled 318 participants from whom two skin snips were taken for microscopic detection of O. volvulus microfilariae (mf). Seizure history was obtained for all PWE and their degree of disability assessed using the modified Rankin scale. Results. Almost all (84.9%) PWE had detectable mf in their skin snips. Onchocerciasis-infected PWE experienced nodding seizures more often than uninfected PWE (p=0.034). Moreover, persons with nodding seizures had more frequent seizures (p<0.001) and higher disability scores (p<0.001), and were more often cognitively impaired and younger at the time of their first epileptic seizure (nine years vs 12 years, p<0.001) compared to PWE without nodding seizures. Based on multivariate models, nodding seizures were associated with higher mf densities (aOR: 1.022; 95% CI: 1.005–1.041). Epilepsy onset at a younger age was associated with a worse outcome. Higher frequency of seizures, longer duration of epilepsy and younger age were associated with increased disability. Regular antiepileptic drug use was associated with better cognitive and disability outcomes. Conclusion. PWE with nodding seizures have a more severe form of onchocerciasis-associated epilepsy, with earlier seizure onset and higher levels of O. volvulus infection. Younger PWE were prone to worse epilepsy outcomes, which would be prevented with regular antiepileptic treatment.

http://www.jle.com/fr/revues/epd/e-docs/persons_with_onchocerciasis_associated_epilepsy_and_nodding_seizures_have_a_more_severe_form_of_epilepsy_with_more_cognitive_impairment_and_higher_levels_of_onchocerca_volvulus_infection_317224/article.phtml?tab=download&pj_key=doc_attach_45993

Persons with onchocerciasis‐associated epilepsy and nodding seizures have a more severe form of epilepsy with more cognitive impairment and higher levels of Onchocerca volvulus infection

Peter Claver Olore

Papers

High prevalence of onchocerciasis-associated epilepsy in villages in Maridi County, Republic of South Sudan: A community-based survey.

Clinical characteristics of onchocerciasis-associated epilepsy in villages in Maridi County, Republic of South Sudan.

Persons with onchocerciasis‐associated epilepsy and nodding seizures have a more severe form of epilepsy with more cognitive impairment and higher levels of Onchocerca volvulus infection