Highlights An epilepsy prevalence of 4.4% was observed in villages in Maridi. Living close to the Maridi river is a major risk factor for epilepsy. Persons with nodding seizures and with other forms of epilepsy live in the same areas. Ivermectin coverage needs to increase to prevent onchocerciasis associated epilepsy.

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. different seizure presentations including nodding syndrome (NS) [2,3]. NS was first investigated in 2001-2 in Lui and Amadi in Western Equatoria region, South Sudan, by a team led by the World Health Organization (WHO) [4]. Three small case control studies (82 pairs in total) performed during these investigations showed that infections with Onchocerca volvulus diagnosed by skin snips were more often

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

Epidemiological evidence links onchocerciasis with the development of epilepsy. The aim of this study was to detect Onchocerca volvulus microfilariae or its bacterial endosymbiont, Wolbachia, in the cerebrospinal fluid (CSF) of persons with onchocerciasis-associated epilepsy (OAE). Methods: Thirteen persons with OAE and O. volvulus skin snip densities of >80 microfilariae were recruited in Maridi County (South Sudan) and their CSF obtained. Cytospin centrifuged preparations of CSF were examined by light microscopy for the presence of O. volvulus microfilariae. DNA was extracted from CSF to detect O. volvulus (O-150 repeat) by quantitative real-time PCR, and Wolbachia (FtsZ gene) by standard PCR.To further investigate whether CSF from onchocerciasis-infected participants could induce seizures, 3-and 7-day old zebrafish larvae were injected with the CSF intracardially and intraperitoneally, respectively. For other zebrafish larvae, CSF was added directly to the larval medium. Results: No microfilariae, parasite DNA, or Wolbachia DNA were detected in any of the CSF samples by light microscopy or PCR. All zebrafish survived the procedures and none developed seizures. Conclusions: The absence of O. volvulus in the CSF suggests that OAE is likely not caused by direct parasite invasion into the central nervous system, but by another phenomenon triggered by O. volvulus infection.

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.

A divergent rhabdovirus was discovered in the bloodstream of a 15-year-old girl with Nodding syndrome from Mundri West County in South Sudan. Nodding syndrome is a progressive degenerative neuropathy of unknown cause affecting thousands of individuals in Sub-Saharan Africa. The index case was previously healthy until she developed head-nodding seizures four months prior to presentation. Virus discovery by VIDISCA-NGS on the patient’s plasma detected multiple sequence reads belonging to a divergent rhabdovirus. The viral load was 3.85 × 103 copies/mL in the patient’s plasma and undetectable in her cerebrospinal fluid. Further genome walking allowed for the characterization of full coding sequences of all the viral proteins (N, P, M, U1, U2, G, U3, and L). We tentatively named the virus “Mundri virus” (MUNV) and classified it as a novel virus species based on the high divergence from other known viruses (all proteins had less than 43% amino acid identity). Phylogenetic analysis revealed that MUNV forms a monophyletic clade with several human-infecting tibroviruses prevalent in Central Africa. A bioinformatic machine-learning algorithm predicted MUNV to be an arbovirus (bagged prediction strength (BPS) of 0.9) transmitted by midges (BPS 0.4) with an artiodactyl host reservoir (BPS 0.9). An association between MUNV infection and Nodding syndrome was evaluated in a case–control study of 72 patients with Nodding syndrome (including the index case) matched to 65 healthy households and 48 community controls. No subject, besides the index case, was positive for MUNV RNA in their plasma. A serological assay detecting MUNV anti-nucleocapsid found, respectively, in 28%, 22%, and 16% of cases, household controls and community controls to be seropositive with no significant differences between cases and either control group. This suggests that MUNV commonly infects children in South Sudan yet may not be causally associated with Nodding syndrome.

Nodding syndrome (NS) is a debilitating yet often neglected neurological disease affecting thousands of children in several sub-Saharan African countries. The cause of NS remains unknown, and effective treatment options are lacking. Moreover, knowledge regarding NS is scarce and is based on a limited number of publications, with no comprehensive overview published to date. Therefore, the aim of this scoping review was to summarise the current evidence and identify existing knowledge gaps in order to help clinicians, scientists, and policymakers develop guidelines for prioritising this severe condition. We searched the Medline (Ovid), Embase (Ovid), Scopus, and Global Health Library databases in accordance with the PRISMA extension for scoping review guidance and in accordance with the Joanna Briggs Institute guidelines and methodology for a scoping review, using keywords describing NS. We then extracted and presented the original data regarding the epidemiology, aetiology, pathophysiology, clinical features, diagnosis, management, and outcomes of NS, as well as community perceptions and the psychosocial and economic impact of NS. Out of 1470 identified articles, a total of 69 were included in this scoping review. Major gaps exist in understanding the aetiology and pathogenesis of NS. Future research is urgently needed not only to address these gaps, but also to study the treatment options, epidemiology, and psychosocial and economic impacts of NS. Innovative interventions and rehabilitation programmes designed to address the psychosocial and economic burdens associated with NS are also urgently needed.

BackgroundNodding syndrome (NS) is a devastating epileptic illness of unknown aetiology mainly affecting children 5–15 years of age. Head nodding distinguishes NS from other forms of epilepsy. Other manifestations of the illness include mental and physical growth retardation. Many children die as a result of falling in fires or drowning. Recently, it was shown that NS is only one of the phenotypic presentations of onchocerciasis associated epilepsy (OAE). Despite the strong epidemiological association between epilepsy and onchocerciasis, the causal mechanism is unknown. After implementation of bi-annual community directed treatment with ivermectin (CDTi) and larviciding of rivers in northern Uganda, new cases of NS have ceased, while new cases continue to emerge in South Sudanese onchocerciasis-endemic areas with an interrupted CDTi programme. This study is designed to evaluate the potential effects of bi-annual CDTi on reducing the incidence of NS/OAE in onchocerciasis-endemic areas in South Sudan.MethodsA pre-intervention door-to-door population-based household survey will be conducted in selected onchocerciasis-endemic villages in Mundri and Maridi Counties, which have a high prevalence of epilepsy. Using a validated questionnaire, the entire village will be screened by community research assistants for suspected epilepsy cases. Suspected cases will be interviewed and examined by a trained clinical officer or medical doctor who will confirm or reject the diagnosis of epilepsy. Bi-annual CDTi will be implemented in the villages and a surveillance system for epilepsy set up. By implementing an epilepsy onchocerciasis awareness campaign we expect to obtain > 90% CDTi coverage of eligible individuals. The door-to-door survey will be repeated two years after the baseline survey. The incidence of NS/OAE will be compared before and after bi-annual CDTi.DiscussionOur study is the first population-based study to evaluate the effect of bi-annual CDTi to reduce the incidence of NS/OAE. If the study demonstrates such a reduction, these findings are expected to motivate communities in onchocerciasis-endemic regions to participate in CDTi, and will encourage policy makers, funders and other stakeholders to increase their efforts to eliminate onchocerciasis.Electronic supplementary materialThe online version of this article (10.1186/s40249-018-0496-2) contains supplementary material, which is available to authorized users.