Assessing Onchocerca volvulus Intensity of Infection and Genetic Diversity Using Mitochondrial Genome Sequencing of Single Microfilariae Obtained before and after Ivermectin Treatment.

Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi County, South Sudan, collected before and 4-5 months after ivermectin treatment. Population genetic analyses identified 52 and 103 mitochondrial DNA haplotypes among the microfilariae from DRC and South Sudan, respectively, with few haplotypes shared between people. The percentage of genotype-based correct assignment to person within DRC was ~88% and within South Sudan ~64%. Rarefaction and extrapolation analysis showed that the genetic diversity in DRC, and even more so in South Sudan, was captured incompletely. The results indicate that the per-person adult worm burden is likely higher in South Sudan than DRC. Analyses of haplotype data from a subsample (n = 4) did not discriminate genetically between pre- and post-treatment microfilariae, confirming that post-treatment microfilariae are not the result of new infections. With appropriate sampling, mitochondrial haplotype analysis could help monitor changes in the number of macrofilariae in a population as a result of treatment, identify cases of potential treatment failure, and detect new infections as an indicator of continuing transmission.

Identification of the onchocerciasis vector in the Kakoi-Koda focus of the Democratic Republic of Congo.

BACKGROUND: The objective of this study was to characterise the vector in a small hyper-endemic focus of onchocerciasis (the Kakoi-Koda focus) which has recently been discovered on the western slopes of the rift valley above Lake Albert. METHODOLOGY/PRINCIPAL FINDINGS: Aquatic stages of blackflies were collected by hand from streams and rivers, and anthropophilic adult females were collected by human landing catches. Using a combination of morphotaxonomy and DNA barcoding, the blackflies collected biting humans within the focus were identified as Simulium dentulosum and Simulium vorax, which were also found breeding in local streams and rivers. Simulium damnosum s.l., Simulium neavei and Simulium albivirgulatum were not found (except for a single site in 2009 where crabs were carrying S. neavei). Anthropophilic specimens from the focus were screened for Onchocerca DNA using discriminant qualitative real-time triplex PCR. One specimen of S. vorax was positive for Onchocerca volvulus in the body, and out of 155 S. dentulosum, 30% and 11% were infected and infective (respectively). CONCLUSIONS/SIGNIFICANCE: Simulium dentulosum currently appears to be the main vector of human onchocerciasis within the Kakoi-Koda focus, and S. vorax may be a secondary vector. It remains possible that S. neavei was the main (or only) vector in the past having now become rare as a result of the removal of tree-cover and land-use changes. Simulium vorax has previously been shown to support the development of O. volvulus in the laboratory, but this is the first time that S. dentulosum has been implicated as a probable vector of onchocerciasis, and this raises the possibility that other blackfly species which are not generally considered to be anthropophilic vectors might become vectors under suitable conditions. Because S. dentulosum is not a vector in endemic areas surrounding the Kakoi-Koda focus, it is probable that the Kakoi-Koda focus is significantly isolated.

No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy.

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.

Serotonin Levels in the Serum of Persons with Onchocerciasis-Associated Epilepsy: A Case-Control Study.

Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we investigated serotonin levels in persons with OAE and controls selected from the Democratic Republic of Congo. Serum serotonin levels were determined by ELISA in 19 persons with OAE, 32 persons with epilepsy without O. volvulus infection, 18 with O. volvulus infection but without epilepsy, and 35 with neither O. volvulus infection nor epilepsy. O. volvulus infection was diagnosed by skin snip testing and/or OV16 antibody detection. Serum serotonin levels were significantly decreased in persons with OAE compared to persons with O. volvulus infection and no epilepsy. In conclusion, an increased serotonin level is unable to explain the pathogenesis of OAE. Other hypotheses to identify the causal mechanism of OAE will need to be investigated.

No Evidence Known Viruses Play a Role in the Pathogenesis of Onchocerciasis-Associated Epilepsy. An Explorative Metagenomic Case-Control Study.

Despite the increasing epidemiological evidence that the Onchocerca volvulus parasite is strongly associated with epilepsy in children, hence the name onchocerciasis-associated epilepsy (OAE), the pathophysiological mechanism of OAE remains to be elucidated. In June 2014, children with unprovoked convulsive epilepsy and healthy controls were enrolled in a case control study in Titule, Bas-Uélé Province in the Democratic Republic of the Congo (DRC) to identify risk factors for epilepsy. Using a subset of samples collected from individuals enrolled in this study (16 persons with OAE and 9 controls) plasma, buffy coat, and cerebrospinal fluid (CSF) were subjected to random-primed next-generation sequencing. The resulting sequences were analyzed using sensitive computational methods to identify viral DNA and RNA sequences. Anneloviridae, Flaviviridae, Hepadnaviridae (Hepatitis B virus), Herpesviridae, Papillomaviridae, Polyomaviridae (Human polyomavirus), and Virgaviridae were identified in cases and in controls. Not unexpectedly, a variety of bacteriophages were also detected in all cases and controls. However, none of the identified viral sequences were found enriched in OAE cases, which was our criteria for agents that might play a role in the etiology or pathogenesis of OAE.

Potential Parasitic Causes of Epilepsy in an Onchocerciasis Endemic Area in the Ituri Province, Democratic Republic of Congo.

A high burden of epilepsy is observed in Africa where parasitological infections are endemic. In 2016, in an Onchocerciasis endemic area in the Logo health zone, in Ituri province in the Democratic Republic of Congo, a door-to-door study showed an epilepsy prevalence of 4.6%, and 50.6% of persons with epilepsy were infected with Onchocerca volvulus. In the current study, the serum of 195 people infected with O. volvulus persons with epilepsy were tested to determine the proportion of co-infections with Taenia solium, Toxocara canis and Strongyloides. These proportions were, respectively, 8.2, 18.5 and 12.8%. Persons with a T. solium co-infection were older than those without co-infection (p = 0.021). In six (37.5%) of the T. solium co-infected persons, the first seizures appeared after the age of 30 years compared to three (2.1%) persons without a co-infection (p < 0.0001). Our study suggests that an O. volvulus infection is the main parasitic cause of epilepsy in the Ituri province, but in some persons, mainly in those with late onset epilepsy and with focal seizures, the epilepsy may be caused by neurocysticercosis. As the population in the area rears pigs, activities to limit T. solium transmission should be implemented.

Community perceptions and attitudes regarding epilepsy and disease cost after implementation of a community-based epilepsy treatment program in onchocerciasis-endemic communities in the Democratic Republic of Congo.

BACKGROUND: In October 2017, a community-based epilepsy treatment program (CBETP) was initiated in the Logo health zone (Ituri province, Democratic Republic of Congo), consisting mainly of community epilepsy education, provision of free antiepileptic drugs (AEDs), and monthly follow-up of persons with epilepsy (PWE). Prior to the implementation of the CBETP, qualitative research had revealed several misconceptions about the cause of epilepsy, major epilepsy-related stigma, and high economic cost for families of PWE mainly because of costly treatment by traditional healers. One year after the implementation of the CBETP, we assessed the perceived effect of this program on the community's perceptions and attitudes regarding epilepsy and on disease costs. METHODS: Focus group discussions (FGD) and semi-structured in-depth interviews (SSI) were conducted with different target groups. Additionally, the cost associated with epilepsy was evaluated using questionnaires administered to 74 PWE and/or their families. RESULTS: Nine FGDs and 16 SSIs were conducted. There was a notable shift in perceptions and attitudes, as most community members no longer believed that epilepsy is contagious, while acknowledging that this condition can be treated in local health centers. Persons with epilepsy and their family experienced less epilepsy-related stigma and consulted less frequently traditional healers; the latter showed a growing willingness to collaborate with health professionals in the management of PWE. The direct and indirect costs for families caring for a PWE decreased by 95.2% and 95.7%, respectively. CONCLUSION: The main perceived benefits of the CBETP were the decrease in misconceptions about epilepsy and epilepsy-related stigma. Families with PWE understood the benefit of seeking health care from trained health professionals rather than with traditional healers. The direct and indirect costs for families to take care of a PWE reduced considerably after the program. However, the cost-effectiveness and long-term sustainability of this approach remain to be assessed.

OV16 Seroprevalence among Persons with Epilepsy in Onchocerciasis Endemic Regions: A Multi-Country Study.

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.

Ivermectin Treatment Response in Onchocerca Volvulus Infected Persons with Epilepsy: A Three-Country Short Cohort Study.

Despite a long history of community-directed treatment with ivermectin (CDTI), a high ongoing Onchocerca volvulus transmission is observed in certain onchocerciasis-endemic regions in Africa with a high prevalence of epilepsy. We investigated factors associated with higher microfilarial (mf) density after ivermectin treatment. Skin snips were obtained from O. volvulus-infected persons with epilepsy before, and 3 to 5 months after ivermectin treatment. Participants were enrolled from 4 study sites: Maridi (South Sudan); Logo and Aketi (Democratic Republic of Congo); and Mahenge (Tanzania). Of the 329 participants, 105 (31.9%) had a post-treatment mf density >20% of the pre-treatment value. The percentage reduction in the geometric mean mf density ranged from 69.0% (5 months after treatment) to 89.4% (3 months after treatment). A higher pre-treatment mf density was associated with increased probability of a positive skin snip after ivermectin treatment (p = 0.016). For participants with persistent microfiladermia during follow-up, a higher number of previous CDTI rounds increased the odds of having a post-treatment mf density >20% of the pre-treatment value (p = 0.006). In conclusion, the high onchocerciasis transmission in the study sites may be due to initially high infection intensity in some individuals. Whether the decreasing effect of ivermectin with increasing years of CDTI results from sub-optimal response mechanisms warrants further research.

Comparison of Diagnostic Tests for Onchocerca volvulus in the Democratic Republic of Congo.

Onchocerciasis is diagnosed by detecting microfilariae in skin snips or by detecting OV16 IgG4 antibodies in blood by either enzyme linked immunosorbent assay (ELISA) or a rapid diagnostic test (RDT). Here, we compare the sensitivity and specificity of these three tests in persons with epilepsy living in an onchocerciasis endemic region in the Democratic Republic of Congo. Skin snips and blood samples were collected from 285 individuals for onchocerciasis diagnosis. Three tests were performed: the OV16 RDT (SD Bioline) and the OV16 ELISA both on serum samples, and microscopic detection of microfilariae in skin snips. The sensitivity and specificity of each test was calculated with the combined other tests as a reference. Microfilariae were present in 105 (36.8%) individuals, with a median of 18.5 (6.5-72.0) microfilariae/skin snip. The OV16 RDT and OV16 ELISA were positive in, respectively, 112 (39.3%) and 143 (50.2%) individuals. The OV16 ELISA had the highest sensitivity among the three tests (83%), followed by the OV16 RDT (74.8%) and the skin snip (71.4%). The OV16 RDT had a higher specificity (98.6%) compared to the OV16 ELISA (84.8%). Our study confirms the need to develop more sensitive tests to ensure the accurate detection of ongoing transmission before stopping elimination efforts.

Urinary N-acetyltyramine-O,ß-glucuronide in Persons with Onchocerciasis-Associated Epilepsy.

We investigated urinary N-acetyltyramine-O,ß-glucuronide (NATOG) levels as a biomarker for active Onchocerca volvulus infection in an onchocerciasis-endemic area in the Democratic Republic of Congo with a high epilepsy prevalence. Urinary NATOG was measured in non-epileptic men with and without O. volvulus infection, and in O. volvulus-infected persons with epilepsy (PWE). Urinary NATOG concentration was positively associated with microfilarial density (p < 0.001). The median urinary NATOG concentration was higher in PWE (3.67 µM) compared to men without epilepsy (1.74 µM), p = 0.017; and was higher in persons with severe (7.62 µM) compared to mild epilepsy (2.16 µM); p = 0.008. Non-epileptic participants with and without O. volvulus infection had similar NATOG levels (2.23 µM and 0.71 µM, p = 0.426). In a receiver operating characteristic curve analysis to investigate the diagnostic value of urinary NATOG, the area under the curve was 0.721 (95% CI: 0.633-0.797). Using the previously proposed cut-off value of 13 µM to distinguish between an active O. volvulus infection and an uninfected state, the sensitivity was 15.9% and the specificity 95.9%. In conclusion, an O. volvulus infection is associated with an increased urinary NATOG concentration, which correlates with the individual parasitic load. However, the NATOG concentration has a low discriminating power to differentiate between infected and uninfected individuals.

Single versus Multiple Dose Ivermectin Regimen in Onchocerciasis-Infected Persons with Epilepsy Treated with Phenobarbital: A Randomized Clinical Trial in the Democratic Republic of Congo.

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.

Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial.

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 onchocerciasis-infected 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 treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975-2.799; p = 0.062). There was no significant difference in the probability of experiencing >50% reduction of the seizure frequency at month 4 between the two treatment arms. Also, treatment with ivermectin did not significantly increase the odds of being seizure-free during the individual follow-up visits. CONCLUSION: Whether ivermectin has an added value in reducing the frequency of seizures in PWE treated with AED remains to be determined. A larger study in persons with OAE on a stable AED regimen and in persons with recent epilepsy onset should be considered to further investigate the potential beneficial effect of ivermectin treatment in persons with OAE. TRIAL REGISTRATION: Registration: www.clinicaltrials.gov; NCT03052998.

Dried Blood Microsampling-Based Therapeutic Drug Monitoring of Antiepileptic Drugs in Children With Nodding Syndrome and Epilepsy in Uganda and the Democratic Republic of the Congo.

Nodding syndrome is a highly debilitating, generalized seizure disorder, affecting children in subregions of sub-Saharan Africa. Despite numerous efforts to uncover the etiology, the exact cause of this syndrome still remains obscure. Therefore, to date, patients only receive symptomatic care, including the administration of first-generation antiepileptic drugs for seizure control. As data on the efficacy of drugs within this population are completely lacking, the aim of this study was to explore how therapeutic drug monitoring could help to understand the differential response to therapy. Considering the challenging environment in which sampling had to be performed (remote areas, devoid of electricity, running water, etc), dried blood matrices [ie, dried blood spots (DBSs)] and volumetric absorptive microsampling (VAMS) were considered fit-for-purpose. In addition, owing to the similarities between the syndrome and other forms of epilepsy, samples originating from patients suffering from (onchocerciasis-associated) epilepsy were included. In total, 68 patients with Nodding syndrome from Uganda, 58 Ugandan patients with epilepsy, and 137 patients with onchocerciasis-associated epilepsy from the Democratic Republic of the Congo were included. VAMS samples and DBS were analyzed using validated methods, involving manual extraction or fully automated extraction, respectively, before quantification using liquid chromatography coupled with tandem mass spectrometry. Analysis revealed that serum concentrations (calculated from DBS) within the respective reference ranges were attained in only 52.9% of the 68 Nodding syndrome patients treated with valproic acid, in 21.4% of the 56 Ugandan epilepsy patients treated with carbamazepine, and in 65.7% of the 137 onchocerciasis-associated epilepsy patients from the Democratic Republic of the Congo treated with phenobarbital. In all other instances, concentrations were subtherapeutic. Furthermore, on comparing DBS with VAMS concentrations, an inexplicable overestimation was observed in the latter. Finally, no obvious link could be observed between the obtained drug concentrations and the number of seizures experienced during the last month before sampling, elaborating the fact that the level of improvement in some patients cannot simply be linked to reaching therapeutic concentrations.

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 investigated the clinical characteristics of onchocerciasis-associated epilepsy (OAE), and the relationship between seizure severity and 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. Sixty-three (44.1%) skin snip-positive PWE had a family history of epilepsy, compared to only 82 (32.9%) skin snip-negative PWE (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 = 0.175; p<0.001) and Aketi (Spearman-rho = 0.249; p = 0.029). In the multivariable model adjusted for age, gender, and previous treatment, high seizure frequency was associated with increasing microfilarial density in Aketi (p = 0.025) but not in Logo (p = 0.148). CONCLUSION: In onchocerciasis-endemic regions in the DRC, a wide spectrum of seizures was observed. The occurrence of Nodding seizures and Nakalanga features, as well as an association between seizure severity and O. volvulus microfilarial density suggest a high OAE prevalence in the study villages. TRIAL REGISTRATION: ClinicalTrials.gov NCT03052998.

Economic Burden of Epilepsy in Rural Ituri, Democratic Republic of Congo.

BACKGROUND: Epilepsy is still very prevalent in Sub-Saharan Africa, particularly in remote, poverty-confronted onchocerciasis-endemic villages. It constitutes a significant burden for the families and communities. However, the financial costs of managing persons with epilepsy (PWE) have not been assessed in these settings. Proper cost analyses will facilitate future health interventions. METHODS: In November 2017, persons with epilepsy (PWE) and their caretakers were recruited at health centres of the Logo health zone in the Democratic Republic of Congo. A pre-tested questionnaire was administered to collect information on both direct and indirect costs of epilepsy, as well as household income of participants. FINDINGS: The weighted mean cost of epilepsy was 241.2 USD per PWE per year (50.2% direct cost, 49.8% indirect cost). Epilepsy-related expenses represented 46.5% of the mean household income. Traditional medicine accounted for 68.2% of the direct cost. An estimated cumulative cost of 1929.6 USD attributable to epilepsy had been incurred by the populations of the Logo health zone for each PWE in the community. INTERPRETATION: Almost half of the household revenue was spent on epilepsy care. Expenses on traditional medicine must be discouraged via education and regular provision of affordable anti-epileptic drugs. Prevention of onchocerciasis-associated epilepsy using optimal control measures will avert additional epilepsy-related costs on the community. Early diagnosis and proper management of epilepsy would be economically beneficial in the study villages.

Comprehensive management of epilepsy in onchocerciasis-endemic areas: lessons learnt from community-based surveys.

BACKGROUND: Onchocerciasis-endemic regions are known to have a high epilepsy prevalence. Limited resources in these areas and poor access to healthcare by persons with epilepsy (PWE) result in a wide anti-epileptic treatment gap, poor seizure control and a high burden of seizure-related complications. Recent community-based surveys highlight the need for epilepsy management strategies suitable for remote onchocerciasis-endemic villages to ensure better health outcomes for PWE. In this paper, we propose a feasible approach to manage PWE in such settings. MAIN TEXT: Improved management of PWE in onchocerciasis-endemic areas may be achieved by decentralizing epilepsy care. Simplified approaches for the diagnosis and treatment of epilepsy may be used by non-physicians, under the supervision of physicians or specialists. To reduce the treatment gap, a regular supply of subsidized anti-epileptic drugs (AED) appropriate for different types of onchocerciasis-associated epilepsy should be instituted. Setting up a community-based epilepsy surveillance system will enable early diagnosis and treatment of PWE thereby preventing complications. Community awareness programs on epilepsy must be implemented to reduce stigma and facilitate the social rehabilitation of PWE. Finally, strengthening onchocerciasis elimination programs by optimizing community-directed treatment with ivermectin (CDTI) and considering alternative treatment strategies might reduce the incidence of epilepsy. CONCLUSIONS: A community-based approach with task-shifting of epilepsy care from specialists to non-physician health workers will reduce epilepsy-associated morbidity. Increased advocacy and collaboration with various stakeholders is needed to establish a sustainable, cost-effective chronic care model for epilepsy that will significantly improve the quality of life of PWE in onchocerciasis-endemic regions.

Community perceptions of epilepsy and its treatment in an onchocerciasis endemic region in Ituri, Democratic Republic of Congo.

BACKGROUND: A recent study in the Logo and Rethy health zones in the Ituri Province in the Democratic Republic of Congo (DRC) reported that the majority of the persons with epilepsy (PWE) had not been treated with anti-epileptic medication (AEM) or had stopped treatment. Prior to the implementation of an epilepsy treatment programme in these health zones, this study investigated the perceptions and experiences regarding epilepsy and its treatment amongst community leaders, PWE and/or their families, traditional healers and health professionals. METHODS: A total of 14 focus group discussions (FGD) and 39 semi-structured interviews (SSI) were conducted with PWE and/or their family members, community leaders, traditional healers, and health professionals in the Logo and Rethy health zones during February 2-19, 2017. RESULTS: In the two health zones, the clinical signs of convulsive epilepsy were recognized by community members. However, a variety of misconceptions about epilepsy were identified including the beliefs that epilepsy is a family-related condition, a contagious disease, is transmitted by insects, saliva or by touching a person of the same sex during seizures, or is caused by evil spirits and witchcraft. The role of traditional healers in spreading these beliefs was revealed. The study also reported sexual abuse on PWE, stigmatisation of PWE and loss of productivity of PWE and their families. Some PWE had been using AEM and traditional treatment but were not convinced about the efficacy of these treatment options. The lack of training of health providers about epilepsy care, financial barriers in obtaining AEM, and the shortage of AEM at primary health facilities were revealed. As remedies, the community requested access to a decentralized center for epilepsy treatment. They also proposed using churches and community health workers as communication channels for information about epilepsy. CONCLUSIONS: Clinical signs of convulsive epilepsy were recognized by the community in the Logo and Rethy health zones but many misconceptions about epilepsy were identified. A comprehensive community-based epilepsy treatment programme with an affordable uninterrupted AEM supply needs to be established. Such a programme should address stigma, misconceptions, sexual abuse and foster the rehabilitation of PWE to alleviate poverty.

Onchocerca volvulus as a risk factor for developing epilepsy in onchocerciasis endemic regions in the Democratic Republic of Congo: a case control study.

BACKGROUND: A high prevalence of epilepsy has been observed in onchocerciasis endemic areas in the Democratic Republic of Congo (DRC). With this study we aimed to investigate whether Onchocerca volvulus infection is a risk factor for developing epilepsy in onchocerciasis endemic regions in the DRC. METHODS: Between October and December 2015, a multi-centre case control study was performed in onchocerciasis endemic health zones (HZ) in the DRC: one study site was situated in Tshopo Province in the HZ of Wanierukula (village of Salambongo) where there had been 13 annual community distributions of treatment with ivermectin (CDTI), a second was situated in Ituri Province in the HZ of Logo (village of Draju) where ivermectin had never been distributed and in the HZ of Rethy (village of Rassia) where there had been THREE CDTI annual campaigns before the study. Individuals with unprovoked convulsive epilepsy of unknown etiology were enrolled as cases (n = 175). Randomly selected healthy members of families without epilepsy cases from the same village and age-groups and were recruited as controls (n = 170). RESULTS: Onchocerciasis associated symptoms (e.g., itching and abnormal skin) were more often present in cases compared to controls (respectively, OR = 2.63, 95% CI: 1.63-4.23, P <  0.0001 and OR = 3.23, 95% CI: 1.48-7.09, P = 0.0034). A higher number of cases was found to present with microfilariae in skin snips and with O. volvulus IgG4 antibodies in the blood compared to controls. Moreover, the microfilariae load in skin snips was 3-10 times higher in cases than controls. CONCLUSIONS: This case control study confirms that O. volvulus is a risk factor for developing epilepsy in onchocerciasis endemic regions in the DRC.

High prevalence of epilepsy in onchocerciasis endemic health areas in Democratic Republic of the Congo.

BACKGROUND: A high prevalence of epilepsy has been observed in many onchocerciasis endemic regions. This study is to estimate the prevalence of active epilepsy and exposure to Onchocerca volvulus infection in a rural population in Ituri province, Democratic Republic of Congo. METHODS: In August 2016, a community-based cross-sectional study was conducted in an onchocerciasis endemic area in the rural health zone of Logo, Ituri Province. Households within two neighbouring health areas were randomly sampled. To identify persons with epilepsy, a three-stage approach was used. In the first stage, all individuals of the selected households were screened for epilepsy by non-medical field workers using a validated 5-item questionnaire. In the second and third stage, suspected cases of epilepsy were examined by non-specialist medical doctors, and by a neurologist, respectively. A case of epilepsy was defined according to the 2014 International League Against Epilepsy (ILAE) guidelines. Exposure to O. volvulus was assessed by testing for IgG4 antibodies to an O. volvulus antigen (OV16 Rapid Test,) in individuals aged 3 years and older. RESULTS: Out of 1389 participants included in the survey, 64 were considered to have active epilepsy (prevalence 4.6%) (95% confidence interval [CI]: 3.6-5.8). The highest age-specific epilepsy prevalence estimate was observed in those aged 20 to 29 years (8.2%). Median age of epilepsy onset was 10 years, with a peak incidence of epilepsy in the 10 to 15 year-old age group. OV16 test results were available for 912 participants, of whom 30.5% (95% CI, 27.6-33.6) tested positive. The prevalence of OV16 positivity in a village ranged from 8.6 to 68.0%. After adjusting for age, gender and ivermectin use, a significant association between exposure to onchocerciasis and epilepsy was observed (adjusted odds ratio = 3.19, 95% CI: 1.63-5.64) (P < 0.001). CONCLUSIONS: A high prevalence of epilepsy and a significant association between epilepsy and exposure to O. volvulus were observed in the population in Ituri province, Democratic Republic of Congo. There is an urgent need to implement a CDTI programme and to scale up an epilepsy treatment and care programme.