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

Background:Around 2007,a nodding syndrome(NS)epidemic appeared in onchocerciasis-endemic districts of northern Uganda,where ivermeain 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.Methods: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 distria(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.Results:A total of 2138 individuals in 390 households were interviewed.In the seleaed 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 100000 persons per year(P=0.002);that of NS decreased from 490 to 43 per 100000 persons per year(P=0.037);and for OFE from 675 to 87 per 100000 persons per year(P=0.024).The median age of affeaed 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.Conclusions: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.

Qualitative evaluation of the outcomes of care and treatment for children and adolescents with nodding syndrome and other epilepsies in Uganda

Background:In 2012,the Ugandan Government declared an epidemic of Nodding Syndrome(NS)in the Northern districts of Gulu,Kitgum,Lamwo and Pader.Treatment guidelines were developed and NS treatment centres were established to provide symptomatic control and rehabilitation.However,a wide gap remained between the predefined care standards and the quality of routine care provided to those affected.This study is to qualitatively assess adherence to accepted clinical care standards for NS;identify gaps in the care of affected children and offer Clinical Support Supervision(CSS)to Primary Health Care(PHC)staff at the treatment centres;and identify psychosocial challenges faced by affected children and their caregivers.Methods:This case study was carried out in the districts of Gulu,Kitgum,Lamwo and Pader in Uganda from September to December in 2015.Employing the 5-stage approach of Clinical Audit,data were collected through direct observations and interviews with PHC providers working in public and private-not-for-profit health facilities,as well as with caregivers and political leaders.The qualitative data was analysed using Seidel model of data processing.Results:Clinical Audit and CSS revealed poor adherence to treatment guidelines.Many affected children had suboptimal NS management resulting in poor seizure control and complications including severe burns.Root causes of these outcomes were frequent antiepileptic drugs stock outs,migration of health workers from their work stations and psychosocial issues.There was hardly any specialized multidisciplinary team(MDT)to provide for the complex rehabilitation needs of the patients and a task shifting model with inadequate support supervision was employed,leading to loss of skills learnt.Reported psychosocial and psychosexual issues associated with NS included early pregnancies,public display of sexual behaviours and child abuse.Conclusions:Despite involvement of relevant MDT members in the development of multidisciplinary NS guidelines,multidisciplinary care was not implemented in practice.There is urgent need to review the NS clinical guidelines.Quarterly CSS and consistent anticonvulsant medication are needed at health facilities in affected communities.Implementation of the existing policies and programs to deal with the psychosocial and psychosexual issues that affect children with NS and other chronic conditions is needed.

Treatment and prevention of epilepsy in onchocerciasis-endemic areas is urgently needed

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.

Epidemiology of onchocerciasis-associated epilepsy in the Mbam and Sanaga river valleys of Cameroon:impact of more than 13 years of ivermectin

Background:A high epilepsy prevalence has been reported in several onchocerciasis-endemic villages along the Mbam and Sanaga river valleys in Cameroon,including Bilomo and Kelleng.We sought to determine the prevalence of epilepsy in these two villages following more than 13 years of community-directed treatment with ivermectin(CDTI).Methods:Door-to-door surveys were performed on the entire resident population in the villages in August 2017 and January 2018.Epilepsy was diagnosed using a 2-step approach:administration of a standardized 5-item questionnaire followed by confirmation by a neurologist.Previously published diagnostic criteria for onchocerciasis-associated epilepsy(OAE)were used.Ov16 serology was done for children aged 7-10 years to assess onchocerciasis transmission.Findings were compared with previous data from these two villages.Results:A total of 1525 individuals(1321 in Bilomo and 204 in Kelleng)in 233 households were surveyed in both villages.The crude prevalence of epilepsy was 4.6%in Bilomo(2017)and 7.8%in Kelleng(2018),including 12(15.6%of cases)persons with epilepsy(PWE)with nodding seizures.The age and sex-standardized prevalence in Kelleng decreased from 13.5%in 2004 to 9.3%in 2018(P<0.001).The median age of PWE shifted from 17(IQR:12-22)years to 24(IQR:20-30)years in Bilomo(P<0.001);and slightly from 24(IQR:14-34)years to 28(IQR:21.25-36.75)years in Kelleng(P=0.112).Furthermore,47.6%of all tested children between 7 and 10 years had Ov16 antibodies.Conclusions:There is a decrease in epilepsy prevalence after 13 years and more of CDTI in both villages.The age-shift observed in PWE suggests that ivermectin may prevent OAE in younger residents.Ov16 seropositivity in children indicates ongoing onchocerciasis transmission possibly due to suboptimal control measures.Our findings support the existence of OAE in Cameroon and highlight the need to strengthen onchocerciasis elimination programs.

Report of the first international workshop on onchocerciasis-associated epilepsy

Background:Recently,several epidemiological studies performed in Onchocerca volvulus-endemic regions have suggested that onchocerciasis-associated epilepsy(OAE)may constitute an important but neglected public health problem in many countries where onchocerciasis is still endemic.Main text:On October 12-14th 2017,the first international workshop on onchocerciasis-associated epilepsy(OAE)was held in Antwerp,Belgium.The workshop was attended by 79 participants from 20 different countries.Recent research findings strongly suggest that O.volvulus is an important contributor to epilepsy,particularly in meso-and hyperendemic areas for onchocerciasis.Infection with O.volvulus is associated with a spectrum of epileptic seizures,mainly generalised tonic-clonic seizures but also atonic neck seizures(nodding),and stunted growth.OAE is characterised by an onset of seizures between the ages of 3-18 years.Multidisciplinary working groups discussed topics such as how to 1)strengthen the evidence for an association between onchocerciasis and epilepsy,2)determine the burden of disease caused by OAE,3)prevent OAE,4)improve the treatment/care for persons with OAE and affected families,5)identify the pathophysiological mechanism of OAE,and 6)deal with misconceptions,stigma,discrimination and gender violence associated with OAE.An OAE Alliance was created to increase awareness about OAE and its public health importance,stimulate research and disseminate research findings,and create partnerships between OAE researchers,communities,advocacy groups,ministries of health,non-governmental organisations,the pharmaceutical industry and funding organizations.Conclusions:Although the exact pathophysiological mechanism underlying OAE remains unknown,there is increasing evidence that by controlling and eliminating onchocerciasis,OAE will also disappear.Therefore,OAE constitutes an additional argument for strengthening onchocerciasis elimination efforts.Given the high numbers of people with epilepsy in O.volvulus-endemic regions,more advocacy is urgently needed to provide anti-epileptic treatment to improve the quality of life of these individuals and their families.

The World Health Organization road map for neglected tropical diseases 2021-2030:implications for onchocerciasis elimination programs

In its new roadmap for neglected tropical diseases,the World Health Organization proposes three important strategic shifts:(i)Stronger accountability which shifting from process to impact indicators;(ii)Intensified cross-cutting approaches;and(iii)Stronger country ownership.In this paper we discuss the implementation of these three strategies in the setting of a high onchocerciasis disease burden in South Sudan.

Stigma and epilepsy in onchocerciasisendemic regions in Africa:a review and recommendations from the onchocerciasisassociated epilepsy working group

Background:In onchocerciasis-endemic areas,particularly in those with a sub-optimal onchocerciasis control programme,a high prevalence of epilepsy is observed.Both onchocerciasis and epilepsy are stigmatizing conditions.The first international workshop on onchocerciasis-associated epilepsy(OAE)was held in Antwerp,Belgium(12-14 October 2017)and during this meeting,an OAE alliance was established.In this paper,we review what is known about epilepsy-associated stigma in onchocerciasis-endemic regions,and present the recommendations of the OAE alliance working group on stigma.Main body:For this scoping review,literature searches were performed on the electronic databases PubMed,Scopus and Science Direct using the search terms"epilepsy AND onchocerciasis AND stigma".Hand searches were also undertaken using Google Scholar,and in total seven papers were identified that addressed epilepsy-related stigma in an onchocercisasis-endemic area.Due to the limited number of published research papers on epilepsyassociated stigma in onchocerciasis-endemic areas,other relevant literature that describes important aspects related to stigma is discussed.The thematic presentation of this scoping review follows key insights on the barriers to alleviating the social consequences of stigma in highly affected onchocerciasis-endemic areas,which were established by experts during the working group on stigma and discrimination at the first international workshop on OAE.These themes are:knowledge gaps,perceived disease aetiology,access to education,marriage restrictions,psycho-social well-being,burden on the care-giver and treatment seeking behaviour.Based on the literature and expert discussions during the OAE working group on stigma,this paper describes important issues regarding epilepsy-related stigma in onchocerciasis-endemic regions and recommends interventions that are needed to reduce stigma and discrimination for the improvement of the psycho-social well-being of persons with epilepsy.Conclusions:Educating healthcare workers and communities about OAE,strengthening onchocerciasis elimination programs,decreasing the anti-epileptic treatment gap,improving the care of epilepsy-related injuries,and prioritising epilepsy research is the way forward to decreasing the stigma associated with epilepsy in onchocerciasis-endemic regions.

The effect of bi-annual community-directed treatment with ivermectin on the incidence of epilepsy in onchocerciasis endemic villages in South Sudan:a study protocol

Background:Nodding 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 onchocerciasisendemic areas in South Sudan.Methods:A 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.Discussion:Our 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.