Evaluation of Onchocerciasis: A Decade of Post Treatment with Ivermectin in Zainabi and Ririwai Doguwa Local Government Area of Kano State

Rapid Assessment Method (RAM) were carried out to assess the current situation of Onchocerciasis after repetition of annual community directed distribution of Ivermectin in Zainabi and Ririwai of Doguwa Local Government area of Kano State. Certain manifestations, like nodules, leopard skin and blindness, were used to measure the endemicity level in the community. The subjects of 30 - 50 years who are engaged in rural occupation, resident in that community, were examined for the presence of nodules, skin lesion and blindness. The common manifestation in both communities is nodules with 3 (3.40%) and 2 (3.44%). Leopard skin and blindness were found in Zainabi with 2 (2.27%) and 2 (2.27%). The manifestation of Onchocerciasis was found in older age groups of 49 - 70 and 50 - 69 respectively, which give an indication that the disease was eliminated in the community due to mass distribution of Ivermectin in the previously known endemic community. We recommend mass distribution of Mectizan in other identified endemic foci.

Elimination of onchocerciasis in Africa by 2025:the need for a broad perspective

Background:In response to the recent publication Is onchocerciasis elimination in Africa feasible by 2025:a perspective based on lessons learnt from the African control programmes"by Dadzie et al.,it is important to clarify and highlight the positive and unequivocal research and operational contributions from the American experience towards the worldwide elimination of human onchocerciasis(river blindness).Main text:The strategies of twice or more rounds of mass drug administration(MDA)of ivermectin per year,as well as the use of OV-16 serology have allowed four American countries to be verified by World Health Organization to have eliminated transmission of Onchocerca volvulus,the etiological agent.These advances were also implemented in Sudan and Uganda;currently,both are the only African countries where ivermectin MDA was safely stopped in several transmission zones.Conclusions:Programmatic treatment and evaluation approaches,pioneered in the Americas,are the most efficient among the existing tools for elimination,and their broader use could catalyze the successful elimination of this disease in Africa.

Impact of five annual rounds of mass drug administration with ivermectin on onchocerciasis in Sierra Leone

Background:Onchocerciasis is endemic in 12 of the 14 health districts of Sierra Leone.Good treatment coverage of community-directed treatment with ivermectin was achieved between 2005 and 2009 after the 11-year civil conflict.Sentinel site surveys were conducted in 2010 to evaluate the impact of five annual rounds of ivermectin distribution.Methods:In total,39 sentinel villages from hyper-and meso-endemic areas across the 12 endemic districts were surveyed using skin snips in 2010.Results were analyzed and compared with the baseline data from the same 39 villages.Results:The average microfilaridermia(MF)prevalence across 39 sentinel villages was 53.10%at baseline.The MF prevalence was higher in older age groups,with the lowest in the age group of 1-9 years(11.00%)and the highest in the age group of 40-49 years(82.31%).Overall mean MF density among the positives was 28.87 microfilariae(mf)/snip,increasing with age with the lowest in the age group of 1-9 years and the highest in the age group of 40-49 years.Males had higher MF prevalence and density than females.In 2010 after five rounds of mass drug administration,the overall MF prevalence decreased by 60.26%from 53.10%to 21.10%;the overall mean MF density among the positives decreased by 71.29%from 28.87 mf/snip to 8.29 mf/snip;and the overall mean MF density among all persons examined decreased by 88.58%from 15.33 mf/snip to 1.75 mf/snip.Ten of 12 endemic districts had>50%reduction in MF prevalence.Eleven of 12 districts had≥50%reduction in mean MF density among the positives.Conclusions:A significant reduction of onchocerciasis MF prevalence and mean density was recorded in all 12 districts of Sierra Leone after five annual MDAs with effective treatment coverage.The results suggested that the onchocerciasis elimination programme in Sierra Leone was on course to reach the objective of eliminating onchocerciasis in the country by the year 2025.Annual MDA with ivermectin should continue in all 12 districts and further evaluations are needed across the country to assist the NTDP with programme decision making.

The positive influence the Onchocerciasis Elimination Program for the Americas has had on Africa programs

A recent article Is onchocerciasis elimination in Africa feasible by 2025:a perspective based on lessons learnt from the African control programmesH in Infectious Diseases of Poverty claimed that undue influence on African programs by concepts developed by the Onchocerciasis Elimination Program of the Americas(OEPA)is detrimental to stopping mass drug administration(MDA)in Africa.This claim is made despite a record year for MDA stoppage in four African countries of>3.5 million treatments in 2018,far exceeding any past OEPA or African Program for Onchocerciasis Control(APOC)stop MDA success.

Progress towards onchocerciasis elimination in the participating countries of the African Programme for Onchocerciasis Control: epidemiological evaluation results

Background:The African Programme for Onchocerciasis Control(APOC)was created in 1995 to establish community-directed treatment with ivermectin(CDTi)in order to control onchocerciasis as a public health problem in 20 African countries that had 80%of the global disease burden.When research showed that CDTi may ultimately eliminate onchocerciasis infection,APOC was given in 2008 the additional objective to determine when and where treatment can be safely stopped.We report the results of epidemiological evaluations undertaken from 2008 to 2014 to assess progress towards elimination in CDTi areas with≥6 years treatment.Methods:Skin snip surveys were undertaken in samples of first-line villages to determine the prevalence of O.volvulus microfilariae.There were two evaluation phases.The decline in prevalence was evaluated in phase 1A.Observed and model-predicted prevalences were compared after correcting for endemicity level and treatment coverage.Bayesian statistics and Monte Carlo simulation were used to classify the decline in prevalence as faster than predicted,on track or delayed.Where the prevalence approached elimination levels,phase 1B was launched to determine if treatment could be safely stopped.Village sampling was extended to the whole CDTi area.Survey data were analysed within a Bayesian framework to determine if stopping criteria(overall prevalence<1.4%and maximum stratum prevalence<5%)were met.Results:In phase 1A 127665 people from 639 villages in 54 areas were examined.The prevalence had fallen dramatically.The decline in prevalence was faster than predicted in 23 areas,on track in another 23 and delayed in eight areas.In phase 1B 108636 people in 392 villages were examined in 22 areas of which 13 met the epidemiological criteria for stopping treatment.Overall,32 areas(25.4 million people)had reached or were close to elimination,18 areas(17.4 million)were on track but required more years treatment,and in eight areas(10.4 million)progress was unsatisfactory.Conclusions:Onchocerciasis has been largely controlled as a public health problem.Great progress has been made towards elimination which already appears to have been achieved for millions of people.For most APOC countries,nationwide onchocerciasis elimination is within reach.

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.

High prevalence of epilepsy in two rural onchocerciasis endemic villages in the Mahenge area,Tanzania,after 20 years of community directed treatment with ivermectin

Background:Epilepsy is a neurological disorder with a multitude of underlying causes,which may include infection with Onchocerca volvulus,the parasitic worm that causes human onchocerciasis.A survey carried out in 1989 revealed a high prevalence of epilepsy(1.02%overall,ranging from 0.51 to 3.71%in ten villages)in the Mahenge area of Ulanga district,an onchocerciasis endemic region in south eastern Tanzania.This study aimed to determine the prevalence and incidence of epilepsy following 20 years of onchocerciasis control through annual community directed treatment with ivermectin(CDTI).Methods:The study was conducted in January 2017 in two suburban and two rural villages in the Mahenge area.Door-todoor household visits were carried out by trained community health workers and data assistants to screen for persons suspected of having epilepsy,using a standardised questionnaire.Persons with suspected epilepsy were then interviewed and examined by a neurologist for case verification.Onchocerciasis associated epilepsy was defined as epilepsy without an obvious cause,with an onset of seizures between the ages of 3-18 years in previously healthy children.In each village,fifty males aged≥20 years were tested for onchocerciasis antibodies using an OV16 rapid test and were examined for presence of onchocerciasis nodules.Children aged 6-10 years were also tested using OV16 tests.Results:5117 individuals(median age 18.5 years,53.2%female)from 1168 households were screened.244(4.8%)were suspected of having epilepsy and invited for neurological assessment.Prevalence of epilepsy was 2.5%,with the rural villages having the highest rate(3.5%vs 1.5%),P<0.001.Overall incidence of epilepsy was 111 cases(95%CI:73-161)per 100000 person-years,while that of onchocerciasis associated epilepsy was 131(95%CI:70-223).Prevalence of OV16 antibodies in adult males and among children 6-10 years old was higher in rural villages than in suburban villages(76.5%vs 50.6,and 42.6%vs 4.7%respectively),(P<0.001),while overall prevalence of onchocerciasis nodules was 1.8%.Conclusions:This survey revealed a high prevalence and incidence of epilepsy in two rural onchocerciasis endemic villages in the Mahenge area.Despite 20 years of CDTI,a high prevalence of OV16 antibodies in children aged 6-10 years suggests on-going O.volvulus transmission.Reasons for the persistence of on-going parasite transmission in the Mahenge area need to be investigated.

Burden of onchocerciasis-associated epilepsy:first estimates and research priorities

Background:Since the 1990s,evidence has accumulated of an increased prevalence of epilepsy in onchocerciasisendemic areas in Africa as compared to onchocerciasis-free areas.Although the causal relationship between onchocerciasis and epilepsy has yet to be proven,there is likely an association.Here we discuss the need for disease burden estimates of onchocerciasis-associated epilepsy(OAE),provide them,detail how such estimates should be refined,and discuss the socioeconomic impact of OAE,including a cost-estimate for anti-epileptic drugs.Main body:Providing OAE burden estimates may aid prevention of epilepsy in onchocerciasis-endemic areas by inciting and informing collaboration between onchocerciasis control programmes and mental health services.Epilepsy not only massively impacts the health of those affected,but it also carries a high socioeconomic burden for the households and communities involved.We used previously published geospatial estimates of onchocerciasis in Africa and a separately published logistic regression model quantifying the association between onchocerciasis and epilepsy to estimate the number of OAE cases.We then applied disability weights for epilepsy to quantify the burden in terms of years of life lived with disability(YLD)and estimate the cost of treatment.We estimate that in 2015 roughly 117000 people were affected by OAE across onchocerciasis-endemic areas previously under the African Programme for Onchocerciases control(APOC)mandate where OAE has ever been reported or suspected,and another 264000 persons in onchocerciasis-endemic areas where OAE has never been investigated before.The total number of YLDs due to OAE was 39300 and 88700 in these areas respectively,based on a weighted mean disability weight of 0.336.The burden of OAE is approximately 13%of the total YLDs attributable to onchocerciasis and 10%of total YLDs attributable to epilepsy.We estimated that by 2015 the total costs of treatment with antiepileptic drug for OAE cases would have been a minimum of 12.4 million US$.Conclusions:These estimates suggest a considerable health,social and economic burden of OAE in Africa.The treatment and care for people with epilepsy,especially in hyperendemic onchocerciasis areas with high epilepsy prevalence thus requires more financial and human resources.

Is onchocerciasis elimination in Africa feasible by 2025:a perspective based on lessons learnt from the African control programmes

Background:Onchocerciasis is found predominantly in Africa where large scale vector control started in 1974.Registration and donation of ivermectin by Merck&Co in 1987 enabled mass treatment with ivermectin in all endemic countries in Africa and the Americas.Although elimination of onchocerciasis with ivermectin was considered feasible only in the Americas,recently it has been shown possible in Africa too,necessitating fundamental changes in technical and operational approaches and procedures.Main body:The American programme(OEPA)operating in onchocerciasis epidemiological settings similar to the mild end of the complex epidemiology of onchocerciasis in Africa,has succeeded in eliminating onchocerciasis from 4 of its 6 endemic countries.This was achieved through biannual mass treatment with ivermectin of 85%of the eligible population,and monitoring and evaluation using serological tests in children and entomological tests.The first African programme(OCP)had a head start of nearly two decades.It employed vector control and accumulated lots of knowledge on the dynamics of onchocerciasis elimination over a wide range of epidemiological settings in the vast expanse of its core area.OCP made extensive use of modelling and operationalised elimination indicators for entomological evaluation and epidemiological evaluation using skin snip procedures.The successor African programme(APOC)employed mainly ivermectin treatment.Initially its objective was to control onchocerciasis as a public health problem but that objective was later expanded to include the elimination of onchocerciasis where feasible.Building on the experience with onchocerciasis elimination of the OCP,APOC has leveraged OCP’s vast modelling experience and has developed operational procedures and indicators for evaluating progress towards elimination and stopping ivermectin mass treatment of onchocerciasis in the complex African setting.Conclusions:Following the closure of APOC in 2015,implementation of onchocerciasis elimination in Africa appears to overlook all the experience that has been accumulated by the African programmes.It is employing predominantly American processes that were developed in a dissimilar setting from the complex African onchocerciasis setting.This is impeding progress towards decisions to stop intervention in many areas that have reached the elimination point.This article summarizes lessons learned in Africa and their importance for achieving elimination in Africa by 2025.

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.

Low prevalence of epilepsy and onchocerciasis after more than 20 years of ivermectin treatment in the Imo River Basin in Nigeria

Background:High epilepsy prevalence and incidence have been reported in areas with high onchocerciasis transmission.Recent findings suggest that proper community-directed treatment with ivermectin(CDTI)is potentially able to prevent onchocerciasis-associated epilepsy(OAE).We assessed the epilepsy prevalence and onchocerciasis transmission in two Nigerian villages following more than 20 years of CDTI.Methods:A cross-sectional door-to-door survey was performed in two villages in the Imo River Basin reported to be mesoendomic for onchocerciasis(Umuoparaodu and Umuezeala).Individuals were screened for epilepsy using a validated 5-item questionnaire.Persons suspected to have epilepsy were examined by a neurologist or a physician with training in epilepsy for confirmation.Onchocerciasis was investigated via skin snip microscopy and rapid diagnostic tests for Ov16 antibodies.Results were compared with previous findings from the Imo river basin.Results:A total of 843 individuals from 257 households in the two villages were encountered.We detected four persons with epilepsy(PWE)giving a crude epilepsy prevalence of 0.5%.This finding differs from observations reported 14 years ago which showed an epilepsy prevalence of 2.8%in the neighbouring village of Umulolo(P=0.0001),and 1.2%from 13 villages in the Imo river basin(P=0.07).The seroprevalence of Ov16 antibodies was found to be 0%.Only 4.6%of skin snips were positive compared to 26.8%in previous surveys(P<0.0001).Ivermectin mass distribution coverage in the study sites in 2017 was 79.7%.Conclusions:A low epilepsy and onchocerciasis prevalence was observed following more than 20 years of CDTI in the Imo River Basin.Absence of Ov16 antibodies indicates minimal transmission of onchocerciasis.These results contrast with observations from areas of high onchocerciasis transmission,where epilepsy prevalence and incidence remain high.Findings from this study suggest that sustained efforts could eventually achieve elimination of onchocerciasis in these villages.

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.

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.

Hypo-endemic onchocerciasis hotspots: defining areas of high risk through micro-mapping and environmental delineation

Background:Onchocerciasis(river blindness)caused by the parasite Onchocercavolvulus and transmitted by riverine Simulium spp.(Black flies)is targeted for elimination in Africa.This is a significant change in strategy from the‘control’of meso-and hyper-endemic areas through mass drug administration(MDA)with Mectizan®(ivermectin),to the‘elimination’in all endemic areas where a range of interventions may be required.The most significant challenges of elimination in low transmission or hypo-endemic areas are two-fold.First,there are vast remote areas where the focality of low transmission is relatively undefined.Second,the treatment with ivermectin increases the risk of serious adverse events(SAEs)in individuals with high parasitaemias of Loa loa,a filarial parasite widespread in Central and West Africa,which causes Tropical eye worm and transmitted by Chrysops spp.(Deer flies).Discussion:We therefore propose novel mapping approaches using remote sensing satellite and modelled environmental data to be used in combination with rapid field surveys to help resolve the problems of targeting the expansion of onchocerciasis elimination activities in L.loa co-endemic areas.First,we demonstrate that micro-stratification overlap mapping(MOM)of available onchocerciasis and loiasis prevalence maps can be used to identify 12 key high risk areas,where low O.volvulusand high L.loa transmission overlap,which we define as“hypo-endemic hotspots”.Second we show that integrated micro-mapping of prevalence data,and the use of environmental data to delineate riverine and forest risk factors associated with Simulium spp.and Chrysops spp.vector habitats can further help to define target intervention areas i.e.secondary hotspots within hotspots,to help avoid the risk of SAEs.Summary:These mapping examples demonstrate the value of bringing prevalence,entomological and ecological information together to develop maps for planned implementation and targeted strategies.This is critical as better mapping may the reduce costs and lower the L.loa associated risks,especially if there are extensive areas of low endemicity that may require treatment with ivermectin or alternative strategies.Novel cost-effective approaches are necessary if elimination of O.volvulus transmission in Africa is to be achieved in an efficient and safe way by the goal of 2025.

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.

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.

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.

Would ivermectin for malaria control be beneficial in onchocerciasis-endemic regions?

Background:There is accumulating evidence supporting the use of ivermectin as a malaria control tool.Recent findings from the repeat ivermectin mass drug administrations for control of malaria trial demonstrated a reduced incidence of malaria in villages which received repeated ivermectin mass drug administration(MDA;six doses)compared to those who had only one round of ivermectin.Several other studies investigating the benefits of ivermectin for malaria purposes are ongoing/planned.Main text:While ivermectin MDA offers promising perspectives in the fight against malaria,we highlight the added benefits and anticipated challenges of conducting future studies in onchocerciasis-endemic regions,which are confronted with a substantial disease burden including onchocerciasis-associated epilepsy.Increasing the frequency of ivermectin MDA in such places may reduce the burden of both malaria and onchocerciasis,and allow for more entomological investigations on both the Anopheles mosquitoes and the blackflies.Upfront,acceptability and feasibility studies are needed to assess the endorsement by the local populations,as well as the programmatic feasibility of implementing ivermectin MDA several times a year.Conclusions:Onchocerciasis-endemic sites would doubly benefit from ivermectin MDA interventions,as these will alleviate onchocerciasis-associated morbidity and mortality,while potentially curbing malaria transmission.Involving onchocerciasis programs and other relevant stakeholders in the malaria/ivermectin research agenda would foster the implementation of pluri-annual MDA in target communities.

Reaching the last mile:main challenges relating to and recommendations to accelerate onchocerciasis elimination in Africa

Background:Onchocerciasis(river blindness),caused by the filarial worm speciesOnchocerca volvulus,is a serious vector-borne neglected tropical disease(NTD)of public health and socioeconomic concern.It is transmitted through the bite of black flies of the genusSimulium,and manifested in dermal and ocular lesions.Ninety-nine percent of the total global risk and burden of onchocerciasis is in Africa.This scoping review examines the key challenges related to the elimination of onchocerciasis by 2020-2025 in Africa,and proposes recommendations to overcome the challenges and accelerate disease elimination.To find relevant articles published in peer-reviewed journals,a search of PubMed and Google Scholar databases was carried out.Main text:Rigorous regional interventions carried out to control and eliminate onchocerciasis in the past four decades in Africa have been effective in bringing the disease burden under control;it is currently not a public health problem in most endemic areas.Notably,transmission of the parasite is interrupted in some hyperendemic localities.Recently,there has been a policy shift from control to complete disease elimination by 2020 in selected countries and by 2025 in the majority of endemic African countries.The WHO has published guidelines for stopping mass drug administration(MDA)and verifying the interruption of transmission and elimination of human onchocerciasis.Therefore,countries have revised their plans,established a goal of disease elimination in line with an evidence based decision to stop MDA and verify elimination,and incorporated it into their NTDs national master plans.Nevertheless,challenges remain pertaining to the elimination of onchocerciasis in Africa.The challenge we review in this paper are:incomplete elimination mapping of all transmission zones,co-endemicity of onchocerciasis and loiasis,possible emergence of ivermectin resistance,uncoordinated cross-border elimination efforts,conflict and civil unrest,suboptimal program implementation,and technical and financial challenges.This paper also proposes recommendations to overcome the challenges and accelerate disease elimination.These are:a need for complete disease elimination mapping,a need for collaborative elimination activities between national programs,a need for a different drug distribution approach in conflict-affected areas,a need for routine monitoring and evaluation of MDA programs,a need for implementing alternative treatment strategies(ATSs)in areas with elimination anticipated beyond 2025,and a need for strong partnerships and continued funding.Conclusions:National programs need to regularly monitor and evaluate the performance and progress of their interventions,while envisaging the complete elimination of onchocerciasis from their territory.Factors hindering the targeted goal of interruption of parasite transmission need to be identified and remedial actions should be taken.If possible and appropriate,ATSs need to be implemented to accelerate disease elimination by 2025.

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.