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Evolution of epilepsy prevalence and incidence in a Tanzanian area endemic for onchocerciasis and the potential impact of community-directed treatment with ivermectin: a cross-sectional study and comparison over 28 years.

ABSTRACT: INTRODUCTION:Worldwide, there are an estimated 50?million people affected by epilepsy. Its aetiology is manifold, and parasitic infections play an important role, specifically onchocerciasis. In onchocerciasis endemic areas, a distinctive form of epilepsy has been described as nodding syndrome, affecting children and causing nodding seizures, mental retardation and debilitating physical development. Onchocerciasis control programmes using community-directed treatment with ivermectin (CDTI) are implemented in endemic countries. This study is designed to contribute to a better understanding of the linkage between the onset of epilepsy, onchocerciasis and CDTI. Comparing the epidemiological data on epilepsy and onchocerciasis from pre-CDTI and 20 years after its introduction will allow identifying a potential impact of ivermectin on the onset of epilepsy. METHODS AND ANALYSIS:The study will be conducted in the Mahenge highlands in Tanzania. Study site selection is based on an in-depth study on epilepsy in that area dating from 1989. CDTI was introduced in 1997. By a door-to-door approach, the population will be screened for epilepsy using a validated questionnaire. Suspected cases will be invited for a neurological examination for case verification. Onchocerciasis prevalence will be assessed by a rapid epidemiological assessment. As an indicator for ongoing transmission, children younger than 10 years of age will be tested for Ov16 antibodies. Ivermectin use will be assessed at household level. Epilepsy data will be analysed in comparison with the 1989 data to reveal pre-CDTI and post-CDTI prevalence and incidence. ETHICS AND DISSEMINATION:The protocol has received ethical approval from the ethics committees of the University of Antwerp, Belgium, and of the National Institut of Medical Research, Dar es Salaam, Tanzania. The findings will be published in peer-reviewed journals, and presented to the health authorities in Tanzania, at national, regional and village level.

SUBMITTER: Greter H

PROVIDER: S-EPMC5884367 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Evolution of epilepsy prevalence and incidence in a Tanzanian area endemic for onchocerciasis and the potential impact of community-directed treatment with ivermectin: a cross-sectional study and comparison over 28 years.

Greter Helena H Mmbando Bruno B Makunde Williams W Mnacho Mohamed M Matuja William W Kakorozya Advocatus A Suykerbuyk Patrick P Colebunders Robert R

BMJ open 20180331 3

<h4>Introduction</h4>Worldwide, there are an estimated 50 million people affected by epilepsy. Its aetiology is manifold, and parasitic infections play an important role, specifically onchocerciasis. In onchocerciasis endemic areas, a distinctive form of epilepsy has been described as nodding syndrome, affecting children and causing nodding seizures, mental retardation and debilitating physical development. Onchocerciasis control programmes using community-directed treatment with ivermectin (CDT ...[more]

PMID: 29605818

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Project description:BackgroundEpilepsy 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).MethodsThe study was conducted in January 2017 in two suburban and two rural villages in the Mahenge area. Door-to-door 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.Results5117 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 100 000 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%.ConclusionsThis 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.

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

Project description:In Burkina Faso, onchocerciasis was no longer a public health problem when the WHO Onchocerciasis Control Programme in West Africa closed at the end in 2002. However, epidemiological surveillance carried out from November 2010 to February of 2011, showed a recrudescence of infection in the Cascades Region. This finding was made at a time when ivermectin, a drug recommended for the treatment of both onchocerciasis and lymphatic filariasis, had been distributed in this area since 2004 for the elimination of lymphatic filariasis. It was surprising that ivermectin distributed for treating lymphatic filariasis had not prevented the recrudescence of onchocerciasis. Faced with this situation, the aim of our study was to evaluate the effectiveness of ivermectin on the onchocerciasis parasite. The percentage reduction in microfilarial load after treatment with ivermectin was used as a proxy measure for assessing possible resistance. A cohort study was carried out with 130 individuals who had tested positive for microfilariae of Onchocerca volvulus in 2010 using microscopic examination of skin-snip biopsies from five endemic villages. Subjects were followed from July 2011 to June 2012. The microfilarial load of each individual was enumerated by skin-snip biopsy in 2010, prior to the first ivermectin treatment against onchocerciasis under community guidelines. All individuals received two ivermectin treatments six months apart. In 2012, the microfilarial loads were determined again, six months after the second round of ivermectin and the reductions in parasite loads were calculated to measure the impact of the drug. The percentage reduction of the microfilarial loads ranged from 87% to 98% in the villages. In all villages, there was a statistically significant difference between the average microfilarial loads in 2010 and 2012. The level of reduction of microfilarial loads suggests that ivermectin is effective against the recrudescent population of O. volvulus in Cascades Region of Burkina Faso. Further investigations would be necessary to determine the causes of the recrudescence of onchocerciasis. (For French language abstract, see S1 Alternative Language Abstract-Translation of the Abstract into French by the authors.).

Project description:BackgroundIn 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 bodyFor 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 epilepsy-associated 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.ConclusionsEducating 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.

Project description:BACKGROUND:Around 2007, a nodding syndrome (NS) epidemic appeared in onchocerciasis-endemic districts of northern Uganda, where ivermectin mass distribution had never been implemented. This study evaluated the effect of community-directed treatment with ivermectin (CDTI) and ground larviciding of rivers initiated after 2009 and 2012 respectively, on the epidemiology of NS and other forms of epilepsy (OFE) in some districts of northern Uganda. 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 district (where CDTI was ongoing since 1993) served as comparative onchocerciasis-endemic sites in which larviciding had never been implemented. The comparison between 2012 and 2017 prevalence and cumulative incidence were done using the Fisher's and Pearson's Chi-square tests at 95% level of significance. RESULTS:A total of 2138 individuals in 390 households were interviewed. In the selected villages of Kitgum and Pader, there was no significant decrease in prevalence of NS and OFE between 2012 and 2017. However, the cumulative incidence of all forms of epilepsy decreased from 1165 to 130 per 100?000 persons per year (P?=?0.002); that of NS decreased from 490 to 43 per 100?000 persons per year (P?=?0.037); and for OFE from 675 to 87 per 100?000 persons per year (P?=?0.024). The median age of affected persons (NS and OFE) shifted from 13.5 (IQR: 11.0-15.0) years in 2012 to 18.0 (IQR: 15.0-20.3) years in 2017; P?<? 0.001. The age-standardized prevalence of OFE in Moyo in 2017 was 4.6%, similar to 4.5% in Kitgum and Pader. 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.

Project description:BACKGROUND:Many studies have reported an association between epilepsy, nodding syndrome (NS), and onchocerciasis (river blindness). A high prevalence of epilepsy has been noted particularly in onchocerciasis hyperendemic areas where onchocerciasis is not or insufficiently controlled with mass ivermectin distribution. There is evidence that increasing the coverage of ivermectin reduces the incidence of epilepsy, and anecdotal evidence suggests a reduction in seizure frequency in onchocerciasis-associated epilepsy (OAE) patients who receive ivermectin. Finding an alternative treatment for epilepsy in these patients will have major consequences. OBJECTIVE:The goal of the study is to assess whether ivermectin treatment decreases the frequency of seizures and leads to seizure freedom in OAE patients, including patients with NS. If we are able to demonstrate such an effect, this would strengthen the argument that onchocerciasis is causing epilepsy and therefore we should increase our efforts to eliminate onchocerciasis. METHODS:We will conduct a randomized clinical trial in the Democratic Republic of Congo to compare seizure freedom in onchocerciasis-infested epilepsy patients who receive immediate ivermectin treatment with delayed (after 4 months) ivermectin treatment. All participants will simultaneously receive antiepilepsy drugs (AEDs) according to local guidelines for epilepsy treatment. The primary endpoint is seizure freedom defined as no seizures during the 4 month of follow-up. Secondary endpoint is significant (>50%) seizure reduction compared to baseline seizure frequency. Reduction of seizures will be compared between ivermectin and nonivermectin arms. RESULTS:Start of enrollment is planned for August 2017, and we expect to have enrolled all 110 participants by December 2017. Results are expected in June 2018. CONCLUSIONS:If ivermectin treatment in addition to AEDs is able to lead to seizure freedom or significantly reduces seizure frequency in OAE patients, this will have major consequences for epilepsy treatment in onchocerciasis-endemic regions. Ivermectin is donated for free and in non Loa-Loa-endemic regions has negligible side effects. Reducing the burden of epilepsy will have a major impact on quality of life and socioeconomic status of families with affected members in Africa. TRIAL REGISTRATION:ClinicalTrials.gov NCT03052998; https://clinicaltrials.gov/ct2/show/NCT03052998 (Archived by WebCite at http://www.webcitation.org/6roFVQSG0).

Dataset Information

Evolution of epilepsy prevalence and incidence in a Tanzanian area endemic for onchocerciasis and the potential impact of community-directed treatment with ivermectin: a cross-sectional study and comparison over 28 years.

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Evolution of epilepsy prevalence and incidence in a Tanzanian area endemic for onchocerciasis and the potential impact of community-directed treatment with ivermectin: a cross-sectional study and comparison over 28 years.

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