From river blindness to river epilepsy: Implications for onchocerciasis elimination programmes

Colebunders, Robert; Fodjo, Joseph Nelson Siewe; Hopkins, Adrian; Hotterbeekx, An; Lakwo, Thomson; Kalinga, Akili; Logora, Makoy Yibi; Basáñez, María‐Gloria

doi:10.1371/journal.pntd.0007407

Cited by 54 publications

(73 citation statements)

References 23 publications

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“…A simple OAE clinical case definition was proposed (Colebunders et al 2018d) and later refined (Colebunders et al 2019). Initially there was a reluctance to use this definition in epidemiological studies (Kaiser et al 2019).…”

Section: Clinical Studiesmentioning

confidence: 99%

“…Initially there was a reluctance to use this definition in epidemiological studies (Kaiser et al 2019). However today there is growing support for using this definition as a tool to identify hotspots of high-ongoing onchocerciasis transmission (Mmbando et al 2018;Colebunders et al 2019). In onchocerciasis-endemic regions with high epilepsy prevalence such as in Cameroon and South Sudan, >70% of PWE satisfied the OAE criteria (Colebunders et al 2018a;Siewe Fodjo et al 2019c).…”

Section: Clinical Studiesmentioning

confidence: 99%

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Nodding syndrome research, lessons learned from the NSETHIO project

et al. 2019

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Background.Until recently, nodding syndrome (NS) was considered as a mysterious disease of unknown etiology. A link between onchocerciasis and epilepsy was suspected for a long time. However, onchocerciasis was not considered as the cause of NS because NS was believed to occur only in onchocerciasis-endemic regions in Uganda, South Sudan, and Tanzania. In October 2015, with funding from the European Research Council, the NSETHIO group launched a trans-disciplinary, multi-country research project to identify the cause of NS and to study the link between onchocerciasis and epilepsy.Methods.We reviewed NSETHIO activities as well as all published papers, and compared project findings with results of previous research on NS.ResultsFindings from the NSETHIO project showed that NS is only one of the clinical manifestations in the wide spectrum of onchocerciasis-associated epilepsy (OAE) that could be prevented by strengthening onchocerciasis elimination programs. NSETHIO demonstrated that OAE is an important neglected public health problem in onchocerciasis-endemic areas with no or a sub-optimally functioning onchocerciasis control strategies.Conclusions.Today there is overwhelming evidence that NS together with the Nakalanga syndrome is clinical presentations of OAE, a condition that could be prevented by strengthening onchocerciasis elimination programs. While research needs to continue to elucidate the pathophysiological mechanisms causing NS, new strategies to accelerate onchocerciasis elimination coupled with community-based surveillance and treatment programs for epilepsy are urgently needed in areas of high Onchocerca volvulus transmission.

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Section: Clinical Studiesmentioning

confidence: 99%

Section: Clinical Studiesmentioning

confidence: 99%

Nodding syndrome research, lessons learned from the NSETHIO project

et al. 2019

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“…Between October and November 2017, a community-based treatment of epilepsy was initiated and 387 persons with confirmed epilepsy (PWE) were enrolled in the program. Ninety-four of them who met the criteria for onchocerciasis-associated epilepsy (OAE) [8], and who experienced at least two seizures per month by the time of assessment, were enrolled in a four-month proof-of-concept trial. A multiple logistic regression analysis showed a borderline insignificant association at 5% significance level between ivermectin treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975-2.799; p = 0.062) [9].…”

Section: Introductionmentioning

confidence: 99%

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

Mandro¹,

Fodjo

Dusabimana

et al. 2020

Pathogens

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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.

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“…A high prevalence of epilepsy has been reported in onchocerciasis-endemic regions, particularly in areas with ongoing onchocerciasis transmission [2]. OAE is characterized by the onset of seizures in previously healthy children between the age of 3-18 years, without an obvious cause for the epilepsy [3]. The spectrum of OAE is wide, ranging from different seizure types to Nodding and Nakalanga syndromes [3].…”

Section: Introductionmentioning

confidence: 99%

“…OAE is characterized by the onset of seizures in previously healthy children between the age of 3-18 years, without an obvious cause for the epilepsy [3]. The spectrum of OAE is wide, ranging from different seizure types to Nodding and Nakalanga syndromes [3]. In a meta-analysis of eight studies in onchocerciasisendemic African countries, Pion et al reported that a 10% increase in the prevalence of onchocerciasis results in a 0.4% increase in epilepsy prevalence [4].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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 onchocerciasisinfected 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

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From river blindness to river epilepsy: Implications for onchocerciasis elimination programmes

Cited by 54 publications

References 23 publications

Nodding syndrome research, lessons learned from the NSETHIO project

Nodding syndrome research, lessons learned from the NSETHIO project

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

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

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