Ivermectin Treatment in Patients With Onchocerciasis-Associated Epilepsy: Protocol of a Randomized Clinical Trial

Colebunders, Robert; Mandro, Michel; Mukendi, Déby; Dolo, Housseini; Suykerbuyk, Patrick; M, Van Oijen

doi:10.2196/resprot.7186

Cited by 21 publications

(22 citation statements)

References 28 publications

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“…To assess whether ivermectin treatment may reduce the seizure frequency and lead to seizure freedom, we conducted a four-month proof-of-concept randomized clinical trial in onchocerciasis-infected PWE. If such a trial shows a beneficial effect of ivermectin administration in PWE, this would lend further support to the hypothesis that onchocerciasis is able to cause epilepsy [14].…”

Section: Introductionmentioning

confidence: 71%

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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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Section: Introductionmentioning

confidence: 71%

“…The latter will receive ivermectin treatment at the end of a 4 month follow-up period. The protocol of this study was published previously [14].…”

Section: Trial Designmentioning

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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“…In addition, persons with epilepsy (PWE) and with parasitological and/or serological evidence of O. volvulus infection were recruited during a clinical trial investigating the effect of ivermectin on seizure frequency [14]. PWE were randomized in two groups according to a 1:1 ratio, with one group receiving phenobarbital and an ivermectin dose of 150 µg/kg and the other group receiving only phenobarbital [15]. After informed consent was obtained, participants were interviewed to document their medical history and a physical examination was performed, including a neurological assessment.…”

Section: Study Population and Sample Collectionmentioning

confidence: 99%

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

Hotterbeekx

Dusabimana

Mandro³

et al. 2020

Pathogens

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We investigated urinary N-acetyltyramine-O,β-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.

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“…77 , 78 There is also an ongoing clinical trial in the Democratic Republic of Congo examining the effect of ivermectin administration in reducing the frequency of OAE, which may have implications for NS patients. 79 Three OV-NS patients have been treated with plasmapheresis or intravenous immunoglobulin for presumed autoimmunity, however the results have not been recorded in sufficient detail to appraise treatment efficacy. 37…”

Section: Autoimmunitymentioning

confidence: 99%

Aetiologies and therapies of nodding syndrome: a systematic review and meta-analysis

Stacey

Woodhouse²,

Welburn³

et al. 2019

Journal of Global Health Reports

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Nodding syndrome (NS) is a childhood epileptic disorder of unknown aetiology confined to parts of South Sudan, Uganda and the United Republic of Tanzania. Patients suffer from atonic seizures that result in characteristic head nodding, and may develop other neurological, endocrinological and psychiatric manifestations. The objective of this study was to adopt a non-judgemental approach to review the hypothesised aetiologies and therapeutic options available for NS. To explore the reported association between NS and Onchocerca volvulus (OV) a meta-analysis of the prevalence of OV among NS cases and controls was performed. Methods MethodsSystematic searching of five electronic databases yielded 26 articles that addressed potential aetiologies of NS and 12 that explored the treatment of NS. R Results esultsNine articles contained data about the prevalence of OV in NS cases that was suitable for inclusion in the meta-analysis. Four broad aetiological themes were identified. 1) Nutritional associations included biomarkers of malnutrition and conflicting reports regarding the consumption of some foodstuffs. 2) Regional conflict and the associated psychological trauma have led to consideration of psychiatric aetiologies. 3) There is a strong epidemiological association between NS and Onchocerca volvulus. The meta-analysis in this study revealed that 68.0% (95% confidence interval (CI)=45.2-87.0) of 416 NS patients were OV+, compared to 46.6% (95% CI=16.4-78.1) of 321 controls. Heterogeneity among both cases (I 2 =95.5%, 95% CI=93.3-97.0) and controls (I 2 =97.1%, 95% CI=95.5-98.2) was high. The difference of 21.4% in OV prevalence between the pooled populations was significant (P<0.0001). It is thought that NS represents a form of onchocerciasis-associated epilepsy, however there are also reported associations with Mansonella pestans and measles virus. 4) Autoantibodies against leiomodin-1 and the voltage-gated potassium channel have been associated with NS. Molecular mimicry between leiomodin-1 and O. volvulus tropomyosin is a recently suggested aetiology. Without a clear aetiology treatment is symptomatic and patients have been shown to improve with a combination of anti-epileptic medication and supportive therapy. C Conclusions onclusionsThe aetiology of NS remains unclear. The leading theory is that NS represents a form of onchocerciasis-associated epilepsy secondary to autoimmunity driven by molecular mimicry. Alternatively, it has been suggested that NS may represent a post-infectious sequelae of measles virus infection. However, each theory currently leaves some questions unanswered. It remains important to understand the aetiology of NS to better prevent or treat future outbreaks.Nodding syndrome (NS) is a neurological condition of unknown aetiology confined to parts of the United Republic of Tanzania (URT), South Sudan and Uganda. The characteristic head nodding that gives the syndrome its name was

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Ivermectin Treatment in Patients With Onchocerciasis-Associated Epilepsy: Protocol of a Randomized Clinical Trial

Cited by 21 publications

References 28 publications

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

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

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

Aetiologies and therapies of nodding syndrome: a systematic review and meta-analysis

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