Special Issue "Onchocerciasis and River Epilepsy"

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: 31 July 2020.

Special Issue Editors

Prof. Dr. Robert Colebunders
Website
Guest Editor
Universiteit Antwerpen, Antwerpen, Belgium
Interests: Onchocerciasis; epilepsy; epidemiology; public health; infectious and tropical diseases
Prof. Jacob Souopgui
Website
Guest Editor
Université libre de Bruxelles (ULB), Brussels, Belgium
Interests: Onchocerciasis; parasite biology; nematodes

Special Issue Information

Dear Colleagues

There is growing epidemiological evidence that onchocerciasis (river blindness) is able to induce epilepsy (onchocerciasis-associated epilepsy (OAE) or river epilepsy) and that this form of epilepsy is an important unrecognized public health problem in many onchocerciasis-endemic regions where onchocerciasis elimination efforts are not or suboptimally implemented. Moreover, recent studies have shown that nodding syndrome and Nakalanga syndrome are phenotypic presentations of OAE. OAE is characterized by an age of onset of epilepsy between 3 and 18 years with a normal psychomotor development prior to the onset and without an obvious cause for epilepsy, such as a history of perinatal anoxia, meningitis/encephalitis, cerebral malaria or head trauma. In the affected communities, clustering of epilepsy cases is observed in households and villages located close to blackfly (Simulium) breeding sites in rapid flowing rivers. A high Onchocerca volvulus microfilarial load in young children correlates with an increased risk of developing epilepsy later in life. It is estimated that in Africa, there are approximately 300,000 persons with OAE which could have been prevented through improved onchocerciasis elimination efforts.

Despite strong epidemiological evidence that O. volvulus is able to trigger seizures, the pathophysiological mechanism of how this may happen remains obscure. Direct invasion of parasites in the central nervous system seems unlikely since no O. volvulus microfilariae or DNA could be detected in the cerebrospinal fluid of persons with OAE, nor in brain samples from persons who died of OAE. It has been suggested that neurotoxic cross-reacting O. volvulus antibodies may play a role, but this has not been confirmed. O. volvulus releases a wide range of excretory/secretory products (ESPs) into the host environment. However, very little is known about the function of these ESP. A better knowledge of the biology of O. volvulus seems to be critical to elucidate the pathophysiology of OAE.

For this Special Issue of Pathogens, we invite you to submit research articles, review articles, short notes, as well as communications that could contribute to a better understanding of the link between onchocerciasis and epilepsy. This includes papers about epidemiological and clinical aspects of OAE, potential pathophysiological mechanisms, basic research about O. volvulus, and very importantly research about how to prevent and treat river epilepsy. We look forward to your contribution.

Prof. Dr. Robert Colebunders
Prof. Jacob Souopgui
Guest Editors

Manuscript Submission Information

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Keywords

  • Onchocerciasis
  • Excretory/secretory products
  • Nematodes
  • Epilepsy
  • Nodding syndrome
  • Nakalanga syndrome
  • Epidemiology

Published Papers (4 papers)

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Research

Open AccessArticle
Focus of Ongoing Onchocerciasis Transmission Close to Bangui, Central African Republic
Pathogens 2020, 9(5), 337; https://doi.org/10.3390/pathogens9050337 - 30 Apr 2020
Abstract
Recently, there were anecdotal reports of a high number of persons with epilepsy, including children with nodding seizures in the Landja Mboko area located about 9 km from the capital city Bangui, Central African Republic. We suspected the area to be endemic for [...] Read more.
Recently, there were anecdotal reports of a high number of persons with epilepsy, including children with nodding seizures in the Landja Mboko area located about 9 km from the capital city Bangui, Central African Republic. We suspected the area to be endemic for onchocerciasis, and that the alleged increase in the number of epilepsy cases was due to ongoing Onchocerca volvulus transmission. However, ivermectin mass drug distribution (MDA) had never been implemented in the area. Therefore we performed an Ov16 antibody prevalence study among children, aged 6–9 years, using the biplex rapid diagnostic test (SD Bioline Oncho/LF biplex IgG4 RDT). The overall Ov16 seroprevalence was 8.9%, and that of lymphatic filariasis (LF) was 1.9%. Ov16 seropositivity was highest in Kodjo (20.0%), a village close to rapids on the river. Our study shows that there is ongoing O. volvulus transmission in the Landja Mboko area. We recommend that the extent of this onchocerciasis focus should be mapped, and the introduction of ivermectin MDA should be considered in these communities. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Open AccessArticle
The Role of the Maridi Dam in Causing an Onchocerciasis-Associated Epilepsy Epidemic in Maridi, South Sudan: An Epidemiological, Sociological, and Entomological Study
Pathogens 2020, 9(4), 315; https://doi.org/10.3390/pathogens9040315 - 24 Apr 2020
Abstract
Background: An epilepsy prevalence of 4.4% was documented in onchocerciasis-endemic villages close to the Maridi River in South Sudan. We investigated the role of the Maridi dam in causing an onchocerciasis-associated epilepsy epidemic in these villages. Methods: Affected communities were visited [...] Read more.
Background: An epilepsy prevalence of 4.4% was documented in onchocerciasis-endemic villages close to the Maridi River in South Sudan. We investigated the role of the Maridi dam in causing an onchocerciasis-associated epilepsy epidemic in these villages. Methods: Affected communities were visited in November 2019 to conduct focus group discussions with village elders and assess the OV16 seroprevalence in 3- to 9-year-old children. Entomological assessments to map blackfly breeding sites and determine biting rates around the Maridi River were conducted. Historical data regarding various activities at the Maridi dam were obtained from the administrative authorities. Results: The Maridi dam was constructed in 1954–1955. Village elders reported an increasing number of children developing epilepsy, including nodding syndrome, from the early 1990s. Kazana 2 (the village closest to the dam; epilepsy prevalence 11.9%) had the highest OV16 seroprevalence: 40.0% among children 3–6 years old and 66.7% among children 7–9 years old. The Maridi dam spillway was found to be the only Simulium damnosum breeding site along the river, with biting rates reaching 202 flies/man/h. Conclusion: Onchocerciasis transmission rates are high in Maridi. Suitable breeding conditions at the Maridi dam, coupled with suboptimal onchocerciasis control measures, have probably played a major role in causing an epilepsy (including nodding syndrome) epidemic in the Maridi area. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Open AccessArticle
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
Pathogens 2020, 9(3), 205; https://doi.org/10.3390/pathogens9030205 - 10 Mar 2020
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Open AccessArticle
Urinary N-acetyltyramine-O,β-glucuronide in Persons with Onchocerciasis-Associated Epilepsy
Pathogens 2020, 9(3), 191; https://doi.org/10.3390/pathogens9030191 - 05 Mar 2020
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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