Special Issue "Onchocerciasis and River Epilepsy"

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editors

Prof. Dr. Robert Colebunders
E-Mail Website
Guest Editor
Global Health Institute, University of Antwerp, Antwerp, Belgium
Interests: COVID-19; HIV; onchocerciasis; epilepsy; epidemiology; public health; infectious and tropical diseases
Special Issues and Collections in MDPI journals
Prof. Dr. Jacob Souopgui
E-Mail Website
Guest Editor
Laboratory of Embryology & Biotechnology, Université Libre de Bruxelles, Gosselies, Belgium
Interests: COVID-19; onchocerciasis; parasite biology; nematodes
Special Issues and Collections in MDPI journals

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 (16 papers)

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Research

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Article
Serotonin Levels in the Serum of Persons with Onchocerciasis-Associated Epilepsy: A Case-Control Study
Pathogens 2021, 10(6), 720; https://doi.org/10.3390/pathogens10060720 - 08 Jun 2021
Viewed by 347
Abstract
Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we [...] Read more.
Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we investigated serotonin levels in persons with OAE and controls selected from the Democratic Republic of Congo. Serum serotonin levels were determined by ELISA in 19 persons with OAE, 32 persons with epilepsy without O. volvulus infection, 18 with O. volvulus infection but without epilepsy, and 35 with neither O. volvulus infection nor epilepsy. O. volvulus infection was diagnosed by skin snip testing and/or OV16 antibody detection. Serum serotonin levels were significantly decreased in persons with OAE compared to persons with O. volvulus infection and no epilepsy. In conclusion, an increased serotonin level is unable to explain the pathogenesis of OAE. Other hypotheses to identify the causal mechanism of OAE will need to be investigated. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
High Prevalence of Epilepsy in an Onchocerciasis-Endemic Area in Mvolo County, South Sudan: A Door-To-Door Survey
Pathogens 2021, 10(5), 599; https://doi.org/10.3390/pathogens10050599 - 14 May 2021
Viewed by 637
Abstract
In June 2020, a door-to-door household survey was conducted in Mvolo County, an onchocerciasis-endemic area in South Sudan. A total of 2357 households containing 15,699 individuals agreed to participate in the study. Of these, 5046 (32.1%, 95% CI: 31.4–32.9%) had skin itching and [...] Read more.
In June 2020, a door-to-door household survey was conducted in Mvolo County, an onchocerciasis-endemic area in South Sudan. A total of 2357 households containing 15,699 individuals agreed to participate in the study. Of these, 5046 (32.1%, 95% CI: 31.4–32.9%) had skin itching and 445 (2.8%, 95% CI: 2.6–3.1%) were blind. An epilepsy screening questionnaire identified 813 (5.1%) persons suspected of having epilepsy. Of them, 804 (98.9%) were seen by a medical doctor, and in 798 (98.1%) the diagnosis of epilepsy was confirmed. The overall epilepsy prevalence was 50.8/1000 (95% CI: 47.6–54.4/1000), while the prevalence of nodding syndrome was 22.4/1000 (95% CI: 20.1–24.9/1000). Younger age, being male, skin itching, blindness, and living in a neighbourhood or village close to the Naam River were risk factors for epilepsy. The annual incidence of epilepsy was 82.8/100,000 (95% CI: 44.1–141.6/100,000). Among children 7–9 years old without epilepsy, 34% were Ov16 seropositive, suggesting high ongoing Onchocerca volvulus transmission, but only 41.9% of them took ivermectin during the last mass distribution. In conclusion, a high prevalence and incidence of epilepsy was observed in Mvolo, South Sudan. Strengthening of the onchocerciasis elimination programme is urgently needed in order to prevent epilepsy in this region. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
Onchocerciasis Prevalence among Persons with Epilepsy in an Onchocerciasis Hypo-Endemic Area in the Democratic Republic of Congo: A Cross-Sectional Study
Pathogens 2021, 10(4), 389; https://doi.org/10.3390/pathogens10040389 - 24 Mar 2021
Viewed by 590
Abstract
A high epilepsy prevalence has been reported in onchocerciasis meso- and hyper-endemic regions in sub-Saharan Africa, including in the Democratic Republic of Congo (DRC). We investigated whether onchocerciasis-associated epilepsy can also be suspected in onchocerciasis hypo-endemic regions. Stored serum samples from 342 patients [...] Read more.
A high epilepsy prevalence has been reported in onchocerciasis meso- and hyper-endemic regions in sub-Saharan Africa, including in the Democratic Republic of Congo (DRC). We investigated whether onchocerciasis-associated epilepsy can also be suspected in onchocerciasis hypo-endemic regions. Stored serum samples from 342 patients admitted with recent onset neurological symptoms admitted to Mosango general hospital, in the Kwilu province, DRC, between 2012 and 2015 were screened for onchocerciasis (OV16) antibodies by ELISA and Taenia solium antigen (using an in-house B158/B60 antigen test). Eighty-one (23.7%; 95% CI 19.5–28.5%) of these samples were positive for OV16 antibodies and 43/340 (12.6%; 95% CI 9.5–16.6%) were positive for T. solium antigen. Of the 58 persons clinically diagnosed with late onset epilepsy of unknown etiology, 19 (32.8%) were OV16 positive and nine (16%) T. solium antigen positive. In total, 16 persons with epilepsy were OV16 positive and T. solium negative, of whom 12 (75%) were between the ages seven to 31 years old, an age rage in which onchocerciasis-associated epilepsy is observed. Our study suggests that in onchocerciasis hypo-endemic areas, in T. solium antigen negative persons with epilepsy, onchocerciasis should be considered as a potential trigger of epilepsy. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
Potential Parasitic Causes of Epilepsy in an Onchocerciasis Endemic Area in the Ituri Province, Democratic Republic of Congo
Pathogens 2021, 10(3), 359; https://doi.org/10.3390/pathogens10030359 - 18 Mar 2021
Viewed by 414
Abstract
A high burden of epilepsy is observed in Africa where parasitological infections are endemic. In 2016, in an Onchocerciasis endemic area in the Logo health zone, in Ituri province in the Democratic Republic of Congo, a door-to-door study showed an epilepsy prevalence of [...] Read more.
A high burden of epilepsy is observed in Africa where parasitological infections are endemic. In 2016, in an Onchocerciasis endemic area in the Logo health zone, in Ituri province in the Democratic Republic of Congo, a door-to-door study showed an epilepsy prevalence of 4.6%, and 50.6% of persons with epilepsy were infected with Onchocerca volvulus. In the current study, the serum of 195 people infected with O. volvulus persons with epilepsy were tested to determine the proportion of co-infections with Taenia solium, Toxocara canis and Strongyloides. These proportions were, respectively, 8.2, 18.5 and 12.8%. Persons with a T. solium co-infection were older than those without co-infection (p = 0.021). In six (37.5%) of the T. solium co-infected persons, the first seizures appeared after the age of 30 years compared to three (2.1%) persons without a co-infection (p < 0.0001). Our study suggests that an O. volvulus infection is the main parasitic cause of epilepsy in the Ituri province, but in some persons, mainly in those with late onset epilepsy and with focal seizures, the epilepsy may be caused by neurocysticercosis. As the population in the area rears pigs, activities to limit T. solium transmission should be implemented. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
Cytokines and Onchocerciasis-Associated Epilepsy, a Pilot Study and Review of the Literature
Pathogens 2021, 10(3), 310; https://doi.org/10.3390/pathogens10030310 - 07 Mar 2021
Viewed by 528
Abstract
Neuro-inflammation may be associated with onchocerciasis-associated epilepsy (OAE) but thus far very few immunological studies have been performed in children with this form of epilepsy. In a pilot study we measured the cytokine levels in cerebrospinal fluid (CSF) of persons with OAE from [...] Read more.
Neuro-inflammation may be associated with onchocerciasis-associated epilepsy (OAE) but thus far very few immunological studies have been performed in children with this form of epilepsy. In a pilot study we measured the cytokine levels in cerebrospinal fluid (CSF) of persons with OAE from Maridi, South Sudan, and from Mosango, Democratic Republic of the Congo (DRC) and compared these results with cytokine levels in CSF of Africans with non-OAE neurological disorders, and Europeans with epilepsy or other neurological conditions. The following cytokines were studied: IL-6, TNF-α, IL1-β, IL-5, IL-4, IL-13, CCL3 (Mip-1α), VEGF-C, VCAM-1. No cytokine was significantly associated with OAE, although a lower IL-13 level was observed in CSF of persons with OAE compared to African controls. Observed cytokine profiles and neuro-inflammation may be the consequence of long-standing epilepsy, concomitant infections and malnutrition. Ideally cytokine levels should be determined in a prospective study in serum and CSF collected at the time of onset of the first seizures. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
An Integrated Approach to Identify New Anti-Filarial Leads to Treat River Blindness, a Neglected Tropical Disease
Pathogens 2021, 10(1), 71; https://doi.org/10.3390/pathogens10010071 - 14 Jan 2021
Cited by 1 | Viewed by 728
Abstract
Filarial worms cause multiple debilitating diseases in millions of people worldwide, including river blindness. Currently available drugs reduce transmission by killing larvae (microfilariae), but there are no effective cures targeting the adult parasites (macrofilaricides) which survive and reproduce in the host for very [...] Read more.
Filarial worms cause multiple debilitating diseases in millions of people worldwide, including river blindness. Currently available drugs reduce transmission by killing larvae (microfilariae), but there are no effective cures targeting the adult parasites (macrofilaricides) which survive and reproduce in the host for very long periods. To identify effective macrofilaricides, we carried out phenotypic screening of a library of 2121 approved drugs for clinical use against adult Brugia pahangi and prioritized the hits for further studies by integrating those results with a computational prioritization of drugs and associated targets. This resulted in the identification of 18 hits with anti-macrofilaricidal activity, of which two classes, azoles and aspartic protease inhibitors, were further expanded upon. Follow up screening against Onchocerca spp. (adult Onchocerca ochengi and pre-adult O. volvulus) confirmed activity for 13 drugs (the majority having IC50 < 10 μM), and a counter screen of a subset against L. loa microfilariae showed the potential to identify selective drugs that prevent adverse events when co-infected individuals are treated. Stage specific activity was also observed. Many of these drugs are amenable to structural optimization, and also have known canonical targets, making them promising candidates for further optimization that can lead to identifying and characterizing novel anti-macrofilarial drugs. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
Effect of Ivermectin Treatment on the Frequency of Seizures in Persons with Epilepsy Infected with Onchocerca volvulus
Pathogens 2021, 10(1), 21; https://doi.org/10.3390/pathogens10010021 - 31 Dec 2020
Viewed by 571
Abstract
A clinical trial performed in the Democratic Republic of Congo (DRC), among persons with epilepsy (PWE) infected with Onchocerca volvulus treated with anti-seizure medication suggested that ivermectin reduces the seizure frequency. We assessed the effect of ivermectin treatment on seizure frequency in PWE [...] Read more.
A clinical trial performed in the Democratic Republic of Congo (DRC), among persons with epilepsy (PWE) infected with Onchocerca volvulus treated with anti-seizure medication suggested that ivermectin reduces the seizure frequency. We assessed the effect of ivermectin treatment on seizure frequency in PWE with and without anti-seizure medication in three onchocerciasis endemic areas (Maridi, South Sudan; Aketi, DRC; and Mahenge, Tanzania). Pre- and 3–5 months post-ivermectin microfilariae densities in skin snips and seizure frequency were assessed. After ivermectin, the median (IQR) percentage reduction in seizure frequency in the study sites ranged from 73.4% (26.0–90.0) to 100% (50.0–100.0). A negative binomial mixed model showed that ivermectin significantly reduced the seizure frequency, with a larger decrease in PWE with a high baseline seizure frequency. Mediation analysis showed that ivermectin reduced the seizure frequencies indirectly through reduction in microfilariae densities but also that ivermectin may have a direct anti-seizure effect. However, given the short half-life of ivermectin and the fact that ivermectin does not penetrate the healthy brain, such a direct anti-seizure effect is unlikely. A randomized controlled trial assessing the ivermectin effect in people infected with O. volvulus who are also PWE on a stable anti-seizure regimen may be needed to clarify the causal relationship between ivermectin and seizure frequency. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
Putative Autoantigen Leiomodin-1 Is Expressed in the Human Brain and in the Membrane Fraction of Newly Formed Neurons
Pathogens 2020, 9(12), 1036; https://doi.org/10.3390/pathogens9121036 - 10 Dec 2020
Cited by 1 | Viewed by 611
Abstract
Nodding syndrome is a pediatric epilepsy disorder associated with Onchocerca volvulus infection, but the mechanism driving this relationship is unclear. One hypothesis proposes that parasite-induced immune responses cross-react with human leiomodin-1 resulting in immune-mediated central nervous system (CNS) damage. However, as leiomodin-1 expression [...] Read more.
Nodding syndrome is a pediatric epilepsy disorder associated with Onchocerca volvulus infection, but the mechanism driving this relationship is unclear. One hypothesis proposes that parasite-induced immune responses cross-react with human leiomodin-1 resulting in immune-mediated central nervous system (CNS) damage. However, as leiomodin-1 expression and epitope availability in human neurons remains uncharacterized, the relevance of leiomodin-1 autoimmunity is unknown. Leiomodin-1 transcript expression was assessed in silico using publicly available ribonucleic acid (RNA) sequencing databases and in tissue by in situ hybridization and quantitative polymerase chain reaction. Abundance and subcellular localization were examined by cell fractionation and immunoblotting. Leiomodin-1 transcripts were expressed in cells of the CNS, including neurons and astrocytes. Protein was detectable from all brain regions examined as well as from representative cell lines and in vitro differentiated neurons and astrocytes. Leiomodin-1 was expressed on the membrane of newly formed neurons, but not neural progenitor cells or mature neurons. Importantly, leiomodin-1 antibodies were only toxic to cells expressing leiomodin-1 on the membrane. Our findings provide evidence that leiomodin-1 is expressed in human neurons and glia. Furthermore, we show membrane expression mediates leiomodin-1 antibody toxicity, suggesting these antibodies may play a role in pathogenesis. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
Entomological Assessment of Onchocerca Species Transmission by Black Flies in Selected Communities in the West Region of Cameroon
Pathogens 2020, 9(9), 722; https://doi.org/10.3390/pathogens9090722 - 02 Sep 2020
Viewed by 849
Abstract
The enormity of the public health burden of onchocerciasis motivated the creation of various large-scale control programs that have depended principally on mass treatment of endemic communities with ivermectin for the elimination of the disease. Parasitological evaluation of Onchocerca species in the West [...] Read more.
The enormity of the public health burden of onchocerciasis motivated the creation of various large-scale control programs that have depended principally on mass treatment of endemic communities with ivermectin for the elimination of the disease. Parasitological evaluation of Onchocerca species in the West Region of Cameroon indicates significant progress in the interruption of parasite transmission in some communities under ivermectin treatment. However, to verify the complete elimination of onchocerciasis, entomological assessment through O-150 PCR poolscreen of black flies is mandatory. Thus, in the present study, we assessed transmission of Onchocerca species using an O-150 PCR technique to screen pools of black flies—in seven onchocerciasis endemic communities (Makouopsap, Bankambe, Lemgo, Tsesse, Ndionzou, Kouffen, and Bayon) in Cameroon. Two thousand black flies were assessed—in each community—for the presence of Onchocerca species DNA. Our results show that the frequency of infective flies was 0.6% in Makouopsap and 0.0% in the other communities. On the other hand, the frequency of infected flies was 0.8% in Makouopsap, 0.2% in Bankambe, 0.1% in Bayon, and 0.0% in Lemgo, Tsesse, Ndionzou, and Kouffen. These results provide entomologic evidence for continuous transmission of Onchocerca species in Makouopsap, risk of active transmission in Bankambe, and Bayon, and a suppressed transmission in the four other studied communities. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
In Silico Design and Validation of OvMANE1, a Chimeric Antigen for Human Onchocerciasis Diagnosis
Pathogens 2020, 9(6), 495; https://doi.org/10.3390/pathogens9060495 - 22 Jun 2020
Cited by 4 | Viewed by 1127
Abstract
The public health goal of onchocerciasis in Africa has advanced from control to elimination. In this light, accurate diagnosis is necessary to determine treatment endpoints and confirm elimination, as well as to conduct surveillance for the identification of any possible recrudescence of the [...] Read more.
The public health goal of onchocerciasis in Africa has advanced from control to elimination. In this light, accurate diagnosis is necessary to determine treatment endpoints and confirm elimination, as well as to conduct surveillance for the identification of any possible recrudescence of the disease. Currently, the monitoring of onchocerciasis elimination relies on the Ov-16 test. However, this test is unable to discriminate between past and active infections. Furthermore, about 15–25% of infected persons are reported to be negative for the Ov-16 test, giving a misleading sense of security to false-negative individuals who might continue to serve as reservoirs for infections. Therefore, we opted to design and validate a more sensitive and specific chimeric antigen (OvMANE1) for onchocerciasis diagnosis, using previously reported immunodominant peptides of O. volvulus, the parasite responsible for the disease. In silico analysis of OvMANE1 predicted it to be more antigenic than its individual peptides. We observed that OvMANE1 reacts specifically and differentially with sera from O. volvulus infected and non-infected individuals, as well as with sera from communities of different levels of endemicity. Moreover, we found that total IgG, unlike IgG4 subclass, positively responded to OvMANE1, strongly suggesting its complementarity to the Ov-16 diagnostic tool, which detects Ov-16 IgG4 antibodies. Overall, OvMANE1 exhibited the potential to be utilized in the development of specific diagnostic tools—based on both antibody capture and antigen capture reactions—which are indispensable to monitor the progress of onchocerciasis elimination programs. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Article
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
Viewed by 1046
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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Article
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
Cited by 5 | Viewed by 957
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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Article
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
Cited by 7 | Viewed by 1447
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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Article
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
Cited by 2 | Viewed by 653
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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Review

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Review
Zoonotic Implications of Onchocerca Species on Human Health
Pathogens 2020, 9(9), 761; https://doi.org/10.3390/pathogens9090761 - 17 Sep 2020
Cited by 1 | Viewed by 940
Abstract
The genus Onchocerca includes several species associated with ungulates as hosts, although some have been identified in canids, felids, and humans. Onchocerca species have a wide geographical distribution, and the disease they produce, onchocerciasis, is generally seen in adult individuals because of its [...] Read more.
The genus Onchocerca includes several species associated with ungulates as hosts, although some have been identified in canids, felids, and humans. Onchocerca species have a wide geographical distribution, and the disease they produce, onchocerciasis, is generally seen in adult individuals because of its large prepatency period. In recent years, Onchocerca species infecting animals have been found as subcutaneous nodules or invading the ocular tissues of humans; the species involved are O. lupi, O. dewittei japonica, O. jakutensis, O. gutturosa, and O. cervicalis. These findings generally involve immature adult female worms, with no evidence of being fertile. However, a few cases with fertile O. lupi, O. dewittei japonica, and O. jakutensis worms have been identified recently in humans. These are relevant because they indicate that the parasite’s life cycle was completed in the new host—humans. In this work, we discuss the establishment of zoonotic Onchocerca infections in humans, and the possibility of these infections to produce symptoms similar to human onchocerciasis, such as dermatitis, ocular damage, and epilepsy. Zoonotic onchocerciasis is thought to be an emerging human parasitic disease, with the need to take measures such as One Health Strategies, in order to identify and control new cases in humans. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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Case Report
Neuropathological Changes in Nakalanga Syndrome—A Case Report
Pathogens 2021, 10(2), 116; https://doi.org/10.3390/pathogens10020116 - 23 Jan 2021
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Abstract
Nakalanga syndrome is a clinical manifestation of onchocerciasis-associated epilepsy characterized by stunting, delayed or absent secondary sexual development and skeletal deformities, and is often accompanied by epileptic seizures. The pathophysiology of Nakalanga syndrome is unknown. Here, we describe the post-mortem findings of a [...] Read more.
Nakalanga syndrome is a clinical manifestation of onchocerciasis-associated epilepsy characterized by stunting, delayed or absent secondary sexual development and skeletal deformities, and is often accompanied by epileptic seizures. The pathophysiology of Nakalanga syndrome is unknown. Here, we describe the post-mortem findings of a 17-year-old female who died with Nakalanga syndrome in northern Uganda. Macroscopic and histopathological examination of all major organs (liver, lungs, kidney and heart), including the brain and the pituitary gland, was performed. The suspected cause of death was malaria, and all major organs and pituitary gland appeared normal, except the lungs, which were edematous consistent with the malaria. Neuropathological changes include signs of neuro-inflammation (gliosis and activated microglia), which co-localized with tau-reactive neurofibrillary tangles and threads. The pathology was most abundant in the frontal cortex, thalamic and hypothalamic regions, and mesencephalon. The choroid plexus showed psammoma bodies. These findings indicate accelerated aging, probably due to repeated seizures. The neuropathological findings were similar to other persons who died with onchocerciasis-associated epilepsy. Examination of the pituitary gland did not reveal new information concerning the underlying pathophysiological mechanism of Nakalanga syndrome. Therefore, more post-mortem studies should be performed. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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