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Seizure Apr 2024This narrative review intends to inform neurologists and public health professionals about Onchocerciasis-Associated Epilepsy (OAE), a neglected public health problem in... (Review)
Review
This narrative review intends to inform neurologists and public health professionals about Onchocerciasis-Associated Epilepsy (OAE), a neglected public health problem in many remote onchocerciasis-endemic areas. For epidemiological purposes, we define OAE as sudden-onset of convulsive and non-convulsive seizure types, including head nodding seizures (nodding syndrome) in a previously healthy child aged 3 to 18 years in the absence of any other obvious cause for epilepsy, all happening within an area with high ongoing Onchocerca volvulus transmission. Several OAE pathophysiological mechanisms have been proposed, but none has been proven yet. Recent population-based studies showed that strengthening onchocerciasis elimination programs was followed by a significant reduction in the incidence of OAE and nodding syndrome. Treating epilepsy in onchocerciasis-endemic regions is challenging. More advocacy is needed to provide uninterrupted, free access to anti-seizure medication to persons with epilepsy in these remote, impoverished areas. It is crucial todevelop policies and increase funding for the prevention and treatment of OAE to reduce the associated burden of disease, notably via the establishment of morbidity management and disability prevention programs (MMDP). Moreover, effective collaboration between onchocerciasis elimination and mental health programs is imperative to alleviate the burden of OAE. This synergy promises reciprocal advantages and underscores the need for a comprehensive approach to address this multifaceted challenge.
PubMed: 38677953
DOI: 10.1016/j.seizure.2024.04.018 -
Pathogens (Basel, Switzerland) Mar 2024Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption,... (Review)
Review
Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption, particularly in sub-Saharan Africa. Its importance as a cause of morbidity and an impediment to economic development in some of the poorest countries in the world motivated the international community to implement several programs to control or eliminate this scourge. Initially, these involved reducing transmission of the causative agent through controlling the vector population. When ivermectin was found to be a very effective drug for treating onchocerciasis, the strategy shifted to mass drug administration (MDA) of endemic communities. In some countries, both vector control and ivermectin MDA have been used together. However, traditional vector control methods involve treating rivers in which the black fly vectors breed with insecticides, a process which is expensive, requires trained personnel to administer, and can be ecologically harmful. In this review, we discuss recent research into alternatives to riverine insecticide treatment, which are inexpensive, ecologically less harmful, and can be implemented by the affected communities themselves. These can dramatically reduce vector densities and, when combined with ivermectin MDA, can accelerate the time to elimination when compared to MDA alone.
PubMed: 38535611
DOI: 10.3390/pathogens13030268 -
PLoS Neglected Tropical Diseases Aug 2023Nodding syndrome (NS) is a phenotypic presentation of onchocerciasis-associated epilepsy (OAE). OAE is an important public health problem in areas with high ongoing...
Nodding syndrome (NS) is a phenotypic presentation of onchocerciasis-associated epilepsy (OAE). OAE is an important public health problem in areas with high ongoing Onchocerca volvulus transmission. OAE, including NS, is preventable by strengthening onchocerciasis elimination programs. The presence of tau in OAE postmortem brains could be the consequence of neuroinflammation directly or indirectly induced by O. volvulus. Omics research is needed to investigate whether O. volvulus worms contain a neurotropic virus.
Topics: Onchocerciasis; Nodding Syndrome; Onchocerca volvulus; Humans
PubMed: 37590176
DOI: 10.1371/journal.pntd.0011523 -
PLoS Neglected Tropical Diseases Aug 2023Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological...
Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, β-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.
Topics: Animals; Humans; Onchocerciasis; Onchocerca volvulus; Nodding Syndrome; Intestinal Volvulus; Epilepsy; Uganda; Cytokines
PubMed: 37535695
DOI: 10.1371/journal.pntd.0011503 -
PLoS Neglected Tropical Diseases May 2024
Topics: Onchocerca volvulus; Humans; Animals; Onchocerciasis; Nodding Syndrome; Epilepsy
PubMed: 38722927
DOI: 10.1371/journal.pntd.0012076 -
Brain Communications 2023Nodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern...
Nodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern sub-Saharan Africa. Previous studies have identified multiple associations-including , antileiomodin-1 antibodies, vitamin B deficiency and measles virus infection-yet, none is proven causal. We conducted a case-control study of children with early-stage nodding syndrome (symptom onset <1 year). Cases and controls were identified through a household survey in the Greater Mundri area in South Sudan. A wide range of parasitic, bacterial, viral, immune-mediated, metabolic and nutritional risk factors was investigated using conventional and state-of-the-art untargeted assays. Associations were examined by multiple logistic regression analysis, and a hypothetical causal model was constructed using structural equation modelling. Of 607 children with nodding syndrome, 72 with early-stage disease were included as cases and matched to 65 household- and 44 community controls. infection (odds ratio 7.04, 95% confidence interval 2.28-21.7), infection (odds ratio 2.33, 95% confidence interval 1.02-5.3), higher antimalarial seroreactivity (odds ratio 1.75, 95% confidence interval 1.20-2.57), higher vitamin E concentration (odds ratio 1.53 per standard deviation increase, 95% confidence interval 1.07-2.19) and lower vitamin B concentration (odds ratio 0.56 per standard deviation increase, 95% confidence interval 0.36-0.87) were associated with higher odds of nodding syndrome. In a structural equation model, we hypothesized that infection, higher vitamin E concentration and fewer viral exposures increased the risk of nodding syndrome while lower vitamin B concentration, and malaria infections resulted from having nodding syndrome. We found no evidence that antileiomodin-1 antibodies, vitamin B and other factors were associated with nodding syndrome. Our results argue against several previous causal hypotheses including . Instead, nodding syndrome may be caused by a complex interplay between multiple pathogens and nutrient levels. Further studies need to confirm these associations and determine the direction of effect.
PubMed: 37731906
DOI: 10.1093/braincomms/fcad223 -
Vaccines Jul 2023Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent...
Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two protein antigens, -103 and -RAL-2 (-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with L3 contained within subcutaneous diffusion chambers demonstrated that -FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive transfer of sera, collected at several time points, from both mice and NHPs immunized with -FUS-1/Advax-CpG transferred protection to naïve mice. These results demonstrate that -FUS-1 with the adjuvant Advax-CpG induces durable protective immunity against in mice and NHPs that is mediated by vaccine-induced humoral factors.
PubMed: 37515028
DOI: 10.3390/vaccines11071212 -
Epilepsia Open Apr 2024Epilepsy imposes a substantial burden on the Democratic Republic of Congo (DRC). These challenges encompass the lack of comprehensive disease surveillance, an unresolved... (Review)
Review
Epilepsy imposes a substantial burden on the Democratic Republic of Congo (DRC). These challenges encompass the lack of comprehensive disease surveillance, an unresolved understanding of its pathophysiology, economic barriers limiting access to essential care, the absence of epilepsy surgical capabilities, and deeply ingrained societal stigmas. Notably, the national prevalence of epilepsy remains undetermined, with research primarily concentrating on infectious factors like Onchocerca volvulus, leaving other potential causes underexplored. Most patients lack insurance, incurring out-of-pocket expenses that often lead them to opt for traditional medicine rather than clinical care. Social stigma, perpetuated by common misconceptions, intensifies the social isolation experienced by individuals living with epilepsy. Additionally, surgical interventions are unavailable, and the accessibility of anti-seizure medications and healthcare infrastructure remains inadequate. Effectively tackling these interrelated challenges requires a multifaceted approach, including conducting research into region-specific factors contributing to epilepsy, increasing healthcare funding, subsidizing the costs of treatment, deploying mobile tools for extensive screening, launching awareness campaigns to dispel myths and reduce stigma, and promoting collaborations between traditional healers and medical practitioners to enhance local understanding and epilepsy management. Despite the difficulties, significant progress can be achieved through sustained and compassionate efforts to understand and eliminate the barriers faced by epilepsy patients in the region. This review outlines essential steps for alleviating the epilepsy burden in the DRC. PLAIN LANGUAGE SUMMARY: There are not enough resources to treat epilepsy in the DRC. PWEs struggle with stigma and the lack of money. Many of them still use traditional medicine for treatment and hold wrong beliefs about epilepsy. That is why there is a need for more resources to make the lives of PWEs better in the DRC.
Topics: Animals; Humans; Democratic Republic of the Congo; Onchocerciasis; Onchocerca volvulus; Epilepsy; Risk Factors
PubMed: 38243880
DOI: 10.1002/epi4.12904 -
Tropical Medicine and Infectious Disease Sep 2023WHO and endemic countries target elimination of transmission of , the parasite causing onchocerciasis. Population genetic analysis of may provide data to improve the...
WHO and endemic countries target elimination of transmission of , the parasite causing onchocerciasis. Population genetic analysis of may provide data to improve the evidence base for decisions on when, where, and for how long to deploy which interventions and post-intervention surveillance to achieve elimination. Development of necessary methods and tools requires parasites suitable for genetic analysis. Based on our experience with microfilariae obtained from different collaborators, we developed a microfilariae transfer procedure for large-scale studies in the Democratic Republic of Congo (DRC) comparing safety and efficacy of ivermectin, the mainstay of current onchocerciasis elimination strategies, and moxidectin, a new drug. This procedure is designed to increase the percentage of microfilariae in skin snips suitable for genetic analysis, improve assignment to metadata, and minimize time and materials needed by the researchers collecting the microfilariae. Among 664 microfilariae from South Sudan, 35.7% and 39.5% failed the mitochondrial and nuclear qPCR assay. Among the 576 microfilariae from DRC, 16.0% and 16.7% failed these assays, respectively. This difference may not only be related to the microfilariae transfer procedure but also to other factors, notably the ethanol concentration in the tubes in which microfilariae were stored (64% vs. ≥75%).
PubMed: 37755906
DOI: 10.3390/tropicalmed8090445