River blindness goes beyond the eye: autoimmune antibodies, cross-reactive with Onchocerca volvulus antigen, detected in brain of patients with Nodding syndrome

Kaiser, C; Pion, Sébastien

doi:10.21037/atm.2017.08.35

Cited by 4 publications

(4 citation statements)

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“…43 Although an immunopathogenic model could provide a plausible explanation for the complex pattern of dysfunction observed in NS, these findings need to be confirmed. [44][45][46] The present case series is completing our previous case report of NS from western Uganda, 5 confirming that this severe and debilitating condition is not confined to the hitherto confirmed areas of Tanzania, South Sudan, and northern Uganda. We suggest that the existence of NS should be systematically searched for in other O. volvulus-endemic areas.…”

Section: Discussionsupporting

confidence: 86%

“…Our findings are in line with widely growing evidence that onchocerciasis, in addition to the known manifestations at the skin and the eye, is causing devastating and in many cases lethal brain disease. 3,5,8,10,35,[38][39][40]43,[46][47][48][49][50][51] This is reenforcing the urgency to persevere and intensify onchocerciasis control measures which have been shown to be feasible and efficient. 52 In this field, Uganda can be considered as an exemplary model having achieved elimination of onchocerciasis in several foci, including the Itwara focus.…”

Section: Discussionmentioning

confidence: 99%

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Onchocerciasis-Associated Epilepsy with Head Nodding Seizures—Nodding Syndrome: A Case Series of 15 Patients from Western Uganda, 1994

Kaiser

Asaba

Rubaale

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Nodding syndrome (NS) is an encephalopathy characterized by the core symptom of epileptic head nodding seizures, affecting children at the age between 3 and 18 years in distinct areas of tropical Africa. A consistent correlation with onchocerciasis was found, but so far, the causation of NS has not been fully clarified. With a systematic analysis of features of a cohort of epilepsy patients examined in the Itwara onchocerciasis focus of western Uganda in 1994, we provide evidence that NS actually occurred in this area at this time, and we demonstrate a correlation between prevalence of NS and that of onchocerciasis in different villages. Following the elimination of onchocerciasis by community-directed treatment with ivermectin and ground larviciding, our data provide a baseline to examine the question whether NS will disappear once its putative cause has been removed.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Onchocerciasis-Associated Epilepsy with Head Nodding Seizures—Nodding Syndrome: A Case Series of 15 Patients from Western Uganda, 1994

Kaiser

Asaba

Rubaale

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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“…cold and food), frequently progressing towards generalized convulsions and accompanied by malnutrition, behaviour problems, delayed physical development, lack of secondary sexual characteristics and cognitive defects [2][3][4][5][6][7] . Since 2009, various investigations into the possible causes have been performed, resulting in several hypotheses with respect to its etiology, however, none of these hypotheses has been formally confirmed [1,2,[7][8][9][10][11][12][13][14][15] . As there is still no known cure, an action plan was developed to provide Nodding syndrome patients with symptomatic care [16] .…”

Section: Introductionmentioning

confidence: 99%

Dried Blood Microsampling-Based Therapeutic Drug Monitoring of Antiepileptic Drugs in Children With Nodding Syndrome and Epilepsy in Uganda and the Democratic Republic of the Congo

Velghe

Delahaye

Ogwang

et al. 2020

Therapeutic Drug Monitoring

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Nodding syndrome is a highly debilitating, generalized seizure disorder, affecting children in subregions of sub-Saharan Africa. Despite many efforts towards finding its etiology, the exact cause of the syndrome still remains obscure. Therefore, to date, patients only receive a symptomatic care, including the administration of first-generation anti-epileptic drugs (AEDs) for seizure control. Since information about medication effectiveness within this population is completely lacking, the aim of this study was to perform therapeutic drug monitoring (TDM) to seek whether an answer could be provided to the question why for some patients the symptoms decrease, whilst in others the epileptic seizures remain poorly controlled. Seeing the challenging context in which sampling needed to take place (remote areas, devoid of electricity, running water, etc.), dried blood matrices (i.e. dried blood spots (DBS) and volumetric absorptive microsampling (VAMS) devices) were considered fit-for-purpose.Seeing the similarities between the syndrome and other forms of epilepsy, also samples originating from patients suffering from (onchocerciasis-associated) epilepsy were included.In total, 68 patients with Nodding syndrome from Uganda, 58 Ugandan patients with epilepsy and 137 patients with onchocerciasis-associated epilepsy from the Democratic Republic of the Congo (DRC) were included in this study. VAMS samples and DBS were analyzed using fully validated methods, involving manual extraction or fully automated extraction, respectively, prior to quantification using liquid chromatography coupled to tandem mass spectrometry.Analysis revealed that serum concentrations (calculated from DBS) within the respective reference ranges were attained for only 52.9% of the 68 Nodding syndrome patients treated with valproic acid, for 21.4% of the 56 Ugandan epilepsy patients treated with carbamazepine, and for 65.7% of the 137 onchocerciasis-associated epilepsy patients from the DRC treated with phenobarbital. In all other instances, concentrations were subtherapeutic. Furthermore, when comparing DBS to VAMS concentrations, an inexplicable overestimation was observed in the latter. Finally, no obvious link could be observed between the obtained drug concentrations and the amount of seizures experienced during the last month before sampling, disclosing the fact that the level of improvement of some patients cannot simply linked to reaching therapeutic concentrations.

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“…There is still however, no clear biomarker for NS and the cause remains unknown despite a consistent epidemiological association with onchocerciasis, a parasitic infection transmitted by the blackfly [7, 13–15]. On-going research is exploring whether NS could be an auto-immune reaction to Onchocerca volvulus (OV)[16, 17] , the parasite causing river blindness [18] or an OV- induced neuro-inflammatory disorder [19] or a post-measles brain disorder triggered by malnutrition [20] or an autism spectrum disorder [21]. Another recent study suggests that NS in Uganda is a neurodegenerative disease [22].…”

Section: Introductionmentioning

confidence: 99%

"Those who died are the ones that are cured". Walking the political tightrope of Nodding Syndrome in northern Uganda: Emerging challenges for research and policy

et al. 2019

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Background Nodding Syndrome was first reported from Tanzania in the 1960s but appeared as an epidemic in Northern Uganda in the 1990s during the LRA civil war. It is characterized by repetitive head nodding, often followed by other types of seizures, developmental retardation and growth faltering with onset occurring in children aged 5–15 years. More than 50 years after the first reports, the aetiology remains unknown and there is still no cure. The recent hypothesis that Nodding Syndrome is caused by onchocerciasis also increases the relevance of onchocerciasis control. Northern Uganda, with its unique socio-political history, adds challenges to the prevention and treatment for Nodding Syndrome. This article aims to show how and why Nodding Syndrome has been politicised in Uganda; how this politicisation has affected health interventions including research and dissemination; and, the possible implications this can have for disease prevention and treatment. Methodology Ethnographic research methods were used triangulating in-depth interviews, focus group discussions, informal conversations and participant observation, for an understanding of the various stakeholders’ perceptions of Nodding Syndrome and how these perceptions impact future interventions for prevention, treatment and disease control. Principal findings Distrust towards the government was a sentiment that had developed in Northern Uganda over several decades of war and was particularly linked to the political control and ethnic divisions between the north and south. This coincided with the sudden appearance of Nodding Syndrome, an unknown epidemic disease of which the cause could not be clearly identified and optimal treatment had not clearly been established. Additionally, the dissemination of the inconclusive results of research conducted in the area lacked sufficient community involvement which further fueled this political distrust. Disease perceptions revolved around rumours that the entire Acholi ethnic group of the north would be annihilated, or that international researchers were making money by stealing study samples. This discouraged some community members from participating in research or from accepting the mass drug administration of ivermectin for prevention and treatment of onchocerciasis. Such rumour and distrust led to suspicions concerning the integrity of the disseminated results, which may negatively impact future disease management and control interventions. Conclusions and recommendations Trust must be built up gradually through transparency and by de-politicising interventions. This can be done by engaging the community at regular intervals during research and data collection and the dissemination of results in addition to involvement during service delivery for prevention and treatment. Maintaining a regular feedback loop with the community will help control rumours, build trust, and improve the preparations for adequate dis...

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River blindness goes beyond the eye: autoimmune antibodies, cross-reactive with Onchocerca volvulus antigen, detected in brain of patients with Nodding syndrome

Cited by 4 publications

References 31 publications

Onchocerciasis-Associated Epilepsy with Head Nodding Seizures—Nodding Syndrome: A Case Series of 15 Patients from Western Uganda, 1994

Onchocerciasis-Associated Epilepsy with Head Nodding Seizures—Nodding Syndrome: A Case Series of 15 Patients from Western Uganda, 1994

Dried Blood Microsampling-Based Therapeutic Drug Monitoring of Antiepileptic Drugs in Children With Nodding Syndrome and Epilepsy in Uganda and the Democratic Republic of the Congo

"Those who died are the ones that are cured". Walking the political tightrope of Nodding Syndrome in northern Uganda: Emerging challenges for research and policy

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