Edridge, A. W. D. and Abd-Elfarag, G. and Deijs, M. and Broeks, M. H. and Cristella, C. and Sie, B. and Vaz, F. M. and Jans, J. J. M. and Calis, J. and Verhoef, H. and Demir, A. and Poppert, S. and Nickel, B. and van Dam, A. and Sebit, B. and Titulaer, M. J. and Verweij, J. J. and de Jong, M. D. and van Gool, T. and Faragher, B. and Verhoeven-Duif, N. M. and Elledge, S. J. and van der Hoek, L. and Boele van Hensbroek, M.. (2023) Parasitic, bacterial, viral, immune-mediated, metabolic and nutritional factors associated with nodding syndrome. Brain Commun, 5 (5). fcad223.
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Official URL: https://edoc.unibas.ch/95950/
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Abstract
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 Onchocerca volvulus, antileiomodin-1 antibodies, vitamin B(6) 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. Mansonella perstans infection (odds ratio 7.04, 95% confidence interval 2.28-21.7), Necator americanus 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(12) 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 Mansonella perstans infection, higher vitamin E concentration and fewer viral exposures increased the risk of nodding syndrome while lower vitamin B(12) concentration, Necator americanus and malaria infections resulted from having nodding syndrome. We found no evidence that Onchocerca volvulus, antileiomodin-1 antibodies, vitamin B(6) and other factors were associated with nodding syndrome. Our results argue against several previous causal hypotheses including Onchocerca volvulus. 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.
Faculties and Departments: | 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Directorate (DIR) > Medical Services (Künzli/Neumayr) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medicine (MED) > Diagnostic (Nickel) |
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UniBasel Contributors: | Poppert, Sven and Nickel, Beatrice |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
ISSN: | 2632-1297 (Electronic)2632-1297 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
Related URLs: | |
Identification Number: |
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edoc DOI: | |
Last Modified: | 24 Oct 2023 08:59 |
Deposited On: | 24 Oct 2023 08:59 |
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