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Edridge, Arthur W D, Abd-Elfarag, Gasim, Deijs, Martin, Broeks, Melissa H, Cristella, Cosimo, Sie, Brandon, Vaz, Frédéric M, Jans, Judith J M, Calis, Job, Verhoef, Hans, Demir, Ayse, Poppert, Sven, Nickel, Beatrice, van Dam, Alje, Sebit, Boy, Titulaer, Maarten J, Verweij, Jaco J, de Jong, Menno D, van Gool, Tom, Faragher, Brian, Verhoeven-Duif, Nanda M, Elledge, Stephen J, van der Hoek, Lia and van Hensbroek, Michael Boele (2023) 'Parasitic, bacterial, viral, immune-mediated, metabolic, and nutritional factors associated with nodding syndrome'. Brain Communications, Vol 5, Issue 5, fcad223.
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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 O. volvulus, antileiomodin-1 antibodies, vitamin B6 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. From 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 [OR] 7.04, 95% confidence interval [CI] 2.28-21.7), Necator americanus infection (OR 2.33, 95% CI 1.02-5.3), higher antimalarial seroreactivity (OR 1.75, 95% CI 1.20-2.57), higher vitamin E concentration (OR 1.53 per standard deviation [SD] increase, 95% CI 1.07-2.19) and lower vitamin B12 concentration (OR 0.56 per SD increase, 95% CI 0.36-0.87) were associated with higher odds of NS. In a structural equation model, we hypothesized that M. perstans infection, higher vitamin E concentration and fewer viral exposures increased the risk of Nodding syndrome while lower vitamin B12 concentration, N. americanus and malaria infections resulted from having Nodding syndrome. We found no evidence that O. volvulus, antileiomodin-1 antibodies, vitamin B6 and other factors were associated with Nodding syndrome. Our results argue against several previous causal hypotheses including O. 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.
| Item Type: | Article |
|---|---|
| Subjects: | QW Microbiology and Immunology > Immunity by Type > QW 551 Acquired immunity. Artificial immunity WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 200 Bacterial infections (General or not elsewhere classified) WC Communicable Diseases > Virus Diseases > General Virus Diseases > WC 500 Virus diseases (General or not elsewhere classified) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 695 Parasitic diseases (General) |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1093/braincomms/fcad223 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 31 Aug 2023 10:02 |
| Last Modified: | 05 Oct 2023 13:52 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/23026 |
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