Response to: ‘Nodding syndrome, many questions remain but we can prevent it by eliminating onchocerciasis’

Olum, Sam; Scolding, Peter; Hardy, Charlotte; Obol, James Henry; Scolding, Neil

doi:10.1093/braincomms/fcaa229

Cited by 4 publications

(1 citation statement)

References 11 publications

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“… 15 Combined with previous epidemiological counterarguments (e.g. that O. volvulus is endemic in many regions where NS has not been reported), 1 , 5 , 30 one obvious explanation is that onchocerciasis does not cause NS. It may also be possible that we failed to show a true association because of recent ivermectin use which is often given in mass drug administration campaigns to treat onchocerciasis.…”

Section: Discussionmentioning

confidence: 95%

Parasitic, bacterial, viral, immune-mediated, metabolic and nutritional factors associated with nodding syndrome

Edridge,

Abd-Elfarag,

Deijs

et al. 2023

Brain Communications

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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.

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