{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T21:41:59Z","timestamp":1769722919427,"version":"3.49.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":228,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007729","name":"Dutch Ministry of Foreign Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007729","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2014including Onchocerca volvulus, antileiomodin-1 antibodies, vitamin B6 deficiency and measles virus infection\u2014yet, none is proven causal. We conducted a case-control study of children with early-stage nodding syndrome (symptom onset &amp;lt;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\u201321.7), Necator americanus infection (odds ratio 2.33, 95% confidence interval 1.02\u20135.3), higher antimalarial seroreactivity (odds ratio 1.75, 95% confidence interval 1.20\u20132.57), higher vitamin E concentration (odds ratio 1.53 per standard deviation increase, 95% confidence interval 1.07\u20132.19) and lower vitamin B12 concentration (odds ratio 0.56 per standard deviation increase, 95% confidence interval 0.36\u20130.87) 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 B12 concentration, Necator americanus and malaria infections resulted from having nodding syndrome. We found no evidence that Onchocerca volvulus, antileiomodin-1 antibodies, vitamin B6 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.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad223","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T12:36:05Z","timestamp":1692189365000},"source":"Crossref","is-referenced-by-count":16,"title":["Parasitic, bacterial, viral, immune-mediated, metabolic and nutritional factors associated with nodding syndrome"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9264-5874","authenticated-orcid":false,"given":"Arthur W D","family":"Edridge","sequence":"first","affiliation":[{"name":"Amsterdam Centre for Global Child Health, Emma Children\u2019s Hospital, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"},{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gasim","family":"Abd-Elfarag","sequence":"additional","affiliation":[{"name":"Amsterdam Centre for Global Child Health, Emma Children\u2019s Hospital, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"},{"name":"Department of Neurology & Psychiatry, College of Medicine, University of Juba , P.O. Box 82, Juba , South Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Deijs","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa H","family":"Broeks","sequence":"additional","affiliation":[{"name":"Department of Genetics, Section Metabolic Diagnostics, University Medical Center Utrecht , 3584 CX Utrecht , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosimo","family":"Cristella","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Sie","sequence":"additional","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Howard Hughes Medical Institute , Boston, MA 02115 , USA"},{"name":"Department of Genetics, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9048-1041","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric M","family":"Vaz","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith J M","family":"Jans","sequence":"additional","affiliation":[{"name":"Department of Genetics, Section Metabolic Diagnostics, University Medical Center Utrecht , 3584 CX Utrecht , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Job","family":"Calis","sequence":"additional","affiliation":[{"name":"Amsterdam Centre for Global Child Health, Emma Children\u2019s Hospital, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"},{"name":"Department of Paediatrics and Child Health, Kamuzu University of Health Sciences , P.O. Box 95, Blantyre , Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-9689","authenticated-orcid":false,"given":"Hans","family":"Verhoef","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition and Health, Wageningen University , 6701 AR Wageningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayse","family":"Demir","sequence":"additional","affiliation":[{"name":"Laboratory for Clinical Chemistry and Hematology, Meander Medical Centre , 3813 TZ Amersfoort , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Poppert","sequence":"additional","affiliation":[{"name":"Diagnostic Centre, Swiss Tropical and Public Health Institute , University of Basel, 4123 Allschwil , Switzerland"},{"name":"University of Basel , 4056 Basel , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Nickel","sequence":"additional","affiliation":[{"name":"Diagnostic Centre, Swiss Tropical and Public Health Institute , University of Basel, 4123 Allschwil , Switzerland"},{"name":"University of Basel , 4056 Basel , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alje","family":"van Dam","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boy","family":"Sebit","sequence":"additional","affiliation":[{"name":"Department of Neurology & Psychiatry, College of Medicine, University of Juba , P.O. Box 82, Juba , South Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten J","family":"Titulaer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus MC University Medical Center , 3000 CA Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaco J","family":"Verweij","sequence":"additional","affiliation":[{"name":"Microvida Laboratory for Medical Microbiology and Immunology, Elisabeth-Tweesteden Hospital , 5022 GC Tilburg , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menno D","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"van Gool","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location University of Amsterdam , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Faragher","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine , Liverpool L3 5QA , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanda M","family":"Verhoeven-Duif","sequence":"additional","affiliation":[{"name":"Department of Genetics, Section Metabolic Diagnostics, University Medical Center Utrecht , 3584 CX Utrecht , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J","family":"Elledge","sequence":"additional","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Howard Hughes Medical Institute , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lia","family":"van der 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