{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:09:12Z","timestamp":1790676552251,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000060","name":"US National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI041764"],"award-info":[{"award-number":["R01AI041764"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"US National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI041764"],"award-info":[{"award-number":["R01AI041764"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"US National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["K23AI116869"],"award-info":[{"award-number":["K23AI116869"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"US Veterans Affairs Medical Research Service"},{"name":"Australian National Health and Medical Research Council"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cerebral malaria (CM) pathogenesis remains incompletely understood. Having shown low systemic levels of tetrahydrobiopterin (BH4), an enzymatic cofactor for neurotransmitter synthesis, we hypothesized that BH4 and BH4-dependent neurotransmitters would likewise be low in cerebrospinal fluid (CSF) in CM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We prospectively enrolled Tanzanian children with CM and children with nonmalaria central nervous system conditions (NMCs). We measured CSF levels of BH4, neopterin, and BH4-dependent neurotransmitter metabolites, 3-O-methyldopa, homovanillic acid, and 5-hydroxyindoleacetate, and we derived age-adjusted z-scores using published reference ranges.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Cerebrospinal fluid BH4 was elevated in CM (n\u2005=\u200549) compared with NMC (n\u2005=\u200551) (z-score 0.75 vs \u22120.08; P\u2005&amp;lt;\u2005.001). Neopterin was increased in CM (z-score 4.05 vs 0.09; P\u2005&amp;lt;\u2005.001), and a cutoff at the upper limit of normal (60 nmol\/L) was 100% sensitive for CM. Neurotransmitter metabolite levels were overall preserved. A higher CSF BH4\/BH2 ratio was associated with increased odds of survival (odds ratio, 2.94; 95% confidence interval, 1.03\u20138.33; P\u2005=\u2005.043).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Despite low systemic BH4, CSF BH4 was elevated and associated with increased odds of survival in CM. Coma in malaria is not explained by deficiency of BH4-dependent neurotransmitters. Elevated CSF neopterin was 100% sensitive for CM diagnosis and warrants further assessment of its clinical utility for ruling out CM in malaria-endemic areas.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiab086","type":"journal-article","created":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T04:41:42Z","timestamp":1613018502000},"page":"1432-1441","source":"Crossref","is-referenced-by-count":7,"title":["Cerebrospinal Fluid Pterins, Pterin-Dependent Neurotransmitters, and Mortality in Pediatric Cerebral Malaria"],"prefix":"10.1093","volume":"224","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5262-1421","authenticated-orcid":false,"given":"Matthew P","family":"Rubach","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA"},{"name":"Duke Global Health Institute, Duke University, Durham, North Carolina, 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