Please use this identifier to cite or link to this item: https://hdl.handle.net/10137/11669
Title: Cerebrospinal fluid pterins, pterin-dependent neurotransmitters, and mortality in pediatric cerebral malaria.
Authors: Rubach, Matthew P
Mukemba, Jackson P
Florence, Salvatore M
Lopansri, Bert K
Hyland, Keith
Simmons, Ryan A
Langelier, Charles
Nakielny, Sara
DeRisi, Joseph L
Yeo, Tsin W
Anstey, Nicholas M
Weinberg, J Brice
Mwaikambo, Esther D
Granger, Donald L
Citation: © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
J Infect Dis. 2021 Feb 22:jiab086. doi: 10.1093/infdis/jiab086.
Abstract: BACKGROUND: 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. METHODS: We prospectively enrolled Tanzanian children with CM and children with non-malaria central nervous system conditions (NMC). We measured CSF levels of BH4, neopterin, and BH4-dependent neurotransmitter metabolites, 3-O-methyldopa, homovanillic acid, and 5-hydroxyindoleacetate, and derived age-adjusted z-scores using published reference ranges. RESULTS: CSF BH4 was elevated in CM (n=49) compared to NMC (n=51) [z-score 0.75 vs. -0.08 (p<0.001)]. Neopterin was increased in CM [z-score 4.05 vs. 0.09 (p<0.001)], and a cut-off 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 (OR 2.94 [1.03-8.33]; p=0.043). CONCLUSION: 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.
Click to open Pubmed Article: https://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed/33617646
Journal title: The Journal of infectious diseases
Publication Date: 2021-02-22
Type: Journal Article
URI: https://hdl.handle.net/10137/11669
DOI: 10.1093/infdis/jiab086
Appears in Collections:(a) NT Health Research Collection

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