Please use this identifier to cite or link to this item:
Title: Cerebrospinal fluid pterins, pterin-dependent neurotransmitters, and mortality in pediatric cerebral malaria.
Authors: Rubach MP
Mukemba JP
Florence SM
Lopansri BK
Hyland K
Simmons RA
Langelier C
Nakielny S
DeRisi JL
Yeo TW
Anstey NM
Weinberg JB
Mwaikambo ED
Granger DL
Citation: © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail:
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:
Journal title: The Journal of infectious diseases
Publication Date: 2021-02-22
Type: Journal Article
DOI: 10.1093/infdis/jiab086
Appears in Collections:(a) NT Health Research Collection

Files in This Item:
There are no files associated with this item.

Items in ePublications are protected by copyright, with all rights reserved, unless otherwise indicated.

Google Media

Google ScholarTM

Who's citing


PubMed References

Who's citing