Cerebrospinal Fluid Pterins, Pterin-Dependent Neurotransmitters, and Mortality in Pediatric Cerebral Malaria Article Swipe
Matthew P. Rubach
,
Jackson Mukemba
,
Salvatore M. Florence
,
Bert K. Lopansri
,
Keith Hyland
,
Ryan Simmons
,
Charles Langelier
,
Sara Nakielny
,
Joseph L. DeRisi
,
Tsin Wen Yeo
,
Nicholas M. Anstey
,
J. Brice Weinberg
,
Esther D. Mwaikambo
,
Donald L. Granger
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1093/infdis/jiab086
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1093/infdis/jiab086
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 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. Results Cerebrospinal fluid BH4 was elevated in CM (n = 49) compared with NMC (n = 51) (z-score 0.75 vs −0.08; P < .001). Neopterin was increased in CM (z-score 4.05 vs 0.09; P < .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, 1.03–8.33; P = .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.
Related Topics
Concepts
Neopterin
Cerebrospinal fluid
Odds ratio
Internal medicine
Cerebral Malaria
Neurotransmitter
Homovanillic acid
Hyperphenylalaninemia
Medicine
Biopterin
Endocrinology
Tetrahydrobiopterin
Gastroenterology
Immunology
Biology
Malaria
Serotonin
Central nervous system
Plasmodium falciparum
Nitric oxide
Biochemistry
Receptor
Phenylalanine
Nitric oxide synthase
Amino acid
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/infdis/jiab086
- OA Status
- green
- Cited By
- 6
- References
- 45
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3130060444
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3130060444Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/infdis/jiab086Digital Object Identifier
- Title
-
Cerebrospinal Fluid Pterins, Pterin-Dependent Neurotransmitters, and Mortality in Pediatric Cerebral MalariaWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-02-11Full publication date if available
- Authors
-
Matthew P. Rubach, Jackson Mukemba, Salvatore M. Florence, Bert K. Lopansri, Keith Hyland, Ryan Simmons, Charles Langelier, Sara Nakielny, Joseph L. DeRisi, Tsin Wen Yeo, Nicholas M. Anstey, J. Brice Weinberg, Esther D. Mwaikambo, Donald L. GrangerList of authors in order
- Landing page
-
https://doi.org/10.1093/infdis/jiab086Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/8682765Direct OA link when available
- Concepts
-
Neopterin, Cerebrospinal fluid, Odds ratio, Internal medicine, Cerebral Malaria, Neurotransmitter, Homovanillic acid, Hyperphenylalaninemia, Medicine, Biopterin, Endocrinology, Tetrahydrobiopterin, Gastroenterology, Immunology, Biology, Malaria, Serotonin, Central nervous system, Plasmodium falciparum, Nitric oxide, Biochemistry, Receptor, Phenylalanine, Nitric oxide synthase, Amino acidTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
6Total citation count in OpenAlex
- Citations by year (recent)
-
2023: 3, 2022: 3Per-year citation counts (last 5 years)
- References (count)
-
45Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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