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- 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
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusion: </bold>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.
- Publication
Journal of Infectious Diseases, 2021, Vol 224, Issue 8, p1432
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiab086