Cerebrospinal fluid pterins, pterin-dependent neurotransmitters, and mortality in pediatric cerebral malaria
| dc.contributor.author | Kalabamu, Florence S. | |
| dc.contributor.author | Mwaikambo, Esther D. | |
| dc.date.accessioned | 2021-05-25T07:00:42Z | |
| dc.date.available | 2021-05-25T07:00:42Z | |
| dc.date.issued | 2021-02-22 | |
| dc.description.abstract | Background Cerebral malaria (CM) pathogenesis remains incompletely understood. Having shownlow systemic levels of tetrahydrobiopterin (BH4), an enzymatic cofactor forneurotransmitter synthesis, we hypothesized that BH4and BH4-dependentneurotransmitters would likewise be low in cerebrospinal fluid (CSF) in CM. Methods We prospectively enrolled Tanzanian children with CM and children with nonmalariacentral nervous system conditions (NMCs). We measured CSF levels of BH4, neopterin,and BH4-dependent neurotransmittermetabolites, 3-O-methyldopa, homovanillic acid,and 5-hydroxyindoleacetate, and we derived age-adjusted z-scores using publishedreference ranges. Results Cerebrospinal fluid BH4was 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 forCM. Neurotransmitter metabolite levels were overall preserved. A higher CSFBH4/BH2ratio 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 BH4was elevated and associated with increased odds ofsurvival in CM. Coma in malaria is not explained by deficiency of BH4-dependentneurotransmitters. Elevated CSF neopterin was 100% sensitive for CM diagnosis andwarrants further assessment of its clinical utility for ruling out CM in malaria-endemicareas. Keywords: cerebralmalaria, neopterin, neurotransmitter, Palciparum, tetrahydrobiopterin | en_US |
| dc.identifier.citation | Rubach, M.P., Mukemba, J.P., Florence, S.M., Lopansri, B.K., Hyland, K., Simmons, R.A., Langelier, C., Nakielny, S., DeRisi, J.L., Yeo, T.W. and Anstey, N.M., 2021. Cerebrospinal fluid pterins, pterin-dependent neurotransmitters, and mortality in pediatric cerebral malaria. The Journal of Infectious Diseases. | en_US |
| dc.identifier.other | https://doi.org/10.1093/infdis/jiab086 | |
| dc.identifier.uri | http://hdl.handle.net/123456789/731 | |
| dc.language.iso | en | en_US |
| dc.publisher | The Journal of Infectious Diseases | en_US |
| dc.subject | Cerebralmalaria | en_US |
| dc.subject | Neopterin | en_US |
| dc.subject | Neurotransmitter | en_US |
| dc.title | Cerebrospinal fluid pterins, pterin-dependent neurotransmitters, and mortality in pediatric cerebral malaria | en_US |
| dc.type | Article | en_US |