Trial reportPLoS pathogens2015
Impaired systemic tetrahydrobiopterin bioavailability and increased oxidized biopterins in pediatric falciparum malaria: association with disease severity.
Trial report in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Systematic review of the role of angiopoietin-1 and angiopoietin-2 in Plasmodium species infections: biomarkers or therapeutic targets?Malaria journal · 2016Pooled it
- Application of a Non-Targeted Metabolomics Study inInternational journal of molecular sciences · 2025Article
- Longitudinal associations of plasma amino acid levels with recovery from malarial coma.Malaria journal · 2024Observational
- Longitudinal associations of plasma amino acid levels with recovery from malarial coma.Research square · 2024Article
- Host metabolomic responses in recurrent P. vivax malaria.Scientific reports · 2024Article
- Tetrahydrobiopterin: Beyond Its Traditional Role as a Cofactor.Antioxidants (Basel, Switzerland) · 2023Review
- Impact of Oxidative Stress on Risk of Death and Readmission in African Children With Severe Malaria: A Prospective Observational Study.The Journal of infectious diseases · 2022Observational
- Neurotransmitters and molecular chaperones interactions in cerebral malaria: Is there a missing link?Frontiers in molecular biosciences · 2022Review
- Cerebrospinal Fluid Pterins, Pterin-Dependent Neurotransmitters, and Mortality in Pediatric Cerebral Malaria.The Journal of infectious diseases · 2021Article
- Vascular Dysfunction in Malaria: Understanding the Role of the Endothelial Glycocalyx.Frontiers in cell and developmental biology · 2021Review
- Innate immunity to malaria-The role of monocytes.Immunological reviews · 2020Review
- Glycocalyx breakdown is increased in African children with cerebral and uncomplicated falciparum malaria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Glycocalyx Breakdown Is Associated With Severe Disease and Fatal Outcome in Plasmodium falciparum Malaria.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Observational
- L-arginine supplementation and thromboxane synthase inhibition increases cerebral blood flow in experimental cerebral malaria.Scientific reports · 2019Article
- Signatures of divergent anti-malarial treatment responses in peripheral blood from adults and young children in Malawi.Malaria journal · 2019Article
- Amino acid derangements in adults with severe falciparum malaria.Scientific reports · 2019Article
- Kinetic and Cross-Sectional Studies on the Genesis of Hypoargininemia in Severe PediatricInfection and immunity · 2019Observational
- Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak.PloS one · 2019Article
- Endothelial Activation: The Ang/Tie Axis in Sepsis.Frontiers in immunology · 2018Review
- Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2017Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Decreased bioavailability of nitric oxide (NO) is a major contributor to the pathophysiology of severe falciparum malaria. Tetrahydrobiopterin (BH4) is an enzyme cofactor required for NO synthesis from L-arginine. We hypothesized that systemic levels of BH₄ would be decreased in children with cerebral malaria, contributing to low NO bioavailability. In an observational study in Tanzania, we measured urine levels of biopterin in its various redox states (fully reduced [BH₄] and the oxidized metabolites, dihydrobiopterin [BH₂] and biopterin [B₀]) in children with uncomplicated malaria (UM, n = 55), cerebral malaria (CM, n = 45), non-malaria central nervous system conditions (NMC, n = 48), and in 111 healthy controls (HC). Median urine BH4 concentration in CM (1.10 [IQR:0.55-2.18] μmol/mmol creatinine) was significantly lower compared to each of the other three groups - UM (2.10 [IQR:1.32-3.14];p<0.001), NMC (1.52 [IQR:1.01-2.71];p = 0.002), and HC (1.60 [IQR:1.15-2.23];p = 0.005). Oxidized biopterins were increased, and the BH4:BH2 ratio markedly decreased in CM. In a multivariate logistic regression model, each Log10-unit decrease in urine BH4 was independently associated with a 3.85-fold (95% CI:1.89-7.61) increase in odds of CM (p<0.001). Low systemic BH4 levels and increased oxidized biopterins contribute to the low NO bioavailability observed in CM. Adjunctive therapy to regenerate BH4 may have a role in improving NO bioavailability and microvascular perfusion in severe falciparum malaria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.