Evidence map›Paper›PMID 33617646›Full record

ArticleThe Journal of infectious diseases2021

Cerebrospinal Fluid Pterins, Pterin-Dependent Neurotransmitters, and Mortality in Pediatric Cerebral Malaria.

Matthew P Rubach, Jackson P Mukemba, Salvatore M Florence, Bert K Lopansri, Keith Hyland, Ryan A Simmons, Charles Langelier, Sara Nakielny, Joseph L DeRisi, Tsin W Yeo and 4 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 8 institutions in 4 countries.

Matthew P RubachDepartment of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA.ORCID 0000-0001-5262-1421
Jackson P MukembaDepartment of Pediatrics, Hubert Kairuki Memorial University, Dar es Salaam, United Republic of Tanzania.
Salvatore M FlorenceDepartment of Pediatrics, Hubert Kairuki Memorial University, Dar es Salaam, United Republic of Tanzania.
Bert K LopansriDepartment of Medicine, Intermountain Healthcare, Salt Lake City, Utah, USA.
Keith HylandMedical Neurogenetics Laboratories, Atlanta, Georgia, USA.
Ryan A SimmonsDuke Global Health Institute, Duke University, Durham, North Carolina, USA.
Charles LangelierDepartment of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0002-6708-4646
Sara NakielnyChan Zuckerberg Biohub, San Francisco, California, USA.
Joseph L DeRisiChan Zuckerberg Biohub, San Francisco, California, USA.
Tsin W YeoGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Australia.
Nicholas M AnsteyGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Australia.
J Brice WeinbergDepartment of Medicine, Duke University and VA Medical Centers, Durham, North Carolina, USA.
Esther D MwaikamboDepartment of Pediatrics, Hubert Kairuki Memorial University, Dar es Salaam, United Republic of Tanzania.
Donald L GrangerDepartment of Medicine, University of Utah School of Medicine and VA Medical Center, Salt Lake City, Utah, USA.
Duke University · USHubert Kairuki Memorial University · TZUniversity of California, San Francisco · USChan Zuckerberg Initiative (United States) · USIntermountain Healthcare · USMenzies School of Health Research · AUNanyang Technological University · SGUniversity of Utah · US

Funding

NITRIC OXIDE AND SEVERE MALARIAR01AI041764 · NIAID · DUKE UNIVERSITY · PI WEINBERG, JOE BRICE · 1997 to 2012
$6.3M
Nitric Oxide and Microvascular Dysfunction in Severe MalariaR01HL130763 · NHLBI · DUKE UNIVERSITY · PI WEINBERG, JOE BRICE · 2015 to 2018
$1.5M
Viral Zoonoses and Severe Febrile Illness in Northern TanzaniaK23AI116869 · NIAID · DUKE UNIVERSITY · PI RUBACH, MATTHEW P · 2016 to 2020
$896k
NHLBI NIH HHS R01 HL130763NIAID NIH HHS K23 AI116869NIAID NIH HHS R01 AI041764
6 · The paper itself

Abstract

backgroundCerebral 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.

methodsWe 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.

resultsCerebrospinal 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).

conclusionDespite 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.

Indexed as

BiopterinsCentral Nervous System DiseasesChildChild, PreschoolFemaleHomovanillic AcidHumansHydroxyindoleacetic AcidInfantMalaria, CerebralMaleNeopterinNeurotransmitter AgentsProspective StudiesPterinsReference Values3-methoxytyrosineBiopterinsHomovanillic AcidHydroxyindoleacetic AcidNeopterinNeurotransmitter AgentsPterinssapropterinTyrosinecerebral malarianeopterinneurotransmitterP falciparumtetrahydrobiopterin

Identifiers

PMID33617646
PMCPMC8682765
OpenAlexW3130060444

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.