Evidence mapPaperPMID 27923948Full record

ArticleThe Journal of infectious diseases2016

Decreased Rate of Plasma Arginine Appearance in Murine Malaria May Explain Hypoargininemia in Children With Cerebral Malaria.

Matthew S Alkaitis, Honghui Wang, Allison K Ikeda, Carol A Rowley, Ian J C MacCormick, Jessica H Chertow, Oliver Billker, Anthony F Suffredini, David J Roberts, Terrie E Taylor and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

18 citing papers in PubMed, 28 citations in OpenAlex.

  1. Application of Multiplatform Mass Spectrometry to the Study ofInternational journal of molecular sciences · 2025
    Article
  2. Article
  3. Article
  4. Article
  5. Diagnosis of cerebral malaria: Tools to reduceFrontiers in cellular and infection microbiology · 2023
    Review
  6. Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy.International journal of molecular sciences · 2022
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Observational
  15. Article
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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

12 authors at 7 institutions in 3 countries.

Matthew S AlkaitisLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville.
Honghui WangCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Allison K IkedaLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville.
Carol A RowleyLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville.
Ian J C MacCormickDepartment of Eye and Vision Science, University of Liverpool.
Jessica H ChertowLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville.
Oliver BillkerWellcome Trust Sanger Institute, Hinxton.
Anthony F SuffrediniCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
David J RobertsRadcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Headington.
Terrie E TaylorMichigan State University, East Lansing.
Karl B SeydelMichigan State University, East Lansing.
Hans C AckermanLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville.
National Institute of Allergy and Infectious Diseases · USBlantyre Institute for Community Ophthalmology · MWNational Institutes of Health · USNational Institutes of Health Clinical Center · USJohn Radcliffe Hospital · GBMalawi-Liverpool-Wellcome Trust Clinical Research Programme · MWWellcome Sanger Institute · GB

Funding

MEDICAL SCIENTIST TRAININGT32GM007753 · HARVARD UNIVERSITY (MEDICAL SCHOOL) · 1985 to 2005
$11.4M
Nitric Oxide and Endothelial Function in Patients with MalariaZIAAI001150 · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2025 to 2025
$2.0M
Department of Health RP-PG-0310-1004NIGMS NIH HHS T32 GM007753Wellcome Trust
6 · The paper itself

Abstract

backgroundPlasmodium infection depletes arginine, the substrate for nitric oxide synthesis, and impairs endothelium-dependent vasodilation. Increased conversion of arginine to ornithine by parasites or host arginase is a proposed mechanism of arginine depletion.

methodsWe used high-performance liquid chromatography to measure plasma arginine, ornithine, and citrulline levels in Malawian children with cerebral malaria and in mice infected with Plasmodium berghei ANKA with or without the arginase gene. Heavy isotope-labeled tracers measured by quadrupole time-of-flight liquid chromatography-mass spectrometry were used to quantify the in vivo rate of appearance and interconversion of plasma arginine, ornithine, and citrulline in infected mice.

resultsChildren with cerebral malaria and P. berghei-infected mice demonstrated depletion of plasma arginine, ornithine, and citrulline. Knock out of Plasmodium arginase did not alter arginine depletion in infected mice. Metabolic tracer analysis demonstrated that plasma arginase flux was unchanged by P. berghei infection. Instead, infected mice exhibited decreased rates of plasma arginine, ornithine, and citrulline appearance and decreased conversion of plasma citrulline to arginine. Notably, plasma arginine use by nitric oxide synthase was decreased in infected mice.

conclusionsSimultaneous arginine and ornithine depletion in malaria parasite-infected children cannot be fully explained by plasma arginase activity. Our mouse model studies suggest that plasma arginine depletion is driven primarily by a decreased rate of appearance.

Indexed as

AnimalsArginaseArginineChildChild, PreschoolChromatography, High Pressure LiquidCitrullineFemaleHumansInfantMalariaMalaria, CerebralMalawiMaleMiceMice, Inbred C57BLArginaseArginineCitrullineOrnithineendotheliumhost responsemetabolismnitric oxideplasmodiumurea cycle

Identifiers

PMID27923948
PMCPMC5142086
OpenAlexW2560087368

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.