Evidence map›Paper›PMID 30753363›Full record

Observational studyClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019

Glycocalyx Breakdown Is Associated With Severe Disease and Fatal Outcome in Plasmodium falciparum Malaria.

Tsin W Yeo, J Brice Weinberg, Daniel A Lampah, Enny Kenangalem, Peggy Bush, Youwei Chen, Richard N Price, Sarah Young, Hao Y Zhang, David Millington and 2 more

Open access · bronzeAbstract readObservational Study
In one paragraph

Observational study in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

30 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Elevated urinary glycosaminoglycans inJournal of medical microbiology · 2026
    Article
  3. Serum Proteomics Reveals Systemic Responses inPathogens (Basel, Switzerland) · 2025
    Article
  4. Febrile temperature enhancesbioRxiv : the preprint server for biology · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. Observational
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Biochemical characteristics of patients with imported malaria.Frontiers in cellular and infection microbiology · 2022
    Article
  17. Biophysical Tools and Concepts Enable Understanding of Asexual Blood Stage Malaria.Frontiers in cellular and infection microbiology · 2022
    Review
  18. Article
  19. Degradation of endothelial glycocalyx in Tanzanian children with falciparum malaria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 5 countries.

Tsin W YeoGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
J Brice WeinbergDuke University School of Medicine and VA Medical Center, Durham, North Carolina.
Daniel A LampahPapuan Health and Community Development Foundation, Timika, Papua, Indonesia.
Enny KenangalemPapuan Health and Community Development Foundation, Timika, Papua, Indonesia.
Peggy BushDuke University School of Medicine and VA Medical Center, Durham, North Carolina.
Youwei ChenDuke University School of Medicine and VA Medical Center, Durham, North Carolina.
Richard N PriceGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
Sarah YoungDuke University School of Medicine and VA Medical Center, Durham, North Carolina.
Hao Y ZhangDuke University School of Medicine and VA Medical Center, Durham, North Carolina.
David MillingtonDuke University School of Medicine and VA Medical Center, Durham, North Carolina.
Donald L GrangerUniversity of Utah and VA Medical Centers, Salt Lake City.
Nicholas M AnsteyGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
Duke University · USMenzies School of Health Research · AUState University of Papua · IDLake City VA Medical Center · USNanyang Technological University · SG

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
NHLBI NIH HHS R01 HL130763NIAID NIH HHS R01 AI041764Wellcome Trust 200909Wellcome Trust 200909/Z/16/Z
6 · The paper itself

Abstract

backgroundInteractions between the endothelium and infected erythrocytes play a major role in the pathogenesis of falciparum malaria, with microvascular dysfunction and parasite sequestration associated with worsening outcomes. The glycocalyx is a carbohydrate-rich layer that lines the endothelium, with multiple roles in vascular homeostasis. The role of the glycocalyx in falciparum malaria and the association with disease severity has not been investigated.

methodsWe prospectively enrolled Indonesian inpatients (aged ≥18 years) with severe (SM) or moderately severe (MSM) falciparum malaria, as defined by World Health Organization criteria, and healthy controls (HCs). On enrollment, blood and urine samples were collected concurrently with measurements of vascular nitric oxide (NO) bioavailability. Urine was assayed for glycocalyx breakdown products (glycosaminoglycans) using a dimethylmethylene blue (GAG-DMMB) and liquid chromatography-tandem mass spectrometry (GAG-MS) assay.

resultsA total of 129 patients (SM = 43, MSM = 57, HC=29) were recruited. GAG-DMMB and GAG-MS (g/mol creatinine) were increased in SM (mean, 95% confidence interval: 3.98, 2.44-5.53 and 6.82, 5.19-8.44) compared to MSM patients (1.78, 1.27-2.29 and 4.87, 4.27-5.46) and HCs (0.22, 0.06-0.37 and 1.24, 0.89-1.59; P < 0.001). In SM patients, GAG-DMMB and GAG-MS were increased in those with a fatal outcome (n = 3; median, interquartile range: 6.72, 3.80-27.87 and 12.15, 7.88-17.20) compared to survivors (n = 39; 3.10, 0.46-4.5 and 4.64, 2.02-15.20; P = 0.03). Glycocalyx degradation was significantly associated with parasite biomass in both MSM (r = 0.48, GAG-DMMB and r = 0.43, GAG-MS; P < 0.001) and SM patients (r = 0.47, P = 0.002 and r = 0.33, P = 0.04) and inversely associated with endothelial NO bioavailability.

conclusionsIncreased endothelial glycocalyx breakdown is associated with severe disease and a fatal outcome in adults with falciparum malaria.

Indexed as

Host-Parasite InteractionsAdolescentAdultEndothelium, VascularErythrocytesFemaleGlycocalyxGlycosaminoglycansHumansIndonesiaMalaria, FalciparumMaleMiddle AgedNitric OxidePlasmodium falciparumProspective StudiesGlycosaminoglycansNitric OxideendotheliumglycocalyxPlasmodium falciparumsevere malaria

Identifiers

PMID30753363
PMCPMC6821254
OpenAlexW2913809202

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.