Evidence map›Paper›PMID 39658124›Full record

ArticleThe Journal of infectious diseases2025

Plasmodium knowlesi Infection Is Associated With Elevated Circulating Biomarkers of Brain Injury and Endothelial Activation.

Cesc Bertran-Cobo, Elin Dumont, Naqib Rafieqin Noordin, Meng-Yee Lai, William Stone, Kevin K A Tetteh, Chris Drakeley, Sanjeev Krishna, Yee-Ling Lau, Samuel C Wassmer

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Lung endothelial cytopathic tau is sufficient to impair long-term potentiation during infection.American journal of respiratory cell and molecular biology · 2026
    Article
  2. Article
  3. Review
4 · The record

Corrections and comments

  • Update of
    2024
5 · Who and what money

Authors and funding

10 authors.

Cesc Bertran-CoboDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, United Kingdom.ORCID 0000-0001-9286-9595
Elin DumontDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, United Kingdom.ORCID 0009-0007-1455-8493
Naqib Rafieqin NoordinDepartment of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.ORCID 0000-0001-8462-9831
Meng-Yee LaiDepartment of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
William StoneDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, United Kingdom.ORCID 0000-0002-6647-0166
Kevin K A TettehDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, United Kingdom.
Chris DrakeleyDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, United Kingdom.
Sanjeev KrishnaDepartment of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.ORCID 0000-0003-0066-0634
Yee-Ling LauDepartment of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.ORCID 0000-0002-2037-2165
Samuel C WassmerDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, United Kingdom.ORCID 0000-0002-6753-3376

Funding

Using Next-Generation Genomics to Study Antimalarial Drug Resistance in IndiaU19AI089676 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CARLTON, JANE M · 2010 to 2023
$22.6M
Investigating the role of cerebral vasoconstriction in cerebral malariaR21AI142472 · NIAID · LONDON SCH/HYGIENE & TROPICAL MEDICINE · PI HOFFMANN, ANGELIKA, WASSMER, SAM · 2019 to 2020
$290k
Medical Research Council UK MR/S009450/1)National Institute of Allergy and Infectious DiseasesNIAID NIH HHS R21 AI142472NIAID NIH HHS U19 AI089676NIH HHS U19AI089676)UK Medical Research Council MR/S009450/1)
6 · The paper itself

Abstract

backgroundMalaria remains a major public health concern with substantial morbidity and mortality worldwide. In Malaysia, the emergence of Plasmodium knowlesi has led to a surge in zoonotic malaria cases and deaths in recent years. Signs of cerebral involvement have been observed in a noncomatose, fatal case of knowlesi infection, but the potential impact of this malaria species on the brain remains unexplored. To address this gap, we investigated circulating levels of brain injury, inflammation, and vascular biomarkers in a cohort of knowlesi-infected patients and controls.

methodsArchived plasma samples from 19 Malaysian patients with symptomatic knowlesi infection and 19 healthy, age-matched controls were analyzed. Fifty-two biomarkers of brain injury, inflammation, and vascular activation were measured. Wilcoxon tests were used to examine group differences, and biomarker profiles were explored through hierarchical clustering heatmap analysis.

resultsBonferroni-corrected analyses revealed significantly elevated brain injury biomarker levels in knowlesi-infected patients, including S100B (P < .0001), Tau (P = .0007), UCH-L1 (P < .0001), αSyn (P < .0001), Park7 (P = .0006), NRGN (P = .0022), and TDP-43 (P = .005). Compared to controls, levels were lower in the infected group for BDNF (P < .0001), CaBD (P < .0001), CNTN1 (P < .0001), NCAM-1 (P < .0001), GFAP (P = .0013), and KLK6 (P = .0126). Hierarchical clustering revealed distinct group profiles for brain injury and vascular activation biomarkers.

conclusionsOur findings highlight for the first time a potential impact of P knowlesi infection on the brain, with specific changes in cerebral injury and endothelial activation biomarker profiles. Further studies are warranted to investigate the pathophysiology and clinical significance of these altered markers, through neuroimaging and long-term neurocognitive assessments.

Indexed as

BiomarkersBrain InjuriesMalariaMalaria, CerebralPlasmodium knowlesiAdultCase-Control StudiesFemaleHumansMalaysiaMaleMiddle AgedYoung AdultBiomarkersbrainmalariaMalaysiaPlasmodium knowlesivascular dysfunction

Identifiers

PMID39658124
PMCPMC12128082

What Socratic holds

Textmetadata
LicenceCC BY
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.