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

Cesc Bertran-Cobo1,2,3, Elin Dumont1, Naqib Rafieqin Noordin4

  • 1Department of Infection Biology, London School of Hygiene and Tropical Medicine, United Kingdom.

The Journal of Infectious Diseases
|December 10, 2024
PubMed
Abstract

Insights

This study reveals Plasmodium knowlesi malaria impacts the brain, showing altered brain injury and vascular biomarkers in infected patients. Further research is needed to understand the clinical significance of these findings.

Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Biomarker Research

Background:

  • Malaria, particularly Plasmodium knowlesi, poses a significant public health threat in Malaysia.
  • Zoonotic malaria cases are increasing, with observed cerebral involvement in fatal P. knowlesi infections.
  • The impact of P. knowlesi on the brain remains largely unexplored, necessitating investigation of relevant biomarkers.

Purpose of the Study:

  • To investigate circulating levels of brain injury, inflammation, and vascular biomarkers in patients with P. knowlesi infection.
  • To compare biomarker profiles between P. knowlesi-infected patients and healthy controls.
  • To identify potential indicators of cerebral involvement associated with P. knowlesi malaria.

Main Methods:

  • Analysis of archived plasma samples from 19 Malaysian patients with symptomatic P. knowlesi infection and 19 healthy controls.
  • Measurement of 52 biomarkers related to brain injury, inflammation, and vascular activation.
  • Statistical analysis using Wilcoxon tests and hierarchical clustering heatmap analysis to compare groups and explore biomarker profiles.

Main Results:

  • Significantly elevated levels of brain injury biomarkers (S100B, Tau, UCH-L1, αSyn, Park7, NRGN, TDP-43) were observed in P. knowlesi-infected patients.
  • Lower levels of certain biomarkers (BDNF, CaBD, CNTN1, NCAM-1, GFAP, KLK6) were found in the infected group compared to controls.
  • Distinct group profiles for brain injury and vascular activation biomarkers were identified through hierarchical clustering.

Conclusions:

  • P. knowlesi infection is associated with a potential impact on the brain, evidenced by altered biomarker profiles.
  • Specific changes in cerebral injury and endothelial activation biomarkers highlight a potential pathophysiological link.
  • Further research, including neuroimaging and neurocognitive assessments, is crucial to elucidate the clinical significance of these findings.
Keywords:
Plasmodium knowlesiMalaysiabrainmalariavascular dysfunction

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