Background: Cerebral malaria (CM) is a severe neurological complication of Plasmodium falciparum infection. A number of pathological findings have been correlated with pediatric CM including sequestration, platelet accumulation, petechial haemorrhage and retinopathy. However, the molecular mechanisms leading to death in CM are not yet fully understood. Methods: A shotgun plasma proteomic study was conducted using samples form 52 Gambian children with CM admitted to hospital. Based on clinical outcome, children were assigned to two groups: reversible and fatal CM. Label-free liquid chromatography-tandem mass spectrometry was used to identify and compare plasma proteins that were differentially regulated in children who recovered from CM and those who died. Candidate biomarkers were validated using enzyme immunoassays. Results: The plasma proteomic signature of children with CM identified 266 proteins differentially regulated in children with fatal CM. Proteins from the coagulation cascade were consistently decreased in fatal CM, whereas the plasma proteomic signature associated with fatal CM underscored the importance of endothelial activation, tissue damage, inflammation, haemolysis and glucose metabolism. The concentration of circulating proteasomes or PSMB9 in plasma was not significantly different in fatal CM when compared with survivors. Plasma PSMB9 concentration was higher in patients who presented with seizures and was significantly correlated with the number of seizures observed in patients with CM during admission. Conclusions: The results indicate that increased tissue damage and hypercoagulability may play an important role in fatal CM. The diagnostic value of this molecular signature to identify children at high risk of dying to optimize patient referral practices should be validated prospectively.
|Original language||English (US)|
|State||Published - Sep 24 2018|
Bibliographical noteFunding Information:
MalariaGEN’s primary funding is from the Wellcome Trust (Grant Number 077383/Z/05/Z) and from the Bill & Melinda Gates Foundation, through the Foundation for the National Institutes of Health (Grant Number 566) as part of the Grand Challenges in Global Health initiative. Wellcome Trust [Grant 090532/Z/09/Z (core facilities Wellcome Trust Centre for Human Genetics)]; C.C‑P is supported by the Medical Research Council (Clinician Scientist Fellow‑ ship: G0701885).
© 2018 The Author(s).
- Acute phase reaction
- Cerebral malaria
- Plasmodium falciparum
ASJC Scopus subject areas
- Infectious Diseases
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Proteomic profiling of the plasma of Gambian children with cerebral malaria
Moussa, E. M. (Creator), Huang, H. (Creator), Thézénas, M. L. (Creator), Fischer, R. (Creator), Ramaprasad, A. (Creator), Sisay-Joof, F. (Creator), Jallow, M. (Creator), Pain, A. (Creator), Kwiatkowski, D. (Creator), Kessler, B. M. (Creator), Casals-Pascual, C. (Creator), Moussa, E. M. (Creator), Huang, H. (Creator), Thézénas, M. L. (Creator), Fischer, R. (Creator), Ramaprasad, A. (Creator), Sisay-Joof, F. (Creator), Jallow, M. (Creator), Kwiatkowski, D. (Creator), Kessler, B. M. (Creator) & Casals-Pascual, C. (Creator), figshare, 2018
DOI: 10.6084/m9.figshare.c.4242833.v1, http://hdl.handle.net/10754/664217