Identifying the Components of Acidosis in Patients With Severe Plasmodium falciparum Malaria Using Metabolomics.
Plasmodium falciparum
malaria
gut-barrier integrity
metabolic acidosis
metabolomics
severe
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
05 05 2019
05 05 2019
Historique:
received:
19
09
2018
accepted:
15
12
2018
pubmed:
20
12
2018
medline:
17
3
2020
entrez:
20
12
2018
Statut:
ppublish
Résumé
Acidosis in severe Plasmodium falciparum malaria is associated with high mortality, yet the pathogenesis remains incompletely understood. The aim of this study was to determine the nature and source of metabolic acids contributing to acidosis in patients with severe falciparum malaria. A prospective observational study was conducted to characterize circulating acids in adults with P. falciparum malaria (n = 107) and healthy controls (n = 45) from Bangladesh using high-resolution liquid chromatography-mass spectrometry metabolomics. Additional in vitro P. falciparum culture studies were performed to determine if parasites release the acids detected in plasma from patients with severe malaria acidosis. We identified previously unmeasured plasma acids strongly associated with acidosis in severe malaria. Metabolomic analysis of P. falciparum parasites in vitro showed no evidence that these acids are released by the parasite during its life cycle. Instead, 10 of the plasma acids could be mapped to a gut microbial origin. Patients with malaria had low L-citrulline levels, a plasma marker indicating reduced gut barrier integrity. Longitudinal data showed the clearance of these newly identified acids was delayed in fatal cases. These data suggest that a compromise in intestinal barrier function may contribute significantly to the pathogenesis of life-threatening acidosis in severe falciparum malaria. NCT02451904.
Sections du résumé
BACKGROUND
Acidosis in severe Plasmodium falciparum malaria is associated with high mortality, yet the pathogenesis remains incompletely understood. The aim of this study was to determine the nature and source of metabolic acids contributing to acidosis in patients with severe falciparum malaria.
METHODS
A prospective observational study was conducted to characterize circulating acids in adults with P. falciparum malaria (n = 107) and healthy controls (n = 45) from Bangladesh using high-resolution liquid chromatography-mass spectrometry metabolomics. Additional in vitro P. falciparum culture studies were performed to determine if parasites release the acids detected in plasma from patients with severe malaria acidosis.
RESULTS
We identified previously unmeasured plasma acids strongly associated with acidosis in severe malaria. Metabolomic analysis of P. falciparum parasites in vitro showed no evidence that these acids are released by the parasite during its life cycle. Instead, 10 of the plasma acids could be mapped to a gut microbial origin. Patients with malaria had low L-citrulline levels, a plasma marker indicating reduced gut barrier integrity. Longitudinal data showed the clearance of these newly identified acids was delayed in fatal cases.
CONCLUSIONS
These data suggest that a compromise in intestinal barrier function may contribute significantly to the pathogenesis of life-threatening acidosis in severe falciparum malaria.
CLINICAL TRIALS REGISTRATION
NCT02451904.
Identifiants
pubmed: 30566600
pii: 5253254
doi: 10.1093/infdis/jiy727
pmc: PMC6500555
doi:
Substances chimiques
Acids
0
Biomarkers
0
Banques de données
ClinicalTrials.gov
['NCT02451904']
Types de publication
Clinical Trial
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1766-1776Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : F32 AI124507
Pays : United States
Organisme : Wellcome Trust
ID : 106698/B14/Z
Pays : United Kingdom
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.
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