Simple jQuery Dropdowns
Please use this identifier to cite or link to this item:
Title: Identifying the Components of Acidosis in Patients with Severe Plasmodium falciparum Malaria Using Metabolomics
Authors: Stije J. Leopold
Aniruddha Ghose
Erik L. Allman
Hugh W.F. Kingston
Amir Hossain
Asok Kumar Dutta
Katherine Plewes
Kesinee Chotivanich
Nicholas P.J. Day
Joel Tarning
Markus Winterberg
Nicholas J. White
Manuel Llinás
Arjen M. Dondorp
Mahidol University
Chittagong Medical College Hospital
Nuffield Department of Clinical Medicine
Pennsylvania State University
Huck Center for Malaria Research
Keywords: Medicine
Issue Date: 1-Jun-2019
Citation: Journal of Infectious Diseases. Vol.219, No.11 (2019), 1766-1776
Abstract: © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. 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.
ISSN: 15376613
Appears in Collections:Scopus 2019

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.