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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 characterise circulating acids in adults with P. falciparum malaria (n=107) and healthy controls (n=45) from Bangladesh using high-resolution LC-MS 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 ten 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. Discussion:These data suggest that a compromise in intestinal barrier function may contribute significantly to the pathogenesis of life-threatening acidosis in severe falciparum malaria.

Original publication

DOI

10.1093/infdis/jiy727

Type

Journal article

Journal

The Journal of infectious diseases

Publication Date

19/12/2018

Addresses

Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.